Clinical and Epidemiological Characteristics of Chikungunya and Dengue Infections in Provincial Hospitals of Davao de Oro, Philippines | 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 Research Article Clinical and Epidemiological Characteristics of Chikungunya and Dengue Infections in Provincial Hospitals of Davao de Oro, Philippines Nestor Arce, Kobporn Boonak, Lee Thunder Bernasor, Christian Joy Salas, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4904666/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Mosquito-borne diseases like dengue and chikungunya are endemic in the tropical region and is a common cause of acute febrile illness in both adults and children. The Philippines, home to over a hundred million residents and visited by several million tourists each year, is one such region where the risk of these diseases is endemic. To better understand the detailed situation, we estimated the proportion of these diseases in the community by conducting a prospective observational study conducted in four provincial hospitals of Davao de Oro, Philippines from February 2019 to February 2020. Serum from 382 study participant was used for laboratory confirmation of dengue or chikungunya either by antigen, antibody or by RT-PCR. Dengue was diagnosed in 57.1%, chikungunya 7.07%, co-infection with both dengue and chikungunya in 7.3%, and the etiology was undetermined in 35.9% of study participants. Common clinical symptoms included fever, headache, and rash, which were overlapping symptoms and clinically indistinguishable at presentation to the hospital, necessitating the need for laboratory diagnostics. The identification of the presence of chikungunya in Davao de Oro calls for increased awareness, improved diagnostics, and integrated disease control measures to manage outbreaks that can occur in dengue endemic regions. acute febrile illness chikungunya dengue coinfection Southeast Asia Philippines Figures Figure 1 1. Introduction Mosquito-borne viruses like dengue and chikungunya are frequent causes of acute febrile illnesses in Southeast Asia(1, 2). Dengue viruses are Orthoflavivirus genus and consist of four distinct serotypes (DENV 1–4), each containing multiple genotypes and offering transient cross-protective immunity(3). Chikungunya virus is an Alphavirus virus and has three genotypes, which includes the West African lineage, East, Central and South African (ECSA) lineage and an Asian lineage(4). During the initial presentation at the hospital, distinguishing between the two diseases can be challenging, as they manifest overlapping symptoms. Laboratory tests, such as antigen or antibody assays, or PCR, are necessary for a definitive diagnosis(5). However, the clinical trajectories of both diseases differ greatly. In dengue, the majority of patients remain asymptomatic, and those who do develop symptoms typically experience a self-limited illness. In some cases, symptoms may include bleeding, plasma leakage, and shock(6). On the other hand, in chikungunya, the majority of patients develop symptoms characterized by arthralgia and arthritis(7). The clinical course is also much longer, with symptoms of arthritis persisting for several months(8). In the Philippines, cases of chikungunya and dengue have been reported since the late 1950s. Dengue has remained a major public health problem in the country, and the growing magnitude of the disease prompted the government to provide free diagnostics for dengue to locals under the national insurance scheme(9). This facilitates large-scale screening of patients presenting to hospitals with acute febrile illness to determine whether they have dengue. Due to the significant disease burden, the Philippines was also the first country in Asia to approve and provide dengue vaccine. In contrast, chikungunya has not garnered as much public health interest, despite evidence of its presence(10, 11). This disparity may be due to the significant higher mortality rates associated with dengue compared to chikungunya. However, chikungunya tends to result in more severe long-term effects, impacting daily activities, causing loss of workdays, and leading to increased unproductiveness(8). A prospective cohort study in Cebu, Philippines, reported a rate of 3 symptomatic chikungunya infections per 100,000 person-years at the end of one year into the outbreak, they also further reported that outbreaks lasted three years(12). The Philippines, composed of 81 provinces, includes Davao de Oro, comprises 11 municipalities, has a population of approximately 767,547 people and features four secondary provincial hospitals located in Montevista, Laak, Pantukan, and Maragusan. Davao de Oro is home to migrants from Luzon and Visayas, as well as ethnic tribes such as the Mansaka, Mandaya, Davaoeno, and Kalagan. The main sources of income in the area are business establishments, banana plantations, and vast silver and gold mines across the province. Chikungunya is likely under-reported in this area due to several reasons. Unlike dengue, which benefits from free diagnostic tests provided by the government to registered Filipinos under national insurance schemes, diagnostic tests for chikungunya are not widely available. Many residents, particularly migrants and their families working in the agriculture and mining sectors of Davao de Oro, may not be registered in the national insurance scheme and therefore lack access to diagnostics. This gap in access to diagnostics could contribute to the under-diagnosis and under-reporting of chikungunya in this region. Understanding the true prevalence of chikungunya in this context is crucial for implementing effective public health strategies and improving healthcare access for all residents of Davao de Oro. In this study, we aimed to estimate the proportion of acute chikungunya and dengue infection among patients with acute febrile illness in four provincial hospitals of Davao de Oro in the Davao region. 2. Materials and Methods This multi-center, prospective study was conducted at four provincial hospitals in Davao de Oro province, located in the southeastern part of the Davao region (see Supplementary Materials, Figure S1). The hospitals included in the study were Montevista Provincial Hospital, Laak Provincial Hospital, Pantukan Provincial Hospital, and Maragusan Provincial Hospital. Patients between the ages of 1 to 65 years who presented to the emergency department with complaints of fever or had experienced at least one episode of fever of 38.5°C or higher within the past week and suspected dengue infection were recruited to the study. Blood samples were collected by venipuncture, and serum was separated by centrifugation and stored at -80°C until analysis. 1.1 Dengue NS1 antigen and IgM/IgG antibody assay A lateral flow rapid point-of-care diagnostic test kit for dengue, manufactured by Chembio Diagnostics, Inc. (NY, USA), was used to detect the dengue NS1 antigen and anti-dengue virus IgM and IgG antibodies. The tests were performed according to the manufacturer's instructions, using 10µL of serum. Results were interpreted 15 minutes after the test was conducted. The test was considered positive if two bands appeared, indicating the presence of NS1 antigen and IgM, along with the control band. If no bands appeared, the test was considered negative. The appearance of IgG alone with the control band indicated a previous infection. If the control band failed to appear, the test was deemed invalid. 1.2 Chikungunya IgM antibody assay To evaluate the presence of anti-chikungunya virus IgM antibodies in this study, we utilized a commercially available indirect enzyme linked immunosorbent assay, EUROIMMUN, Lübeck, Germany. The assay was performed in accordance with the manufacturer’s instructions as singlicates. In brief, 10µL of serum was diluted with the buffer solution provided by the manufacturer and added into a pre-coated 96 well microplate with a serum dilution of 1:100. Following this the microplate underwent three wash cycles with a working strength wash buffer, and the antibodies were identified by the addition of an enzyme conjugate (peroxidase-labelled anti-human IgM). Subsequently, a substrate solution containing THM/H 2 O 2 was added to induce the development of a blue color. The process was halted by the addition of 0.5M sulfuric acid, and the photometric measurement was recorded at a wavelength of 450 nm. The optical density was used to quantify the concentration of specifically anti-chikungunya virus antibodies present in the serum samples. Results were evaluated through a semiquantitative approach, calculating a ratio of the extinction of the patient serum sample over the extinction of the calibrator. This ratio was interpreted as follows as =0.8 to = 1.1 as positive. 