A Real-World Safety Analysis of Infection-Related Adverse Events Associated with Belimumab, Rituximab, and TNF-α Inhibitors Using the FAERS Database

A Real-World Safety Analysis of Infection-Related Adverse Events Associated with Belimumab, Rituximab, and TNF-α Inhibitors Using the FAERS Database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article A Real-World Safety Analysis of Infection-Related Adverse Events Associated with Belimumab, Rituximab, and TNF-α Inhibitors Using the FAERS Database Wang Sisi, Shao Liu, Sheng Deng, Yuting Huang, Rong Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6638648/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 16 You are reading this latest preprint version Abstract Objective The study aims to evaluate infection-related safety profiles of belimumab, rituximab, and TNF-α inhibitors using the FDA Adverse Event Reporting System (FAERS) database. Methods A disproportionality analysis combining Reporting Odds Ratios (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) was conducted on FAERS data from Q1 2014 to Q2 2024. Results Belimumab and rituximab are more likely to cause progressive multifocal leukoencephalopathy(PML), while infliximab show a greater variety tuberculosis(TB)-related AEs than other biological agents. Rituximab exhibited a risk association with hepatitis B virus reactivation and sepsis-related AEs. Most of these infection AEs are listed in drug packaging labels, our study also identified some rare and potential AEs such as cutaneous leishmaniasis, gallbladder empyema, leprosy, chikungunya virus infection and dengue fever. Conclusion Belimumab, rituximab, and TNF-α inhibitors exhibit distinct infection risks.. Clinicians should prioritize monitoring for severe events like PML, TB, and hepatitis B viral reactivation. However, epidemiological investigations and further causality assessments are required. Health sciences/Health care/Drug regulation Health sciences/Health care/Therapeutics/Adverse effects Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Belimumab, as a human immunoglobulin G1λ monoclonal antibody (mAb) targeting B lymphocyte stimulator, was approved by the US Food and Drug Administration(FDA) and European Medicine Agency(EMA) in 2011 for the treatment of systemic lupus erythematosus (SLE )1,2 .Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody approved in 1997 ,which is widely used for the treatment of lymphoma 3 , rheumatoid arthritis(RA) 4 , immune thrombocytopenia 5 , and chronic lymphocytic leukemia 6 . Adalimumab(ADA), etanercept(ETN), infliximab(INF), golimumab(GOL), and certolizumab pegol(CZB), are inhibitor of tumor necrosis factor alpha(TNF-α), which are an indispensable part for the treatment of (RA), juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (PS) and Crohn's disease (CD) 7 – 11 . Biologics targeting TNF-α, B cells (rituximab/belimumab) have revolutionized autoimmune disease management. The preservation of immune homeostasis through systemic, cellular, and molecular coordination may paradoxically predispose patients to novel immune dysregulation patterns and iatrogenic complications when employing TNF-α inhibitors or biologics, therefore infections are one of the common adverse reactions associated with the use of biologics.While package inserts highlight common risks, real-world patterns of rare infections remain poorly characterized. This study leverages the FAERS database to identify underreported infection signals associated with these agents.Currently, there is no comprehensive study about infections and infestations related AEs of belimumab, rituximab and five TNF-α inhibitors after their long-term usage. As a platform for the public to collect and analyze the adverse drug events, the FDA Adverse Event Reporting System(FAERS) is a spontaneous reporting database due to the international and domestically reporters 12 . We aims to conduct a thorough analysis based on the FAERS data to reveal the real-world safety issues of the above seven biologics. Methods FEARS Procedure All the related FAERS data throughout the period of first quarter of 2014 to the second quarter of 2024 was analyzed using the MySQL8.0 data analytical platform and Microsoft Excel. Infection-related adverse events linked to belimumab were queried using their generic name “belimumab” and the trade name “Benlysta”. We also conducted the same procedure on rituximab(Mabthera), a CD20 antibody for the treatment of lymphoma and rheumatoid arthritis, as well as tumor necrosis factor(TNF) inhibitors including adalimumab(Humira), etanercept(Enbrel), infliximab(Remicade), golimumab(Simponi), certolizumab pegol(Cimzia). To ensure the accuracy of the results about the association between infection-related adverse reactions and the drugs mentioned above, only role_cod as primary suspected was incorporated. Infection-related AEs from the ‘REAC’ database were identified by the Medical Dictionary of Regulator Activities(MedDRA 25.0). The preferred terms(PTs) corresponding to the SOC names which are infections and infestations were selected in the study(Fig. 1 ). Statistical analysis To quantify the correlation between the seven biological pharmaceuticals and infection-related adverse reactions, disproportionality signal analysis, such as reporting odds ratios(ROR) and bayesian confidence propagation neural network(BCPNN) was utilized for the signal mining. The positive signal outcome could be more comprehensive and reliable throughout the combination of the two algorithms. Ratio imbalance measurement algorithm, calculation formula and detection thresholds were exhibited as follows (Tables 1 , 2 ). Table 1 The 2×2 contingency table Drug-related AEs Non-drug-related AEs total Drug a b a + b Non-drug c d c + d total a + c b + d N = a + b + c + d Table 2 Formula and thresholds Algorithm formula thresholds ROR ROR= a ≥ 3 SE( ln ROR)= \(\:\sqrt{\frac{1}{a}+\frac{1}{b}+\frac{1}{c}+\frac{1}{d}}\) 95% CI > 1 95% CI = \(\:{e}^{ln\left(ROR\right)\pm\:1.96SE}\) BCPNN IC= \(\:{\text{log}}_{2}\frac{a(a+b+c+d)}{(a+b)(a+c)}\) IC(025) > 0 E(IC)= \(\:{\text{log}}_{2}\frac{(a+\gamma\:11)(a+b+c+d+\alpha\:)(a+b+c+d+\beta\:)}{(a+b+c+d+1+\gamma\:)(a+b+\alpha\:1)(a+c+\beta\:1)}\) V(IC)= \(\:\frac{1}{{(\text{ln}2)}^{2}}\left[\frac{(a+b+c+d)-a+\gamma\:-\gamma\:11}{(q+\gamma\:11)(1+a+b+c+d+\gamma\:)}+\frac{(a+b+c+d)-(a+b)+\alpha\:-\alpha\:1}{(a+b+\alpha\:1)(1+a+b+c+d+\alpha\:)}+\frac{(a+b+c+d+\alpha\:)-(a+c)+\beta\:-\beta\:1}{(a+b+\beta\:1)(1+a+b+c+d+\beta\:)}\right]\) γ=γ11 \(\:\frac{(a+b+c+d+\alpha\:)(a+b+c+d+\beta\:)}{(a+b+\alpha\:1)(a+c+\beta\:1)}\) IC−2SD = E(IC)−2 \(\:\sqrt{\text{V}\left(\text{I}\text{C}\right)}\) \(\:a\) 1=β1 = 1 \(\:a\) =β=2 γ11 = 1 AE:adverse effect; ROR:reporting odds ratios; CI:confidence interval; IC:information component;BCPNN:Bayesian confidence propagation neural network; IC025:lower limit of the 95%CI. Results Descriptive Analysis From the 2014Q1 to the 2024Q2, a total of 14,350,328 AEs reports were screened after the deduplication. Out of these, the number of infection-related AE reports for belimumab, rituximab, adalimumab, etanercept, infliximab, golimumab and certolizumab pegol were 1,913(1.07%), 21,380(12.00%), 50,345(28.25%), 54,363(30.51%), 25,972(14.57%), 15,721(8.82%) and 8,521(4.78%), respectively. The characteristics of the AE reports for the seven biological pharmaceuticals are presented in Table 3 . According to the results, the population reporting AEs of all the drugs included in the research were predominantly women, especially for belimumab(94.91%). It was speculated that belimumab is typically used for the treatment of systemic lupus erythematosus(SLE),which is more prevalent in female patients. Patients aged 18–64 years old account for the majority in the light of available age data. It is worth noting that when comparing the outcomes for the seven drugs, rituximab had the highest ratio of death(15.89%) caused by infection and infestation-related AEs. As for the reporting country, belimumab(67.84%), adalimumab(73.13%), etanercept(81.87%) and certolizumab pegol(76.84%) are mainly reported in United States, while rituximab(11.57%), infliximab(16.37%) and golimumab(13.37%) are mainly reported in other countries. The median time to onset for belimumab, rituximab was 75d (IQR15, 357),103d (IQR18, 987), infection-related AEs occurred approximately 3 months after drug administration; the median time to onset for adalimumab, etanercept, and certolizumab was 147d (IQR 39, 661), 247d (IQR 48, 1436) and 188d (IQR 44, 556) with infection-related AEs occurring approximately 6 months after dosing; the median time to onset for infliximab and golimumab was 342 d (IQR 37, 1435) and 362d (IQR 96, 1044) with infection-related AEs occurring more than 12 months after dosing. Based on the reports with TTO data, further analysis of the time of onset (Fig. 2) showed that the induction of infection-related AEs by the seven biologics was mainly concentrated within 90 days after treatment with the drugs, and the possibility of inducing infection-related AEs also existed after 720 days post-dose. Figure 2.Time-to-onset analysis of infection-related AEs induced by seven biologics. Disproportionality analysis We investigated the association spectrum between infections and infestations related AEs at the PT level and seven drugs. It is indicated that the five mostly reported infections and infestations AEs are nasopharyngitis (n = 24581, ROR = 1.96), pneumonia ( n = 21580, ROR = 1.08), covid-19 ( n = 16380, ROR = 1.18), infection ( n = 16202, ROR = 1.89) and sinusitis (n = 16139, ROR = 2.48). On the basis of the ROR values and IC signal strength, top 20 PTs of belimumab, rituximab and TNF inhibitors are list in Table 4. Table 3 Clinical characteristics of reported drugs-induced infections and infestions Characteristic belimumab rituximab adalimumab etanercept infliximab golimumab certolizumab pegol Total cases 1913 21380 50345 54363 25972 15721 8521 Gender Data avaliable 1828 9965 48262 53579 23312 15215 8219 Female 1735(94.91%) 5545(55.86%) 33569(69.56%) 41361(77.20%) 13607(58.37%) 10992(72.24%) 6509(79.19%) Male 93(5.09%) 4420(44.14%) 14693(30.44%) 12218(22.80%) 9705(41.63%) 4223(27.76%) 1710(20.81%) Age Data avaliable 1121 8499 30875 46802 18907 11226 4814 64 74(6.60%) 3482(40.97%) 8872(28.73%) 13555(28.96%) 3244(17.16%) 3409(30.37%) 902(18.74%) Median(IQR) 47(36–56) 61(47–70) 57(43–66) 58(49–66) 43(27–59) 57(44–67) 53(40–62) Outcome of AEs Data avaliable 1229 21153 29914 18907 25039 14634 3297 Hospitalization 412(33.52%) 6610(31.25%) 12897(43.11%) 4439(23.48%) 7151(28.56%) 4223(28.86%) 785(23.81%) Disability 8(0.65%) 312(1.47%) 386(1.29%) 117(0.62%) 154(0.62%) 65(0.45%) 41(1.24%) Life threatening 21(1.71%) 468(2.21%) 211(0.70%) 103(0.54%) 241(0.96%) 77(0.53%) 14(0.42%) death 47(3.82%) 3361(15.89%) 871(2.91%) 322(1.70%) 621(2.48%) 286(1.95%) 37(1.12%) Congenital anomaly 1(0.08%) 16(0.08%) 28(0.09%) 4(0.02%) 14(0.06%) 1(0.01%) 3(0.09%) Other serious outcome 740(60.21%) 10385(49.09%) 15494(51.79%) 13911(73.58%) 16856(67.32%) 9980(68.20%) 2416(73.28%) Required intervention 0 1(0.00%) 27(0.09%) 11(0.06%) 2(0.01%) 2(0.01%) 1(0.03%) Report countries Data avaliable 1903 21380 46668 54341 25927 15712 8520 United states 1291(67.84%) 2473(11.57%) 34130(73.13%) 44489(81.87%) 4245(16.37%) 2100(13.37%) 6547(76.84%) Other countries 612(32.16%) 18907(88.43%) 12538(26.87%) 9852(18.13%) 21682(83.63%) 13612(86.63%) 1973(23.16%) Time to onset, days, IQR(Q1-Q3) 75(15,357) 103(18,987) 147(39, 661) 245(48,1436) 342(37,1435) 362(86,1044) 188(44,556) Time to onset, days, min, max 0,1958 0,6574 0,7556 0,8410 0,7145 0,5325 0, 4199 Table 4. Top 20signal strength of adverse events if infection