Cause Of Acute Febrile Illness Research Articles

Evaluating Antibiotic Misuse and Cost Analysis Among Hospitalized Dengue Virus-Infected Adults: Insights From a Retrospective Cohort Study.

Dengue is a prevalent cause of acute febrile illness, predominantly in Asia, where it necessitates supportive care without the need for antibiotics. This study aimed to evaluate antibiotic usage and analyze hospitalization costs among adults infected with the dengue virus. This retrospective cohort study was conducted at the Hospital for Tropical Diseases, Thailand, in 2022. Two independent reviewers assessed all adult cases with confirmed dengue from 2016 to 2021. Determinants of inappropriateness were analyzed using Poisson regression. The study included 249 participants with over half presenting with severe dengue or dengue with warning signs upon admission. The cumulative incidence of antibiotic use was 9.3% (95% CI, 8.23-10.47), predominantly involving empirical treatment strategies. Ceftriaxone and doxycycline were the most frequently prescribed antibiotics. Notably, patients who received empirical antibiotics showed no definite or presumed bacterial infections. Among those who received definite strategies, inappropriate durations, including both short treatments and the overuse of broad-spectrum antibiotics, were observed. A private ward admission was identified as a significant predictor of inappropriate use, with an incidence rate ratio of 4.15 (95% CI, 1.16-14.82) compared with intensive care unit admission. Direct medical costs did not differ significantly between appropriate and inappropriate uses. The incidence of antibiotic use among dengue cases was moderate; however, inappropriate use by indication was observed. Antimicrobial stewardship strategies should be encouraged, particularly in patients with dengue with warning signs admitted to a general or private ward. Direct medical costs between appropriate and inappropriate use were comparable.

Mayaro Virus as the cause of Acute Febrile Illness in the Colombian Amazon Basin.

Mayaro Fever (MF) is a tropical disease caused by the Mayaro virus (MAYV), with outbreaks documented in Latin America. A hospital-based fever surveillance in Leticia, Colombian Amazon, collected sera from 1,460 patients aged 5-89 between December 2020 and April 2023. Dengue and malaria were the main diagnoses (19.4 and 5.8%, respectively), leaving 71.4% of cases unidentified after testing. Metagenomic sequencing and real-time RT-qPCR testing identified MAYV in two patients (25-year-old male and an 80-year-old female) exhibiting typical symptoms, of MF including rash, joint pain, and fever. Phylogenetics analysis of these two viruses revealed a close relationship to Peruvian strains within the MAYV D genotype. The study of AFI in Leticia, Colombia, identified dengue as prevalent, with malaria, COVID-19, Influenza, and Zika viruses also detected. Despite extensive testing, most cases remained unexplained until metagenomic sequencing revealed MAYV, previously unseen in Colombia but known in neighboring countries. This study presents the first near full-length genomes of MAYV in Colombia, highlighting the need for further seroprevalence studies and enhanced surveillance to understand and control the spread of the virus in the region.

A toolkit for planning and implementing acute febrile illness (AFI) surveillance.

Acute febrile illness (AFI) is a broad clinical syndrome with a wide range of potential infectious etiologies. The lack of accessible, standardized approaches to conducting AFI etiologic investigations has contributed to significant global gaps in data on the epidemiology of AFI. Based on lessons learned from years of supporting AFI sentinel surveillance worldwide, the U.S. Centers for Disease Control and Prevention developed the toolkit for planning and implementing AFI surveillance, described here. This toolkit provides a comprehensive yet flexible framework to guide researchers, public health officials, and other implementers in developing a strategy to identify and/or monitor the potential causes of AFI. The toolkit comprises a cohesive set of planning aids and supporting materials, including an implementation framework, generic protocol, several generic forms (including screening, case report, specimen collection and testing, and informed consent and assent), and a generic data dictionary. These materials incorporate key elements intended to harmonize approaches for AFI surveillance, as well as setting-specific components and considerations for adaptation based on local surveillance objectives and limitations. Appropriate adaptation and implementation of this toolkit may generate data that expand the global AFI knowledge base, strengthen countries' surveillance and laboratory capacity, and enhance outbreak detection and response efforts.

Etiology of Acute Febrile Illnesses in Adults in the Defense Community in French Guiana.