1.3 RNA extraction and Reverse Transcription Polymerase Chain Reaction for Chikungunya. Viral RNA was extracted from 150uL of serum using an RNA extraction kit (Bioneer AccuPrep® viral RNA extraction kit, Daejeon,Korea) according to the manufacturer’s instruction. Quantification of CHIKV genomes was conducted using the TaqMAn quantitative real-time RT PCR method employing specific primers and a probe designed to target the 1200 bp region of the Nsp1 gene of CHIKV, as detailed in a previous study (ref. PMID:36016427) A standard curve was drawn using CHIKV RNA that was prepared from a CHIKV strain TM009_2009 (ON406426). The standard curve was prepared from six dilutions containing 10 1 to 10 6 PFU/mL, and the detection limit was determined to be about 10 2 PFU/mL. 1.4 Reverse Transcription Polymerase Chain Reaction for Dengue A previously described techniques for RNA quantification, which was performed using a One-Step SYBR® Prime Script RT-PCR Kit II from Takara Bio Inc. (Kusatsu, Japan). cDNA synthesis from RNA was carried out using reverse transcriptase Prime Script RTase, and polymerase chain reaction amplification was conducted with TaKaRa Ex Taq HS(13). 1.5 Statistical analysis A One-way ANOVA was used to assess parametric variables across multiple groups such as days of fever and haematocrit level, while the Mann-Whitney U-test was employed to evaluate differences in nonparametric variables between groups such as age, WBC and Platelete. The chi-square test was utilized to assess categorical variables, and Fisher's exact test was applied specifically when more than 20% of cells had expected frequencies less than 5.A P-value of less than 0.05 was considered significant for all tests performed. All statistical analyses were conducted using Microsoft Excel and STATA version 17 for MacOS 14.5 (23F79). 3. Results Over a 14-month study period, 382 patients were screened for chikungunya and dengue at four provincial hospitals in Davao de Oro, Philippines. Amongst these cases identified as acute febrile undifferentiated illness, 27 (7.07%) tested positive for circulating anti-chikungunya IgM, 190 (49.74%) tested positive for dengue infection, with the detection of both dengue NS1 antigen and anti-dengue IgM antibody. Additionally, 28 (7.33%) were identified as co-infected with both chikungunya and dengue, as their serum tested positive for anti-chikungunya IgM and also showed positive results for dengue NS1 and anti-dengue IgM. The remaining 137 cases (35.86%) had undetermined infectious etiologies, as both dengue and chikungunya were excluded as shown in Fig. 1 . 3.1 Demographic and Epidemiological Characteristics The age distribution varied significantly between the two diseases (p = 0.057), with median ages of 12 years for chikungunya and 17.5 years for dengue. Similarly, the median age was 17 years for cases identified as co-infected and for those who tested negative for both dengue and chikungunya, where the infective etiology remained unknown. The gender distribution, male: female across infection groups was as follows: chikungunya (9:18), dengue (103:87), co-infection (14:14), and unknown etiology (80:57). Although there appeared to be a higher proportion of females with chikungunya compared to dengue. 3.2 Hematological profile of the study cohort The mean hematocrit levels were similar across groups, ranging from 40.7–43.3%. Leukocyte count showed significant differences among groups (p = 0.0046). The median leukocytes were lowest in cases with co-infections 3.3 x10 3 per microliter, with a range of 1.3 to 8.7 x10 3 /uL in cases with dengue infection the leukocytes mean was 3.7x10 3 /all, and in cases with chikungunya infection (4.05x x10 3 /all. In the group where the etiology was undetermined the mean leukocytes was 4.5x10 3 /µL. The median platelet counts were lowest in dengue infections (119 x 10^9/L, range: 30–395), followed by mixed infections (122 x 10^9/L, range: 40–255), unknown cases (126 x 10^9/L, range: 40–413), and highest in chikungunya infections (144 x 10^9/L, range: 90–332). This trend aligns with the known association between dengue and thrombocytopenia, while suggesting that chikungunya may have less impact on platelet counts. count also showed notable, though not statistically significant, variations among groups (p = 0.0511). 3.3 Clinical Manifestations of Chikungunya, Dengue and Febrile cases with Undetermined Etiology Fever was the most prevalent symptom across all infection groups, affecting all cases. The mean duration of fever was also similar, ranging from 3.5 to 3.7 days (p = 0.7). Headache was another common symptom, affecting 66.7% of chikungunya patients, 73.2% of dengue patients, 75% of patients with co-infections, and 67.1% of unknown cases (p = 0.6). Retroorbital pain, often associated with dengue fever, showed no significant differences among groups (p = 0.50), ranging from 7.9% in dengue to 14.8% in chikungunya cases. Musculoskeletal symptoms also varied among groups. Arthralgia was more prevalent in chikungunya (44.4%) and co-infections (42.9%) compared to dengue (32.6%) and unknown cases (29.9%) (p = 0.33). Myalgia, however, showed similar prevalence across groups (32.1% − 37.0%, p = 0.98). Gastrointestinal symptoms showed some variations among groups. Nausea was more common in co-infections (78.6%) compared to other groups (p = 0.19), while vomiting followed a similar pattern: mixed (64.3%), dengue (53.7%), chikungunya (44.4%), and unknown (46%) (p = 0.22). Interestingly, diarrhea was relatively uncommon, with the highest prevalence in the unknown group (11%) and lowest in chikungunya (3.7%) (p = 0.214). Abdominal pain was most frequent in dengue infections (61.6%) compared to other groups (p = 0.087), potentially indicating a more severe gastrointestinal involvement in dengue cases. Neurological involvement, represented by confusion, was rare across all groups. However, it was slightly more prevalent in chikungunya (3.7%) and co-infections (3.6%) compared to dengue (0.5%) and cases with unknown etiology (0%) (p = 0.072). Rash was more common in chikungunya (59.3%) and dengue (63.7%) infections compared to co-infections (28.6%) (p = 0.052). 3.4 Distribution proportion of cases presenting to Provincial Hospitals. The distribution of cases among the four provincial hospitals showed statistically significant differences (p = 0.018). Laak Provincial Hospital reported relatively even distribution infection of cases across types, with 37% of chikungunya cases, 29.5% of dengue cases, 28.6% of co-infections, and 29.2% of unknown cases with that of Pantukan Provincial hospital, with 37.0% of chikungunya cases, 27.4% of dengue cases, higher rate on co-infections at 46.4%. and 25.6% of unknown cases. Maragusan Provincial Hospital had a notably lower proportion of chikungunya cases (14.8%) compared to dengue (3.2%) and no co-infections. Montevista Provincial Hospital, in contrast, had a higher proportion of dengue cases (40%) compared to chikungunya (11.1%) and co-infections (25%), as shown in Table 1 Table 1 Comparison of Disease Groups in the study cohort. Patient cohort, n = 382 CHIKV + ve n = 27 DENV + ve n = 190 CHIKV + ve DENV + ve n = 28 CHIKV -ve DENV -ve n = 137 P value Laak Provincial Hospital 37.0% 29.5% 28.6% 29.2% 0.018 Maragusan Provincial Hospital 14.8% 3.2% 0% 6.6% Montevista Provincial Hospital 11.1% 40% 25% 38.7% Pantukan Provincial Hospital 37.0% 27.4% 46.4% 25.6% Fever > 38.5 o C 100% 100% 100% 100% N/A Day of illness 3.7 ± 1.3 3.7 ± 1.3 3.6 ± 1.7 3.5 ± 1.4 0.700 Age 12 (1–49) 18 (0–65] 17 [0–43] 17 [0–65] 0.057 Gender ratio, male:female 9:18 103:87 14:14 80:57 0.117 Headache 66.7% 73.2% 75% 67.1% 0.605 Retroorbital pain 14.8% 7.9% 14.3% 10.9% 0.503 Arthralgia 44.4% 32.6% 42.9% 29.9% 0.334 Myalgia 37.0% 34.2% 32.1% 35.0% 0.982 Nausea 51.9% 63.7% 78.6% 60.6% 0.194 Vomiting 44.4% 53.7% 64.3% 46% 0.224 Diarrhea 3.7% 10% 0 11% 0.228 Abdominal pain 37.0% 61.6% 39.3% 37.2% 0.087 Rash 59.3% 63.7% 28.6% 49.6% 0.052 Confusion 3.7% 0.5% 3.6% 0 0.072 Hematocrit % 40.7 ± 5.5 42.5 ± 5.7 41.0 ± 4.0 43.3 ± 5.4 0.058 Neutrophils % 0.59 ± 0.19 0.52 ± 0.17 0.41 ± 0.22 0.51 ± 0.18 0.036 Lymphocytes % 0.385 (0.07–0.99) 0.33 (0.07–0.8) 0.41 (0.1–0.82) 0.36 (0.05–0.78) 0.371 Leukocytes x10 3 /uL 4.05 (2.1–9.2) 3.7 (1.4–19.5) 3.3 (1.3–8.7) 4.5 (1.7–19.4) 0.004 Platelets x10 3 /uL 144 (90–332) 119 (30–395) 122 (40–255) 126 (40–413) 0.051 Dengue NS1 0% 71.05% 92.86% 0% 0000 Anti-chikungunya IgM 100% 0% 100% 0% 0.000 Anti-dengue IgM 0% 51.58% 46.43% 0% 0.000 Anti-dengue IgG 59.26% 48.42% 39.29% 67.88% 0.001 Chikungunya RT-PCR 0.52% 0 0.52 0 N/A Dengue RT-PCR 0 56.54% 0 42.41 N/A Age is provided as median with maximum and the minmum range, while all other continuous variables are provided as Mean ± SD. P value was determined at < 0.005. Chi-square analysis was used for catergorical compasion of symptoms and Mann Whitney non-parametric test for continous variables. 