Etiology Of Acute Febrile Illness Research Articles

Epstein-Barr Virus in the RIVERA Case-Control Study of Acute Febrile Illness: Acute Mononucleosis Nearly Absent as an Etiology in the Peruvian Amazon.

Large diagnostic panels allow for pathogens with high or low likelihood of causing attributable illness to be tested simultaneously. Infectious mononucleosis (IM) due to primary infection with Epstein-Barr virus (EBV) is a common cause of acute febrile illness (AFI) in case series from high-income countries, though its contribution to AFI in tropical low-income settings is unclear. As part of a case-control study using multiplex quantitative polymerase chain reaction (qPCR) diagnostics, we set out to determine if primary EBV infection was an underrecognized cause of AFI in the Peruvian Amazon. Presence of EBV DNA in whole-blood samples was equally prevalent among febrile cases and afebrile controls (34.6% [247/714] versus 35.7% [248/695]) and was not correlated with classic IM symptoms. Given the clear lack of clinical significance of the whole-blood PCR results, additional testing was pursued to ascertain the true prevalence of IM among cases of AFI in this population. The presence of EBV DNA in plasma, a marker of active EBV-related processes, was detected in 7% (5/68). Anti-EBNA-1 IgG, a late marker of prior infection, was tested via ELISA and detected in 4/5 of the plasma-positive patients, thereby excluding an acute primary EBV infection in all but one patient. Infectious mononucleosis due to primary infection with EBV was not an important etiology of AFI in the Peruvian Amazon, despite high rates of initial test positivity.

A clinicoepidemiological study of serologically diagnosed acute febrile illness in a teaching hospital, Kolkata

ABSTRACT Introduction: Similar presenting manifestations in early phase and lack of awareness of aetiology of acute febrile illness (AFI) are major challenges in management of AFI. Material and Methods: This was a retrospective observational cross-sectional study conducted in the Department of Microbiology, NRS Medical College, from 1 July 2022 to 30 June 2023 in serologically diagnosed febrile patients attending the outpatient department or admitted. Clinical and epidemiological data and laboratory parameters were recorded in a pretested structured questionnaire study tool, and collected data were analysed on MS-Excel sheets with various charts and tables. Results: A total of 1711 serologically diagnosed febrile patients showed preponderance of dengue (38.3%), followed by leptospirosis (25%), scrub typhus (23.9%), malaria (12.6%), and enteric fever (1.92%). A majority of cases were male, less than 40 years of age, and from the rural population (73.2%), except in malaria (urban = 79.6%). The mean duration of fever was 9 days. Febrile cases were recorded maximum during the monsoon and postmonsoon periods (66.5%). The common manifestations are fever, headache (46.2%), pain abdomen (7.8%), nausea, and vomiting (9.4%). Thrombocytopenia with bleeding manifestation was higher in dengue (18%) cases. Mortality in dengue cases was recorded with multiorgan dysfunction syndrome (MODS). Scrub typhus cases showed seizure (8.3%) and altered sensorium (5%) due to fatal meningoencephalitis. Fatality in leptospirosis was mostly due to acute kidney injury (29.5%) and Weil’s disease (4.4%). Conclusion: Misdiagnosis or incorrect diagnosis and delay in initiation of appropriate treatment results in increased morbidity and mortality in AFI. Determination of epidemiological features and clinical manifestations of AFI along with timely correct diagnosis will benefit clinicians in proper treatment initiation, thereby reducing morbidity and mortality.

Clinical characteristics of enteric fever and performance of TUBEX TF IgM test in Indonesian hospitals.