In tropical countries, acute febrile illnesses represent a complex clinical problem for general practitioners. We describe the prevalence of different etiologies of acute febrile illnesses occurring among French service members and their families, excluding children, in general practice in French Guiana. From June 2017 to March 2020, patients with a fever ≥ 37.8°C with a duration of less than 15 days who sought medical care at the army medical centers in Cayenne and Kourou were prospectively enrolled. Based on clinical presentation, blood, urine, nasopharyngeal, and stool samples were collected for diagnostic testing for viruses, bacteria, and parasites (by direct examination, microscopic examination of blood smears, culture, serology, or polymerase chain reaction), and standardized biological tests were systematically performed. Among 175 patients retained for analysis, fever with nonspecific symptoms was predominant (46.9%), with 10 Plasmodium vivax malaria cases, 8 dengue infections, and 6 cases of Q fever. The second most frequent cause of acute febrile illness was upper respiratory tract infections (32.0%) due to influenza virus (n = 18) or human rhinovirus (n = 10). Among the causes of acute febrile illness in French Guiana, clinicians should first consider arboviruses and malaria, as well as Q fever in cases of elevated C-reactive protein with nonspecific symptoms and influenza in cases of signs and symptoms associated with upper respiratory tract infections. Despite an expanded microbiological search, the etiology of 51.4% of acute febrile illnesses remain unknown. Further investigations will be necessary to identify the etiology of acute febrile illnesses, including new pathogens, in French Guiana.

Study of Clinical and Demographic Profile of Scrub Typhus Patients Admitted to a Tertiary Care Hospital in Central India

Objectives: To study epidemiological characteristics, clinical features, laboratory findings, and clinical outcomes in cases of scrub typhus. Additionally, the study aims to identify the predictors of disease severity.Methods: This cross-sectional study was conducted in the Department of General Medicine at Dr PDM Medical College in Amaravati, India. The study duration was 6 months, from July 2023 to December 2023. All clinically confirmed patients with scrub typhus were evaluated through history, clinical examination, and appropriate laboratory investigations. The clinical and laboratory profiles, hospital course, and outcomes were analyzed. Organ dysfunction upon admission was assessed using the sequential organ failure assessment (SOFA) score.Results: A total of 200 cases were included in the study. The majority of the cases were in the age range of 31-40 years, and most of them were males. The highest number of scrub typhus cases occurred in September. The most common presenting symptoms were fever (81%), followed by nausea (37.5%), generalized weakness (34%), abdominal pain, eschar (21.5%), breathlessness, and cough (21% each), headache (19%), vomiting (15%), and altered sensorium (4.5%). The majority of patients (72.5%) did not experience any complications, while 55 patients (27.5%) developed multi-organ dysfunction syndrome (MODS) as a complication. The mortality rate was 1%.Conclusion: Scrub typhus is a significant cause of acute febrile illness in the Vidarbha region of Maharashtra. It can present with various clinical manifestations, with or without an eschar. Early diagnosis and appropriate treatment of these cases can lead to minimal complications.

Integration of population-level data sources into an individual-level clinical prediction model for dengue virus test positivity.

The differentiation of dengue virus (DENV) infection, a major cause of acute febrile illness in tropical regions, from other etiologies, may help prioritize laboratory testing and limit the inappropriate use of antibiotics. While traditional clinical prediction models focus on individual patient-level parameters, we hypothesize that for infectious diseases, population-level data sources may improve predictive ability. To create a clinical prediction model that integrates patient-extrinsic data for identifying DENV among febrile patients presenting to a hospital in Thailand, we fit random forest classifiers combining clinical data with climate and population-level epidemiologic data. In cross-validation, compared to a parsimonious model with the top clinical predictors, a model with the addition of climate data, reconstructed susceptibility estimates, force of infection estimates, and a recent case clustering metric significantly improved model performance.

SEROPREVALENCE OF SCRUB TYPHUS AND LEPTOSPIROSIS IN PATIENTS WITH ACUTE FEBRILE ILLNESS IN A TERTIARY CARE HOSPITAL, VIJAYAWADA, A.P