4. Discussion 4.1 Proportion of Chikungunya and Dengue in study cohort Our results demonstrate that among patients presenting with acute febrile illness in Davao de Oro, dengue remains the predominant arboviral infection, accounting for 49.74% of cases. However, the detection of chikungunya in 7.07% of cases, along with 7.33% co-infections, highlights the emergence of chikungunya as a significant concern in the region. This proportion has previously not been reported in this region as in some areas of the Philippines(14). This findings from Davao de Oro suggest that chikungunya may be more widespread than currently recognized. Furthermore, co-infections present a unique challenge in terms of diagnosis, clinical management, and potential disease severity. It has been previously reported that global pooled prevalence of dengue and chikungunya coinfection is 2.5% (95% CI: 1.8–3.4). To our knowledge there is no specific data about prevalence of co-infection in the Philippines prior this study. Nevertheless, co-infection from Asia, as a region, has the highest coinfection prevalence at 3.3% (95% CI: 2.3–4.6)(15). Our results suggest that co-infected patients may exhibit overlapping of symptoms characteristic of both viral infections, potentially complicating clinical assessment, and management. However, one-third of cases (35.86%) where neither chikungunya nor dengue and the infective etiology remained undetermined. Here, we postulate this group of cases might have other Orthoflaviviruses such as Zika virus, Japanese encephalitis virus(16, 17). As these viruses remain endemic in the region, should be considered in the differential diagnosis for an arboviral infection in Southeast Asia. Among other viral etiologies to consider, stratified according to age groups—children, adolescents, and adults—are DNA viruses such as human herpesviruses 4 and 5, which can present as mononucleosis, and HHV6, HHV7, or parvovirus B19, which can manifest as erythema infectiosum(18). Children and adolescents may be at risk of these infections. Other RNA viruses to consider in patients with febrile exanthema and enanthema include measles, rubella, and HIV(19–21). If there has been exposure to insects such as ticks or sick domestic animals, and all the above possibilities have been ruled out, we also suggest to screen for the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) or bacterial illnesses such as rickettsiosis, leptospirosis, and salmonellosis(22–24). This plethora of pathogens reflects the complexity of diagnosing acute febrile illnesses in tropical regions, emphasizing the need for broader diagnostic capabilities to identify other potential pathogens causing similar clinical presentations(25). 4.2. Clinical Manifestations and Hematological Profile of Chikungunya and Dengue The overlap in clinical symptoms between chikungunya and dengue infections poses a significant challenge for differential diagnosis based on clinical findings at presentation alone. Our study found that fever, headache, and myalgia were common across all groups, consistent with previous reports(2). The higher prevalence of arthralgia in chikungunya (44.4%) and co-infected cases (42.9%) compared to dengue (32.6%) aligns with the characteristic joint pain associated with acute chikungunya infection(7). This finding highlights the importance of considering chikungunya in cases presenting as acute febrile illness with prominent joint pain, especially with articular tenderness and peripheral joint involvement(8). Arthralgia can be exhibited with contagions we have described above. For example, rubella infection in adults can involve polyarthralgia of large joints, and similar clinical manifestations or arthropathy are also reported in adults with parvovirus B19. Interestingly, our study found a higher prevalence of rash in both chikungunya (59.3%) and dengue (63.7%) cases compared to co-infections (28.6%). While rash is a known feature of both infections, the lower prevalence in co-infections is unexpected. Nevertheless, febrile rash might be missed without careful physical examination. Especially blanchable rashes associated with arboviral infections(26). Dengue warning signs, such as abdominal pain, were observed more frequently in dengue cases (61.6%) compared to chikungunya (37.0%) and co-infections (39.3%). In resource-limited settings where dengue rapid diagnostics are unavailable, a clinical diagnosis can be made by considering the epidemiology, symptoms, and warning signs. Warning signs like abdominal pain are very useful in monitoring the clinical trajectory of suspected dengue cases, allowing for effective patient triage and prompt management(5). In addition to identifying warning signs, the hematological profile can be used to monitor the progression of the disease. Specifically, in dengue, the hematological profile reflects dynamic bone marrow suppression, resulting in leukopenia. Leukocyte counts are among the first indicators to increase during recovery. Significantly lower leukocyte counts in dengue and co-infected cases, compared to chikungunya and cases of unknown etiology, are consistent with the known leukopenia associated with dengue infection(5). The trend towards lower platelet counts in dengue and co-infected cases, although not statistically significant, is consistent with the thrombocytopenia commonly observed in dengue(5). The relatively higher platelet counts in chikungunya cases suggest that severe thrombocytopenia is less likely in chikungunya infection, which could be a useful distinguishing feature in clinical settings(2). 4.3 Distribution Chikungunya and Dengue in Provincial Hospitals of Davao de Oro The significant differences in case distribution among the four provincial hospitals highlight the importance of considering local epidemiological patterns in arboviral disease surveillance and control.The higher proportion of chikungunya cases in Laak Provincial Hospital and Pantukan provincial Hospital for instance, suggests a potential localized outbreak or environmental factors favoring chikungunya transmission in that area. Conversely, the higher proportion of dengue cases in Montevista Provincial Hospital indicates that dengue remains the dominant arboviral threat in some parts of the region. Furthermore, these findings suggest that chikungunya may be significantly underreported in Davao de Oro. The lack of routine diagnostic testing for chikungunya, combined with its clinical similarity to dengue, likely contributes to underdiagnosis and underreporting. This situation is exacerbated by the focus on dengue in national health programs, including the provision of free dengue diagnostics under the national insurance scheme(9). The high proportion of cases with undetermined etiology (35.86%) underscores the diagnostic challenges in resource-limited settings, impacting patient management and hindering disease surveillance and public health planning. The co-circulation of chikungunya and dengue viruses in Davao de Oro necessitates enhanced surveillance through comprehensive arboviral programs, improved access to diagnostic tests, and clinical education to distinguish between chikungunya and dengue. 5. Conclusions Dengue in Davao de Oro maybe the leading arboviral infection (49.74%), amongst patients with acute undifferentiated febrile illness. The presence of chikungunya, previously underreported, suggests a wider circulation of arboviral infection in Davao de Oro. The variations in case distribution across hospitals reflects the need for localized surveillance and improved diagnostics to enhance public health strategies in endemic regions like the Philippines. Abbreviations CHIKV Chikungunya Virus DENV Dengue Virus RT-PCR Real-time reverse transcriptase-polymerase chain reaction SFTSV Severe Fever with Thrombocytopenia Syndrome Virus Declarations Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki, and the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University approved the protocol (Certificate of Approval No. MUTM 2019-015-01, February 25,2019) and approved by the Ethics Review Committee of the Compostela Valley Provincial Hospital Montevista, Davao de Oro Province (Case 005, January 25,2019). Informed consent was obtained from all study participants in the study as well as their written permission to publish this paper. Consent for publication: All authors have read and agreed to the published version of the manuscript. Availability of data and material: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy of study participants. Competing interests: The authors declare no conflicts of interest. Funding: This research was funded by Mahidol Norway Capacity Building Initiative for ASEAN and Mahidol University Faculty of Clinical Tropical Medicine. Authors' contributions – Conceptualization, NAJ; KB; LTB, CJS; VL; BP; WP and PC methodology, NAJ; KB; LTB, CJS; VL; BP; WP and PC validation, NAJ; KB; AP, PLA, and PC formal analysis, NAJ; KB; BP; AP.; PLA and PC; investigation, NAJ; KB; LTB, CJS and PC; resources, NAJ; KB; LTB, CJS and PC data curation, NAJ; KB; AP, PLA writing—original draft preparation, NAJ; AP, HAI; and PC writing—review and editing, NAJ; KB; LTB, CJS; AP, PAL; HAI; VL; WP and PC supervision, PC; and WP; project administration, NAJ; KB; LTB, CJS and PC; funding acquisition, PC. Acknowledgements: The authors are grateful to all the study participants who volunteered to be part of this important study, which is part of the author’s doctoral thesis. The authors would also like to express their sincere appreciation and thank all the staff at the four Provincial Hospitals in Davao de Oro who are taking care and comforting patients in these four hospitals. 