Acute clinical features and persistence of joint pain in probable cases of Chikungunya Fever in Eritrea

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Persistent arthralgia following chikungunya fever is common and requires advanced pharmacological interventions as pain does not respond well to analgesics. Objective The study aimed to describe the acute clinical features of probable cases of chikungunya fever and risk factors associated with the persistence of joint pain. Methods A prospective, descriptive cohort study was conducted on probable cases of chikungunya fever from October 2018 to March 2019 following the chikungunya outbreak of October 2018 in the Tesseney subzone of Eritrea. Results A total of 203 probable cases of chikungunya fever were enrolled, majority being males (68%) with a mean age of 39.2 years. The acute phase symptoms include the triad of polyarthralgia (97%), fever (96.1%), and skin rash (56.7%). Commonly affected joint sites were the wrist (59.4%) and interphalangeal joints of the hands (56.9%). Fever had a mean duration of 4.1 ± 3 days, while headache had a mean duration of 3.8 ± 3 days. Skin rash was maculopapular which was pruritic (85.2%) with common involved sites were the hands (71%) and trunk (46.5%). Complete blood count during the initial visit showed lymphocytosis (64.5%) and granulocytopenia (43.3%). Joint pain persisted at three months in 52.1% of cases and at six months in 21.7% of the cases. Age > 41 (p = 0.001, OR: 1.588; 95% CI: 0.935–2.695) and having the O-type blood group (p = 0.033, OR: 0.704; 95% CI: 0.448–1.105) were found to be significant risk factors for the persistence of joint pain. Conclusion Our study indicates polyarthralgia, fever, and skin rash as a triad of symptoms during the acute phase. Persistent arthralgia was a frequent long-term complication of chikungunya fever in which increasing age was identified to be a significant risk factor. Chikungunya fever clinical features persistent joint pain Eritrea Figures Figure 1 Introduction Chikungunya fever (CHIKF) is a crippling mosquito-borne viral disease that has become a major public health concern in recent years. The name “chikungunya” is derived from the Makonde word meaning ‘he, who walks bends up” in reference to the stooped posture developed due to the arthritic symptoms of the disease.( 1 – 3 ) The disease is caused by the chikungunya virus (CHIKV) which is transmitted to humans through the bite of infected Aedes aegypti and Aedes albopictus mosquitoes.( 1 , 2 ) The etiologic agent is a single-stranded positive sense RNA virus identified as an arbovirus of the Alphavirus genus.( 2 , 4 ) Human and other vertebrate host (i.e., monkeys, rodents, birds, etc.) serve as reservoirs during CHIK epidemics.( 2 ) The virus has two distinct transmissions cycles based on the geographical location and human settlement density: enzootic and sylvatic (urban).( 2 ) The enzootic cycles mainly occurs on African tropical regions where arboreal mosquitoes transmit the virus to nonhuman primates which serve as the main reservoir host.( 2 ) The sylvatic cycle is concentrated in urban centers where the virus is transmitted via the Ae. aegypti and Ae. albopictus mosquitos from human-to-human.( 2 ) The enzootic cycle allows interhuman transmission during outbreaks as well as reducing the probability of eliminating the virus circulation in an environment.( 2 , 5 ) CHIKV was first isolated in Tanzania in 1953, later spreading across sub-Saharan Africa.( 6 ) Three distinct strains of CHIKV have been identified based on phylogenetic analysis: West African, East-Central-South African (ECSA), and the Asian lineage.( 7 ) Before 2000, CHIKV was largely restricted within the sub-Saharan African region, but later the ECSA strain re-emerged within the Kenya coast and spread across the Indian Ocean islands, simultaneously evolving into a new strain called Indian Ocean lineage (IOL).( 7 ) Major CHIK outbreaks emerged across the Indian Ocean islands between 2004 and 2007 and infected more than 272,000 people, most notably on Reunion island.( 8 , 9 ) The Reunion island epidemic of 2005–2006 reported 270,000 infected cases, approximately a third of the island’s population.( 8 ) Major epidemics, such as found in Reunion Island, can cause significant productivity loss and immense economic cost, especially for developing countries.( 10 ) After 2004, CHIKV outbreaks were later documented in Italy, Bangladesh, Cameroon, and France, likely due to international travelers who, during the Reunion epidemic, likely became infected and, when returning home, dispersed the CHIKV to other countries.( 6 ) Presently, CHIKV has a wide geographical distribution, including North and South America, Europe, Asia, and the Pacific Islands, with an estimated global incidence of more than 6 million confirmed cases worldwide.( 8 ) Ecological factors such as temperature, availability of breeding sites, rainfall, vegetation, and globalization contribute to CHIKV dissemination which impacts human migration and the range of mosquito prone areas. Human demographic changes (migration, international travel, tourism, global trade, etc.) linked to population movements has largely been affected by the chikungunya virus.( 2 , 10 – 12 ) CHIKV, like the dengue and zika virus, are commonly classified as arthritogenic viruses as these viruses cause musculoskeletal inflammatory disease in humans.( 13 ) Upon infection, CHIKV has an incubation period of 3–7 days, but may last as long as fourteen days.( 6 , 14 ) Seroprevalence studies have demonstrated that 30–40% of CHIKV infected individuals can be asymptomatic, but the majority (60–80%) of infected individuals are symptomatic.( 14 , 15 ) After the incubation period, sudden onset of high-grade fever, polyarthralgia, headache, myalgia, and transient maculopapular skin rash commonly develop.( 13 , 14 ) In addition, swollen joints, tenosynovitis, vomiting, and nausea have also been observed.( 10 ) Chikungunya fever is rarely fatal with an acute crippling phase that lasts 1–2 weeks followed by convalescence. However, in a subset of people, joint pain and swelling can last for months to years and often fluctuating, leading to long-term persistent polyarthralgia.( 3 , 8 , 9 , 15 ) CHIKV pathogenesis of arthropathy is likely attributed to CHIKV residing and replicating within muscle and joint tissue. Although recent advances have shed light on the CHIK infection, the immunopathogenic mechanism of CHIKV resulting in arthralgia still remains unclear.( 6 ) Chronic polyarthralgia is described to possess both neuropathic and nociceptive characteristics, requiring advanced pharmacological interventions as pain does not respond well with analgesics.( 3 ) Diagnosis of a CHIK infection is often performed via molecular detection of a viral genome and/or identification of a virus-specific antibody in a laboratory setting.( 10 , 15 ) Reverse transcription–polymerase chain reaction (RT-PCR) is often used for molecular detection from a blood sample; ELISA, immunofluorescence assay, and rapid immunochromatographic test are performed for serologic analysis to capture virus-specific antibodies from a patient’s serum (IgM antibody or demonstrating rising titer of IgG antibody).( 6 , 10 , 18 , 19 ) Differential diagnosis may be required as CHIKV manifestations may co-exist with as other similar alphaviruses, such as dengue.( 15 ) Differential diagnosis from dengue infection is often based on the presence of hemoconcentration, while symptoms of high-grade fever and joint pain are known only to be exhibited in CHIKV infection.( 10 ) No vaccines or specific antiviral drug have yet been introduced to prevent or treat CHIKF, but individuals previously infected are believed to incur life-long immunity.( 7 , 15 , 20 ) New studies, however, have reported several novel preclinical vaccines are in development with limited number of clinical trials, but more time is required before these vaccines are approved for the global market.( 6 ) Thus, treatment of CHIK is largely focused on symptomatic relief with the use of anti-inflammatory drugs as the viral disease has a relatively low-fatality rate. Nevertheless, little is known about the viral-host interactions, cellular factors involved in viral pathogenesis, and role of immune system during the course of chikungunya fever, which hinders the development of effective vaccines and management strategies for the disease. The reemergence of chikungunya epidemics in different parts of the world and their related economic burden incited the need to study the clinical features of this disease. Eritrea’s subtropical climate is suitable for the transmission of mosquito-borne diseases, such as chikungunya fever. The first cases of chikungunya fever was reported in Tesseney subzone during the October 2018 outbreak.( 21 ) Our aim in carrying out this study is to describe the acute clinical features of probable cases of chikungunya fever and the risk factors associated with the persistence of polyarthralgia. Objective General Objective The primary objective of this study was to describe acute clinical features of probable cases of chikungunya fever and the risk factors for persistence of arthralgia. Specific Objective To describe the acute clinical features of probable cases of chikungunya fever during the acute prodromal phase. To identify risk factors associated with the persistent of arthralgia. Material and Methods Study Design This was a prospective, descriptive cohort hospital-based study at the Tesseney Community Hospital. Study Area Tesseney hospital is a community hospital in the Gash-Barka region of Eritrea which serves the catchment population of 87,992 individuals distributed in an area of 1,096.83 km 2 . The hospital provides inpatient and outpatient services, delivery service, laboratory services, imaging unit, physiotherapy unit, and possess a 115-bed capacity. Study Population Probable chikungunya fever cases that met the clinical and epidemiological criteria during the October 2018 chikungunya fever outbreak were included as the study population. Inclusion Criteria All probable cases of chikungunya fever who had signs and symptoms of acute febrile illness during the outbreak and tested negative for malaria and dengue fever were included in the study. Exclusion Criteria All probable cases of chikungunya fever who had signs and symptoms of acute febrile illness during the outbreak and returning with positive results for malaria and dengue fever were excluded from the study. Sampling Procedure Non-probability convenience sampling method was used with inclusion of all probable cases of chikungunya fever based on clinical symptoms and epidemiological data. Data Collection Method of Data Collection Data collection was conducted by interviewing and examining probable cases of chikungunya fever by pre-designed questionnaire. All cases were assessed for regional and systemic manifestations by general practitioners. The follow-up of the patients was conducted monthly for six months with each manifestation documented during their visit. Laboratory Investigations Serologic analysis for each possible chikungunya fever case was not feasible. However, during the outbreak, a sample of 30 patient was collected and sent to a regional WHO virology laboratory in Kenya for chikungunya virus analysis. All samples reported positive for chikungunya fever and the criteria of chikungunya fever outbreak was met. Five mL. of venous blood was drawn from each enrolled patient to investigate malaria and dengue fever using rapid tests. A complete blood count was also performed only on the initial visit with blood group and respective Rh factor being identified for each patient. Data Analysis and Interpretation The collected data was tabulated and analyzed using Epi-info software and further analyzed via SPSS software version 26. Data were presented as frequencies and percentages. The chi-square test was used as a significance test with p-value < 0.05 considered as statistically significant. Further logistical regression analysis was also performed. Case Definitions : Table 1 – 2 refer to chikungunya infection criteria and case definition used during our study based on the European Centre for Disease Control.