Accurate diagnosis of enteric fever is challenging, particularly in low- and middle-income countries, due to the overlap of clinical and laboratory features with other pathogens. To better understand the difficulties in enteric fever diagnosis, we evaluated the characteristics of patients clinically diagnosed with enteric fever and the real-world performance of TUBEX TF, one of the most used tests in Indonesia. Patients were recruited through the AFIRE (Etiology of Acute Febrile Illness Requiring Hospitalization) study at eight Indonesian hospitals. Blood culture was performed for all patients, and TUBEX TF was performed for suspected enteric cases. Salmonella PCR and ELISA tests were performed at a reference lab. Sensitivity and specificity of TUBEX TF and IgM and IgG anti-S. Typhi ELISA were determined. Of 301 patients clinically diagnosed with enteric fever, 50 (16.6%) were confirmed by blood culture and/or PCR. Confirmed cases were mostly school-aged children presenting with fever, anorexia, dizziness and/or abdominal pain with normal leukocyte count or leukopenia. TUBEX TF demonstrated a sensitivity of 97.6% to 70.7% and specificity of 38.3% to 67.2% at cutoffs of 4 and 6, respectively. Acute IgG demonstrated the best sensitivity and specificity, at 90.7% and 82.7%, respectively, and the best ROC characteristics. A substantial proportion of enteric fever was misdiagnosed at all study hospitals, likely due to the overlap of clinical characteristics and lab parameters with those of other common pathogens. The TUBEX TF rapid serological assay demonstrated suboptimal performance in our setting and tended to over-diagnose enteric fever. The role of IgG from acute specimens for identification of enteric fever cases merits additional consideration.

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.

Outbreak investigation of acute febrile illness from the Himalayan foothills: Solving the puzzle of fever.

In September 2022, Panchkula Civil Hospital reported an outbreak of acute febrile illness (AFI) in Pinjore, located in the Himalayan foothills, Haryana, North India. There was an upsurge of fever cases. Blood samples were taken from suspected patients (n = 58) with AFI and subjected to serology of dengue, chikungunya, Japanese encephalitis, leptospira and scrub typhus. The samples were also screened for West Nile & Zika virus RNA using real-time PCR. Viral strains were characterized by sequencing. Of the 58 cases of AFI, Dengue could be identified in 45 (77.58%) followed by JE and Chikungunya in 2 cases each (3.44%), respectively. Among Dengue positive cases, 44 had monoinfection (97.77%) and 1 patient had dengue and JE. None were positive for Zika, West Nile, Scrub typhus, and Leptospira with the testing protocol. Four patients developed dengue with warning signs, such as abdominal pain in one patient and recurrent vomiting in the remaining three. The dengue serotype could be determined in 17 samples and revealed serotype 2. Molecular evolution analysis based on the complete envelope gene revealed that all DENV-2 strains (n = 13) circulated in the outbreak area belonged to the DENV-2 cosmopoliton genotype. In the early stages of infection, relying only on clinical manifestations is ineffective, so both molecular and serological assays along with clinical diagnosis are noteworthy for determining the aetiology of AFI.

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.

Etiology of acute febrile illness in the peruvian amazon as determined by modular formatted quantitative PCR: a protocol for RIVERA, a health facility-based case-control study

BackgroundThe study of the etiology of acute febrile illness (AFI) has historically been designed as a prevalence of pathogens detected from a case series. This strategy has an inherent unrealistic assumption that all pathogen detection allows for causal attribution, despite known asymptomatic carriage of the principal causes of acute febrile illness in most low- and middle-income countries (LMICs). We designed a semi-quantitative PCR in a modular format to detect bloodborne agents of acute febrile illness that encompassed common etiologies of AFI in the region, etiologies of recent epidemics, etiologies that require an immediate public health response and additional pathogens of unknown endemicity. We then designed a study that would delineate background levels of transmission in the community in the absence of symptoms to provide corrected estimates of attribution for the principal determinants of AFI.MethodsA case-control study of acute febrile illness in patients ten years or older seeking health care in Iquitos, Loreto, Peru, was planned. Upon enrollment, we will obtain blood, saliva, and mid-turbinate nasal swabs at enrollment with a follow-up visit on day 21–28 following enrollment to attain vital status and convalescent saliva and blood samples, as well as a questionnaire including clinical, socio-demographic, occupational, travel, and animal contact information for each participant. Whole blood samples are to be simultaneously tested for 32 pathogens using TaqMan array cards. Mid-turbinate samples will be tested for SARS-CoV-2, Influenza A and Influenza B. Conditional logistic regression models will be fitted treating case/control status as the outcome and with pathogen-specific sample positivity as predictors to attain estimates of attributable pathogen fractions for AFI.DiscussionThe modular PCR platforms will allow for reporting of all primary results of respiratory samples within 72 h and blood samples within one week, allowing for results to influence local medical practice and enable timely public health responses. The inclusion of controls will allow for a more accurate estimate of the importance of specific prevalent pathogens as a cause of acute illness.Study RegistrationProject 1791, Registro de Proyectos de Investigación en Salud Pública (PRISA), Instituto Nacional de Salud, Perú.