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Am J Trop Med Hyg. 2015;93(6):1318-24. Irekeola AA, Engku Nur Syafirah EAR, Islam MA, Shueb RH. Global prevalence of dengue and chikungunya coinfection: A systematic review and meta-analysis of 43,341 participants. Acta Trop. 2022;231:106408. Alera MT, Hermann L, Tac-An IA, Klungthong C, Rutvisuttinunt W, Manasatienkij W, et al. Zika virus infection, Philippines, 2012. Emerg Infect Dis. 2015;21(4):722-4. Lopez AL, Raguindin PF, Aldaba JG, Avelino F, Sy AK, Heffelfinger JD, et al. Epidemiology of Japanese encephalitis in the Philippines prior to routine immunization. Int J Infect Dis. 2021;102:344-51. Vista ES, Weisman MH, Ishimori ML, Chen H, Bourn RL, Bruner BF, et al. Strong viral associations with SLE among Filipinos. Lupus Sci Med. 2017;4(1):e000214. Ching PK, Zapanta MJ, de Los Reyes VC, Tayag E, Magpantay R. Investigation of a measles outbreak in Cordillera, Northern Philippines, 2013. Western Pac Surveill Response J. 2016;7(3):1-5. Lopez AL, Raguindin PF, Silvestre MA, Fabay XC, Vinarao AB, Manalastas R. Rubella and Congenital Rubella Syndrome in the Philippines: A Systematic Review. Int J Pediatr. 2016;2016:8158712. Gangcuangco LMA, Eustaquio PC. The State of the HIV Epidemic in the Philippines: Progress and Challenges in 2023. Trop Med Infect Dis. 2023;8(5). Van Dijck C, Van Esbroeck M, Rutsaert R. A 54-year-old Philippine sailor with fever and jaundice. Acta Clin Belg. 2016;71(5):319-22. Galay RL, Talactac MR, Ambita-Salem BV, Chu DMM, Costa L, Salangsang CMA, et al. Molecular Detection of Rickettsia Spp. and Coxiella Burnetii in Cattle, Water Buffalo, and Rhipicephalus (Boophilus) Microplus Ticks in Luzon Island of the Philippines. Trop Med Infect Dis. 2020;5(2). Putri A, Charoenwisedsil R, Techavachara N, Imad H, Chinpraditsuk S, Thaipadungpanit J, et al. Severe leptospirosis with rhabdomyolysis in a traveller visiting Thailand. J Travel Med. 2024;31(1). Imad HA, Lakanavisid P, Pisutsan P, Trerattanavong K, Ngamprasertchai T, Matsee W, et al. A Case Report of Secondary Syphilis Co-Infected with Measles: A Diagnostic Dilemma with Fever and Rash. Trop Med Infect Dis. 2022;7(5). Imad HA. Febrile Rash: An Early Diagnostic Clue to Infectious Illness in Travelers Returning from Thailand. Reports. 2024. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-4904666","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":349188781,"identity":"7813e3ed-c2e8-4ce7-be16-ec65b90d275d","order_by":0,"name":"Nestor Arce","email":"","orcid":"","institution":"Jose Maria College Foundation, Inc. College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Nestor","middleName":"","lastName":"Arce","suffix":""},{"id":349188782,"identity":"3c490ea2-1f58-4d7b-b9f6-067f9f9efda0","order_by":1,"name":"Kobporn Boonak","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Kobporn","middleName":"","lastName":"Boonak","suffix":""},{"id":349188783,"identity":"cf853267-e948-4e39-9910-fe861f2b4ac7","order_by":2,"name":"Lee Thunder Bernasor","email":"","orcid":"","institution":"Jose Maria College Foundation, Inc. College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Lee","middleName":"Thunder","lastName":"Bernasor","suffix":""},{"id":349188784,"identity":"ce041c42-5eb5-4d7b-9c2f-254011ca82d9","order_by":3,"name":"Christian Joy Salas","email":"","orcid":"","institution":"University of the Immaculate Conception College of Nursing","correspondingAuthor":false,"prefix":"","firstName":"Christian","middleName":"Joy","lastName":"Salas","suffix":""},{"id":349188785,"identity":"fb037117-680d-444d-81f9-6fa7a4b1dacf","order_by":4,"name":"Anastasia Putri","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Anastasia","middleName":"","lastName":"Putri","suffix":""},{"id":349188786,"identity":"7f27a146-17f7-4de3-855b-73e229a07112","order_by":5,"name":"Pyae Linn Aung","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Pyae","middleName":"Linn","lastName":"Aung","suffix":""},{"id":349188787,"identity":"889672c6-e33c-48ea-bdb1-3a3fedd48885","order_by":6,"name":"Hisham Ahmed Imad","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Hisham","middleName":"Ahmed","lastName":"Imad","suffix":""},{"id":349188788,"identity":"1a10223a-e61b-4399-b641-1e8a2c788759","order_by":7,"name":"Wirongrong Chierakul","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Wirongrong","middleName":"","lastName":"Chierakul","suffix":""},{"id":349188789,"identity":"e857a377-b3a3-4dbb-9f38-faaa91adc651","order_by":8,"name":"Viravarn Luvira","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Viravarn","middleName":"","lastName":"Luvira","suffix":""},{"id":349188790,"identity":"31149a8a-7135-42e9-b5e6-6296109a7aa7","order_by":9,"name":"Benjaluck Phonrat","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Benjaluck","middleName":"","lastName":"Phonrat","suffix":""},{"id":349188791,"identity":"8e67a747-51a9-4f84-86b3-00cbdad282ae","order_by":10,"name":"Weerapong Phumratanaprapin","email":"","orcid":"","institution":"Mahidol University","correspondingAuthor":false,"prefix":"","firstName":"Weerapong","middleName":"","lastName":"Phumratanaprapin","suffix":""},{"id":349188792,"identity":"5b2924dc-b0b7-40fc-aaf9-a99fd3cdcd76","order_by":11,"name":"Prakaykaew Charunwatthana","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABJUlEQVRIiWNgGAWjYHACZiBOgLFsGBgkGBskGArAAmzEaEmDajEA84nSchioBYTwaDGXPvzY4Gdbmjy/RALj54Ka89H8s5sbb3wwYJDnb+A/9gCLFsu+NOPE3rYcw5kzEpilZxy7nTvjzsFmyxkGDIYzDjCzG2DRYnCGwfgAb1sF44bbCWzMPGy3cxtuJLZJ8xgwMG4AOkwCqxb2zwf/tlXY7wdr+Xcudz5Uiz1uLTzGybxtOYkbpIFaeNsO5G6AaknEpcWyh6fYWOZcWvKM+w+bpXn7knM33kgE+UUiecZhZjNsWsx52DdLvilLtu3vOXzwM883u9x5N9If3vhQYWPb3974DKvDQAQjOPwZG5AlJCARhksLwx/skqNgFIyCUTAKwAAAxWdgNQ/+dUsAAAAASUVORK5CYII=","orcid":"","institution":"Mahidol University","correspondingAuthor":true,"prefix":"","firstName":"Prakaykaew","middleName":"","lastName":"Charunwatthana","suffix":""}],"badges":[],"createdAt":"2024-08-13 06:47:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4904666/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4904666/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66379006,"identity":"d497d369-df53-45f2-9ad1-9107f4cc7c97","added_by":"auto","created_at":"2024-10-11 06:40:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":7840,"visible":true,"origin":"","legend":"\u003cp\u003eThe proportion of dengue and chikungunya amongst 382 patients with acute undifferentiated febrile illness.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4904666/v1/4cb8adc62c619727e19c9987.png"},{"id":66379329,"identity":"3f6154fd-9c06-48a6-ae84-57f6557ed044","added_by":"auto","created_at":"2024-10-11 06:48:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":647261,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4904666/v1/25da045c-0668-4ceb-8265-dd9562ea787c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical and Epidemiological Characteristics of Chikungunya and Dengue Infections in Provincial Hospitals of Davao de Oro, Philippines","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eMosquito-borne viruses like dengue and chikungunya are frequent causes of acute febrile illnesses in Southeast Asia(1, 2). Dengue viruses are \u003cem\u003eOrthoflavivirus\u003c/em\u003e genus and consist of four distinct serotypes (DENV 1\u0026ndash;4), each containing multiple genotypes and offering transient cross-protective immunity(3). Chikungunya virus is an Alphavirus virus and has three genotypes, which includes the West African lineage, East, Central and South African (ECSA) lineage and an Asian lineage(4). During the initial presentation at the hospital, distinguishing between the two diseases can be challenging, as they manifest overlapping symptoms. Laboratory tests, such as antigen or antibody assays, or PCR, are necessary for a definitive diagnosis(5).\u003c/p\u003e \u003cp\u003eHowever, the clinical trajectories of both diseases differ greatly. In dengue, the majority of patients remain asymptomatic, and those who do develop symptoms typically experience a self-limited illness. In some cases, symptoms may include bleeding, plasma leakage, and shock(6). On the other hand, in chikungunya, the majority of patients develop symptoms characterized by arthralgia and arthritis(7). The clinical course is also much longer, with symptoms of arthritis persisting for several months(8).\u003c/p\u003e \u003cp\u003eIn the Philippines, cases of chikungunya and dengue have been reported since the late 1950s. Dengue has remained a major public health problem in the country, and the growing magnitude of the disease prompted the government to provide free diagnostics for dengue to locals under the national insurance scheme(9). This facilitates large-scale screening of patients presenting to hospitals with acute febrile illness to determine whether they have dengue. Due to the significant disease burden, the Philippines was also the first country in Asia to approve and provide dengue vaccine.