( 15 ) Table 1 Chikungunya infection criteria definitions. Criteria Definition Clinical Acute onset of fever greater than 38.5°C and severe arthralgia/ arthritis not explained by other medical conditions. Epidemiological Residing or having visited epidemic areas, having reported transmission within 15 days prior to the onset of symptoms. Laboratory At least one of the following tests in the acute phase: • Virus isolation • Presence of viral RNA by RT-PCR • Presence of virus specific IgM antibodies in single serum sample collected in acute or convalescent stage. • Four-fold increase in IgG values in samples collected at least three weeks apart Table 2 Chikungunya infection case definitions. Case Definition Possible Case Patient meeting clinical criteria. Probable Case Patient meeting both the clinical and epidemiological criteria. Confirmed Case Patient meeting the laboratory criteria, irrespective of the clinical presentation. Ethical Clearance : Ethical approval was obtained from the zonal branch of the Ministry of Health, Research and Ethics Review Committee and written informed consent was sought from each patient. Data confidentiality was assured by coding the personal identifiers and removing identifiers from the final analysis. Results Based on an epidemiological data and clinical criteria, a total of 203 probable cases of CHIKF were included in the study. The study observed a high male-to-female sex ratio of 2.1:1 (males = 68%; females = 32%) with a mean age of 39.2 years old. Most of patients were 25–35 years old (40.9%) and 20.7% above 45 years old. Regarding occupational frequencies, healthcare workers (47.8%) and civil servants (30.5%) working in the town (teachers, immigration staff, commercial bank staff, telecommunication staff) ranked the most common profession, followed by subzone administration staff (21.7%). Majority of patients reached either college-level (51.7%) or secondary education (32.5%) with only 5.4% of cases being illiterate working as cleaners and gatekeepers. From our study, 51.2% identified as O-type blood group with a large portion of cases possessing the positive Rh antigen factor (96.4%) (Table 3 ). Table 3 Socio-demographic data, including blood group and Rh factor, of probable cases of chikungunya fever. Variables Characteristics n Percentage (%) Age 18–25 26 12.8 25–30 41 20.2 31–35 42 20.7 36–40 36 17.7 41–45 16 7.9 ˃45 42 20.7 Sex Male 138 68.0 Female 65 32.0 Occupation Health Workers 97 47.8 Immigration Staff 21 10.3 Teachers 12 5.9 Subzone Administration Staff 44 21.7 Bank Staff 9 4.4 Telecommunication Staff 20 9.9 Educational status Illiterate 11 5.4 Elementary 15 7.4 Junior 6 3.0 Secondary 66 32.5 College 105 51.7 Blood group “A” 44 21.7 “B” 38 18.7 “AB” 17 8.4 “O” 104 51.2 Rh factor Positive 192 94.6 Negative 11 5.4 During the acute phase (first visit), common reported symptoms were polyarthralgia (97%), fever (96.1%), gastrointestinal symptoms (64.5%), headache (62%) and skin rash (56.7%) (Table 4 ). Joint pain was the main symptom with the most frequent affected joints being the wrist (59.4%), interphalangeal joints of the hands (56.9%), and knee (53.8%) (Table 4 ). Arthralgia gradually reduced over the course of the study period, persisting at the sixth month in only 21.7% of the cases (Fig. 1 ). Arthralgia was largely symmetrical (84.3%) during the acute phase, but over time, the symmetry of joint pain gradually reduced to 78% reported during the last visit. Fever was the second leading symptom with the mean duration of 4.1 ± 3 days and was commonly responded with antipyretics in 95.9% of cases. Fever was accompanied by epistaxis is minority of the patients (0.6%). Headache was also common symptom with a mean duration of 3.8 ± 3 days (Table 5 ). In terms of dermatological features, 56.7% of cases experienced transient maculopapular rash which was largely pruritic (85.2% of skin rash cases) with the most involved anatomical sites being the hands (71%), trunk (46.5%), and face (45.6%) (Table 4 ). Table 4 Common skin rash sites and joint sites involved with transient maculopapular rash and polyarthralgia, respectively. Common Skin Rash Sites Percentage (%) Hands 71.9 Trunk 46.5 Face 45.6 Legs 31.6 Palms and Sole 25.4 Scrotum 7.9 Oral Cavity 6.1 Common Polyarthralgia Joint Sites Wrist 59.4 Interphalangeal Joints of the Hand 56.9 Knee 53.8 Ankles 47.7 Shoulder 40.1 Spine 39.1 Elbow 35 Hip 15.2 Table 5 Clinical presentation of probable cases of chikungunya fever with related duration for fever and headache during the acute phase. Clinical Presentation Percentage (%) Mean (days) Standard Deviation (days) Median (days) Fever 96.1 4.1 3 3 Headache 62 3.8 3 3 Skin Rash 56.7 - - - Polyarthralgia 97 - - - Gastrointestinal symptoms were experienced by 64.5% of cases with anorexia (80.9%), nausea (41.2%), and vomiting (32.2%) as the highest ranked symptoms (Table 6 ). Lymphadenopathy was found in 44.3% of cases with greatest affliction amongst inguinal lymph node (67.8%) followed by cervical lymph nodes (51.1%). Ocular symptoms were seen in 32.5% of cases in which retro-orbital pain (27.1%) was the main presented eye symptom followed by conjunctival hyperemia (24%) (Table 6 ). CBC showed lymphocytosis (64.5%), granulocytopenia (43.3%), and mild anemia (31%) were the most common abnormal hematological findings, follow by leukopenia (16.7%) and granulocytosis (14.3%) (Table 7 ). Table 6 Lymphadenopathic features, GI manifestations, and ocular symptoms of probable cases of chikungunya fever during the acute phase. Clinical Manifestations Percentage (%) Lymphadenopathy 44.3 Inguinal 67.8 Cervical 51.1 Retro-auricular 34.4 Axially 21.1 GI Manifestations 64.5 Anorexia 80.9 Nausea 41.2 Vomiting 32.1 Weight Loss 10.7 Abdominal Pain 6.9 Diarrhea 6.1 Ocular Symptoms 32.5 Retro-orbital Pain 27 Conjunctival Hyperemia 24 Visual Problem 13 Eye Congestion 9 Table 7 Abnormal hematological findings from CBC profile. Hematological Findings Percentage (%) Lymphocytosis 64.5 Granulocytopenia 43.3 Mild Anemia 31 Reduced Hematocrit 17.2 Leukopenia 16.7 Granulocytosis 14.3 Thrombocytopenia 10.8 At the end of the acute phase, patients continued to be monitored via monthly follow-up visits for the remainder of the 6-month study period. The main clinical features that continued to be monitored were joint pain and joint swelling. Across the entire study period, cases ages 25–35 and greater 45 years old expressed higher and consistent frequencies of joint pain and joint swelling compared to other age groups, with the exception of joint swelling reported higher among 36–40 age group. Health workers followed by administration workers continued to experience higher levels of CHIKF symptoms compared to other professional groups. The same pattern was found with educational status as individuals possessing college or secondary level education had higher levels of CHIKF symptoms compared to groups of lower educational status (Table 8 ). Logistical regression was performed to further analyze significant factors associated with persistent of joint pain and joint swelling. Patient’s age > 41 years (p = 0.001, OR: 1.588; 95% CI: 0.935–2.695) and occupation (p = 0.003; OR: 0.370 95% CI: 0.194–0.707), O blood type (p = 0.033, OR: 1.153; 95% CI: 0.843–1.579) showed significant association with the likelihood for the persistent of joint pain (Table 8 ). Joint pain was often accompanied by joint swelling (42.1% of joint pain cases) with being female (p = 0.001, OR: 0.355; 95% CI: 0.216–0.583) and possessing O-type blood group (p = 0.02; OR: 1.836; 95% CI: 0.820–4.110) as significant predisposing factors to experiencing joint swelling (Table 8 ). Table 8 Joint pain and joint swelling features of probable chikungunya fever patients counted during monthly follow-up for the entire six-month study period. Variables Joint pain Joint swelling Percentage (%) P-value OR (95%CI lower-upper) Percentage (%) P-value OR (95%CI lower-upper) Age 18–25 8 0.001* 1 6.9 0.306 1 25–30 16.8 0.173 (0.106–0.281) 18.6 0.506 (0.192–1.333) 31–35 21.0 0.427 (0.290–0.628) 14.7 0.687 (0.345–1.368) 36–40 17.3 0.576 (0.384–0.863) 21.6 0.519 (0.240–1.120) 41–45 10.9 0.665 (0.447–0.988) 7.8 0.865 (0.439–1.705) ˃45 26.1 1.588 (0.935–2.695) 30.4 0.509 (0.207–1.250) Sex Male 65.8 0.100 1 47.1 0.001* 1 Female 34.2 0.355 (0.216–0.583) 52.9 0.355 (0.216–0.583) Occupation Health Workers 47.2 0.003* 1 55.9 0.15 1 Immigration Staff 9.1 0.829 (0.543–1.267) 5.9 0.702 (0.342–1.439) Teacher 4.6 0.777 (0.456–1.324) 2.0 0.396 (0.132–1.186) Subzone Administration Staff 22.1 0.370 (0.194–0.707) 16.7 0.270 (0.053–1.834) Bank Staff 6.5 1.002 (0.629–1.596) 5.9 0.527 (0.230–1.206) Telecommunication Staff 10.4 3.538 (1.645–7.610) 13.7 0.305 (0.094–0.989) Educational status Illiterate 6 0.44 1 6.9 0.902 1 Elementary 6.7 0.684 (0.378–1.238) 6.9 0.506 (0.191–1.341) Junior 3.4 0.506 (0.299–0.856) 4.9 0.550 (0.201-1.500) Secondary 33.7 1.106 (0.540–2.268) 33.3 0.753 (0.221–2.566) Post-secondary 59.2 0.687 (0.494–0.957) 48.0 0.738 (0.396–1.375) Blood Group “A” 24.4 0.033* 1 16.7 0.02* 1 “B” 19.5 1.153 (0.843–1.579) 16.7 0.586 (0.315–1.091) “AB” 7 1.143 (0.820–1.594) 12.7 0.804 (0.428–1.511) “O” 49 0.704 (0.448–1.105) 53.9 1.836 (0.820–4.110) Rh Factor Positive 95 0.565 1 94.1 0.67 1 Negative 5 1.268 (0.745–2.159) 5.9 0.874 (0.303–2.524) Discussion Chikungunya virus is responsible for the recent explosive outbreaks of debilitating disease in humans. This arthritogenic virus has re-emerged in many tropical and subtropical regions due to its genomic polymorphism which increase the vector susceptibility.( 16 ) Global warming/climate change, globalization with significant increase in international travels, and adaptation of virus to new vectors has also increased the vector susceptibility and transmission capacity.( 13 , 19 ) CHIKV most probably first emerged as a human pathogen in the 18th century, but currently has been identified in nearly 80 countries across 5 continents.( 10 ) Most epidemics of chikungunya fever occurred in tropical or subtropical areas; Eritrea’s subtropical climate is suitable for Aedes mosquitoes and the transmission of mosquito-borne diseases, such as CHIKF. The first confirmed CHIK outbreak in Eritrea was found within the Tesseney subzone in October 2018. This study aims to describe the clinical features of probable cases of chikungunya fever during and following the October 2018 outbreak as well as the risk factors associated with the persistence of polyarthralgia within the Tesseney subzone of Eritrea. The clinical manifestations of CHIKF depend on the host-viral interactions which determine the course of infection and key to understanding viral pathogenesis and treatment.( 22 , 23 ) During the acute phase, our patients mainly presented with sudden onset of high-grade fever (96.1%) and polyarthralgia (97%), follow by headache (62%) and skin rash (56.7%). Our results align with previous literature which reports the typical triad of symptoms during the acute stage of CHIKF: high-grade fever, skin rash, and polyarthralgia.( 2 , 8 , 15 , 16 ) Prospective studies performed in the Philippines and Maldives also exhibited similar frequencies of high-grade fever (94.3% in Philippines; 100% in Maldives) and arthralgia (98.6% in Philippines; 82% in Maldives) with only a difference in skin rash incidence (87.1% in Philippines; 54% in Maldives).( 8 , 16 ) Cross-sectional analyses done in Columbia and Bangladesh after CHIKV outbreaks reported arthralgia (91.2% in Columbia; 99.2% in Bangladesh) and skin rash (44.7% in Columbia; 50.2% in Bangladesh) in similar frequency, but high-grade fever in different frequency (50% in Columbia; 100% in Bangladesh).( 24 , 25 ) These difference in occurrence to commonly reported symptoms could be attributed to host-viral interactions.( 23 ) A case study in Brazil illustrates this idea as a patient with pain from a previous finger joint injury was reignited upon CHIK infection and was hypothesized that the CHIKV targeted and exacerbated the latent injury.( 13 ) Interestingly, a longitudinal cohort study in Sri Lanka found a unusually high expression of acute polyarthritis (45%) that later progressed to chronic polyarthritis (99% of acute polyarthritis cases) with a reduced frequency of skin rash symptoms (20%) commonly reported in the literature, showcasing the uncertainties of CHIK manifestations.( 5 ) Acute arthralgia (97%) was highly expressed amongst our patients which aligns with results of previous studies and general pathology of CHIK manifestation.( 4 , 5 , 8 , 15 , 16 ) Within our study, the most involved joint sites were the wrist (59.4%), interphalangeal joints of the hands (56.9%), knee (53.8%), and ankles (47.7%). Joint sites involvement for arthralgia in a Bangladesh study were similar with the wrist (54.1%) and small joints in the hand (46.8%) as primary joint sites.