The viral etiology of acute febrile illness of in Dhaka, Bangladesh in the year of 2017

BackgroundThis is sometimes a challenge to identify the etiologies of acute febrile illnesses (AFI) due to non-specific clinical presentation as well as limited availability of diagnostic facilities. Bangladesh is very much suitable for vector borne viral infections like Dengue, Chikungunya and Zika due to hot and humid climate. MethodIn 2017 during the period of April to November there was an outbreak of febrile illness in Dhaka city, the capital of Bangladesh. With the aim to explore the situation Institute of Epidemiology, Disease Control and Research (IEDCR) took an initiative to investigate the etiology of febrile illness. Sixteen hundred and thirty two patients with history of acute onset of fever with or without arthalgia and rash, who attended to IEDCR,were tested for Dengue, Chikungunya and Zika by multiplex PCR. ResultsAmong them 66%, 7% and 0.4% were positive for Chikungunya, Dengue and co-infected with both pathogens respectively. Dengue virus positive serum samples were further analyzed for serotyping and found re-emergence of DEN-3 in the circulation along with existing serotypes DEN-1 and DEN-2. ConclusionConsidering the climatic condition and existence of domestic and peri-domestic setup in Bangladesh correlates with persistent mosquito breeding and survival as well as transmissibility of vector borne viral diseases. Thus continuous surveillance is required from public health point of view for prevention and control of arboviral diseases in Bangladesh.

Rickettsial Infections Are Neglected Causes of Acute Febrile Illness in Teluk Intan, Peninsular Malaysia.

Rickettsial infections are among the leading etiologies of acute febrile illness in Southeast Asia. However, recent data from Malaysia are limited. This prospective study was conducted in Teluk Intan, Peninsular Malaysia, during January to December 2016. We recruited 309 hospitalized adult patients with acute febrile illness. Clinical and biochemistry data were obtained, and patients were stratified into mild and severe infections based on the sepsis-related organ failure (qSOFA) scoring system. Diagnostic assays including blood cultures, real-time PCR, and serology (IFA and MAT) were performed. In this study, pathogens were identified in 214 (69%) patients, of which 199 (93%) patients had a single etiology, and 15 (5%) patients had >1 etiologies. The top three causes of febrile illness requiring hospitalization in this Malaysian study were leptospirosis (68 (32%)), dengue (58 (27%)), and rickettsioses (42 (19%)). Fifty-five (18%) patients presented with severe disease with a qSOFA score of ≥2. Mortality was documented in 38 (12%) patients, with the highest seen in leptospirosis (16 (42%)) followed by rickettsiosis (4 (11%)). While the significance of leptospirosis and dengue are recognized, the impact of rickettsial infections in Peninsular Malaysia remains under appreciated. Management guidelines for in-patient care with acute febrile illness in Peninsular Malaysia are needed.