and infestation of the seven drugs. Biologics Infections and infestations related PTs N ROR(95%CI) IC(IC025) Belimumab Herpes zoster cutaneous disseminated 10 31.21(16.56-58.82) 4.9(2.17) Ear infection staphylococcal 4 27.83(10.24-75.62) 4.74(0.83) Herpes zoster meningitis 6 24.7(10.94-55.78) 4.58(1.39) Urinary tract infection staphylococcal 5 12.84(5.3-31.1) 3.66(0.92) Gastroenteritis bacterial 4 10.05(3.74-26.96) 3.31(0.54) Skin bacterial infection 7 7.03(3.34-14.8) 2.8(0.97) Lymph gland infection 4 6.66(2.49-17.82) 2.72(0.35) Pulpitis dental 7 5.01(2.38-10.53) 2.32(0.71) Dengue fever 13 4.62(2.68-7.97) 2.2(1.1) Aspergillus infection 6 4.29(1.92-9.57) 2.09(0.45) Pelvic inflammatory disease 6 4.28(1.92-9.56) 2.09(0.45) Enteritis infectious 11 4.25(2.35-7.69) 2.08(0.9) Acarodermatitis 6 3.93(1.76-8.77) 1.97(0.37) Gastroenteritis salmonella 4 3.85(1.44-10.28) 1.94(0) JC virus infection 7 3.62(1.72-7.61) 1.85(0.42) Herpes virus infection 24 3.48(2.33-5.2) 1.79(1.08) Meningitis cryptococcal 6 3.28(1.47-7.32) 1.71(0.21) Infectious mononucleosis 8 3.23(1.61-6.46) 1.69(0.4) Disseminated tuberculosis 7 3.04(1.45-6.39) 1.6(0.25) Breast abscess 4 2.9(1.08-7.73) 1.53(-0.22) Rituximab Progressive multifocal leukoencephalopathy 769 25.70(23.85-27.69) 4.53(4.42) Pneumocystis jirovecii infection 72 19.69(15.48-25.04) 4.19(3.87) Hepatitis B reactivation 220 18.57(16.19-21.30) 4.11(3.92) Epstein-Barr virus infection reactivation 55 14.67(11.18-19.26) 3.8(3.43) Encephalitis viral 50 14.29(10.75-19.01) 3.76(3.38) Pneumonia cytomegaloviral 63 12.11(9.4-15.6) 3.53(3.19) Cytomegalovirus infection reactivation 144 11.64(9.85-13.76) 3.45(3.25) Pneumocystis jirovecii pneumonia 416 11.03(9.99-12.17) 3.40(3.26) Viral infection 212 9.60(8.37-11.02) 3.21(3.02) Polyomavirus-associated nephropathy 69 9.54(7.5-12.14) 3.2(2.88) Helicobacter infection 345 9.43(8.46-10.50) 3.18(3.03) Hepatitis B 155 9.28(7.90-10.89) 3.16(2.94) Cytomegalovirus infection 463 8.72(7.95-9.57) 3.07(2.94) Hepatitis E 52 8.51(6.45-11.22) 3.04(2.67) Aspergillus infection 211 8.38(7.30-9.61) 3.02(2.83) Pseudomonal sepsis 42 8.2(6.03-11.15) 2.99(2.59) Adenovirus infection 73 7.63(6.05-9.64) 2.89(2.58) Epstein-Barr virus infection 143 7.58(6.42-8.95) 2.88(2.65) Cytomegalovirus viraemia 102 7.40(6.08-9.02) 2.85(2.58) Herpes simplex 113 7.16(5.94-8.64) 2.80(2.54) Adalimumab Abscess intestinal 472 10.08(9.08-11.18) 2.97(2.82) Chikungunya virus infection 115 6.28(5.14-7.68) 2.43(2.11) Post procedural sepsis 91 5.85(4.70-7.36) 2.35(1.98) Cutaneous leishmaniasis 28 5.07(3.40-7.56) 2.17(1.46) Tuberculosis liver 7 4.78(2.16-10.61) 2.16(0.56) Purulent discharge 382 4.32(3.88-4.81) 1.97(1.81) Furuncle 825 4.19(3.90-4.51) 1.93(1.82) Uveitis 1419 3.74(3.53-3.95) 1.78(1.70) Abdominal abscess 388 3.56(3.21-3.96) 1.72(1.57) Latent tuberculosis 192 3.23(2.76-3.75) 1.59(1.37) Pharyngitis streptococcal 925 3.11(2.91-3.33) 1.54(1.44) Gallbladder empyema 6 3.13(1.35-7.24) 1.55(0.09) Subcutaneous abscess 391 3.10(2.80-3.44) 1.54(1.39) Abscess 1297 3.09(2.92-3.28) 1.54(1.45) Gastrointestinal infection 759 3.02(2.80-3.25) 1.50(1.39) Anal abscess 503 2.91(2.65-3.18) 1.45(1.32) Rash pustular 421 2.68(2.42-2.96) 1.34(1.20) Tuberculosis 845 2.66(2.48-2.86) 1.34(1.24) Fungal skin infection 278 2.49(2.20-2.81) 1.25(1.07) Infectious mononucleosis 126 2.41(2.01-2.89) 1.21(0.94) Etanercept Viral upper respiratory tract infection 389 3.32(3.00-3.69) 1.66(1.52) Latent tuberculosis 132 3.11(2.61-3.71) 1.57(1.33) Nasopharyngitis 8922 2.27(2.22-2.32) 1.12(1.09) Sinusitis 6167 2.96(2.89-3.04) 1.49(1.45) Pharyngitis streptococcal 609 2.86(2.64-3.11) 1.46(1.34) Arthritis infective 246 2.59(2.28-2.95) 1.32(1.15) Gastroenteritis viral 539 2.42(2.22-2.64) 1.23(1.11) Chikungunya virus infection 35 2.42(1.72-3.40) 1.23(0.79) Tooth infection 663 2.37(2.19-2.56) 1.20(1.09) Furuncle 347 2.36(2.12-2.63） 1.20(1.04) Upper respiratory tract infection 2101 2.28(2.18-2.38) 1.14(1.08) Bronchitis 3190 2.06(1.99-2.14) 1.00(0.95) Localised infection 1036 2.06(1.94-2.20) 1.01(0.92) Ear infection 1136 1.99(1.87-2.11) 0.96(0.87) Tuberculosis 451 1.98(1.78-2.17) 0.95(0.82) Influenza 4391 1.85(1.79-1.91) 0.85(0.81) Infection 4750 1.74(1.69-1.79) 0.76(0.72) Gastric infection 139 1.72(1.46-2.04) 0.76(0.53) Uveitis 482 1.70(1.55-1.86) 0.74(0.61) Tooth abscess 352 1.70(1.53-1.89) 0.74(0.59) Infliximab Intestinal tuberculosis 34 37.21(25.56-54.15) 4.91(4.45) Tuberculous pleurisy 59 33.13(24.99-43.92) 4.77(4.42) Peritoneal tuberculosis 40 31.46(22.38-44.23) 4.71(4.29) Lymph node tuberculosis 77 25.29(19.86-32.19) 4.45(4.13) Leishmaniasis 43 25.27(18.29-34.9) 4.44(4.04) Pulmonary tuberculosis 416 25.04(22.57-27.79) 4.43(4.29) Histoplasmosis disseminated 118 20.91(17.24-25.35) 4.21(3.95) Tuberculosis 1082 17.33(16.26-18.46) 3.95(3.87) Disseminated tuberculosis 298 17.12(15.81-19.30) 3.95(3.78) Sinusitis bacterial 135 16.27(13.62-19.44) 3.88(3.65) Histoplasmosis 120 16.19(13.41-19.55) 3.88(3.63) Anal abscess 554 15.94(14.60-17.40) 3.85(3.73) Legionella infection 34 14.07(9.9-19.99) 3.69(3.25) Salmonellosis 106 13.51(11.07-16.48) 3.64(3.37) Rectal abscess 137 12.10(10.17-14.41) 3.49(3.26) Listeriosis 60 10.91(8.39-14.17) 3.36(3.01) Infectious mononucleosis 103 9.55（7.82-11.65) 3.17(2.90) Cytomegalovirus colitis 102 9.39(7.68-11.47) 3.15(2.88) Abscess 766 8.66(8.05-9.32) 3.03(2.93) Clostridium difficile infection 1158 8.26(7.78-8.77) 2.96(2.88) Golimumab Dengue fever 149 27.95(23.65-33.04) 4.69(4.23) Chikungunya virus infection 33 17.46(12.30-24.78) 4.06(3.01) Leprosy 6 13.80(5.84-25.84) 3.27(0.30) Lower respiratory tract infection 1579 12.45(11.83-13.10) 3.54(3.46) Tuberculosis 322 10.75(9.61-12.01) 3.38(3.17) Latent tuberculosis 49 8.49(6.39-11.27) 3.05(0.04) Tonsillitis 121 8.35(6.97-10.00) 3.03(2.68) Herpes virus infection 97 7.01(5.73-8.57) 2.78(2.41) Erysipelas 87 6.66(5.39-8.24) 2.71(2.31) Pharyngitis 231 6.46(5.67-7.36) 2.66(2.44) Extrapulmonary tuberculosis 4 6.43(2.39-17.30) 2.66(0.42) Tooth abscess 175 6.38(5.49-7.41) 2.45(2.38) Herpes zoster cutaneous disseminated 4 5.96(2.22-10.01) 2.55(0.42) Leptospirosis 5 5.78(2.39-13.99) 2.51(0.35) Pyelonephritis 110 5.09(4.22-6.15) 2.33(2.00) Kidney infection 249 4.78(4.22-5.42) 2.23(2.03) Arthritis infective 55 4.26(3.26-5.55) 2.07(1.61) Appendicitis 94 4.18(3.41-5.12) 2.05(1.70) Cellulitis 524 4.15(3.80-4.52) 2.03(1.89) Uveitis 156 4.11(3.51-4.82) 2.02(1.76) certolizumab pegol Intestinal tuberculosis 6 8.78(3.89-19.84) 3.09(2.21) Legionella infection 8 4.97(2.47-10.02) 2.29(1.50) Lymph node tuberculosis 6 4.14(2.14-8.01) 2.03(1.27) Tuberculosis 137 3.18(2.69-3.77) 1.66(1.42) Tuberculous pleurisy 5 3.76(1.56-9.10) 1.90(0.98) Pharyngitis streptococcal 122 2.98(2.49-3.57) 1.56(1.31) Lymph gland infection 5 2.91(1.21-7.04) 1.53(0.61) Abscess 120 2.07(1.73-2.48) 1.04(0.79) Sinusitis 752 1.85(1.72-1.99) 0.88(0.77) Herpes zoster 400 1.80(1.63-1.99) 0.84(0.70) Fungal infection 200 1.71(1.48-1.96) 0.76(0.57) Furuncle 46 1.63(1.22-2.18) 0.70(0.31) Gastroenteritis viral 68 1.59(1.25-2.02) 0.67(0.34) Infection 753 1.45(1.35-1.56) 0.53(0.43) Staphylococcal infection 143 1.44(1.22-1.70) 0.52(0.29) Upper respiratory tract infection 246 1.39(1.27-1.58) 0.47(0.29) Tooth infection 74 1.38(1.10-1.73) 0.46(0.15) Kidney infection 94 1.27(1.04-1.56) 0.34(0.06) Skin infection 54 1.26(0.96-1.65) 0.33(-0.03) Eye infection 55 1.25(0.96-1.64) 0.33(-0.03) Discussion Our study reveals distinct infection profiles across belimumab, rituximab, and TNF-α inhibitors. Progressive multifocal leukoencephalopathy (PML) is a rare but deadly brain disorder caused by reactivation of the polyomavirus JC 13 . Notably, rituximab-associated PML emerges as a sentinel event with the highest ROR (25.70) and mortality (26.14%), aligning with prior case-series reporting high fatality rate in rituximab-treated PML patients 14 . This finding underscores the need for JC-virus serostatus monitoring in high-risk populations.ROR and IC value with belimumab(ROR = 1.80, IC = 0.84) is lower than rituximab but higher than TNF-α inhibitors (Fig. 3 and Fig. 4). A research have been reported a risk classification for immunosuppressive treatment-associated PML, in which rituximab and belimumab were ranked in the same class 15 . Tuberculosis remains a leading cause of infectious death worldwide over a century 16 . A study analyzed 70 reports of tuberculosis after infliximab therapy received before May 29, 2001, therefore they obtained a conclusion that active tuberculosis may develop soon after the initiation of treatment with infliximab 17 .In contrast, infliximab exhibits a unique TB risk profile, with extrapulmonary TB signals (ROR = 47.89) exceeding pulmonary manifestations. This aligns with mechanistic studies demonstrating TNF-α's critical role in granuloma formation 18 , particularly in extrapulmonary compartments. Clinicians should prioritize latent TB screening before initiating infliximab, especially in endemic regions. Hepatitis B virus infection is a major public health problem worldwide 19 . Hepatitis B virus can cause liver disease, which is also a major risk factor for hepatocellular carcinoma 20 . Our study identifies a distinct risk landscape for hepatitis B virus (HBV) reactivation among the evaluated biologics. Rituximab exhibits the strongest association with HBV reactivation (ROR = 18.57, IC = 4.11), positioning it as a high-risk agent. This finding aligns with AGA guidelines categorizing rituximab and TNF-α inhibitors as high/moderate risk agents, respectively. Notably, belimumab does not demonstrate significant HBV reactivation signals in our dataset, contrasting with prior reports suggesting potential risks with B-cell depleting therapies. The absence of belimumab-associated HBV reactivation signals in this analysis may reflect distinct pharmacodynamic properties, such as preserved T-cell function or reduced immunosuppressive burden compared to rituximab. However, these results should be interpreted cautiously due to the retrospective nature of FAERS data and potential underreporting biases. Sepsis, a syndrome of organ dysfunction caused by infectious factors, has high morbidity and mortality 21 .It is estimated that there were nearly 31.5 billion sepsis patients around the world based on recent epidemiological survey 22 .Therefore, as a serious AE, sepsis is worth noting. Rituximab was reported to induce sepsis in a 50-year-old female with idiopathic membranous nephropathy in 2018 23 .Conversely, rituximab's sepsis signals (pseudomonal sepsis ROR = 8.2, bacterial sepsis ROR = 6.1, escherichia sepsis ROR = 4.79 ) highlight the importance of preemptive antimicrobial prophylaxis in neutropenic patients. While TNF-α inhibitors collectively demonstrate elevated TB risks, adalimumab and golimumab exhibit unexpected signals for arboviral infections, such as chikungunya virus infection(adalimumab) and dengue fever(golimumab). This finding warrants mechanistic exploration—potential hypotheses is geographical prescribing biases. Because most chikungunya virus infection and dengue fever AE reports are from Brazil and Colombia. In addition to the AEs listed on the drug packaging labels, our study also reveals some rare infections and infestations AEs. Such as cutaneous leishmaniasis, gallbladder empyema and leprosy. The limitations of our study should not be overlook. Firstly, we utilized FAERS database to implement a retrospective pharmacovigilance analysis. The FEARS database has some inherent defect, such as incomplete clinical characteristics of patients and not all reporters are healthcare professionals 24 . Secondly, the absence of information on the total population using belimumab, rituximab and TNF inhibitors resulted in the deficiency of AEs incidence. Finally, the disproportionality analysis only provide evidence of associations between target drugs and AEs but could not prove causality. Furthermore, more clinical trail researches are essential to validate the findings. Conclusion Using FAERS database, we conducted a comprehensive and systematic investigation to reveal the association between infections and infestations related AEs and seven biologics widely used to immune system diseases. Rituximab have higher risk to cause PML,sepsis,hepatitis B virus and reactivation,thus it is more likely to cause serious outcomes. Most of these infections and infestations related AEs are listed in drug packaging label, but we also found some rare infections scarcely reported. Physicians should pay more attention on the serious infections induced by belimumab,rituximab and TNF inhibitors in clinical practice.Moreover,further causality assessment is required. Declarations Author Contribution Wang Sisi contributed to conception, study design and analyzed data. All author contributed to editing and revising the manuscript. All authors read and approved the final manuscript. Data Availability The FAERS database records used in this investigation are publicly retrievable via the FDA's platform at the persistent https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html. References Rodziewicz, M. et al. Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study. Lancet Rheumatol. 5 , e284–e292. 10.1016/S2665-9913(23)00091-7 (2023). Halpern, W. G. et al. Chronic administration of belimumab, a BLyS antagonist, decreases tissue and peripheral blood B-lymphocyte populations in cynomolgus monkeys: Pharmacokinetic, pharmacodynamic, and toxicologic effects. Toxicol. Sci. 91 , 586–599. 10.1093/toxsci/kfj148 (2006). Coiffier, B. et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 346 , 235–242. 10.1056/NEJMoa011795 (2002). Scott, D. L., Wolfe, F. & Huizinga, T. W. J. Rheumatoid arthritis. LANCET 376, 1094–1108, (2010). 10.1016/S0140-6736(10)60826-4 Provan, D. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. BLOOD 115 , 168–186. 10.1182/blood-2009-06-225565 (2010). Porter, D. L., Levine, B. L., Kalos, M., Bagg, A. & June, C. H. Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia. N. Engl. J. Med. 365 , 725–733. 10.1056/NEJMoa1103849 (2011). Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann. Rheum. Dis. 79 , 685–699. 10.1136/annrheumdis-2019-216655 (2020). Kavanaugh, A. et al. Golimumab, a New Human Tumor Necrosis Factor α Antibody, Administered Every Four Weeks as a Subcutaneous Injection in Psoriatic Arthritis Twenty-Four-Week Efficacy and Safety Results of a Randomized, Placebo-Controlled Study. Arthritis Rheum. 60 , 976–986. 10.1002/art.24403 (2009). Woolacott, N. et al. Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation. Health Technol. Assess. 10 , 1– (2006). Lichtenstein, G. R., Abreu, M. T., Cohen, R. & Tremaine, W. American Gastroenterological Association institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. GASTROENTEROLOGY 130 , 940–987. 10.1053/j.gastro.2006.01.048 (2006). Burmester, G. R., Panaccione, R., Gordon, K. B., McIlraith, M. J. & Lacerda, A. P. M. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease. Ann. Rheum. Dis. 72 , 517–524. 10.1136/annrheumdis-2011-201244 (2013). Rodriguez, E. M., Staffa, J. A. & Graham, D. J. The role of databases in drug postmarketing surveillance. Pharmacoepidemiol. Drug Saf. 10 , 407–410. https://doi.org/10.1002/pds.615 (2001). Carson, K. R. et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. BLOOD 113 , 4834–4840. 10.1182/blood-2008-10-186999 (2009). Tan, C. S. & Koralnik, I. J. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 9 , 425–437. 10.1016/S1474-4422(10)70040-5 (2010). Chahin, S. & Berger, J. R. A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy. J. Neurovirol. 21 , 623–631. 10.1007/s13365-014-0303-1 (2015). Lozano, R. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. LANCET 380, 2095–2128, (2012). 10.1016/S0140-6736(12)61728-0 Keane, J. et al. Tuberculosis associated with infliximab, a tumor necrosis factor (alpha)-neutralizing agent. N. Engl. J. Med. 345 , 1098–1104. 10.1056/NEJMoa011110 (2001). Dorhoi, A. & Kaufmann, S. H. E. Tumor necrosis factor alpha in mycobacterial infection. Semin. Immunol. 26 , 203–209. 10.1016/j.smim.2014.04.003 (2014). Trépo, C., Chan, H. L. Y. & Lok, A. Hepatitis B virus infection. LANCET 384 , 2053–2063. 10.1016/S0140-6736(14)60220-8 (2014). Shen, C., Jiang, X., Li, M. & Luo, Y. Hepatitis Virus and Hepatocellular Carcinoma: Recent Advances. CANCERS 15, (2023). 10.3390/cancers15020533 Cho, W. et al. Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents. J. Med. Chem. 60 , 170–179. 10.1021/acs.jmedchem.6b00954 (2017). Baker, K. P. et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 48 , 3253–3265. 10.1002/art.11299 (2003). Cheong, J. & Ooi, K. Rituximab-induced serum sickness in the treatment of idiopathic membranous nephropathy. Clin. KIDNEY J. 11 , 51–53. 10.1093/ckj/sfx072 (2018). Reich, L. Extreme duplication' in the USFDA adverse events reporting system database. Drug Saf. 30 , 551–554. 10.2165/00002018-200730060-00009 (2007). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6638648","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":479081139,"identity":"784fe645-d988-4120-b40f-f2fcf86cf57b","order_by":0,"name":"Wang Sisi","email":"","orcid":"","institution":"Department of Pharmacy,Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Sisi","suffix":""},{"id":479081143,"identity":"147a3da3-9bd3-42b5-8496-0a29b3e5506a","order_by":1,"name":"Shao Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYBACPmYGBiBikONnbz4AETpAQAsbVIuxZM+xBCK1MEC0JG64kWNApBZ2HuPPBTU2IC0fP/5sY5Dju5HA+LkAr8N4zKRnHEsznnnm7WZp3jagC28kMEvPIKCFmYftsGzf8dxtzIxtIBcmAAXxazH+zPPvMGPDgZxnjECH1ROjxQDonsOKE07ksDEAHZZgQFgLW5k0b18aKJCNpXnOSRjOPPOwWRqfFn7+w5s/83yzAUXlw48/ymzk+Y4nH/yMTws6kABixgYSNIyCUTAKRsEowAYAJdJFI8lexNUAAAAASUVORK5CYII=","orcid":"","institution":"Department of Pharmacy,Xiangya Hospital of Central South University","correspondingAuthor":true,"prefix":"","firstName":"Shao","middleName":"","lastName":"Liu","suffix":""},{"id":479081147,"identity":"fc084544-b193-45a0-a280-6adebeb8057e","order_by":2,"name":"Sheng Deng","email":"","orcid":"","institution":"Department of Pharmacy,Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Deng","suffix":""},{"id":479081148,"identity":"07bccb69-a87a-4d28-8f13-d89320d29ea2","order_by":3,"name":"Yuting Huang","email":"","orcid":"","institution":"Department of Pharmacy,Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Huang","suffix":""},{"id":479081151,"identity":"30a5be00-9752-41dd-8810-36bd1201d33f","order_by":4,"name":"Rong Yang","email":"","orcid":"","institution":"Department of Pharmacy,Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Rong","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2025-05-11 08:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6638648/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6638648/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-26999-7","type":"published","date":"2025-12-03T15:58:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":85965928,"identity":"27696d6d-ffae-4225-995b-2cb01c0d085d","added_by":"auto","created_at":"2025-07-03 16:51:42","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":247451,"visible":true,"origin":"","legend":"\u003cp\u003eA flow diagram of the study\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6638648/v1/2cd3b5f37e6ca3d9c294f785.jpg"},{"id":85966428,"identity":"91b3617c-026a-4234-b2cf-73d1043e0439","added_by":"auto","created_at":"2025-07-03 16:59:42","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2097348,"visible":true,"origin":"","legend":"\u003cp\u003eTime-to-onset analysis of infection-related AEs induced by seven biologics.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6638648/v1/50d789c135969f012bc3a229.jpg"},{"id":85965937,"identity":"dbaef72b-4180-465e-bc94-cfa854200155","added_by":"auto","created_at":"2025-07-03 16:51:42","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":246783,"visible":true,"origin":"","legend":"\u003cp\u003eA heatmap showing the associations between seven biologics and infection-related adverse effects.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6638648/v1/4424acb0018ec79bbcd05095.png"},{"id":85965930,"identity":"7ea80549-5baa-4e7a-b32b-537ffffeb2ae","added_by":"auto","created_at":"2025-07-03 16:51:42","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":66639,"visible":true,"origin":"","legend":"\u003cp\u003eROR and 95% CI values of infection-related PTs for the seven biologics.(a)Progressive multifocal leukoencephalopathy;(b)Tuberculosis;(c)sepsis.\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6638648/v1/af2c760b74c7dba235c8f5f0.jpg"},{"id":97724642,"identity":"28c02e68-72a0-4f12-9af0-4bdc42b0ff55","added_by":"auto","created_at":"2025-12-08 16:13:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3761152,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6638648/v1/0bf954d0-f6be-4961-8384-fe7c67bd1cc4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Real-World Safety Analysis of Infection-Related Adverse Events Associated with Belimumab, Rituximab, and TNF-α Inhibitors Using the FAERS Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBelimumab, as a human immunoglobulin G1λ monoclonal antibody (mAb) targeting B lymphocyte stimulator, was approved by the US Food and Drug Administration(FDA) and European Medicine Agency(EMA) in 2011 for the treatment of systemic lupus erythematosus (SLE\u003csup\u003e)1,2\u003c/sup\u003e.Rituximab is a chimeric anti-CD20 IgG1 monoclonal antibody approved in 1997 ,which is widely used for the treatment of lymphoma\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, rheumatoid arthritis(RA)\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e, immune thrombocytopenia\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, and chronic lymphocytic leukemia\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Adalimumab(ADA), etanercept(ETN), infliximab(INF), golimumab(GOL), and certolizumab pegol(CZB), are inhibitor of tumor necrosis factor alpha(TNF-α), which are an indispensable part for the treatment of (RA), juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (PS) and Crohn's disease (CD)\u003csup\u003e\u003cspan additionalcitationids=\"CR8 CR9 CR10\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Biologics targeting TNF-α, B cells (rituximab/belimumab) have revolutionized autoimmune disease management.\u003c/p\u003e \u003cp\u003eThe preservation of immune homeostasis through systemic, cellular, and molecular coordination may paradoxically predispose patients to novel immune dysregulation patterns and iatrogenic complications when employing TNF-α inhibitors or biologics, therefore infections are one of the common adverse reactions associated with the use of biologics.While package inserts highlight common risks, real-world patterns of rare infections remain poorly characterized. This study leverages the FAERS database to identify underreported infection signals associated with these agents.Currently, there is no comprehensive study about infections and infestations related AEs of belimumab, rituximab and five TNF-α inhibitors after their long-term usage. As a platform for the public to collect and analyze the adverse drug events, the FDA Adverse Event Reporting System(FAERS) is a spontaneous reporting database due to the international and domestically reporters\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. We aims to conduct a thorough analysis based on the FAERS data to reveal the real-world safety issues of the above seven biologics.