( 24 ) Contrarily, arthralgia was more expressed among weight-bearing joints (i.e., ankles and knees) within previous Sri Lanka (74% for ankles), Philippines (60% for ankles), and Columbia (74.1% for ankles) studies.( 5 , 8 , 25 ) Joint site frequency was relatively high among all joint groups in our findings, thus minor differences amongst sites are likely not significant in understanding CHIK infection patterns in joint site involvement. Transient maculopapular rash, stomatitis, and oral ulcers are often seen in adults while retro-orbital pain, vomiting, and diarrhea commonly exhibited in children.( 15 ) 56.7% of our cases experienced transient maculopapular skin rash with 0.6% experiencing epistaxis most likely associated to the hemorrhagic complication of the virus. Bangladesh (50.2%) and Maldives (50%) found roughly half of their patients develop maculopapular skin rash similar to our study.( 16 , 24 ) Skin rashes were frequently exhibited on the hands (71%) and trunk (46.5%) which corresponds with a study in Columbia that exhibited the hands and limbs as frequent skin rash sites.( 25 ) However, a seroprevalence study done in the rural areas of Chandrapur, Maharashtra, India. reported frequent rash sites on the knees (71%), feet (56%), and fingers and palms (54%) as the most common locations, emphasizing that the importance of viral-host interactions imposing irregularities in symptom manifestations.( 20 , 26 ) The literature often reports that, following the acute phase (7–10 days), CHIV infection can develop into a chronic phase with persistent rheumatoid-like symptoms that can persist for months to years.( 15 , 20 , 25 , 27 ) The majority of CHIK infected individuals become symptom-free four months after initial symptoms with only a minority developing persistent, debilitating arthralgia.( 2 , 22 ) CHIK-induced persistent arthralgia is hypothesized to derive from prolongation of the acute inflammatory course of viral infection within joint and muscle tissue, however the mechanism in which CHIKV RNA persist within joint and muscle tissue still remains unknown.( 7 ) Within our study, only 21.6% of cases continued with persistent joint pain at six months past the initial infection. The association of chronic joint pain and CHIKV has been assessed in only a few studies, but generally infer that only a minority of cases return with CHIK-induced chronic arthralgia.( 2 , 3 , 22 ) A cohort study following a 2014–2015 CHIK epidemic in Columbia found roughly 1/4th of the serologically confirmed study cases developed persistent polyarthralgia.( 27 ) A seroprevalence study performed in the US Virgin Islands showed 12% of the islanders continue to report polyarthralgia one year after the initial CHIK outbreak, likely attributing the finding to the CHIK virus infection. Forms of persistent arthralgia have also been described in a 1980 retrospective study performed in South Africa which exhibited episodic stiffness and pain in 3.7% of cases, persistent stiffness without pain in 2.8%, and persistent painful restriction of joint movements in 5.6%.( 15 ) In our study, age above 41 years old (p = 0.001, OR: 1.588; 95% CI: 0.935–2.695), working in health or administrative job (p = 0.003; OR: 0.370 95% CI: 0.194–0.707), and having O-type blood group (p = 0.033, OR: 1.153; 95% CI: 0.843–1.579) were factors significantly associated with increased risk of persistent joint pain upon CHIK infection. In terms of age, CHIK-induced arthralgia is more commonly found in adults compared to children likely due to the nature of the immune system.( 16 ) Younger persons possess a more robust immune system able to clear viremia more effectively compared to an adult’s immune system, thus reducing the probability of CHIKV affecting musculoskeletal tissue attributed to joints.( 16 ) Higher frequencies of joint pain among health and administrative workers could be explained as most of these workers were older in age with jobs that immobilize them for long working hours. Additionally, during the initial phases of the outbreak at the Tesseney subzone, the hospital crowded wards of CHIK infected patients fostered an environment where the Aedes mosquito may spread the virus from infected to noninfected individuals. Thus, healthcare staff may have contracted the viral disease as a result of treating patients, contributing to higher number of health workers being affected with CHIKF during the study. However, there is no clear explanation for O-type blood group association with increased risk of joint pain, but the high proportion of cases with O-type blood group compared to other blood types may have a bias on this finding. Joint swelling often accompanied arthralgia with being female (p = 0.001, OR: 0.355; 95% CI: 0.216–0.583) possessing significant protective association for joint swelling, while O-type blood group (p = 0.02; OR: 1.836; 95% CI: 0.820–4.110) having significant risk association with joint swelling. Though our study is novel in raising female protective association in joint swelling, the question of female predisposition to arthralgia has already been raised in some studies, but there is yet a clear answer for the cause of the result.( 4 , 5 , 16 ) Our study was subject to a number of limitations. First, confirmation of CHIK infection on all probable cases via serological and/or molecular analysis was neither economical nor feasible within the study. Ruling out other febrile disease (dengue and malaria fever) cannot confirm the detection of CHIK. Therefore, a probable case definition based on the European Centre for Disease Control was used as an alternative diagnostic criterion. Second, though nomadic people likely initiated the outbreak, the study design was restricted to non-probability convenience patient sampling as the nomadic lifestyle was not suitable to follow for long periods of time. Third, patients with persistent polyarthralgia at 6 months were not followed then after, therefore the complete long-term clinical picture for persistence of joint pain was not obtained in our study. Conclusion Our finding indicated that polyarthralgia, fever, and skin rash are a triad of symptoms during acute prodromal phase of CHIK, accompanied by bowel habit alteration, lymphadenopathy, and ocular pain. Persistent joint pain was a frequent long-term complication of CHIKF found in a subset of cases. Individuals above the age of 41 were found to be risk factor for persistence of joint pain. Further studies are needed to determine the association CHIKV infection and chronic arthralgia as well as chronic CHIK-induced complications and associated risk factors. Recommendations Currently, there is no effective vaccine for prevention; so, mosquito-based surveillance and control is the appropriate strategy to control and contain the infection. Vector control methods should be implemented and mobilized in endemic areas with municipalities and communities being aware about the preventive measures. At an individual level, wearing long-sleeved shirts, using mosquito repellent, and sleeping under a mosquito bed net may reduce the chances of being bitten by an infected mosquito. Since an immunologic etiology is suspected in chronic cases of CHIK, a short course of steroids may be useful, but care must be taken to monitor all adverse events of the drug and should not be continued indefinitely. Additionally, cold compresses have been reported to reduce joint pain and swelling. Abbreviations World Health Organization (WHO), Chikungunya (CHIK), Chikungunya fever (CHIKF), Chikungunya virus (CHIKV), Enzyme-linked immunosorbent assay (ELISA), Reverse-transcription polymerase chain reaction (RT-PCR), East-Central-South African (ESCA), Indian Ocean lineage (IOL), Gastrointestinal (GI), confidence interval (CI). Declarations Ethical approval: Ethical approval was obtained from zonal branch of Ministry of Health Research and Ethical Approval Committee and a written informed consent obtained from the patient to participate in this report and publish. Conflict of interest: Authors have no any conflict of interest to disclose Availability of data and material: All available information is included in the manuscript. Fund : The research had no any source of fund Consent: A written informed consent was taken from the patients and data confidentiality was secured Author’s contribution Conceptualization: Okbu Frezgi, Data Curation: Okbu Frezgi, Ghide Ghebrewelde, Henok Tekie, Tsegezab Kiflezgi, Abdelaziz Mohamedsied, Yonas Tekie. Formal Analysis: Okbu Frezgi, Mediahine Asrat. Methodology: Okbu Frezgi, Mediahine Asrat, Ghide Ghebrewelde, Henok Tekie, Tsegezab Kiflezgi, Abdelaziz Mohamedsied, Yonas Tekie. Visualization : Tewaldemedhine Gebrejesus Supervision: Okbu Frezgi , Araia Berhane Writing – Original Draft : Okbu Frezgi Writing – Review & Editing: Okbu Frezgi, Araia Berhane, Tewaldemedhine Gebrejesus. Acknowledgment: We wish to acknowledge our colleagues who supported our work. We also acknowledge our families and friends who supported the work indirectly. Authors acknowledges the staff of Tesseney hospital: Kibrom T, Abraham T, Teckle T, Abel Alem, Samuel W, Hussein M, and Awet Mebrahtu. Author’s information Okbu Frezgi, MD, Obstetrics and Gynaecology unit, Orotta College of Medicine and Health Science, Post-graduate, Ministry of Health, Asmara, Eritrea. Email. [email protected] Araia Berhane, MD MSc, Communicable Disease Control Division, Ministry of Health, Asmara, Eritrea. Email: [email protected] Ghide Gebreweld, MD, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email [email protected] Henok Tekie, MD, Norther Red Sea zone, Ministry of Health, Massawa, Eritrea. Email [email protected] Abdulaziz Mohamed Sied, MD, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email: Tsegezeab Kiflezgi, MD, Adi Keih Hospital, Zoba Debu, Ministry of Health, Adi Keih, Eritrea. Email [email protected] Yonas Tekie, BSN, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email [email protected] Medhanie Asrat, BS, National Statistics Office, Asmara Eritrea. Email [email protected] Tewaldemedhine Gebrejesus, BS, National Tuberculosis and Leprosy Control Program of Eritrea, Ministry of Health, Asmara, Eritrea. Email: [email protected] References Khongwichit S, Chansaenroj J, Thongmee T, Benjamanukul S, Wanlapakorn N, Chirathaworn C, et al. Large-scale outbreak of chikungunya virus infection in Thailand, 2018-2019. PLoS One. 2021;16(3). Fini R, Marques IC dos S, Carvalho DO, Pedrosa MC, Araújo HC de, Cáceres MFL, et al. Chikungunya Fever: Biology and Epidemiological Aspects. In: Vector-Borne Diseases & Treatment. p. 1–22. Andrade DC De, Jean S, Clavelou P, Dallel R, Bouhassira D. Chronic pain associated with the chikungunya fever: long lasting burden of an acute illness. BMC Infect Dis. 2010;10(31). Lakshmi V, Neeraja M, Subbalaxmi MVS, Parida MM, Dash PK, Santhosh SR, et al. Clinical features and molecular diagnosis of chikungunya fever from south India. Clin Infect Dis. 2008;46(9):1436–42. Kularatne SAM, Weerasinghe SC, Gihan C, Wickramsinghe S, Dharmarathne S, Abeyrathna A, et al. Epidemiology, clinical manifestations, and long-term outcomes of a major outbreak of chikungunya in a hamlet in Sri Lanka, in 2007: a longitudinal cohort study. J Trop Med. 2012; de Lima Cavalcanti TYV, Pereira MR, de Paula SO, Franca RF de O. A review on chikungunya virus epidemiology, pathogenesis and current vaccine development. Viruses. 2022;14:969. Kril V, Aïqui-reboul-paviet O, Briant L, Amara A. New insights into chikungunya virus infection and pathogenesis. Annu Rev Virol. 2021;8:327–47. Gutierrez-rubio AK, Magbitang AD, Penserga EG. A three-month follow up of musculoskeletal manifestions in chikungunya fever. Philipp J Intern Med. 2014;52(1):1–5. Virology H. Chikungunya association with different presentation at tertiary care centre. J Hum Virol Retrovirology. 2017;6(1):6–9. Atalay T, Kaygusuz S, Azkur AK. A study of the chikungunya virus in humans in Turkey. Turkish J Med Sci. 2017;47:1161–4. Sissoko D, Moendandze A, Malvy D, Giry C, Ezzedine K, Louis J, et al. Seroprevalence and Risk Factors of Chikungunya Virus Infection in Mayotte , Indian Ocean , 2005-2006 : A Population-Based Survey. 2008;3(8):2005–6. Tanay A. Chikungunya fever presenting as a systemic disease with fever, arthritis and rash: Our experience in Israel. Isr Med Assoc J. 2016;18(3–4):162–3. Eyer-Silva W de A, Neto H de BP, Silva GAR da, Ferry FR de A. A case of chikungunya virus disease presenting with remarkable acute arthritis of a previously damaged finger joint. J Brazilian Soc Trop Med. 2016;49. Faisal A. Clinical Management of Chikungunya Fever: Guideline for Health Facilities in Maldives. 