RELATIONSHIP OF OUTCOMES BETWEEN DIFFERENT ETIOLOGIES AND SEVERITY GROUPS OF PATIENTS PRESENTING WITH ACUTE FEBRILE ILLNESS WITH TRANSAMINITIS

Background: Acute febrile illness (AFI) is defined as a fever lasting less than 14 days with no evidence of organ-specific symptoms or signs of infection. Our aim was to determine the most common etiology of AFI with transaminitis and to find the relationship between clinical and laboratory investigation profile, as well as outcomes of illness. Methods: This is a hospital based prospective study conducted in Chitwan Medical College and Teaching Hospital (CMC-TH) from 17 April 2021 to 18 October 2021. All patients &gt;15 years of age admitted with acute febrile illness and elevated transaminases under Pulmonary and Critical Care Medicine (PCCM) Unit of CMCTH were enrolled consecutively. Results: The mean age of the patients (n=103) was 45.1 ± 16.8 years. There were almost equal proportion of males and females. The most common presenting symptom (besides fever) was headache, followed by myalgia, with a median duration of 5 days. Scrub typhus was the commonest diagnosis (60, 58.3%). A diagnosis of Acute Undifferentiated Febrile Illness (AUFI) was given in (39, 37.9%) patients. The three transaminitis severity groups (mild, moderate and severe) were not significantly different by age, gender and comorbidity status. Acute kidney injury and multi-organ dysfunction syndrome (MODS) were significantly associated with severe transaminitis (P&lt;0.05). The mortality rate was also higher in the severe transaminitis group. Conclusions: Scrub typhus has emerged as the most common cause of Acute Febrile Illness with transaminitis requiring hospital admission in this part of the country. Scrub typhus should be suspected in all patients who report with AFI with transaminitis in endemic areas.

Aetiologies of acute undifferentiated febrile illness at the emergency ward of the University of Gondar Hospital, Ethiopia.

Causes of acute febrile illness (AFI) often remain undetermined in developing countries, due to overlap of symptoms and limited available diagnostics. We aimed to assess the aetiology of AFI in adults in a referral hospital in northwest Ethiopia. While all participants were tested for malaria by rapid diagnostic test (RDT), microscopy was only done on physician's request. Dengue virus (DENV) infections were detected using an RDT and ELISAs and dengue, yellow fever and chikungunya cases were identified by PCR. Bacterial aetiologies were investigated using blood culture and PCR. The aetiology of acute infection was identified for 20.5% of 200 patients enrolled. Eleven percent tested positive for Plasmodium, while microscopy was only requested for half of the identified malaria cases. For 4.0% of the Plasmodium-infected patients, an acute or past DENV (co-)infection was detected. We found 7.5% acute and 13.0% past DENV - all serotype 3 - infections. Bacterial infections were observed in 4.5% of the patients. Malaria is still a considerable aetiology of AFI and dengue is underrecognised. There are areas where both diseases occur concomitantly, and the DENV-3 serotype presumably spreads from Sudan to northern Ethiopia. As only 20.5% of the aetiologies were identified, a broader testing platform is required.

Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study

IntroductionIn rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This...

Aetiology of acute febrile illness among children attending a tertiary hospital in southern Ethiopia