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eFEARS Procedure\u003c/p\u003e \u003cp\u003eAll the related FAERS data throughout the period of first quarter of 2014 to the second quarter of 2024 was analyzed using the MySQL8.0 data analytical platform and Microsoft Excel. Infection-related adverse events linked to belimumab were queried using their generic name \u0026ldquo;belimumab\u0026rdquo; and the trade name \u0026ldquo;Benlysta\u0026rdquo;. We also conducted the same procedure on rituximab(Mabthera), a CD20 antibody for the treatment of lymphoma and rheumatoid arthritis, as well as tumor necrosis factor(TNF) inhibitors including adalimumab(Humira), etanercept(Enbrel), infliximab(Remicade), golimumab(Simponi), certolizumab pegol(Cimzia). To ensure the accuracy of the results about the association between infection-related adverse reactions and the drugs mentioned above, only role_cod as primary suspected was incorporated. Infection-related AEs from the \u0026lsquo;REAC\u0026rsquo; database were identified by the Medical Dictionary of Regulator Activities(MedDRA 25.0). The preferred terms(PTs) corresponding to the SOC names which are infections and infestations were selected in the study(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eTo quantify the correlation between the seven biological pharmaceuticals and infection-related adverse reactions, disproportionality signal analysis, such as reporting odds ratios(ROR) and bayesian confidence propagation neural network(BCPNN) was utilized for the signal mining. The positive signal outcome could be more comprehensive and reliable throughout the combination of the two algorithms. Ratio imbalance measurement algorithm, calculation formula and detection thresholds were exhibited as follows (Tables\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e,\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe 2\u0026times;2 contingency table\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrug-related AEs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-drug-related AEs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003etotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-drug\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003etotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFormula and thresholds\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlgorithm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eformula\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ethresholds\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROR=\u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSE(\u003cem\u003eln\u003c/em\u003eROR)=\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sqrt{\\frac{1}{a}+\\frac{1}{b}+\\frac{1}{c}+\\frac{1}{d}}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%\u003cem\u003eCI\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95%\u003cem\u003eCI =\u003c/em\u003e \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{e}^{ln\\left(ROR\\right)\\pm\\:1.96SE}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCPNN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC=\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\text{log}}_{2}\\frac{a(a+b+c+d)}{(a+b)(a+c)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIC(025)\u0026thinsp;\u0026gt;\u0026thinsp;0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eE(IC)=\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\text{log}}_{2}\\frac{(a+\\gamma\\:11)(a+b+c+d+\\alpha\\:)(a+b+c+d+\\beta\\:)}{(a+b+c+d+1+\\gamma\\:)(a+b+\\alpha\\:1)(a+c+\\beta\\:1)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eV(IC)=\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{1}{{(\\text{ln}2)}^{2}}\\left[\\frac{(a+b+c+d)-a+\\gamma\\:-\\gamma\\:11}{(q+\\gamma\\:11)(1+a+b+c+d+\\gamma\\:)}+\\frac{(a+b+c+d)-(a+b)+\\alpha\\:-\\alpha\\:1}{(a+b+\\alpha\\:1)(1+a+b+c+d+\\alpha\\:)}+\\frac{(a+b+c+d+\\alpha\\:)-(a+c)+\\beta\\:-\\beta\\:1}{(a+b+\\beta\\:1)(1+a+b+c+d+\\beta\\:)}\\right]\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eγ=γ11\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\frac{(a+b+c+d+\\alpha\\:)(a+b+c+d+\\beta\\:)}{(a+b+\\alpha\\:1)(a+c+\\beta\\:1)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC\u0026minus;2SD\u0026thinsp;=\u0026thinsp;E(IC)\u0026minus;2\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\sqrt{\\text{V}\\left(\\text{I}\\text{C}\\right)}\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:a\\)\u003c/span\u003e\u003c/span\u003e1=β1\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003cp\u003e\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:a\\)\u003c/span\u003e\u003c/span\u003e=β=2\u003c/p\u003e \u003cp\u003eγ11\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAE:adverse effect; ROR:reporting odds ratios; CI:confidence interval; IC:information component;BCPNN:Bayesian confidence propagation neural network; IC025:lower limit of the 95%CI.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDescriptive Analysis\u003c/h2\u003e \u003cp\u003eFrom the 2014Q1 to the 2024Q2, a total of 14,350,328 AEs reports were screened after the deduplication. Out of these, the number of infection-related AE reports for belimumab, rituximab, adalimumab, etanercept, infliximab, golimumab and certolizumab pegol were 1,913(1.07%), 21,380(12.00%), 50,345(28.25%), 54,363(30.51%), 25,972(14.57%), 15,721(8.82%) and 8,521(4.78%), respectively.\u003c/p\u003e \u003cp\u003eThe characteristics of the AE reports for the seven biological pharmaceuticals are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. According to the results, the population reporting AEs of all the drugs included in the research were predominantly women, especially for belimumab(94.91%). It was speculated that belimumab is typically used for the treatment of systemic lupus erythematosus(SLE),which is more prevalent in female patients. Patients aged 18\u0026ndash;64 years old account for the majority in the light of available age data. It is worth noting that when comparing the outcomes for the seven drugs, rituximab had the highest ratio of death(15.89%) caused by infection and infestation-related AEs. As for the reporting country, belimumab(67.84%), adalimumab(73.13%), etanercept(81.87%) and certolizumab pegol(76.84%) are mainly reported in United States, while rituximab(11.57%), infliximab(16.37%) and golimumab(13.37%) are mainly reported in other countries.\u003c/p\u003e \u003cp\u003eThe median time to onset for belimumab, rituximab was 75d (IQR15, 357),103d (IQR18, 987), infection-related AEs occurred approximately 3 months after drug administration; the median time to onset for adalimumab, etanercept, and certolizumab was 147d (IQR 39, 661), 247d (IQR 48, 1436) and 188d (IQR 44, 556) with infection-related AEs occurring approximately 6 months after dosing; the median time to onset for infliximab and golimumab was 342 d (IQR 37, 1435) and 362d (IQR 96, 1044) with infection-related AEs occurring more than 12 months after dosing. Based on the reports with TTO data, further analysis of the time of onset (Fig.\u0026nbsp;2) showed that the induction of infection-related AEs by the seven biologics was mainly concentrated within 90 days after treatment with the drugs, and the possibility of inducing infection-related AEs also existed after 720 days post-dose.\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;2.Time-to-onset analysis of infection-related AEs induced by seven biologics.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDisproportionality analysis\u003c/h3\u003e\n\u003cp\u003eWe investigated the association spectrum between infections and infestations related AEs at the PT level and seven drugs. It is indicated that the five mostly reported infections and infestations AEs are nasopharyngitis (n\u0026thinsp;=\u0026thinsp;24581, ROR\u0026thinsp;=\u0026thinsp;1.96), pneumonia ( n\u0026thinsp;=\u0026thinsp;21580, ROR\u0026thinsp;=\u0026thinsp;1.08), covid-19 ( n\u0026thinsp;=\u0026thinsp;16380, ROR\u0026thinsp;=\u0026thinsp;1.18), infection ( n\u0026thinsp;=\u0026thinsp;16202, ROR\u0026thinsp;=\u0026thinsp;1.89) and sinusitis (n\u0026thinsp;=\u0026thinsp;16139, ROR\u0026thinsp;=\u0026thinsp;2.48). On the basis of the ROR values and IC signal strength, top 20 PTs of belimumab, rituximab and TNF inhibitors are list in Table\u0026nbsp;4.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of reported drugs-induced infections and infestions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ebelimumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003erituximab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eadalimumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eetanercept\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003einfliximab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003egolimumab\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ecertolizumab pegol\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1913\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50345\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54363\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15721\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData avaliable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1828\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9965\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48262\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53579\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e23312\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1735(94.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5545(55.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33569(69.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41361(77.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13607(58.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10992(72.24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6509(79.19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(5.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4420(44.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14693(30.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12218(22.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9705(41.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4223(27.76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1710(20.81%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData avaliable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8499\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46802\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4814\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(2.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e462(5.44%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e932(3.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1136(2.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2567(13.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e517(4.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e108(2.24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;18and\u0026thinsp;\u0026le;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1015(90.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4555(53.59%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21071(68.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32111(68.61%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14158(74.88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7300(65.03%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3804(79.02%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74(6.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3482(40.