2019. World Health Organization Regional Office for South-East Asia. Guidelines on Clinical Management of Chikungunya Fever. New Delhi; 2008. Imad HA, Phadungsombat, Juthamas Nakayama EE, Suzuki K, Ibrahim AM, Afaa A, Azeema A, et al. Clinical features of acute chikungunya virus infection in children and adults during an outbreak in the Maldives. Am J Top Med Hyg. 2021;105(4):946–54. Division of Vector-Borne Diseases. Chikungunya: Vector Surveillance and Control in the United States. Larrieu S, Pouderoux N, Pistone T, Filleul L, Receveur M-C, Sissoko D, et al. Factors associated with persistence of arthralgia among chikungunya virus-infected travellers: report of 42 French cases. J Clin Virol. 2010;47(1):85–8. Pouriayevali MH, Rezaei F, Jalali T, Baniasadi V, Fazlalipour M, Mostafavi E, et al. Imported cases of chikungunya virus in Iran. BMC Infect Dis. 2019; Hennessey MJ, Ellis EM, Delorey MJ, Panella AJ, Kosoy OI, Kirking HL, et al. Seroprevalence and symptomatic attack rate of chikungunya virus infection, United States Virgin Islands, 2014–2015. Am J Trop Med Hyg. 2018;99(5):1321–6. Johnson BW, Russell BJ, Goodman CH. Laboratory diagnosis of chikungunya virus infections and commercial sources for diagnostic assays. J Infect Dis. 2016;214(Suppl 5):S471–4. Hawman DW, Stoermer KA, Montgomery SA, Pal P, Oko L, Diamond MS, et al. Chronic joint disease caused by persistent chikungunya virus infection is controlled by the adaptive immune response. J Virol. 2013;87(24). Long KM, Whitmore AC, Ferris MT, Sempowski GD, McGee C, Trollinger B, et al. Dendritic cell immunoreceptor regulates chikungunya virus pathogenesis in mice. J Virol. 2013;87(10). Rahman M, Jakaria SK, Sayed B, Kabir AKMH, Mallik U, Hasan R, et al. Clinical and laboratory characteristics of an acute chikungunya outbreak in Bangladesh in 2017. Am J Top Med Hyg. 2019;100(2):405–10. Rueda JC, Santos AM, Angarita J, Giraldo RB, Saldarriaga E, Giovanny J, et al. Demographic and clinical characteristics of chikungunya patients from six Colombian cities, 2014 – 2015. Emerg Microbes Infect. 2019;8(1):1490–500. Kawle AP, Nayak AR, Bhullar SS, Borkar SR, Patankar SD, Daginawala HF, et al. Seroprevalence and clinical manifestations of chikungunya virus infection in rural areas of Chandrapur, Maharashtra, India. J Vector Borne Dis. 2017;54(1):35–43. Chang A, Encinales L, Porras A, Pacheco N, Rield SP, Martins KAO, et al. Frequency of chronic joint pain following chikungunya virus infection: A Coloumbian cohort study. Arthritis Rheumatol. 2018;70(4):578–84. 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3853568","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":269694147,"identity":"f564afb4-0b41-48bc-9183-78ef86636b75","order_by":0,"name":"Okbu Frezgi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBACPhiDH0QkFBChhQ3GkGwAaTEgRYvBATBJjBaJ3McvPrbdkzc+vzrxwwMDBnl+sQOEtKSbWc5sKzbcduPtZgmgwwxnzk4gpCWNzZh3WwLjthtnN4C0JBjcJkbL320J9ptnnN38g1gtzI8ZtyUkbuDv3UakLTzP2Bh7/yUkz7jBu80iwUCCsF/42dOYP/w4k2Db3392880fFTby/NIEtIDdBqYkwColCCoHAeYPEPsOEKV6FIyCUTAKRiAAALawQYU7Y2mJAAAAAElFTkSuQmCC","orcid":"","institution":"Orotta National Referral Maternity Hospital, Ministry of Health","correspondingAuthor":true,"prefix":"","firstName":"Okbu","middleName":"","lastName":"Frezgi","suffix":""},{"id":269694148,"identity":"ed07f7ec-efeb-4229-8fa6-421799b3951b","order_by":1,"name":"Araia Berhane","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Araia","middleName":"","lastName":"Berhane","suffix":""},{"id":269694149,"identity":"3209277d-dfca-4bc3-81a0-4a1057a58803","order_by":2,"name":"Ghide Ghebrewelde","email":"","orcid":"","institution":"Tesseney Hospital, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Ghide","middleName":"","lastName":"Ghebrewelde","suffix":""},{"id":269694150,"identity":"8d4512e3-5c25-4fe9-8781-07095c89ab6d","order_by":3,"name":"Henok Tekie","email":"","orcid":"","institution":"Tesseney Hospital, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Henok","middleName":"","lastName":"Tekie","suffix":""},{"id":269694151,"identity":"20e28430-f004-4631-b9f5-1a31d4c8ab28","order_by":4,"name":"Tsegezab Kiflezgi","email":"","orcid":"","institution":"Tesseney Hospital, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Tsegezab","middleName":"","lastName":"Kiflezgi","suffix":""},{"id":269694152,"identity":"0971d537-7931-4676-8f24-2c4aee065a0d","order_by":5,"name":"Abdelaziz Mohamedsied","email":"","orcid":"","institution":"Tesseney Hospital, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Abdelaziz","middleName":"","lastName":"Mohamedsied","suffix":""},{"id":269694153,"identity":"09f90b70-000e-4c49-a525-d7583c633f0e","order_by":6,"name":"Yonas Tekie","email":"","orcid":"","institution":"Tesseney Hospital, Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Yonas","middleName":"","lastName":"Tekie","suffix":""},{"id":269694154,"identity":"bc71b455-14cc-42f5-9db7-607d1d73e999","order_by":7,"name":"Medhanie Asrat","email":"","orcid":"","institution":"Statistical data processing at national statistics office, Eritrea","correspondingAuthor":false,"prefix":"","firstName":"Medhanie","middleName":"","lastName":"Asrat","suffix":""},{"id":269694155,"identity":"3572ac7d-36d0-4dad-bfdf-17a8291657ea","order_by":8,"name":"Tewaldemedhine Gebrejesus","email":"","orcid":"","institution":"Volunteer at National Tuberculosis and Leprosy Control Program of Eritrea, Virginia, USA","correspondingAuthor":false,"prefix":"","firstName":"Tewaldemedhine","middleName":"","lastName":"Gebrejesus","suffix":""}],"badges":[],"createdAt":"2024-01-11 13:29:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3853568/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3853568/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50390558,"identity":"698df26c-47d3-4a2c-b1ba-4dbce16d4b0d","added_by":"auto","created_at":"2024-01-30 18:42:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13625,"visible":true,"origin":"","legend":"\u003cp\u003ePersistence of chikungunya-induced joint pain based on monthly follow-up reports across the entire study period.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3853568/v1/4105b6acd9fa09395c7765e5.png"},{"id":50933838,"identity":"333e7b2b-768b-4c2e-90ff-a8b56e0263c6","added_by":"auto","created_at":"2024-02-09 19:52:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":529322,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3853568/v1/8c8741e5-5391-4fcb-9979-16ee6501ce8f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute clinical features and persistence of joint pain in probable cases of Chikungunya Fever in Eritrea","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChikungunya fever (CHIKF) is a crippling mosquito-borne viral disease that has become a major public health concern in recent years. The name \u0026ldquo;chikungunya\u0026rdquo; is derived from the Makonde word meaning \u0026lsquo;he, who walks bends up\u0026rdquo; in reference to the stooped posture developed due to the arthritic symptoms of the disease.(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) The disease is caused by the chikungunya virus (CHIKV) which is transmitted to humans through the bite of infected \u003cem\u003eAedes aegypti\u003c/em\u003e and \u003cem\u003eAedes albopictus\u003c/em\u003e mosquitoes.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The etiologic agent is a single-stranded positive sense RNA virus identified as an arbovirus of the \u003cem\u003eAlphavirus\u003c/em\u003e genus.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Human and other vertebrate host (i.e., monkeys, rodents, birds, etc.) serve as reservoirs during CHIK epidemics.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The virus has two distinct transmissions cycles based on the geographical location and human settlement density: enzootic and sylvatic (urban).(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The enzootic cycles mainly occurs on African tropical regions where arboreal mosquitoes transmit the virus to nonhuman primates which serve as the main reservoir host.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The sylvatic cycle is concentrated in urban centers where the virus is transmitted via the \u003cem\u003eAe. aegypti\u003c/em\u003e and \u003cem\u003eAe. albopictus\u003c/em\u003e mosquitos from human-to-human.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) The enzootic cycle allows interhuman transmission during outbreaks as well as reducing the probability of eliminating the virus circulation in an environment.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCHIKV was first isolated in Tanzania in 1953, later spreading across sub-Saharan Africa.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Three distinct strains of CHIKV have been identified based on phylogenetic analysis: West African, East-Central-South African (ECSA), and the Asian lineage.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Before 2000, CHIKV was largely restricted within the sub-Saharan African region, but later the ECSA strain re-emerged within the Kenya coast and spread across the Indian Ocean islands, simultaneously evolving into a new strain called Indian Ocean lineage (IOL).(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Major CHIK outbreaks emerged across the Indian Ocean islands between 2004 and 2007 and infected more than 272,000 people, most notably on Reunion island.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) The Reunion island epidemic of 2005\u0026ndash;2006 reported 270,000 infected cases, approximately a third of the island\u0026rsquo;s population.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Major epidemics, such as found in Reunion Island, can cause significant productivity loss and immense economic cost, especially for developing countries.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) After 2004, CHIKV outbreaks were later documented in Italy, Bangladesh, Cameroon, and France, likely due to international travelers who, during the Reunion epidemic, likely became infected and, when returning home, dispersed the CHIKV to other countries.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Presently, CHIKV has a wide geographical distribution, including North and South America, Europe, Asia, and the Pacific Islands, with an estimated global incidence of more than 6\u0026nbsp;million confirmed cases worldwide.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Ecological factors such as temperature, availability of breeding sites, rainfall, vegetation, and globalization contribute to CHIKV dissemination which impacts human migration and the range of mosquito prone areas. Human demographic changes (migration, international travel, tourism, global trade, etc.) linked to population movements has largely been affected by the chikungunya virus.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCHIKV, like the dengue and zika virus, are commonly classified as arthritogenic viruses as these viruses cause musculoskeletal inflammatory disease in humans.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Upon infection, CHIKV has an incubation period of 3\u0026ndash;7 days, but may last as long as fourteen days.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Seroprevalence studies have demonstrated that 30\u0026ndash;40% of CHIKV infected individuals can be asymptomatic, but the majority (60\u0026ndash;80%) of infected individuals are symptomatic.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) After the incubation period, sudden onset of high-grade fever, polyarthralgia, headache, myalgia, and transient maculopapular skin rash commonly develop.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) In addition, swollen joints, tenosynovitis, vomiting, and nausea have also been observed.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Chikungunya fever is rarely fatal with an acute crippling phase that lasts 1\u0026ndash;2 weeks followed by convalescence. However, in a subset of people, joint pain and swelling can last for months to years and often fluctuating, leading to long-term persistent polyarthralgia.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) CHIKV pathogenesis of arthropathy is likely attributed to CHIKV residing and replicating within muscle and joint tissue. Although recent advances have shed light on the CHIK infection, the immunopathogenic mechanism of CHIKV resulting in arthralgia still remains unclear.