Two significant causes of acute febrile illness are Scrub typhus and Leptospirosis, these zoonotic illnesses are primarily transmitted by rodents. Both illnesses present with similar and non-specific clinical symptoms, have a similar seasonal trend and can be identified by IgM ELISA. This study aims at identifying the presence of antibodies to scrub typhus and leptospirosis and their co-infection in patients of all age groups by IgM ELISA. Data was collected retrospectively over a period of four years, from January 2019 to September 2023 and analysis was done. A total number of 320 samples were received at the laboratory during the study period and IgM ELISA was performed for both scrub typhus and leptospirosis for all the samples received.Of the 320 samples tested, IgM ELISA for Scrub typhus was positive in 72(22.5%), Leptospirosis in 23(7.18%) and 6(1.87%) for both Scrub typhus and Leptospirosis were seen. Seroprevalence of Scrub typhus was more in Male population whereas Female predominance was observed in Leptospirosis. Age group in our study ranged from 0-60 years and most of the infected individuals are from Rural areas.As both leptospirosis and scrub typhus present with similar clinical features, co-infection of these two diseases may occur and require early diagnosis which helps the physician in treating the cases. IgM is a cost effective method of diagnosis of these zoonotic infections and plays a major role in early diagnosis therby reducing the morbidity and mortality in health care settings.

Hemophagocytic lymphohistiocytosis-a rare life threatening association with scrub typhus: case report

Scrub typhus is an important cause of acute febrile illness and one of the re-emerging infectious diseases in India particularly in southern Rajasthan. Hemophagocytic lympho-histiocytosis (HLH) results from an uncontrolled and ineffective hyperinflammatory response to a variety of triggers. HLH is further subdivided into primary and secondary type. We present a case of Scrub typhus which presented with multiple organ dysfunction syndrome (MODS) and secondary HLH which is a rare entity. A 9-month-old male child presented with high grade fever with encephalopathy. Examination showed hepatosplenomegaly, cervical Lymph adenopathy with eschar mark visible on abdomen. Scrub typhus was suspected on clinical grounds and further investigations were done. Serological diagnosis was strongly positive for scrub typhus. Initially, child did not respond to doxycycline, so further investigations were done to rule out HLH which fits into criteria of secondary HLH as per the revised HLH 2004 protocol. In view of secondary HLH and MODS methylprednisolone was added to treatment. Child responded to steroids and there was complete recovery. Scrub typhus patient with progressive MODS, in spite of appropriate antimicrobial therapy should raise the suspicion of secondary HLH which is rare but life-threatening condition and steroids plays an important role in the management of this condition.

Blindness as a presenting feature of leptospiral infection: A case report and review of literature

Leptospira is an emerging cause of acute febrile illness in India, which is acquired through contact of skin with contaminated water and soil. Generally, leptospirosis has mild, self-limiting course; rarely, multiple organ dysfunction can occur like aseptic meningitis (20%) and Weil’s disease (10%). Here, we report a case of bilateral optic neuritis in a girl child who presented with blindness following Leptospira infection. On ophthalmological examination, she could appreciate hand movements close to face and had afferent pupillary defect bilaterally. Fundoscopy showed normal fundus with no signs of disc edema. Magnetic resonance imaging (MRI) of brain and orbit showed bilateral hyperintensities in the optic nerve. Visual evoked potential showed prolonged latency in p100 wave in both eyes, suggestive of bilateral optic neuritis. She was diagnosed with Leptospira infection with aseptic meningitis and retrobulbar optic neuritis. She was treated conservatively. She responded well with improvement of visual acuity to 6/6 at the time of discharge.

Procalcitonin Levels for Prognosis of Scrub Typhus Patients: A Retrospective Observational Analysis from a Tertiary Care Centre in Northern India

Introduction: Scrub typhus is a major cause of acute febrile illness in India. It presents with various clinical features that vary from fever to multiorgan dysfunction. Similar symptoms and presentations cause difficulty in diagnosis. Therefore, it is important to have early and prompt diagnosis with better prognostic markers to decrease morbidity and mortality. Aim: To determine the prognosis of scrub typhus patients based on the Procalcitonin (PCT) levels. Materials and Methods: This retrospective observational study was conducted in the Microbiology Department of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Uttar Pradesh, India, from January 2022 to January 2023. A total of 120 patients admitted to the hospital, who tested positive for Scrub typhus IgM by ELISA during this period and had a negative blood culture, were included in this study. Data analysis was conducted from February 2023 to April 2023. PCT levels of all these patients at the time of admission were recorded. The demographic information, laboratory parameters, and treatment regimen of these patients were also compiled. Statistical analysis was performed, and p-value was used to determine statistical significance. Results: The majority of the patients belonged to the age group of 21-40 years. Among these, elevated PCT values (ranging from 0.05-89.4 ng/mL) were observed in 112 (93.33%) patients. Twelve (10%) patients died during the study period, and all of them had elevated PCT levels. Among these, six developed septic shock with Multiple Organ Dysfunction Syndrome (MODS). Increased leukocyte values, elevated liver enzymes such as Aspartate Aminotransferase (SGOT/AST) and Alanine Transferase (SGPT/ALT), abnormal coagulation profile, and abnormal renal profile with elevated urea and uric acid levels were found to be significantly associated with scrub typhus patients with elevated PCT values. Conclusion: There is a need to address the role of prognostic markers in the management of scrub typhus patients. This may lead to breakthroughs in the field of diagnostic research and help improve the prognosis of these patients.