\u003c/p\u003e \u003cp\u003eIn contrast, chikungunya has not garnered as much public health interest, despite evidence of its presence(10, 11). This disparity may be due to the significant higher mortality rates associated with dengue compared to chikungunya. However, chikungunya tends to result in more severe long-term effects, impacting daily activities, causing loss of workdays, and leading to increased unproductiveness(8). A prospective cohort study in Cebu, Philippines, reported a rate of 3 symptomatic chikungunya infections per 100,000 person-years at the end of one year into the outbreak, they also further reported that outbreaks lasted three years(12).\u003c/p\u003e \u003cp\u003eThe Philippines, composed of 81 provinces, includes Davao de Oro, comprises 11 municipalities, has a population of approximately 767,547 people and features four secondary provincial hospitals located in Montevista, Laak, Pantukan, and Maragusan. Davao de Oro is home to migrants from Luzon and Visayas, as well as ethnic tribes such as the Mansaka, Mandaya, Davaoeno, and Kalagan. The main sources of income in the area are business establishments, banana plantations, and vast silver and gold mines across the province.\u003c/p\u003e \u003cp\u003eChikungunya is likely under-reported in this area due to several reasons. Unlike dengue, which benefits from free diagnostic tests provided by the government to registered Filipinos under national insurance schemes, diagnostic tests for chikungunya are not widely available. Many residents, particularly migrants and their families working in the agriculture and mining sectors of Davao de Oro, may not be registered in the national insurance scheme and therefore lack access to diagnostics. This gap in access to diagnostics could contribute to the under-diagnosis and under-reporting of chikungunya in this region. Understanding the true prevalence of chikungunya in this context is crucial for implementing effective public health strategies and improving healthcare access for all residents of Davao de Oro. In this study, we aimed to estimate the proportion of acute chikungunya and dengue infection among patients with acute febrile illness in four provincial hospitals of Davao de Oro in the Davao region.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThis multi-center, prospective study was conducted at four provincial hospitals in Davao de Oro province, located in the southeastern part of the Davao region (see Supplementary Materials, Figure S1). The hospitals included in the study were Montevista Provincial Hospital, Laak Provincial Hospital, Pantukan Provincial Hospital, and Maragusan Provincial Hospital. Patients between the ages of 1 to 65 years who presented to the emergency department with complaints of fever or had experienced at least one episode of fever of 38.5\u0026deg;C or higher within the past week and suspected dengue infection were recruited to the study. Blood samples were collected by venipuncture, and serum was separated by centrifugation and stored at -80\u0026deg;C until analysis.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Dengue NS1 antigen and IgM/IgG antibody assay\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA lateral flow rapid point-of-care diagnostic test kit for dengue, manufactured by Chembio Diagnostics, Inc. (NY, USA), was used to detect the dengue NS1 antigen and anti-dengue virus IgM and IgG antibodies. The tests were performed according to the manufacturer's instructions, using 10\u0026micro;L of serum. Results were interpreted 15 minutes after the test was conducted. The test was considered positive if two bands appeared, indicating the presence of NS1 antigen and IgM, along with the control band. If no bands appeared, the test was considered negative. The appearance of IgG alone with the control band indicated a previous infection. If the control band failed to appear, the test was deemed invalid.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Chikungunya IgM antibody assay\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eTo evaluate the presence of anti-chikungunya virus IgM antibodies in this study, we utilized a commercially available indirect enzyme linked immunosorbent assay, EUROIMMUN, L\u0026uuml;beck, Germany. The assay was performed in accordance with the manufacturer\u0026rsquo;s instructions as singlicates. In brief, 10\u0026micro;L of serum was diluted with the buffer solution provided by the manufacturer and added into a pre-coated 96 well microplate with a serum dilution of 1:100. Following this the microplate underwent three wash cycles with a working strength wash buffer, and the antibodies were identified by the addition of an enzyme conjugate (peroxidase-labelled anti-human IgM). Subsequently, a substrate solution containing THM/H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e was added to induce the development of a blue color. The process was halted by the addition of 0.5M sulfuric acid, and the photometric measurement was recorded at a wavelength of 450 nm. The optical density was used to quantify the concentration of specifically anti-chikungunya virus antibodies present in the serum samples. Results were evaluated through a semiquantitative approach, calculating a ratio of the extinction of the patient serum sample over the extinction of the calibrator. This ratio was interpreted as follows as \u0026lt;\u0026thinsp;0.8 negative, \u0026gt;=0.8 to \u0026lt;\u0026thinsp;1.1 borderline and \u0026gt;\u0026thinsp;=\u0026thinsp;1.1 as positive.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.3 RNA extraction and Reverse Transcription Polymerase Chain Reaction for Chikungunya.\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eViral RNA was extracted from 150uL of serum using an RNA extraction kit (Bioneer AccuPrep\u0026reg; viral RNA extraction kit, Daejeon,Korea) according to the manufacturer\u0026rsquo;s instruction. Quantification of CHIKV genomes was conducted using the TaqMAn quantitative real-time RT PCR method employing specific primers and a probe designed to target the 1200 bp region of the Nsp1 gene of CHIKV, as detailed in a previous study (ref. PMID:36016427)\u003c/p\u003e \u003cp\u003eA standard curve was drawn using CHIKV RNA that was prepared from a CHIKV strain TM009_2009 (ON406426). The standard curve was prepared from six dilutions containing 10\u003csup\u003e1\u003c/sup\u003e to 10\u003csup\u003e6\u003c/sup\u003e PFU/mL, and the detection limit was determined to be about 10\u003csup\u003e2\u003c/sup\u003e PFU/mL.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.4 Reverse Transcription Polymerase Chain Reaction for Dengue\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA previously described techniques for RNA quantification, which was performed using a One-Step SYBR\u0026reg; Prime Script RT-PCR Kit II from Takara Bio Inc. (Kusatsu, Japan). cDNA synthesis from RNA was carried out using reverse transcriptase Prime Script RTase, and polymerase chain reaction amplification was conducted with TaKaRa Ex Taq HS(13).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e1.5 Statistical analysis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA One-way ANOVA was used to assess parametric variables across multiple groups such as days of fever and haematocrit level, while the Mann-Whitney U-test was employed to evaluate differences in nonparametric variables between groups such as age, WBC and Platelete. The chi-square test was utilized to assess categorical variables, and Fisher's exact test was applied specifically when more than 20% of cells had expected frequencies less than 5.A P-value of less than 0.05 was considered significant for all tests performed. All statistical analyses were conducted using Microsoft Excel and STATA version 17 for MacOS 14.5 (23F79).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOver a 14-month study period, 382 patients were screened for chikungunya and dengue at four provincial hospitals in Davao de Oro, Philippines. Amongst these cases identified as acute febrile undifferentiated illness, 27 (7.07%) tested positive for circulating anti-chikungunya IgM, 190 (49.74%) tested positive for dengue infection, with the detection of both dengue NS1 antigen and anti-dengue IgM antibody. Additionally, 28 (7.33%) were identified as co-infected with both chikungunya and dengue, as their serum tested positive for anti-chikungunya IgM and also showed positive results for dengue NS1 and anti-dengue IgM. The remaining 137 cases (35.86%) had undetermined infectious etiologies, as both dengue and chikungunya were excluded as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Demographic and Epidemiological Characteristics\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe age distribution varied significantly between the two diseases (p\u0026thinsp;=\u0026thinsp;0.057), with median ages of 12 years for chikungunya and 17.5 years for dengue. Similarly, the median age was 17 years for cases identified as co-infected and for those who tested negative for both dengue and chikungunya, where the infective etiology remained unknown. The gender distribution, male: female across infection groups was as follows: chikungunya (9:18), dengue (103:87), co-infection (14:14), and unknown etiology (80:57). Although there appeared to be a higher proportion of females with chikungunya compared to dengue.