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Chronic polyarthralgia is described to possess both neuropathic and nociceptive characteristics, requiring advanced pharmacological interventions as pain does not respond well with analgesics.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDiagnosis of a CHIK infection is often performed via molecular detection of a viral genome and/or identification of a virus-specific antibody in a laboratory setting.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Reverse transcription\u0026ndash;polymerase chain reaction (RT-PCR) is often used for molecular detection from a blood sample; ELISA, immunofluorescence assay, and rapid immunochromatographic test are performed for serologic analysis to capture virus-specific antibodies from a patient\u0026rsquo;s serum (IgM antibody or demonstrating rising titer of IgG antibody).(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Differential diagnosis may be required as CHIKV manifestations may co-exist with as other similar alphaviruses, such as dengue.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Differential diagnosis from dengue infection is often based on the presence of hemoconcentration, while symptoms of high-grade fever and joint pain are known only to be exhibited in CHIKV infection.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eNo vaccines or specific antiviral drug have yet been introduced to prevent or treat CHIKF, but individuals previously infected are believed to incur life-long immunity.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) New studies, however, have reported several novel preclinical vaccines are in development with limited number of clinical trials, but more time is required before these vaccines are approved for the global market.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Thus, treatment of CHIK is largely focused on symptomatic relief with the use of anti-inflammatory drugs as the viral disease has a relatively low-fatality rate. Nevertheless, little is known about the viral-host interactions, cellular factors involved in viral pathogenesis, and role of immune system during the course of chikungunya fever, which hinders the development of effective vaccines and management strategies for the disease. The reemergence of chikungunya epidemics in different parts of the world and their related economic burden incited the need to study the clinical features of this disease. Eritrea\u0026rsquo;s subtropical climate is suitable for the transmission of mosquito-borne diseases, such as chikungunya fever. The first cases of chikungunya fever was reported in Tesseney subzone during the October 2018 outbreak.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Our aim in carrying out this study is to describe the acute clinical features of probable cases of chikungunya fever and the risk factors associated with the persistence of polyarthralgia.\u003c/p\u003e \u003cdiv id=\"Sec2\" class=\"Section2\"\u003e \u003ch2\u003eObjective\u003c/h2\u003e \u003cdiv id=\"Sec3\" class=\"Section3\"\u003e \u003ch2\u003eGeneral Objective\u003c/h2\u003e \u003cp\u003eThe primary objective of this study was to describe acute clinical features of probable cases of chikungunya fever and the risk factors for persistence of arthralgia.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSpecific Objective\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo describe the acute clinical features of probable cases of chikungunya fever during the acute prodromal phase.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTo identify risk factors associated with the persistent of arthralgia.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was a prospective, descriptive cohort hospital-based study at the Tesseney Community Hospital.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStudy Area\u003c/h2\u003e \u003cp\u003eTesseney hospital is a community hospital in the Gash-Barka region of Eritrea which serves the catchment population of 87,992 individuals distributed in an area of 1,096.83 km\u003csup\u003e2\u003c/sup\u003e. The hospital provides inpatient and outpatient services, delivery service, laboratory services, imaging unit, physiotherapy unit, and possess a 115-bed capacity.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eProbable chikungunya fever cases that met the clinical and epidemiological criteria during the October 2018 chikungunya fever outbreak were included as the study population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eInclusion Criteria\u003c/h2\u003e \u003cp\u003eAll probable cases of chikungunya fever who had signs and symptoms of acute febrile illness during the outbreak and tested negative for malaria and dengue fever were included in the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eExclusion Criteria\u003c/h2\u003e \u003cp\u003eAll probable cases of chikungunya fever who had signs and symptoms of acute febrile illness during the outbreak and returning with positive results for malaria and dengue fever were excluded from the study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eSampling Procedure\u003c/h2\u003e \u003cp\u003eNon-probability convenience sampling method was used with inclusion of all probable cases of chikungunya fever based on clinical symptoms and epidemiological data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003eMethod of Data Collection\u003c/h2\u003e \u003cp\u003eData collection was conducted by interviewing and examining probable cases of chikungunya fever by pre-designed questionnaire. All cases were assessed for regional and systemic manifestations by general practitioners. The follow-up of the patients was conducted monthly for six months with each manifestation documented during their visit.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory Investigations\u003c/h2\u003e \u003cp\u003eSerologic analysis for each possible chikungunya fever case was not feasible. However, during the outbreak, a sample of 30 patient was collected and sent to a regional WHO virology laboratory in Kenya for chikungunya virus analysis. All samples reported positive for chikungunya fever and the criteria of chikungunya fever outbreak was met. Five mL. of venous blood was drawn from each enrolled patient to investigate malaria and dengue fever using rapid tests. A complete blood count was also performed only on the initial visit with blood group and respective Rh factor being identified for each patient.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis and Interpretation\u003c/h2\u003e \u003cp\u003eThe collected data was tabulated and analyzed using Epi-info software and further analyzed via SPSS software version 26. Data were presented as frequencies and percentages. The chi-square test was used as a significance test with p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered as statistically significant. Further logistical regression analysis was also performed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eCase Definitions\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e refer to chikungunya infection criteria and case definition used during our study based on the European Centre for Disease Control.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChikungunya infection criteria definitions.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCriteria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAcute onset of fever greater than 38.5\u0026deg;C and severe arthralgia/ arthritis not explained by other medical conditions.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidemiological\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResiding or having visited epidemic areas, having reported transmission within 15 days prior to the onset of symptoms.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAt least one of the following tests in the acute phase:\u003c/p\u003e \u003cp\u003e\u0026bull; Virus isolation\u003c/p\u003e \u003cp\u003e\u0026bull; Presence of viral RNA by RT-PCR\u003c/p\u003e \u003cp\u003e\u0026bull; Presence of virus specific IgM antibodies in single serum sample collected in acute or convalescent stage.\u003c/p\u003e \u003cp\u003e\u0026bull; Four-fold increase in IgG values in samples collected at least three weeks apart\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChikungunya infection case definitions.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePossible Case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient meeting clinical criteria.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProbable Case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient meeting both the clinical and epidemiological criteria.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConfirmed Case\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient meeting the laboratory criteria, irrespective of the clinical presentation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eEthical Clearance\u003c/b\u003e:\u003c/h2\u003e \u003cp\u003eEthical approval was obtained from the zonal branch of the Ministry of Health, Research and Ethics Review Committee and written informed consent was sought from each patient. Data confidentiality was assured by coding the personal identifiers and removing identifiers from the final analysis.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eBased on an epidemiological data and clinical criteria, a total of 203 probable cases of CHIKF were included in the study. The study observed a high male-to-female sex ratio of 2.1:1 (males\u0026thinsp;=\u0026thinsp;68%; females\u0026thinsp;=\u0026thinsp;32%) with a mean age of 39.2 years old. Most of patients were 25\u0026ndash;35 years old (40.9%) and 20.7% above 45 years old. Regarding occupational frequencies, healthcare workers (47.8%) and civil servants (30.5%) working in the town (teachers, immigration staff, commercial bank staff, telecommunication staff) ranked the most common profession, followed by subzone administration staff (21.7%). Majority of patients reached either college-level (51.7%) or secondary education (32.5%) with only 5.4% of cases being illiterate working as cleaners and gatekeepers. From our study, 51.2% identified as O-type blood group with a large portion of cases possessing the positive Rh antigen factor (96.4%) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSocio-demographic data, including blood group and Rh factor, of probable cases of chikungunya fever.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u0026ndash;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e˃45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eOccupation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHealth Workers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eImmigration Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTeachers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSubzone Administration Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBank Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTelecommunication Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eEducational status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIlliterate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eElementary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJunior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCollege\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eBlood group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ldquo;A\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ldquo;B\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e18.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ldquo;AB\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ldquo;O\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRh factor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e94.