The Chikungunya virus: A reemerging cause of acute febrile illness in the high jungle of northern Peru

Background The Chikungunya virus (CHIKV) is an emerging arthropod-borne virus (arbovirus) that causes undifferentiated acute febrile illness. Cases of CHIKV may be under-reported in Peru, given the various difficulties in diagnosing it, such as lack of diagnostic tests in remote areas, the passive nature of epidemiological surveillance, and co-circulation of other arthropod-borne pathogens. Therefore, a study was conducted in the high jungle of northern Peru to determine the prevalence of CHIKV among febrile patients and describe their clinical characteristics. Methods A cross-sectional study was conducted in the province of Jaen, Cajamarca, located in the high jungle of northern Peru. Patients attending primary healthcare centers within Cajamarca’s Regional Health Directorate were enrolled. The study took place from June 2020 through June 2021. Patients were eligible if they sought outpatient healthcare for a clinical diagnosis of acute febrile illness (AFI). Serum samples were collected from all patients, and the diagnosis of CHIKV was determined using real-time RT-PCR, as well as the detection of IgM antibodies by ELISA. A logistic regression model was employed to identify the risk factors for CHIKV, and the odds ratios (ORs) were calculated, along with their corresponding 95% confidence intervals (95% CI). Results A total of 1 047 patients with AFI were included during the study period. CHIKV was identified in 130 patients of 1 047 (12.4%). Among the CHIKV positive cases, 84 of 130 (64.6%) were diagnosed by RT-PCR, 42 of 130 (32.3%) by IgM ELISA detection, and 4 of 130 (3.1%) by both assays. The majority of patients with CHIKV infection fell within the 18–39 years age group (50.0%), followed by the 40–59 years age group (23.9%) and those with 60 years or older (10.8%). The most common clinical symptoms observed in patients with CHIKV infection were headache (85.4%), myalgias (72.3%), and arthralgias (64.6%). The highest number of positive CHIKV cases occurred in May (23.1%), followed by March (20.0%) and February (13.8%) of 2021. Conclusion The study reports a considerable frequency of CHIKV infections among patients with AFI from the high jungle of northern Peru. These findings highlight the importance of recognizing CHIKV as an ongoing pathogen with continuous transmission in various areas of Peru. It is crucial to enhance epidemiological surveillance by implementing reliable diagnostic techniques, as the clinical symptoms of CHIKV infection can be nonspecific.

Changing Trends in the Clinical Suspicion of Scrub Typhus in Acute Febrile Illness Patients

Abstract Introduction: Scrub typhus is an important and widespread cause of acute febrile illness (AFI), which can be diagnosed easily by serological assay. Methods: All cases of AFI were sent for Scrub Typhus serology by rapid Enzyme Linked Immuno-Sorbent Assay (ELISA) method. Anyone found positive was admitted for further evaluation. Results: In this series 80 % had liver abnormality, 80 % had ARDS, 40 % had renal failure, 40 % had eschar and 80 % of them had MODS. Only 20 % had clinical features of encephalitis with MRI brain haemorrhagic transformation of infarct. All patients responded well to treatment with Doxycycline with hospitalization of around 7-10 days. Conclusion: This case series highlights the importance of keeping a high index of clinical suspicion to exclude scrub typhus in all AFI patients.

Coinfection of Malaria and Bacterial Pathogens among Acute Febrile Patients in Selected Clinics in Ghana.