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Hematological profile of the study cohort\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe mean hematocrit levels were similar across groups, ranging from 40.7\u0026ndash;43.3%.\u003c/p\u003e \u003cp\u003eLeukocyte count showed significant differences among groups (p\u0026thinsp;=\u0026thinsp;0.0046). The median leukocytes were lowest in cases with co-infections 3.3 x10\u003csup\u003e3\u003c/sup\u003e per microliter, with a range of 1.3 to 8.7 x10\u003csup\u003e3\u003c/sup\u003e/uL in cases with dengue infection the leukocytes mean was 3.7x10\u003csup\u003e3\u003c/sup\u003e/all, and in cases with chikungunya infection (4.05x x10\u003csup\u003e3\u003c/sup\u003e/all. In the group where the etiology was undetermined the mean leukocytes was 4.5x10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L. The median platelet counts were lowest in dengue infections (119 x 10^9/L, range: 30\u0026ndash;395), followed by mixed infections (122 x 10^9/L, range: 40\u0026ndash;255), unknown cases (126 x 10^9/L, range: 40\u0026ndash;413), and highest in chikungunya infections (144 x 10^9/L, range: 90\u0026ndash;332). This trend aligns with the known association between dengue and thrombocytopenia, while suggesting that chikungunya may have less impact on platelet counts. count also showed notable, though not statistically significant, variations among groups (p\u0026thinsp;=\u0026thinsp;0.0511).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Clinical Manifestations of Chikungunya, Dengue and Febrile cases with Undetermined Etiology\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eFever was the most prevalent symptom across all infection groups, affecting all cases. The mean duration of fever was also similar, ranging from 3.5 to 3.7 days (p\u0026thinsp;=\u0026thinsp;0.7). Headache was another common symptom, affecting 66.7% of chikungunya patients, 73.2% of dengue patients, 75% of patients with co-infections, and 67.1% of unknown cases (p\u0026thinsp;=\u0026thinsp;0.6). Retroorbital pain, often associated with dengue fever, showed no significant differences among groups (p\u0026thinsp;=\u0026thinsp;0.50), ranging from 7.9% in dengue to 14.8% in chikungunya cases.\u003c/p\u003e \u003cp\u003eMusculoskeletal symptoms also varied among groups. Arthralgia was more prevalent in chikungunya (44.4%) and co-infections (42.9%) compared to dengue (32.6%) and unknown cases (29.9%) (p\u0026thinsp;=\u0026thinsp;0.33). Myalgia, however, showed similar prevalence across groups (32.1% \u0026minus;\u0026thinsp;37.0%, p\u0026thinsp;=\u0026thinsp;0.98).\u003c/p\u003e \u003cp\u003eGastrointestinal symptoms showed some variations among groups. Nausea was more common in co-infections (78.6%) compared to other groups (p\u0026thinsp;=\u0026thinsp;0.19), while vomiting followed a similar pattern: mixed (64.3%), dengue (53.7%), chikungunya (44.4%), and unknown (46%) (p\u0026thinsp;=\u0026thinsp;0.22). Interestingly, diarrhea was relatively uncommon, with the highest prevalence in the unknown group (11%) and lowest in chikungunya (3.7%) (p\u0026thinsp;=\u0026thinsp;0.214). Abdominal pain was most frequent in dengue infections (61.6%) compared to other groups (p\u0026thinsp;=\u0026thinsp;0.087), potentially indicating a more severe gastrointestinal involvement in dengue cases.\u003c/p\u003e \u003cp\u003eNeurological involvement, represented by confusion, was rare across all groups. However, it was slightly more prevalent in chikungunya (3.7%) and co-infections (3.6%) compared to dengue (0.5%) and cases with unknown etiology (0%) (p\u0026thinsp;=\u0026thinsp;0.072).\u003c/p\u003e \u003cp\u003eRash was more common in chikungunya (59.3%) and dengue (63.7%) infections compared to co-infections (28.6%) (p\u0026thinsp;=\u0026thinsp;0.052).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Distribution proportion of cases presenting to Provincial Hospitals.\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe distribution of cases among the four provincial hospitals showed statistically significant differences (p\u0026thinsp;=\u0026thinsp;0.018). Laak Provincial Hospital reported relatively even distribution infection of cases across types, with 37% of chikungunya cases, 29.5% of dengue cases, 28.6% of co-infections, and 29.2% of unknown cases with that of Pantukan Provincial hospital, with 37.0% of chikungunya cases, 27.4% of dengue cases, higher rate on co-infections at 46.4%. and 25.6% of unknown cases. Maragusan Provincial Hospital had a notably lower proportion of chikungunya cases (14.8%) compared to dengue (3.2%) and no co-infections. Montevista Provincial Hospital, in contrast, had a higher proportion of dengue cases (40%) compared to chikungunya (11.1%) and co-infections (25%), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e \u003c/div\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\u003eComparison of Disease Groups in the study cohort.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient cohort, n\u0026thinsp;=\u0026thinsp;382\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCHIKV\u0026thinsp;+\u0026thinsp;ve\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDENV\u0026thinsp;+\u0026thinsp;ve\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;190\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCHIKV\u0026thinsp;+\u0026thinsp;ve\u003c/p\u003e \u003cp\u003eDENV\u0026thinsp;+\u0026thinsp;ve\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;28\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCHIKV -ve\u003c/p\u003e \u003cp\u003eDENV -ve\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;137\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaak Provincial Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaragusan Provincial Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMontevista Provincial Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePantukan Provincial Hospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u0026thinsp;\u0026gt;\u0026thinsp;38.5\u003csup\u003eo\u003c/sup\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDay of illness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.700\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 \u003cp\u003e12 (1\u0026ndash;49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (0\u0026ndash;65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 [0\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 [0\u0026ndash;65]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender ratio, male:female\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9:18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103:87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14:14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e80:57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.605\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetroorbital pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.503\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.334\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.982\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.224\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.51\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.385 (0.07\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.33 (0.07\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41 (0.1\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.36 (0.05\u0026ndash;0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.371\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukocytes x10\u003csup\u003e3\u003c/sup\u003e/uL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.05 (2.1\u0026ndash;9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.7 (1.4\u0026ndash;19.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3 (1.3\u0026ndash;8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5 (1.7\u0026ndash;19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets x10\u003csup\u003e3\u003c/sup\u003e/uL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144 (90\u0026ndash;332)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119 (30\u0026ndash;395)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (40\u0026ndash;255)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e126 (40\u0026ndash;413)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDengue NS1\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\u003e71.05%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92.86%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-chikungunya IgM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-dengue IgM\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\u003e51.58%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.43%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-dengue IgG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.26%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.42%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.29%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.88%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChikungunya RT-PCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.52%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDengue RT-PCR\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\u003e56.54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eN/A\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=\"BlockQuote\"\u003e \u003cp\u003eAge is provided as median with maximum and the minmum range, while all other continuous variables are provided as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. P value was determined at \u0026lt;\u0026thinsp;0.005. Chi-square analysis was used for catergorical compasion of symptoms and Mann Whitney non-parametric test for continous variables.