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8872(28.73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13555(28.96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3244(17.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3409(30.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e902(18.74%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian(IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(36\u0026ndash;56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61(47\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57(43\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58(49\u0026ndash;66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e43(27\u0026ndash;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57(44\u0026ndash;67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e53(40\u0026ndash;62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome of\u003c/p\u003e \u003cp\u003eAEs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData avaliable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1229\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18907\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25039\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14634\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3297\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e412(33.52%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6610(31.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12897(43.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4439(23.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7151(28.56%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4223(28.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e785(23.81%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(0.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e312(1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e386(1.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e117(0.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e154(0.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e65(0.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e41(1.24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife threatening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21(1.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e468(2.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e211(0.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e103(0.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e241(0.96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e77(0.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14(0.42%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003edeath\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(3.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3361(15.89%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e871(2.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e322(1.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e621(2.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e286(1.95%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e37(1.12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital anomaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(0.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28(0.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(0.02%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14(0.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1(0.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3(0.09%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther serious outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e740(60.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10385(49.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15494(51.79%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13911(73.58%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16856(67.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9980(68.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2416(73.28%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRequired\u003c/p\u003e \u003cp\u003eintervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27(0.09%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11(0.06%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2(0.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2(0.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1(0.03%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReport countries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eData avaliable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21380\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15712\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8520\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited states\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1291(67.84%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2473(11.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34130(73.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44489(81.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4245(16.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2100(13.37%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6547(76.84%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther countries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e612(32.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18907(88.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12538(26.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9852(18.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21682(83.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13612(86.63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1973(23.16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to onset, days, IQR(Q1-Q3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75(15,357)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103(18,987)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147(39, 661)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e245(48,1436)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e342(37,1435)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e362(86,1044)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e188(44,556)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to onset, days, min, max\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0,1958\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0,6574\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0,7556\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0,8410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0,7145\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0,5325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0, 4199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 4. Top 20signal strength of adverse events if infection and infestation of the seven drugs.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eBiologics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfections and infestations related PTs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003eROR(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eIC(IC025)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBelimumab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes zoster cutaneous disseminated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e31.21(16.56-58.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.9(2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEar infection staphylococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e27.83(10.24-75.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.74(0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes zoster meningitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e24.7(10.94-55.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.58(1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUrinary tract infection staphylococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e12.84(5.3-31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.66(0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastroenteritis bacterial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e10.05(3.74-26.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.31(0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSkin bacterial infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.03(3.34-14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.8(0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLymph gland infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.66(2.49-17.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.72(0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePulpitis dental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.01(2.38-10.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.32(0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eDengue fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.62(2.68-7.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.2(1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAspergillus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.29(1.92-9.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.09(0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePelvic inflammatory disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.28(1.92-9.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.09(0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEnteritis infectious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.25(2.35-7.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.08(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAcarodermatitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.93(1.76-8.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.97(0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastroenteritis salmonella\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.85(1.44-10.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.94(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eJC virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.62(1.72-7.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.85(0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.48(2.33-5.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.79(1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eMeningitis cryptococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.28(1.47-7.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.71(0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfectious mononucleosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.23(1.61-6.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.69(0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eDisseminated tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.04(1.45-6.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.6(0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eBreast abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.9(1.08-7.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.53(-0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRituximab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eProgressive multifocal leukoencephalopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e769\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e25.70(23.85-27.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.53(4.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePneumocystis jirovecii infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e19.69(15.48-25.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.19(3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHepatitis B reactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e18.57(16.19-21.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.11(3.