Malaria remains the leading cause of acute febrile illness (AFI) in Africa despite successful control measures and programs. Acute febrile illnesses can be misdiagnosed as malaria as a result of the overlapping spectrum of nonspecific symptoms or may not be pursued because of limited diagnostic capabilities. This study investigated potential etiologies of AFIs in Ghana and determined the relationship between coinfection between malaria and Q fever, leptospirosis, and culturable bacteria in febrile patients. Participants were enrolled between July 2015 and December 2019 from four Ghanaian military treatment facilities. Of the 399 febrile participants, 222 (55.6%) males and 177 (44.6%) females were enrolled. Malaria was diagnosed in 275 (68.9%) participants. Malaria coinfection occurred with leptospirosis, Q fever, and blood-cultured bacteria in 11/206 (5.3%), 24/206 (11.7%), and 6/164 (3.7%) participants, respectively. Among the 124 malaria-negative samples, the positivity rates were 4.1% (3/74), 8.1% (6/74), and 3.6% (2/56) for leptospirosis, Q fever, and bacterial pathogens isolated from blood culture, respectively. The majority of documented clinical signs and symptoms were not significantly associated with specific diseases. Approximately 10% of malaria-positive participants also had evidence suggesting the presence of a bacterial coinfection. Therefore, even in the case of a positive malaria test, other pathogens contributing to febrile illness should be considered. Understanding the frequency of malaria coinfection and other etiological agents responsible for AFIs will improve diagnosis and treatment and better inform public health knowledge gaps in Ghana.

Better diagnostic tools needed to distinguish typhoid from other causes of acute febrile illness

Better diagnostic tools needed to distinguish typhoid from other causes of acute febrile illness

Mite Bite Underlying A Lid Swelling - A Rare Presentation Of Scrub Typhus

Scrub Typhus, a vector-borne and zoonotic disease by Orientia tsutsugamushi, is one of the causes of acute febrileillness in India. In endemic regions where Scrub Typhus is prevalent, healthcare providers should keep an eye out and be verysuspicious about this disease, especially when encountering patients with acute febrile illness and exposure to mite-infested areas.Prompt recognition and appropriate diagnostic testing, such as serological assays or molecular methods, are essential for accuratediagnosis. Once diagnosed, treatment with appropriate antibiotics, such as doxycycline or azithromycin, can effectively manageScrub Typhus and prevent complications. Early initiation of treatment is crucial to reduce the chance of severe disease and potentialmortality. This case report highlights the importance of considering Scrub Typhus as a potential differential diagnosis in lid infectionsand acute febrile illnesses, particularly in areas where the disease is endemic. Healthcare providers should be aware of the diverseclinical presentations and remain vigilant to ensure timely and accurate diagnosis, leading to appropriate management and improvedpatient outcomes. Public health efforts should also focus on increasing awareness about Scrub Typhus, its prevention, and earlydetection to minimize the burden of this often underdiagnosed disease. In this case report, we presented a child with febrile illnessand unilateral lid swelling misdiagnosed as stye. The presence of eschar prompted an investigation of Scrub typhus, which waspositive. This case is reported as the lid is an unusual site for eschar formation. To reiterate, scrub typhus should be considered adifferential diagnosis in lid infections and acute febrile illness, particularly in endemic areas.

SCRUB TYPHUS - A RE-EMERGING DISEASE: ESTIMATING THE BURDEN AND OUTCOME OF SCRUB TYPHUS IN A TERTIARY CARE CENTRE

Background: Scrub typhus is regarded as an important cause of acute febrile illness. If not diagnosed early, it is often tends to be fatal. Methods: A Prospective Observational study was carried out among patients reporting with fever in a tertiary care hospital at Delhi. Weil Felix test and rapid test for scrub typhus was performed on the patient samples. Results: A total of 265 cases were screened for typhus group of fever, of these 26 (9.1%) patients (18 males and 8 females) were diagnosed having rickettsial fever. Out of these, 24 (92.3%) were diagnosed having scrub typhus fever. Conclusions:In present study, we observed 9.1% seropositivity in acute febrile illness. We conclude that a simple Weil Felix test should be included in routine workup of fever cases and a strong suspicion should be there where other laboratory tests remain inconclusive in endemic areas like Delhi-NCR.

Once Forgotten Now Re-emerging: Scrub Typhus Infection in Pediatric Patients From North West India.