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.4\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\u003eDuring the acute phase (first visit), common reported symptoms were polyarthralgia (97%), fever (96.1%), gastrointestinal symptoms (64.5%), headache (62%) and skin rash (56.7%) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Joint pain was the main symptom with the most frequent affected joints being the wrist (59.4%), interphalangeal joints of the hands (56.9%), and knee (53.8%) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Arthralgia gradually reduced over the course of the study period, persisting at the sixth month in only 21.7% of the cases (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Arthralgia was largely symmetrical (84.3%) during the acute phase, but over time, the symmetry of joint pain gradually reduced to 78% reported during the last visit. Fever was the second leading symptom with the mean duration of 4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3 days and was commonly responded with antipyretics in 95.9% of cases. Fever was accompanied by epistaxis is minority of the patients (0.6%). Headache was also common symptom with a mean duration of 3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3 days (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). In terms of dermatological features, 56.7% of cases experienced transient maculopapular rash which was largely pruritic (85.2% of skin rash cases) with the most involved anatomical sites being the hands (71%), trunk (46.5%), and face (45.6%) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCommon skin rash sites and joint sites involved with transient maculopapular rash and polyarthralgia, respectively.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommon Skin Rash Sites\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHands\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrunk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFace\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLegs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePalms and Sole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eScrotum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Cavity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCommon Polyarthralgia Joint Sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWrist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterphalangeal Joints of the Hand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKnee\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnkles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShoulder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElbow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical presentation of probable cases of chikungunya fever with related duration for fever and headache during the acute phase.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Presentation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandard Deviation (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian (days)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\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\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin Rash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyarthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\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\u003eGastrointestinal symptoms were experienced by 64.5% of cases with anorexia (80.9%), nausea (41.2%), and vomiting (32.2%) as the highest ranked symptoms (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Lymphadenopathy was found in 44.3% of cases with greatest affliction amongst inguinal lymph node (67.8%) followed by cervical lymph nodes (51.1%). Ocular symptoms were seen in 32.5% of cases in which retro-orbital pain (27.1%) was the main presented eye symptom followed by conjunctival hyperemia (24%) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). CBC showed lymphocytosis (64.5%), granulocytopenia (43.3%), and mild anemia (31%) were the most common abnormal hematological findings, follow by leukopenia (16.7%) and granulocytosis (14.3%) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLymphadenopathic features, GI manifestations, and ocular symptoms of probable cases of chikungunya fever during the acute phase.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Manifestations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphadenopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInguinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetro-auricular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAxially\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGI Manifestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnorexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.9\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\u003e41.2\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\u003e32.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight Loss\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.7\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\u003e6.9\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\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOcular Symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetro-orbital Pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConjunctival Hyperemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual Problem\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEye Congestion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAbnormal hematological findings from CBC profile.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological Findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGranulocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild Anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReduced Hematocrit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeukopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGranulocytosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.8\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\u003eAt the end of the acute phase, patients continued to be monitored via monthly follow-up visits for the remainder of the 6-month study period. The main clinical features that continued to be monitored were joint pain and joint swelling. Across the entire study period, cases ages 25\u0026ndash;35 and greater 45 years old expressed higher and consistent frequencies of joint pain and joint swelling compared to other age groups, with the exception of joint swelling reported higher among 36\u0026ndash;40 age group. Health workers followed by administration workers continued to experience higher levels of CHIKF symptoms compared to other professional groups. The same pattern was found with educational status as individuals possessing college or secondary level education had higher levels of CHIKF symptoms compared to groups of lower educational status (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Logistical regression was performed to further analyze significant factors associated with persistent of joint pain and joint swelling. Patient\u0026rsquo;s age\u0026thinsp;\u0026gt;\u0026thinsp;41 years (p\u0026thinsp;=\u0026thinsp;0.001, OR: 1.588; 95% CI: 0.935\u0026ndash;2.695) and occupation (p\u0026thinsp;=\u0026thinsp;0.003; OR: 0.370 95% CI: 0.194\u0026ndash;0.707), O blood type (p\u0026thinsp;=\u0026thinsp;0.033, OR: 1.153; 95% CI: 0.843\u0026ndash;1.579) showed significant association with the likelihood for the persistent of joint pain (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). Joint pain was often accompanied by joint swelling (42.1% of joint pain cases) with being female (p\u0026thinsp;=\u0026thinsp;0.001, OR: 0.355; 95% CI: 0.216\u0026ndash;0.583) and possessing O-type blood group (p\u0026thinsp;=\u0026thinsp;0.02; OR: 1.836; 95% CI: 0.820\u0026ndash;4.110) as significant predisposing factors to experiencing joint swelling (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eJoint pain and joint swelling features of probable chikungunya fever patients counted during monthly follow-up for the entire six-month study period.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"char\" char=\".\" 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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eJoint pain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eJoint swelling\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95%CI lower-upper)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePercentage (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOR (95%CI lower-upper)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ndash;30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.173 (0.106\u0026ndash;0.281)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.506 (0.192\u0026ndash;1.333)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.427 (0.290\u0026ndash;0.628)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.687 (0.345\u0026ndash;1.368)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e36\u0026ndash;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.576 (0.384\u0026ndash;0.863)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.519 (0.240\u0026ndash;1.120)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e41\u0026ndash;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.665 (0.447\u0026ndash;0.988)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.865 (0.439\u0026ndash;1.705)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e˃45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.588 (0.935\u0026ndash;2.695)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.509 (0.207\u0026ndash;1.250)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.355 (0.216\u0026ndash;0.583)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.355 (0.216\u0026ndash;0.583)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eOccupation\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealth Workers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmigration Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.829 (0.543\u0026ndash;1.267)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.702 (0.342\u0026ndash;1.439)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTeacher\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.777 (0.456\u0026ndash;1.324)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.396 (0.132\u0026ndash;1.186)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubzone Administration Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.370 (0.194\u0026ndash;0.707)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.270 (0.053\u0026ndash;1.834)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBank Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.002 (0.629\u0026ndash;1.596)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.527 (0.230\u0026ndash;1.206)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTelecommunication Staff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.538 (1.645\u0026ndash;7.610)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.305 (0.094\u0026ndash;0.989)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eEducational status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIlliterate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.902\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElementary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.684 (0.378\u0026ndash;1.238)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.506 (0.191\u0026ndash;1.341)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJunior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.506 (0.299\u0026ndash;0.856)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.550 (0.201-1.500)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.106 (0.540\u0026ndash;2.268)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.753 (0.221\u0026ndash;2.566)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-secondary\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.687 (0.494\u0026ndash;0.957)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.738 (0.396\u0026ndash;1.375)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eBlood Group\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ldquo;A\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.033*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.02*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ldquo;B\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.153 (0.843\u0026ndash;1.579)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.586 (0.315\u0026ndash;1.091)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ldquo;AB\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.143 (0.820\u0026ndash;1.594)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.804 (0.428\u0026ndash;1.511)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ldquo;O\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.704 (0.448\u0026ndash;1.105)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.836 (0.820\u0026ndash;4.110)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eRh Factor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.565\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.268 (0.745\u0026ndash;2.159)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.874 (0.303\u0026ndash;2.524)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eChikungunya virus is responsible for the recent explosive outbreaks of debilitating disease in humans. This arthritogenic virus has re-emerged in many tropical and subtropical regions due to its genomic polymorphism which increase the vector susceptibility.