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEpstein-Barr virus infection reactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e14.67(11.18-19.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.8(3.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEncephalitis viral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e14.29(10.75-19.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.76(3.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePneumonia cytomegaloviral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e12.11(9.4-15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.53(3.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCytomegalovirus infection reactivation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e11.64(9.85-13.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.45(3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePneumocystis jirovecii pneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e416\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e11.03(9.99-12.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.40(3.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eViral infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.60(8.37-11.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.21(3.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePolyomavirus-associated nephropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.54(7.5-12.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.2(2.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHelicobacter infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.43(8.46-10.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.18(3.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHepatitis B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.28(7.90-10.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.16(2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCytomegalovirus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e463\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.72(7.95-9.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.07(2.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHepatitis E\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.51(6.45-11.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.04(2.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAspergillus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.38(7.30-9.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.02(2.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePseudomonal sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.2(6.03-11.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.99(2.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAdenovirus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.63(6.05-9.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.89(2.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEpstein-Barr virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.58(6.42-8.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.88(2.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCytomegalovirus viraemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.40(6.08-9.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.85(2.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes simplex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e113\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.16(5.94-8.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.80(2.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eAdalimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAbscess intestinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e10.08(9.08-11.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.97(2.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eChikungunya virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.28(5.14-7.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.43(2.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePost procedural sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.85(4.70-7.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.35(1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCutaneous leishmaniasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.07(3.40-7.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.17(1.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis liver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.78(2.16-10.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.16(0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePurulent discharge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.32(3.88-4.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.97(1.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eFuruncle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.19(3.90-4.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.93(1.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.74(3.53-3.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.78(1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAbdominal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.56(3.21-3.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.72(1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLatent tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.23(2.76-3.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.59(1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePharyngitis streptococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e925\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.11(2.91-3.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.54(1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGallbladder empyema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.13(1.35-7.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.55(0.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSubcutaneous abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.10(2.80-3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.54(1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAbscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.09(2.92-3.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.54(1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastrointestinal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.02(2.80-3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.50(1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAnal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e503\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.91(2.65-3.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.45(1.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eRash pustular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.68(2.42-2.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.34(1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e845\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.66(2.48-2.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.34(1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eFungal skin infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e278\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.49(2.20-2.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.25(1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfectious mononucleosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.41(2.01-2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.21(0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eEtanercept\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eViral upper respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.32(3.00-3.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.66(1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLatent tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.11(2.61-3.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.57(1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eNasopharyngitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e8922\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.27(2.22-2.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.12(1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSinusitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.96(2.89-3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.49(1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePharyngitis streptococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.86(2.64-3.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.46(1.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eArthritis infective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.59(2.28-2.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.32(1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastroenteritis viral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.42(2.22-2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.23(1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eChikungunya virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.42(1.72-3.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.23(0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTooth infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e663\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.37(2.19-2.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.20(1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eFuruncle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.36(2.12-2.63）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.20(1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUpper respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e2101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.28(2.18-2.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.14(1.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eBronchitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e3190\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.06(1.99-2.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.00(0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLocalised infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.06(1.94-2.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.01(0.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEar infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.99(1.87-2.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.96(0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e451\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.98(1.78-2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.95(0.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfluenza\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.85(1.79-1.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.85(0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4750\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.74(1.69-1.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.76(0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastric infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.72(1.46-2.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.76(0.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.70(1.55-1.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.74(0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTooth abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.70(1.53-1.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.74(0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eInfliximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eIntestinal tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e37.21(25.56-54.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.91(4.