BackgroundThe diagnosis of non-malarial aetiologies, which now represent the majority of febrile illnesses, has remained problematic in settings with limited laboratory capacity. We aimed to describe common aetiologies of acute febrile illness among children in a setting where malaria transmission has declined.MethodsA prospective cross-sectional study was conducted among children aged at least 2 months and under 13 years presenting with fever (temperature of ≥37.5 °C or a history of fever in the past 48 h) to Hawassa Comprehensive Specialized Hospital, southern Ethiopia, from May 2018 through February 2019. Clinical and demographic data were gathered for consecutive participants, and malaria microscopy, HIV testing, and blood and urine cultures were performed regardless of clinical presentation. Additionally, stool analyses (culture and rotavirus/adenovirus RDT) and throat swab for group A Streptococcus (GAS) and urine Streptococcus pneumoniae were performed by RDTs for children with specific conditions. The antimicrobial susceptibility of bacterial isolates was determined using disc diffusion method.ResultsDuring the study period 433 children were recruited, median age 20 months (range, 2 months – 12 years) and 178 (41.1%) female. Malaria was diagnosed in 14 (3.2%) of 431 children, and 3 (0.7%) had HIV infection. Bacteraemia or fungaemia was detected in 27 (6.4%) of 421 blood cultures, with Staphylococcus aureus isolated in 16 (3.8%). Urinary tract infections (UTIs) were detected in 74 (18.4%) of 402, with Escherichia coli isolated in 37 (9.2%). Among 56 children whose stool specimens were tested, 14 (25%) were positive for rotavirus, 1 (1.8%) for Salmonella Paratyphi A, and 1 (1.8%) for Shigella dysenteriae. Among those with respiratory symptoms, a throat swab test for GAS and urine test for S. pneumoniae were positive in 28 (15.8%) of 177 and 31 (17.0%) of 182, respectively. No test was positive for a pathogen in 266 (61.4%) of 433 participants. Bacterial isolates were frequently resistant to ampicillin, trimethoprim-sulfamethoxazole, tetracycline, and amoxicillin and clavulanic acid.ConclusionOur results showed low proportions of malaria and bacteraemia among febrile children. In contrast, the frequent detection of UTI emphasize the need to support enhanced diagnostic capacity to ensure appropriate antimicrobial intervention.

Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial

BackgroundThe management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the ‘just-in-case’ use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections.Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)?MethodsWe designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion.DiscussionThis study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs.Trial registrationClinicaltrials.gov NCT04081051. Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019

Rickettsioses as Major Etiologies of Unrecognized Acute Febrile Illness, Sabah, East Malaysia.

Orientia tsutsugamushi, spotted fever group rickettsioses, and typhus group rickettsioses (TGR) are reemerging causes of acute febrile illness (AFI) in Southeast Asia. To further delineate extent, we enrolled patients >4 weeks of age with nonmalarial AFI in Sabah, Malaysia, during 2013-2015. We confirmed rickettsioses (past or acute, IgG titer >160) in 126/354 (36%) patients. We confirmed acute rickettsioses (paired 4-fold IgG titer rise to >160) in 38/145 (26%) patients: 23 O. tsutsugamushi, 9 spotted fever group, 4 TGR, 1 O. tsutsugamushi/spotted fever group, and 1 O. tsutsugamushi/TGR. PCR results were positive in 11/319 (3%) patients. Confirmed rickettsioses were more common in male adults; agricultural/plantation work and recent forest exposure were risk factors. Dizziness and acute hearing loss but not eschars were reported more often with acute rickettsioses. Only 2 patients were treated with doxycycline. Acute rickettsioses are common (>26%), underrecognized, and untreated etiologies of AFI in East Malaysia; empirical doxycycline treatment should be considered.

Aetiology of acute febrile illness in children in a high malaria transmission area in West Africa

ObjectivesAreas with declining malaria transmission in sub-Saharan Africa have recently witnessed important changes in the aetiology of childhood acute febrile illness (AFI). We describe the aetiology of AFI in a high malaria transmission area in rural Burkina Faso. MethodsIn a prospective hospital-based diagnostic study, children aged 3 months to 15 years with AFI were recruited and assessed using a systematic diagnostic protocol, including blood cultures, whole blood PCR on a selection of bacterial pathogens, malaria diagnostics and a multiplex PCR on nasopharyngeal swabs targeting 21 viral and 4 bacterial respiratory pathogens. ResultsA total of 589 children with AFI were enrolled from whom an infectious disease was considered in 575 cases. Acute respiratory tract infections, malaria and invasive bacterial infections (IBI) accounted for 179 (31.1%), 175 (30.4%) and 75 (13%) of AFI cases respectively; 16 (21.3%) of IBI cases also had malarial parasitaemia. A viral pathogen was demonstrated from the nasopharynx in 157 children (90.7%) with respiratory tract symptoms. Of all children with viral respiratory tract infections, 154 (92.4% received antibiotics, whereas no antibiotic was provided in 13 (17%) of IBI cases. ConclusionsViral respiratory infections are a common cause of childhood AFI in high malaria transmission areas, next to malaria and IBI. These findings highlight the importance of interventions to improve targeted treatment with antimicrobials. Most patients with viral infections received antibiotics unnecessarily, while a considerable number with IBI did not receive antibiotics.