Background Scrub typhus is an important cause of acute febrile illness in children. It is one of the re-emerging infections in the Asia Pacific region. It is caused by the gram-negative bacteriaOrientia tsutsugamushiand is spread by the bite of trombiculid mites. The initial symptomatology is nonspecific with fever, headache, vomiting, etc. The presence of eschar is said to be pathognomic. It is a systemic illness, and vasculitis is the basic pathogenic mechanism. Materials and methods A retrospective observational study was conducted in two medical colleges and associated hospitals of western Uttar Pradesh (UP) and Rajasthan, India. Case files of 21 confirmed cases of scrub typhus admitted from April 2021 to October 2022 were reviewed. Scrub typhus was suspected in children with acute undifferentiated fever, and suggestive signs and symptoms were confirmed serologically with IgM enzyme-linked immunoassay (ELISA). Demographic and clinical details were noted. Results During the study period, a total of 335 cases of acute undifferentiated fever were seen, and 6.2% of them were diagnosed as having scrub typhus infection on detailed investigation. The most common symptom was fever in 100% of them, vomiting in 57.1%, abdomen pain in 42.8%, and diarrhea in 19%. Maculopapular, erythematous rash was present in 19% of cases. None of the patients had eschar. Microvascular leakage was the main complication in 28.5%.Unusual complications seen were empyema and valvulitis in 4.7% of patients. Conclusion Scrub typhus is also seen in urban setups and in dry arid areas like Rajasthan and North West UP. So, relevant investigations should be a part of the evaluation in pediatric patients with acute undifferentiated fever.Eschar can be absent, and empyema and valvulitis are some uncommon complications. A high degree of suspicion and early diagnosis are essential as an undiagnosed infection is rapidly fatal.

Wide distribution of Mediterranean and African spotted fever agents and the first identification of Israeli spotted fever agent in ticks in Uganda.

Rickettsia microorganisms are causative agents of several neglected emerging infectious diseases in humans transmitted by arthropods including ticks. In this study, ticks were collected from four geographical regions of Uganda and pooled in sizes of 1-179 ticks based on location, tick species, life stage, host, and time of collection. Then, they were tested by real-time PCR for Rickettsia species with primers targeting gltA, 17kDa and ompA genes, followed by Sanger sequencing of the 17kDa and ompA genes. Of the 471 tick pools tested, 116 (24.6%) were positive for Rickettsia spp. by the gltA primers. The prevalence of Rickettsia varied by district with Gulu recording the highest (30.1%) followed by Luwero (28.1%) and Kasese had the lowest (14%). Tick pools from livestock (cattle, goats, sheep, and pigs) had the highest positivity rate, 26.9%, followed by vegetation, 23.1%, and pets (dogs and cats), 19.7%. Of 116 gltA-positive tick pools, 86 pools were positive using 17kDa primers of which 48 purified PCR products were successfully sequenced. The predominant Rickettsia spp. identified was R. africae (n = 15) in four tick species, followed by R. conorii (n = 5) in three tick species (Haemaphysalis elliptica, Rhipicephalus appendiculatus, and Rh. decoloratus). Rickettsia conorii subsp. israelensis was detected in one tick pool. These findings indicate that multiple Rickettsia spp. capable of causing human illness are circulating in the four diverse geographical regions of Uganda including new strains previously known to occur in the Mediterranean region. Physicians should be informed about Rickettsia spp. as potential causes of acute febrile illnesses in these regions. Continued and expanded surveillance is essential to further identify and locate potential hotspots with Rickettsia spp. of concern.

Murine typhus is a common cause of acute febrile illness in Bandung, Indonesia.

Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast Asia but is rarely reported in Indonesia. The current study aimed to describe the clinical characteristics of MT cases in Bandung, West Java. Non-confirmed AFI cases (n = 176) from a prospective cohort study of whom paired serum samples (acute (T1), midterm (T2), or convalescent (T3)) were available were screened using MT serology. IgG against R. typhi was detected in the T2 or T3 samples using an in-house ELISA. Positive IgG samples were further screened for the presence of IgM. If both IgM and IgG were positive, the endpoint titer of T1, T2, or T3 was determined. In cases with a fourfold increase in titer, real-time PCR of T1 samples was performed to detect R. typhi DNA. In total, 71/176 (40.3%) patients tested positive for IgG antibody, and 26 AFI cases were confirmed as MT (23 cases by PCR, 3 cases by fourfold titer increased IgG or IgM titer). The most common clinical symptoms in the confirmed cases were headache (80%), arthralgia (73%), malaise (69%), and myalgia (54%). In these cases, the presumptive clinical diagnoses were typhoid fever (43.2%), dengue (38.5%), and leptospirosis (19.2%). MT was not considered in any of the patients, and no patients received doxycycline. These findings confirmed that MT is an important cause of AFI in Indonesia. MT should be included in the differential diagnosis of AFI, and empirical treatment with doxycycline should be considered.

Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda

BackgroundHistorically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda.MethodsA prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul’s Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables.ResultsOf the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2–93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001).ConclusionMalaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.