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculous pleurisy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e33.13(24.99-43.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.77(4.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePeritoneal tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e31.46(22.38-44.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.71(4.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLymph node tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e25.29(19.86-32.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.45(4.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLeishmaniasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e25.27(18.29-34.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.44(4.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePulmonary tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e416\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e25.04(22.57-27.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.43(4.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHistoplasmosis disseminated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e20.91(17.24-25.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.21(3.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e17.33(16.26-18.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.95(3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eDisseminated tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e17.12(15.81-19.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.95(3.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSinusitis bacterial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e16.27(13.62-19.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.88(3.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHistoplasmosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e16.19(13.41-19.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.88(3.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAnal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e554\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e15.94(14.60-17.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.85(3.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLegionella infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e14.07(9.9-19.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.69(3.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSalmonellosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e13.51(11.07-16.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.64(3.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eRectal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e12.10(10.17-14.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.49(3.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eListeriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e10.91(8.39-14.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.36(3.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfectious mononucleosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.55（7.82-11.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.17(2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCytomegalovirus colitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e9.39(7.68-11.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.15(2.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAbscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.66(8.05-9.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.03(2.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eClostridium difficile infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.26(7.78-8.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.96(2.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003eGolimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eDengue fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e27.95(23.65-33.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.69(4.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eChikungunya virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e17.46(12.30-24.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4.06(3.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLeprosy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e13.80(5.84-25.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.27(0.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLower respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e1579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e12.45(11.83-13.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.54(3.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e10.75(9.61-12.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.38(3.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLatent tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.49(6.39-11.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.05(0.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTonsillitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.35(6.97-10.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.03(2.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes virus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e7.01(5.73-8.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.78(2.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eErysipelas\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.66(5.39-8.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.71(2.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePharyngitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e231\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.46(5.67-7.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.66(2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eExtrapulmonary tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.43(2.39-17.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.66(0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTooth abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e6.38(5.49-7.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.45(2.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes zoster cutaneous disseminated\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.96(2.22-10.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.55(0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLeptospirosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.78(2.39-13.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.51(0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePyelonephritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e5.09(4.22-6.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.33(2.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eKidney infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.78(4.22-5.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.23(2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eArthritis infective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.26(3.26-5.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.07(1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAppendicitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.18(3.41-5.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.05(1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eCellulitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e524\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.15(3.80-4.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.03(1.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e156\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.11(3.51-4.82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.02(1.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 81px;\"\u003e\n \u003cp\u003ecertolizumab pegol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eIntestinal tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e8.78(3.89-19.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3.09(2.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLegionella infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.97(2.47-10.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.29(1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLymph node tuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e4.14(2.14-8.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e2.03(1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.18(2.69-3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.66(1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTuberculous pleurisy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e3.76(1.56-9.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.90(0.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003ePharyngitis streptococcal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.98(2.49-3.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.56(1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eLymph gland infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.91(1.21-7.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.53(0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eAbscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e2.07(1.73-2.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.04(0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSinusitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e752\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.85(1.72-1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.88(0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eHerpes zoster\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.80(1.63-1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.84(0.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eFungal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.71(1.48-1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.76(0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eFuruncle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.63(1.22-2.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.70(0.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eGastroenteritis viral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.59(1.25-2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.67(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e753\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.45(1.35-1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.53(0.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eStaphylococcal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.44(1.22-1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.52(0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eUpper respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e246\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.39(1.27-1.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.47(0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eTooth infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.38(1.10-1.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.46(0.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eKidney infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.27(1.04-1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.34(0.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eSkin infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.26(0.96-1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.33(-0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 81px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003eEye infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 53px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 110px;\"\u003e\n \u003cp\u003e1.25(0.96-1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.33(-0.