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Global warming/climate change, globalization with significant increase in international travels, and adaptation of virus to new vectors has also increased the vector susceptibility and transmission capacity.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) CHIKV most probably first emerged as a human pathogen in the 18th century, but currently has been identified in nearly 80 countries across 5 continents.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Most epidemics of chikungunya fever occurred in tropical or subtropical areas; Eritrea\u0026rsquo;s subtropical climate is suitable for \u003cem\u003eAedes\u003c/em\u003e mosquitoes and the transmission of mosquito-borne diseases, such as CHIKF. The first confirmed CHIK outbreak in Eritrea was found within the Tesseney subzone in October 2018. This study aims to describe the clinical features of probable cases of chikungunya fever during and following the October 2018 outbreak as well as the risk factors associated with the persistence of polyarthralgia within the Tesseney subzone of Eritrea.\u003c/p\u003e \u003cp\u003eThe clinical manifestations of CHIKF depend on the host-viral interactions which determine the course of infection and key to understanding viral pathogenesis and treatment.(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) During the acute phase, our patients mainly presented with sudden onset of high-grade fever (96.1%) and polyarthralgia (97%), follow by headache (62%) and skin rash (56.7%). Our results align with previous literature which reports the typical triad of symptoms during the acute stage of CHIKF: high-grade fever, skin rash, and polyarthralgia.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Prospective studies performed in the Philippines and Maldives also exhibited similar frequencies of high-grade fever (94.3% in Philippines; 100% in Maldives) and arthralgia (98.6% in Philippines; 82% in Maldives) with only a difference in skin rash incidence (87.1% in Philippines; 54% in Maldives).(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Cross-sectional analyses done in Columbia and Bangladesh after CHIKV outbreaks reported arthralgia (91.2% in Columbia; 99.2% in Bangladesh) and skin rash (44.7% in Columbia; 50.2% in Bangladesh) in similar frequency, but high-grade fever in different frequency (50% in Columbia; 100% in Bangladesh).(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) These difference in occurrence to commonly reported symptoms could be attributed to host-viral interactions.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) A case study in Brazil illustrates this idea as a patient with pain from a previous finger joint injury was reignited upon CHIK infection and was hypothesized that the CHIKV targeted and exacerbated the latent injury.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Interestingly, a longitudinal cohort study in Sri Lanka found a unusually high expression of acute polyarthritis (45%) that later progressed to chronic polyarthritis (99% of acute polyarthritis cases) with a reduced frequency of skin rash symptoms (20%) commonly reported in the literature, showcasing the uncertainties of CHIK manifestations.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAcute arthralgia (97%) was highly expressed amongst our patients which aligns with results of previous studies and general pathology of CHIK manifestation.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Within our study, the most involved joint sites were the wrist (59.4%), interphalangeal joints of the hands (56.9%), knee (53.8%), and ankles (47.7%). Joint sites involvement for arthralgia in a Bangladesh study were similar with the wrist (54.1%) and small joints in the hand (46.8%) as primary joint sites.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) Contrarily, arthralgia was more expressed among weight-bearing joints (i.e., ankles and knees) within previous Sri Lanka (74% for ankles), Philippines (60% for ankles), and Columbia (74.1% for ankles) studies.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Joint site frequency was relatively high among all joint groups in our findings, thus minor differences amongst sites are likely not significant in understanding CHIK infection patterns in joint site involvement. Transient maculopapular rash, stomatitis, and oral ulcers are often seen in adults while retro-orbital pain, vomiting, and diarrhea commonly exhibited in children.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) 56.7% of our cases experienced transient maculopapular skin rash with 0.6% experiencing epistaxis most likely associated to the hemorrhagic complication of the virus. Bangladesh (50.2%) and Maldives (50%) found roughly half of their patients develop maculopapular skin rash similar to our study.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) Skin rashes were frequently exhibited on the hands (71%) and trunk (46.5%) which corresponds with a study in Columbia that exhibited the hands and limbs as frequent skin rash sites.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) However, a seroprevalence study done in the rural areas of Chandrapur, Maharashtra, India. reported frequent rash sites on the knees (71%), feet (56%), and fingers and palms (54%) as the most common locations, emphasizing that the importance of viral-host interactions imposing irregularities in symptom manifestations.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe literature often reports that, following the acute phase (7\u0026ndash;10 days), CHIV infection can develop into a chronic phase with persistent rheumatoid-like symptoms that can persist for months to years.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) The majority of CHIK infected individuals become symptom-free four months after initial symptoms with only a minority developing persistent, debilitating arthralgia.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) CHIK-induced persistent arthralgia is hypothesized to derive from prolongation of the acute inflammatory course of viral infection within joint and muscle tissue, however the mechanism in which CHIKV RNA persist within joint and muscle tissue still remains unknown.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Within our study, only 21.6% of cases continued with persistent joint pain at six months past the initial infection. The association of chronic joint pain and CHIKV has been assessed in only a few studies, but generally infer that only a minority of cases return with CHIK-induced chronic arthralgia.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) A cohort study following a 2014\u0026ndash;2015 CHIK epidemic in Columbia found roughly 1/4th of the serologically confirmed study cases developed persistent polyarthralgia.(\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) A seroprevalence study performed in the US Virgin Islands showed 12% of the islanders continue to report polyarthralgia one year after the initial CHIK outbreak, likely attributing the finding to the CHIK virus infection. Forms of persistent arthralgia have also been described in a 1980 retrospective study performed in South Africa which exhibited episodic stiffness and pain in 3.7% of cases, persistent stiffness without pain in 2.8%, and persistent painful restriction of joint movements in 5.6%.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our study, age above 41 years old (p\u0026thinsp;=\u0026thinsp;0.001, OR: 1.588; 95% CI: 0.935\u0026ndash;2.695), working in health or administrative job (p\u0026thinsp;=\u0026thinsp;0.003; OR: 0.370 95% CI: 0.194\u0026ndash;0.707), and having O-type blood group (p\u0026thinsp;=\u0026thinsp;0.033, OR: 1.153; 95% CI: 0.843\u0026ndash;1.579) were factors significantly associated with increased risk of persistent joint pain upon CHIK infection. In terms of age, CHIK-induced arthralgia is more commonly found in adults compared to children likely due to the nature of the immune system.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Younger persons possess a more robust immune system able to clear viremia more effectively compared to an adult\u0026rsquo;s immune system, thus reducing the probability of CHIKV affecting musculoskeletal tissue attributed to joints.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Higher frequencies of joint pain among health and administrative workers could be explained as most of these workers were older in age with jobs that immobilize them for long working hours. Additionally, during the initial phases of the outbreak at the Tesseney subzone, the hospital crowded wards of CHIK infected patients fostered an environment where the \u003cem\u003eAedes\u003c/em\u003e mosquito may spread the virus from infected to noninfected individuals. Thus, healthcare staff may have contracted the viral disease as a result of treating patients, contributing to higher number of health workers being affected with CHIKF during the study. However, there is no clear explanation for O-type blood group association with increased risk of joint pain, but the high proportion of cases with O-type blood group compared to other blood types may have a bias on this finding. Joint swelling often accompanied arthralgia with being female (p\u0026thinsp;=\u0026thinsp;0.001, OR: 0.355; 95% CI: 0.216\u0026ndash;0.583) possessing significant protective association for joint swelling, while O-type blood group (p\u0026thinsp;=\u0026thinsp;0.02; OR: 1.836; 95% CI: 0.820\u0026ndash;4.110) having significant risk association with joint swelling. Though our study is novel in raising female protective association in joint swelling, the question of female predisposition to arthralgia has already been raised in some studies, but there is yet a clear answer for the cause of the result.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOur study was subject to a number of limitations. First, confirmation of CHIK infection on all probable cases via serological and/or molecular analysis was neither economical nor feasible within the study. Ruling out other febrile disease (dengue and malaria fever) cannot confirm the detection of CHIK. Therefore, a probable case definition based on the European Centre for Disease Control was used as an alternative diagnostic criterion. Second, though nomadic people likely initiated the outbreak, the study design was restricted to non-probability convenience patient sampling as the nomadic lifestyle was not suitable to follow for long periods of time. Third, patients with persistent polyarthralgia at 6 months were not followed then after, therefore the complete long-term clinical picture for persistence of joint pain was not obtained in our study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur finding indicated that polyarthralgia, fever, and skin rash are a triad of symptoms during acute prodromal phase of CHIK, accompanied by bowel habit alteration, lymphadenopathy, and ocular pain. Persistent joint pain was a frequent long-term complication of CHIKF found in a subset of cases. Individuals above the age of 41 were found to be risk factor for persistence of joint pain. Further studies are needed to determine the association CHIKV infection and chronic arthralgia as well as chronic CHIK-induced complications and associated risk factors.\u003c/p\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations\u003c/h2\u003e \u003cp\u003eCurrently, there is no effective vaccine for prevention; so, mosquito-based surveillance and control is the appropriate strategy to control and contain the infection. Vector control methods should be implemented and mobilized in endemic areas with municipalities and communities being aware about the preventive measures. At an individual level, wearing long-sleeved shirts, using mosquito repellent, and sleeping under a mosquito bed net may reduce the chances of being bitten by an infected mosquito. Since an immunologic etiology is suspected in chronic cases of CHIK, a short course of steroids may be useful, but care must be taken to monitor all adverse events of the drug and should not be continued indefinitely. Additionally, cold compresses have been reported to reduce joint pain and swelling.