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Proportion of Chikungunya and Dengue in study cohort\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eOur results demonstrate that among patients presenting with acute febrile illness in Davao de Oro, dengue remains the predominant arboviral infection, accounting for 49.74% of cases. However, the detection of chikungunya in 7.07% of cases, along with 7.33% co-infections, highlights the emergence of chikungunya as a significant concern in the region. This proportion has previously not been reported in this region as in some areas of the Philippines(14). This findings from Davao de Oro suggest that chikungunya may be more widespread than currently recognized.\u003c/p\u003e \u003cp\u003eFurthermore, co-infections present a unique challenge in terms of diagnosis, clinical management, and potential disease severity. It has been previously reported that global pooled prevalence of dengue and chikungunya coinfection is 2.5% (95% CI: 1.8\u0026ndash;3.4). To our knowledge there is no specific data about prevalence of co-infection in the Philippines prior this study. Nevertheless, co-infection from Asia, as a region, has the highest coinfection prevalence at 3.3% (95% CI: 2.3\u0026ndash;4.6)(15). Our results suggest that co-infected patients may exhibit overlapping of symptoms characteristic of both viral infections, potentially complicating clinical assessment, and management.\u003c/p\u003e \u003cp\u003eHowever, one-third of cases (35.86%) where neither chikungunya nor dengue and the infective etiology remained undetermined. Here, we postulate this group of cases might have other Orthoflaviviruses such as Zika virus, Japanese encephalitis virus(16, 17). As these viruses remain endemic in the region, should be considered in the differential diagnosis for an arboviral infection in Southeast Asia.\u003c/p\u003e \u003cp\u003eAmong other viral etiologies to consider, stratified according to age groups\u0026mdash;children, adolescents, and adults\u0026mdash;are DNA viruses such as human herpesviruses 4 and 5, which can present as mononucleosis, and HHV6, HHV7, or parvovirus B19, which can manifest as erythema infectiosum(18). Children and adolescents may be at risk of these infections. Other RNA viruses to consider in patients with febrile exanthema and enanthema include measles, rubella, and HIV(19\u0026ndash;21). If there has been exposure to insects such as ticks or sick domestic animals, and all the above possibilities have been ruled out, we also suggest to screen for the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) or bacterial illnesses such as rickettsiosis, leptospirosis, and salmonellosis(22\u0026ndash;24). This plethora of pathogens reflects the complexity of diagnosing acute febrile illnesses in tropical regions, emphasizing the need for broader diagnostic capabilities to identify other potential pathogens causing similar clinical presentations(25).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Clinical Manifestations and Hematological Profile of Chikungunya and Dengue\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe overlap in clinical symptoms between chikungunya and dengue infections poses a significant challenge for differential diagnosis based on clinical findings at presentation alone. Our study found that fever, headache, and myalgia were common across all groups, consistent with previous reports(2). The higher prevalence of arthralgia in chikungunya (44.4%) and co-infected cases (42.9%) compared to dengue (32.6%) aligns with the characteristic joint pain associated with acute chikungunya infection(7). This finding highlights the importance of considering chikungunya in cases presenting as acute febrile illness with prominent joint pain, especially with articular tenderness and peripheral joint involvement(8). Arthralgia can be exhibited with contagions we have described above. For example, rubella infection in adults can involve polyarthralgia of large joints, and similar clinical manifestations or arthropathy are also reported in adults with parvovirus B19.\u003c/p\u003e \u003cp\u003eInterestingly, our study found a higher prevalence of rash in both chikungunya (59.3%) and dengue (63.7%) cases compared to co-infections (28.6%). While rash is a known feature of both infections, the lower prevalence in co-infections is unexpected. Nevertheless, febrile rash might be missed without careful physical examination. Especially blanchable rashes associated with arboviral infections(26).\u003c/p\u003e \u003cp\u003eDengue warning signs, such as abdominal pain, were observed more frequently in dengue cases (61.6%) compared to chikungunya (37.0%) and co-infections (39.3%). In resource-limited settings where dengue rapid diagnostics are unavailable, a clinical diagnosis can be made by considering the epidemiology, symptoms, and warning signs. Warning signs like abdominal pain are very useful in monitoring the clinical trajectory of suspected dengue cases, allowing for effective patient triage and prompt management(5).\u003c/p\u003e \u003cp\u003eIn addition to identifying warning signs, the hematological profile can be used to monitor the progression of the disease. Specifically, in dengue, the hematological profile reflects dynamic bone marrow suppression, resulting in leukopenia. Leukocyte counts are among the first indicators to increase during recovery. Significantly lower leukocyte counts in dengue and co-infected cases, compared to chikungunya and cases of unknown etiology, are consistent with the known leukopenia associated with dengue infection(5).\u003c/p\u003e \u003cp\u003eThe trend towards lower platelet counts in dengue and co-infected cases, although not statistically significant, is consistent with the thrombocytopenia commonly observed in dengue(5). The relatively higher platelet counts in chikungunya cases suggest that severe thrombocytopenia is less likely in chikungunya infection, which could be a useful distinguishing feature in clinical settings(2).\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Distribution Chikungunya and Dengue in Provincial Hospitals of Davao de Oro\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe significant differences in case distribution among the four provincial hospitals highlight the importance of considering local epidemiological patterns in arboviral disease surveillance and control.The higher proportion of chikungunya cases in Laak Provincial Hospital and Pantukan provincial Hospital for instance, suggests a potential localized outbreak or environmental factors favoring chikungunya transmission in that area. Conversely, the higher proportion of dengue cases in Montevista Provincial Hospital indicates that dengue remains the dominant arboviral threat in some parts of the region. Furthermore, these findings suggest that chikungunya may be significantly underreported in Davao de Oro. The lack of routine diagnostic testing for chikungunya, combined with its clinical similarity to dengue, likely contributes to underdiagnosis and underreporting. This situation is exacerbated by the focus on dengue in national health programs, including the provision of free dengue diagnostics under the national insurance scheme(9).\u003c/p\u003e \u003cp\u003eThe high proportion of cases with undetermined etiology (35.86%) underscores the diagnostic challenges in resource-limited settings, impacting patient management and hindering disease surveillance and public health planning. The co-circulation of chikungunya and dengue viruses in Davao de Oro necessitates enhanced surveillance through comprehensive arboviral programs, improved access to diagnostic tests, and clinical education to distinguish between chikungunya and dengue.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eDengue in Davao de Oro maybe the leading arboviral infection (49.74%), amongst patients with acute undifferentiated febrile illness. The presence of chikungunya, previously underreported, suggests a wider circulation of arboviral infection in Davao de Oro. The variations in case distribution across hospitals reflects the need for localized surveillance and improved diagnostics to enhance public health strategies in endemic regions like the Philippines.