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study reveals distinct infection profiles across belimumab, rituximab, and TNF-\u0026alpha; inhibitors. Progressive multifocal leukoencephalopathy (PML) is a rare but deadly brain disorder caused by reactivation of the polyomavirus JC\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Notably, rituximab-associated PML emerges as a sentinel event with the highest ROR (25.70) and mortality (26.14%), aligning with prior case-series reporting high fatality rate in rituximab-treated PML patients\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. This finding underscores the need for JC-virus serostatus monitoring in high-risk populations.ROR and IC value with belimumab(ROR\u0026thinsp;=\u0026thinsp;1.80, IC\u0026thinsp;=\u0026thinsp;0.84) is lower than rituximab but higher than TNF-\u0026alpha; inhibitors (Fig.\u0026nbsp;3 and Fig.\u0026nbsp;4). A research have been reported a risk classification for immunosuppressive treatment-associated PML, in which rituximab and belimumab were ranked in the same class\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eTuberculosis remains a leading cause of infectious death worldwide over a century\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. A study analyzed 70 reports of tuberculosis after infliximab therapy received before May 29, 2001, therefore they obtained a conclusion that active tuberculosis may develop soon after the initiation of treatment with infliximab\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.In contrast, infliximab exhibits a unique TB risk profile, with extrapulmonary TB signals (ROR\u0026thinsp;=\u0026thinsp;47.89) exceeding pulmonary manifestations. This aligns with mechanistic studies demonstrating TNF-\u0026alpha;\u0026apos;s critical role in granuloma formation\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, particularly in extrapulmonary compartments. Clinicians should prioritize latent TB screening before initiating infliximab, especially in endemic regions.\u003c/p\u003e\n\u003cp\u003eHepatitis B virus infection is a major public health problem worldwide\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Hepatitis B virus can cause liver disease, which is also a major risk factor for hepatocellular carcinoma\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Our study identifies a distinct risk landscape for hepatitis B virus (HBV) reactivation among the evaluated biologics. Rituximab exhibits the strongest association with HBV reactivation (ROR\u0026thinsp;=\u0026thinsp;18.57, IC\u0026thinsp;=\u0026thinsp;4.11), positioning it as a high-risk agent. This finding aligns with AGA guidelines categorizing rituximab and TNF-\u0026alpha; inhibitors as high/moderate risk agents, respectively. Notably, belimumab does not demonstrate significant HBV reactivation signals in our dataset, contrasting with prior reports suggesting potential risks with B-cell depleting therapies. The absence of belimumab-associated HBV reactivation signals in this analysis may reflect distinct pharmacodynamic properties, such as preserved T-cell function or reduced immunosuppressive burden compared to rituximab. However, these results should be interpreted cautiously due to the retrospective nature of FAERS data and potential underreporting biases.\u003c/p\u003e\n\u003cp\u003eSepsis, a syndrome of organ dysfunction caused by infectious factors, has high morbidity and mortality\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.It is estimated that there were nearly 31.5\u0026nbsp;billion sepsis patients around the world based on recent epidemiological survey\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e.Therefore, as a serious AE, sepsis is worth noting. Rituximab was reported to induce sepsis in a 50-year-old female with idiopathic membranous nephropathy in 2018\u003csup\u003e23\u003c/sup\u003e.Conversely, rituximab\u0026apos;s sepsis signals (pseudomonal sepsis ROR\u0026thinsp;=\u0026thinsp;8.2, bacterial sepsis ROR\u0026thinsp;=\u0026thinsp;6.1, escherichia sepsis ROR\u0026thinsp;=\u0026thinsp;4.79 ) highlight the importance of preemptive antimicrobial prophylaxis in neutropenic patients.\u003c/p\u003e\n\u003cp\u003eWhile TNF-\u0026alpha; inhibitors collectively demonstrate elevated TB risks, adalimumab and golimumab exhibit unexpected signals for arboviral infections, such as chikungunya virus infection(adalimumab) and dengue fever(golimumab). This finding warrants mechanistic exploration\u0026mdash;potential hypotheses is geographical prescribing biases. Because most chikungunya virus infection and dengue fever AE reports are from Brazil and Colombia. In addition to the AEs listed on the drug packaging labels, our study also reveals some rare infections and infestations AEs. Such as cutaneous leishmaniasis, gallbladder empyema and leprosy.\u003c/p\u003e\n\u003cp\u003eThe limitations of our study should not be overlook. Firstly, we utilized FAERS database to implement a retrospective pharmacovigilance analysis. The FEARS database has some inherent defect, such as incomplete clinical characteristics of patients and not all reporters are healthcare professionals\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Secondly, the absence of information on the total population using belimumab, rituximab and TNF inhibitors resulted in the deficiency of AEs incidence. Finally, the disproportionality analysis only provide evidence of associations between target drugs and AEs but could not prove causality. Furthermore, more clinical trail researches are essential to validate the findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eUsing FAERS database, we conducted a comprehensive and systematic investigation to reveal the association between infections and infestations related AEs and seven biologics widely used to immune system diseases. Rituximab have higher risk to cause PML,sepsis,hepatitis B virus and reactivation,thus it is more likely to cause serious outcomes. Most of these infections and infestations related AEs are listed in drug packaging label, but we also found some rare infections scarcely reported. Physicians should pay more attention on the serious infections induced by belimumab,rituximab and TNF inhibitors in clinical practice.Moreover,further causality assessment is required.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eWang Sisi contributed to conception, study design and analyzed data. All author contributed to editing and revising the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe FAERS database records used in this investigation are publicly retrievable via the FDA's platform at the persistent https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRodziewicz, M. et al. Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study. \u003cem\u003eLancet Rheumatol.\u003c/em\u003e \u003cb\u003e5\u003c/b\u003e, e284\u0026ndash;e292. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S2665-9913(23)00091-7\u003c/span\u003e\u003cspan address=\"10.1016/S2665-9913(23)00091-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHalpern, W. G. et al. Chronic administration of belimumab, a BLyS antagonist, decreases tissue and peripheral blood B-lymphocyte populations in cynomolgus monkeys: Pharmacokinetic, pharmacodynamic, and toxicologic effects. \u003cem\u003eToxicol. 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Extreme duplication' in the USFDA adverse events reporting system database. \u003cem\u003eDrug Saf.\u003c/em\u003e \u003cb\u003e30\u003c/b\u003e, 551\u0026ndash;554. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2165/00002018-200730060-00009\u003c/span\u003e\u003cspan address=\"10.2165/00002018-200730060-00009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2007).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6638648/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6638648/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe study aims to evaluate infection-related safety profiles of belimumab, rituximab, and TNF-α inhibitors using the FDA Adverse Event Reporting System (FAERS) database.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA disproportionality analysis combining Reporting Odds Ratios (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) was conducted on FAERS data from Q1 2014 to Q2 2024.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBelimumab and rituximab are more likely to cause progressive multifocal leukoencephalopathy(PML), while infliximab show a greater variety tuberculosis(TB)-related AEs than other biological agents. Rituximab exhibited a risk association with hepatitis B virus reactivation and sepsis-related AEs. Most of these infection AEs are listed in drug packaging labels, our study also identified some rare and potential AEs such as cutaneous leishmaniasis, gallbladder empyema, leprosy, chikungunya virus infection and dengue fever.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eBelimumab, rituximab, and TNF-α inhibitors exhibit distinct infection risks.. Clinicians should prioritize monitoring for severe events like PML, TB, and hepatitis B viral reactivation. However, epidemiological investigations and further causality assessments are required.\u003c/p\u003e","manuscriptTitle":"A Real-World Safety Analysis of Infection-Related Adverse Events Associated with Belimumab, Rituximab, and TNF-α Inhibitors Using the FAERS Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-03 16:51:37","doi":"10.21203/rs.3.rs-6638648/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-11T05:36:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-09T07:40:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-01T08:27:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90069820825404541253485573237456550511","date":"2025-08-27T06:43:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"256719356808819229078901134873133290228","date":"2025-08-27T05:49:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"44853412942750813600780687399462473014","date":"2025-08-10T03:24:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87954482986780467216841396904101858865","date":"2025-07-29T10:35:20+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-25T12:16:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116319974194821587338944429228662585261","date":"2025-07-24T06:33:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-12T08:39:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"142727045223209706842313160540388859633","date":"2025-07-11T04:30:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-01T04:10:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-01T04:08:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-27T19:57:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-27T04:00:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-11T08:47:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b2cbf102-f8c9-4440-9357-a83ad156183e","owner":[],"postedDate":"July 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":50869782,"name":"Health sciences/Health care/Drug regulation"},{"id":50869783,"name":"Health sciences/Health care/Therapeutics/Adverse effects"}],"tags":[],"updatedAt":"2025-12-08T16:09:53+00:00","versionOfRecord":{"articleIdentity":"rs-6638648","link":"https://doi.org/10.1038/s41598-025-26999-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-03 15:58:03","publishedOnDateReadable":"December 3rd, 2025"},"versionCreatedAt":"2025-07-03 16:51:37","video":"","vorDoi":"10.1038/s41598-025-26999-7","vorDoiUrl":"https://doi.org/10.1038/s41598-025-26999-7","workflowStages":[]},"version":"v1","identity":"rs-6638648","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6638648","identity":"rs-6638648","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}