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eWorld Health Organization (WHO), Chikungunya (CHIK), Chikungunya fever (CHIKF), Chikungunya virus (CHIKV), Enzyme-linked immunosorbent assay (ELISA), Reverse-transcription polymerase chain reaction (RT-PCR), East-Central-South African (ESCA), Indian Ocean lineage (IOL), Gastrointestinal (GI), confidence interval (CI).\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003e Ethical approval was obtained from zonal branch of Ministry of Health Research and Ethical Approval Committee and a written informed consent obtained from the patient to participate in this report and publish.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e Authors have no any conflict of interest to disclose\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material:\u003c/strong\u003e All available information is included in the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFund\u003c/strong\u003e: The research had no any source of fund\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent:\u0026nbsp;\u003c/strong\u003eA written informed consent was taken from the patients and data confidentiality was secured\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e Okbu Frezgi,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Curation:\u003c/strong\u003e Okbu Frezgi, Ghide Ghebrewelde, Henok Tekie, Tsegezab Kiflezgi, Abdelaziz Mohamedsied, Yonas Tekie.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFormal Analysis:\u003c/strong\u003e Okbu Frezgi, Mediahine Asrat.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e Okbu Frezgi, Mediahine Asrat, Ghide Ghebrewelde, Henok Tekie, Tsegezab Kiflezgi, Abdelaziz Mohamedsied, Yonas Tekie.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVisualization\u003c/strong\u003e: Tewaldemedhine Gebrejesus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupervision:\u0026nbsp;\u003c/strong\u003eOkbu Frezgi , Araia Berhane\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting \u0026ndash; Original Draft\u003c/strong\u003e: Okbu Frezgi\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWriting \u0026ndash; Review \u0026amp; Editing:\u003c/strong\u003e Okbu Frezgi, Araia Berhane, Tewaldemedhine Gebrejesus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe wish to acknowledge our colleagues who supported our work. We also acknowledge our families and friends who supported the work indirectly.\u003c/p\u003e\n\u003cp\u003eAuthors acknowledges the staff of Tesseney hospital: Kibrom T, Abraham T, Teckle T, Abel Alem, Samuel W, Hussein M, and Awet Mebrahtu.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor\u0026rsquo;s information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOkbu Frezgi, MD, Obstetrics and Gynaecology unit, Orotta College of Medicine and Health Science, Post-graduate, Ministry of Health, Asmara, Eritrea. Email. [email protected]\u003c/p\u003e\n\u003cp\u003eAraia Berhane, MD MSc, Communicable Disease Control Division, Ministry of Health, Asmara, Eritrea. Email: [email protected]\u003c/p\u003e\n\u003cp\u003eGhide Gebreweld, MD, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email [email protected]\u003c/p\u003e\n\u003cp\u003eHenok Tekie, MD, Norther Red Sea zone, Ministry of Health, Massawa, Eritrea. Email [email protected]\u003c/p\u003e\n\u003cp\u003eAbdulaziz Mohamed Sied, MD, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTsegezeab Kiflezgi, MD, Adi Keih Hospital, Zoba Debu, Ministry of Health, Adi Keih, Eritrea. Email [email protected]\u003c/p\u003e\n\u003cp\u003eYonas Tekie, BSN, Tesseney Hospital, Zoba Gash Barka, Ministry of Health, Tesseney, Eritrea. Email [email protected]\u003c/p\u003e\n\u003cp\u003eMedhanie Asrat, BS, National Statistics Office, Asmara Eritrea. Email [email protected]\u003c/p\u003e\n\u003cp\u003eTewaldemedhine Gebrejesus, BS, National Tuberculosis and Leprosy Control Program of Eritrea, Ministry of Health, Asmara, Eritrea. Email: [email protected]\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKhongwichit S, Chansaenroj J, Thongmee T, Benjamanukul S, Wanlapakorn N, Chirathaworn C, et al. 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Epidemiology, clinical manifestations, and long-term outcomes of a major outbreak of chikungunya in a hamlet in Sri Lanka, in 2007: a longitudinal cohort study. J Trop Med. 2012; \u003c/li\u003e\n\u003cli\u003ede Lima Cavalcanti TYV, Pereira MR, de Paula SO, Franca RF de O. A review on chikungunya virus epidemiology, pathogenesis and current vaccine development. Viruses. 2022;14:969. \u003c/li\u003e\n\u003cli\u003eKril V, A\u0026iuml;qui-reboul-paviet O, Briant L, Amara A. New insights into chikungunya virus infection and pathogenesis. Annu Rev Virol. 2021;8:327\u0026ndash;47. \u003c/li\u003e\n\u003cli\u003eGutierrez-rubio AK, Magbitang AD, Penserga EG. A three-month follow up of musculoskeletal manifestions in chikungunya fever. Philipp J Intern Med. 2014;52(1):1\u0026ndash;5. \u003c/li\u003e\n\u003cli\u003eVirology H. Chikungunya association with different presentation at tertiary care centre. J Hum Virol Retrovirology. 2017;6(1):6\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eAtalay T, Kaygusuz S, Azkur AK. A study of the chikungunya virus in humans in Turkey. Turkish J Med Sci. 2017;47:1161\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eSissoko D, Moendandze A, Malvy D, Giry C, Ezzedine K, Louis J, et al. Seroprevalence and Risk Factors of Chikungunya Virus Infection in Mayotte , Indian Ocean , 2005-2006 : A Population-Based Survey. 2008;3(8):2005\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eTanay A. Chikungunya fever presenting as a systemic disease with fever, arthritis and rash: Our experience in Israel. Isr Med Assoc J. 2016;18(3\u0026ndash;4):162\u0026ndash;3. \u003c/li\u003e\n\u003cli\u003eEyer-Silva W de A, Neto H de BP, Silva GAR da, Ferry FR de A. A case of chikungunya virus disease presenting with remarkable acute arthritis of a previously damaged finger joint. J Brazilian Soc Trop Med. 2016;49. \u003c/li\u003e\n\u003cli\u003eFaisal A. Clinical Management of Chikungunya Fever: Guideline for Health Facilities in Maldives. 2019. \u003c/li\u003e\n\u003cli\u003eWorld Health Organization Regional Office for South-East Asia. Guidelines on Clinical Management of Chikungunya Fever. New Delhi; 2008. \u003c/li\u003e\n\u003cli\u003eImad HA, Phadungsombat, Juthamas Nakayama EE, Suzuki K, Ibrahim AM, Afaa A, Azeema A, et al. Clinical features of acute chikungunya virus infection in children and adults during an outbreak in the Maldives. Am J Top Med Hyg. 2021;105(4):946\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eDivision of Vector-Borne Diseases. Chikungunya: Vector Surveillance and Control in the United States. \u003c/li\u003e\n\u003cli\u003eLarrieu S, Pouderoux N, Pistone T, Filleul L, Receveur M-C, Sissoko D, et al. Factors associated with persistence of arthralgia among chikungunya virus-infected travellers: report of 42 French cases. J Clin Virol. 2010;47(1):85\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003ePouriayevali MH, Rezaei F, Jalali T, Baniasadi V, Fazlalipour M, Mostafavi E, et al. Imported cases of chikungunya virus in Iran. BMC Infect Dis. 2019; \u003c/li\u003e\n\u003cli\u003eHennessey MJ, Ellis EM, Delorey MJ, Panella AJ, Kosoy OI, Kirking HL, et al. Seroprevalence and symptomatic attack rate of chikungunya virus infection, United States Virgin Islands, 2014\u0026ndash;2015. Am J Trop Med Hyg. 2018;99(5):1321\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eJohnson BW, Russell BJ, Goodman CH. Laboratory diagnosis of chikungunya virus infections and commercial sources for diagnostic assays. J Infect Dis. 2016;214(Suppl 5):S471\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eHawman DW, Stoermer KA, Montgomery SA, Pal P, Oko L, Diamond MS, et al. Chronic joint disease caused by persistent chikungunya virus infection is controlled by the adaptive immune response. J Virol. 2013;87(24). \u003c/li\u003e\n\u003cli\u003eLong KM, Whitmore AC, Ferris MT, Sempowski GD, McGee C, Trollinger B, et al. Dendritic cell immunoreceptor regulates chikungunya virus pathogenesis in mice. J Virol. 2013;87(10). \u003c/li\u003e\n\u003cli\u003eRahman M, Jakaria SK, Sayed B, Kabir AKMH, Mallik U, Hasan R, et al. Clinical and laboratory characteristics of an acute chikungunya outbreak in Bangladesh in 2017. Am J Top Med Hyg. 2019;100(2):405\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eRueda JC, Santos AM, Angarita J, Giraldo RB, Saldarriaga E, Giovanny J, et al. Demographic and clinical characteristics of chikungunya patients from six Colombian cities, 2014 \u0026ndash; 2015. Emerg Microbes Infect. 2019;8(1):1490\u0026ndash;500. \u003c/li\u003e\n\u003cli\u003eKawle AP, Nayak AR, Bhullar SS, Borkar SR, Patankar SD, Daginawala HF, et al. Seroprevalence and clinical manifestations of chikungunya virus infection in rural areas of Chandrapur, Maharashtra, India. J Vector Borne Dis. 2017;54(1):35\u0026ndash;43. \u003c/li\u003e\n\u003cli\u003eChang A, Encinales L, Porras A, Pacheco N, Rield SP, Martins KAO, et al. Frequency of chronic joint pain following chikungunya virus infection: A Coloumbian cohort study. Arthritis Rheumatol. 2018;70(4):578\u0026ndash;84. \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":"Chikungunya fever, clinical features, persistent joint pain, Eritrea","lastPublishedDoi":"10.21203/rs.3.rs-3853568/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3853568/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChikungunya fever is a mosquito-borne viral illness that has re-emerged as an important global concern. Persistent arthralgia following chikungunya fever is common and requires advanced pharmacological interventions as pain does not respond well to analgesics.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe study aimed to describe the acute clinical features of probable cases of chikungunya fever and risk factors associated with the persistence of joint pain.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA prospective, descriptive cohort study was conducted on probable cases of chikungunya fever from October 2018 to March 2019 following the chikungunya outbreak of October 2018 in the Tesseney subzone of Eritrea.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 203 probable cases of chikungunya fever were enrolled, majority being males (68%) with a mean age of 39.2 years. The acute phase symptoms include the triad of polyarthralgia (97%), fever (96.1%), and skin rash (56.7%). Commonly affected joint sites were the wrist (59.4%) and interphalangeal joints of the hands (56.9%). Fever had a mean duration of 4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3 days, while headache had a mean duration of 3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3 days. Skin rash was maculopapular which was pruritic (85.2%) with common involved sites were the hands (71%) and trunk (46.5%). Complete blood count during the initial visit showed lymphocytosis (64.5%) and granulocytopenia (43.3%). Joint pain persisted at three months in 52.1% of cases and at six months in 21.7% of the cases. Age\u0026thinsp;\u0026gt;\u0026thinsp;41 (p\u0026thinsp;=\u0026thinsp;0.001, OR: 1.588; 95% CI: 0.935\u0026ndash;2.695) and having the O-type blood group (p\u0026thinsp;=\u0026thinsp;0.033, OR: 0.704; 95% CI: 0.448\u0026ndash;1.105) were found to be significant risk factors for the persistence of joint pain.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOur study indicates polyarthralgia, fever, and skin rash as a triad of symptoms during the acute phase. Persistent arthralgia was a frequent long-term complication of chikungunya fever in which increasing age was identified to be a significant risk factor.\u003c/p\u003e","manuscriptTitle":"Acute clinical features and persistence of joint pain in probable cases of Chikungunya Fever in Eritrea","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 18:42:53","doi":"10.21203/rs.3.rs-3853568/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"79511f24-3610-4243-a3df-26295d9d91e1","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-09T19:44:26+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-30 18:42:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3853568","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3853568","identity":"rs-3853568","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}