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCHIKV\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Chikungunya Virus\u003c/p\u003e\n\u003cp\u003eDENV\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Dengue Virus\u003c/p\u003e\n\u003cp\u003eRT-PCR \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Real-time reverse transcriptase-polymerase chain reaction\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSFTSV \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Severe Fever with Thrombocytopenia Syndrome Virus\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki, and the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University approved the protocol (Certificate of Approval No. MUTM 2019-015-01, February 25,2019) and approved by the Ethics Review Committee of the Compostela Valley Provincial Hospital Montevista, Davao de Oro Province (Case 005, January 25,2019). Informed consent was obtained from all study participants in the study as well as their written permission to publish this paper.\u003c/p\u003e\n\u003cp\u003eConsent for publication: All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003eAvailability of data and material: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy of study participants.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding: This research was funded by Mahidol Norway Capacity Building Initiative for ASEAN and Mahidol University Faculty of Clinical Tropical Medicine.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions \u0026ndash; Conceptualization, NAJ; KB; LTB, CJS; VL; BP; WP and PC methodology, NAJ; KB; LTB, CJS; VL; BP; WP and PC validation, NAJ; KB; AP, PLA, and PC formal analysis, NAJ; KB; BP; AP.; PLA and PC; investigation, NAJ; KB; LTB, CJS and PC; resources, NAJ; KB; LTB, CJS and PC data curation, NAJ; KB; AP, PLA \u0026nbsp; writing\u0026mdash;original draft preparation, NAJ; AP, HAI; and PC writing\u0026mdash;review and editing, NAJ; KB; LTB, CJS; AP, PAL; HAI; VL; WP and PC supervision, PC; and WP; project administration, NAJ; KB; LTB, CJS and PC; funding acquisition, PC.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements: The authors are grateful to all the study participants who volunteered to be part of this important study, which is part of the author\u0026rsquo;s doctoral thesis. The authors would also like to express their sincere appreciation and thank all the staff at the four Provincial Hospitals in Davao de Oro who are taking care and comforting patients in these four hospitals. Special thanks to Udomsak Silachamroon, whose fostering of an environment of academic excellence and encouragement greatly influenced the publication of this report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLuvira V, Silachamroon U, Piyaphanee W, Lawpoolsri S, Chierakul W, Leaungwutiwong P, et al. Etiologies of Acute Undifferentiated Febrile Illness in Bangkok, Thailand. Am J Trop Med Hyg. 2019;100(3):622-9.\u003c/li\u003e\n\u003cli\u003eImad HA, Phadungsombat J, Nakayama EE, Kludkleeb S, Matsee W, Ponam T, et al. Chikungunya Manifestations and Viremia in Patients WhoPresented to the Fever Clinic at Bangkok Hospital for Tropical Diseases during the 2019 Outbreak in Thailand. Trop Med Infect Dis. 2021;6(1).\u003c/li\u003e\n\u003cli\u003eGuzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016;2:16055.\u003c/li\u003e\n\u003cli\u003eSchwartz O, Albert ML. Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol. 2010;8(7):491-500.\u003c/li\u003e\n\u003cli\u003eImad HA, Phadungsombat J, Nakayama EE, Chatapat L, Pisutsan P, Matsee W, et al. A Cluster of Dengue Cases in Travelers: A Clinical Series from Thailand. Trop Med Infect Dis. 2021;6(3).\u003c/li\u003e\n\u003cli\u003eImad HA, Phumratanaprapin W, Phonrat B, Chotivanich K, Charunwatthana P, Muangnoicharoen S, et al. Cytokine Expression in Dengue Fever and Dengue Hemorrhagic Fever Patients with Bleeding and Severe Hepatitis. Am J Trop Med Hyg. 2020;102(5):943-50.\u003c/li\u003e\n\u003cli\u003eImad HA, Phadungsombat J, Nakayama EE, Suzuki K, Ibrahim AM, Afaa A, et al. Clinical Features of Acute Chikungunya Virus Infection in Children and Adults during an Outbreak in the Maldives. Am J Trop Med Hyg. 2021;105(4):946-54.\u003c/li\u003e\n\u003cli\u003eImad HA, Matsee W, Kludkleeb S, Asawapaithulsert P, Phadungsombat J, Nakayama EE, et al. Post-Chikungunya Virus Infection Musculoskeletal Disorders: Syndromic Sequelae after an Outbreak. Trop Med Infect Dis. 2021;6(2).\u003c/li\u003e\n\u003cli\u003eAlberto NRI, Alberto IRI, Eala MAB, Dee EC, Canal JPA. Availability of essential diagnostics in the Philippines. Lancet Reg Health West Pac. 2022;19:100375.\u003c/li\u003e\n\u003cli\u003eCenters for Disease C. Chikungunya fever among U.S. Peace Corps volunteers--Republic of the Philippines. MMWR Morb Mortal Wkly Rep. 1986;35(36):573-4.\u003c/li\u003e\n\u003cli\u003eSrikiatkhachorn A, Alera MT, Lago CB, Tac-An IA, Villa D, Fernandez S, et al. Resolution of a Chikungunya Outbreak in a Prospective Cohort, Cebu, Philippines, 2012-2014. Emerg Infect Dis. 2016;22(10):1852-4.\u003c/li\u003e\n\u003cli\u003eYoon IK, Alera MT, Lago CB, Tac-An IA, Villa D, Fernandez S, et al. High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines. PLoS Negl Trop Dis. 2015;9(5):e0003764.\u003c/li\u003e\n\u003cli\u003eWang WK, Lee CN, Kao CL, Lin YL, King CC. Quantitative competitive reverse transcription-PCR for quantification of dengue virus RNA. J Clin Microbiol. 2000;38(9):3306-10.\u003c/li\u003e\n\u003cli\u003eVelasco JM, Valderama MT, Lopez MN, Chua D, Jr., Latog R, 2nd, Roque V, Jr., et al. Chikungunya Virus Infections Among Patients with Dengue-Like Illness at a Tertiary Care Hospital in the Philippines, 2012-2013. Am J Trop Med Hyg. 2015;93(6):1318-24.\u003c/li\u003e\n\u003cli\u003eIrekeola AA, Engku Nur Syafirah EAR, Islam MA, Shueb RH. 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Western Pac Surveill Response J. 2016;7(3):1-5.\u003c/li\u003e\n\u003cli\u003eLopez AL, Raguindin PF, Silvestre MA, Fabay XC, Vinarao AB, Manalastas R. Rubella and Congenital Rubella Syndrome in the Philippines: A Systematic Review. Int J Pediatr. 2016;2016:8158712.\u003c/li\u003e\n\u003cli\u003eGangcuangco LMA, Eustaquio PC. The State of the HIV Epidemic in the Philippines: Progress and Challenges in 2023. Trop Med Infect Dis. 2023;8(5).\u003c/li\u003e\n\u003cli\u003eVan Dijck C, Van Esbroeck M, Rutsaert R. A 54-year-old Philippine sailor with fever and jaundice. Acta Clin Belg. 2016;71(5):319-22.\u003c/li\u003e\n\u003cli\u003eGalay RL, Talactac MR, Ambita-Salem BV, Chu DMM, Costa L, Salangsang CMA, et al. Molecular Detection of Rickettsia Spp. and Coxiella Burnetii in Cattle, Water Buffalo, and Rhipicephalus (Boophilus) Microplus Ticks in Luzon Island of the Philippines. Trop Med Infect Dis. 2020;5(2).\u003c/li\u003e\n\u003cli\u003ePutri A, Charoenwisedsil R, Techavachara N, Imad H, Chinpraditsuk S, Thaipadungpanit J, et al. Severe leptospirosis with rhabdomyolysis in a traveller visiting Thailand. J Travel Med. 2024;31(1).\u003c/li\u003e\n\u003cli\u003eImad HA, Lakanavisid P, Pisutsan P, Trerattanavong K, Ngamprasertchai T, Matsee W, et al. A Case Report of Secondary Syphilis Co-Infected with Measles: A Diagnostic Dilemma with Fever and Rash. Trop Med Infect Dis. 2022;7(5).\u003c/li\u003e\n\u003cli\u003eImad HA. Febrile Rash: An Early Diagnostic Clue to Infectious Illness in Travelers Returning from Thailand. Reports. 2024.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute febrile illness, chikungunya, dengue, coinfection, Southeast Asia, Philippines","lastPublishedDoi":"10.21203/rs.3.rs-4904666/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4904666/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMosquito-borne diseases like dengue and chikungunya are endemic in the tropical region and is a common cause of acute febrile illness in both adults and children. The Philippines, home to over a hundred million residents and visited by several million tourists each year, is one such region where the risk of these diseases is endemic. To better understand the detailed situation, we estimated the proportion of these diseases in the community by conducting a prospective observational study conducted in four provincial hospitals of Davao de Oro, Philippines from February 2019 to February 2020. Serum from 382 study participant was used for laboratory confirmation of dengue or chikungunya either by antigen, antibody or by RT-PCR. Dengue was diagnosed in 57.1%, chikungunya 7.07%, co-infection with both dengue and chikungunya in 7.3%, and the etiology was undetermined in 35.9% of study participants. Common clinical symptoms included fever, headache, and rash, which were overlapping symptoms and clinically indistinguishable at presentation to the hospital, necessitating the need for laboratory diagnostics. The identification of the presence of chikungunya in Davao de Oro calls for increased awareness, improved diagnostics, and integrated disease control measures to manage outbreaks that can occur in dengue endemic regions.\u003c/p\u003e","manuscriptTitle":"Clinical and Epidemiological Characteristics of Chikungunya and Dengue Infections in Provincial Hospitals of Davao de Oro, Philippines","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-11 06:40:32","doi":"10.21203/rs.3.rs-4904666/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"
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