The usefulness of Cell Population Data of leucocytes in accurately predicting the etiology of acute febrile illness

The usefulness of Cell Population Data of leucocytes in accurately predicting the etiology of acute febrile illness

Dengue viral infection in Indonesia: Epidemiology, diagnostic challenges, and mutations from an observational cohort study.

BackgroundDengue virus (DENV) infection is a major cause of acute febrile illness in Indonesia. Diagnostic inaccuracy may occur due to its varied and non-specific presentation. Characterization of DENV epidemiology, clinical presentation, and virology will facilitate appropriate clinical management and public health policy.Methodology/Principal findingsA multicenter observational cohort study was conducted in Indonesia to assess causes of acute fever requiring hospitalization. Clinical information and specimens were collected at enrollment, 14–28 days, and 3 months from 1,486 children and adults. Total of 468 (31.9%) cases of DENV infection were confirmed by reference laboratory assays. Of these, 414 (88.5%) were accurately diagnosed and 54 had been misdiagnosed as another infection by sites. One hundred initially suspected dengue cases were finally classified as ‘non-dengue’; other pathogens were identified in 58 of those cases. Mortality of DENV infection was low (0.6%). Prior DENV exposure was found in 92.3% of subjects >12 years. DENV circulated year-round in all cities, with higher incidence from January to March. DENV-3 and DENV-1 were the predominant serotypes. This study identified DENV-1 with TS119(C→T) substitution in the serotyping primer annealing site, leading to failure of serotype determination.Conclusions/SignificanceDENV is a common etiology of acute febrile illness requiring hospitalization in Indonesia. Diagnostic accuracy at clinical sites merits optimization since misdiagnosis of DENV infection and over-estimation of dengue can negatively impact management and outcomes. Mutation at the annealing site of the serotyping primer may confound diagnosis. Clinicians should consider following diagnostic algorithms that include DENV confirmatory testing. Policy-makers should prioritize development of laboratory capacity for diagnosis of DENV.

Aetiology of acute febrile illness: a multicentre study from the province of Kerala in southern India.

Acute febrile illness with varied aetiology but similar symptoms is common in tropical countries. This prospective, multicentre study was conducted in selected centres in the province of Kerala in India principally to analyse the aetiology of acute febrile illnesses in adult patients over the course of one year. Overall, 1324 patients were included in the study. The most common cause was dengue in 576 patients (43.5%). In 396 (29.9%), the exact aetiology could not be identified. Other causes, in order, were leptospirosis, enteric fever, malaria, respiratory tract infection, urinary tract infection and typhus. When such a wide variation with a significant number of 'indeterminate' cases exists, especially in such a small area and with limited resources, the onus is on public health authorities to draw up an 'easy-to-use algorithm' to tackle epidemics of febrile illness, particularly in the monsoon season.

Vector-Borne Disease is a Common Cause of Hospitalized Febrile Illness in India.

Acute febrile illness (AFI) is a major cause of morbidity and mortality in India and other resource-limited settings, yet systematic etiologic characterization of AFI has been limited. We prospectively enrolled adults (N = 970) and children (age 6 months to 12 years, N = 755) admitted with fever from the community to Sassoon General Hospital in Pune, India, from July 2013 to December 2015. We systematically obtained a standardized clinical history, basic laboratory testing, and microbiologic diagnostics on enrolled participants. Results from additional testing ordered by treating clinicians were also recorded. A microbiological diagnosis was found in 549 (32%) participants; 211 (12%) met standardized case definitions for pneumonia and meningitis without an identified organism; 559 (32%) were assigned a clinical diagnosis in the absence of a confirmed diagnosis; and 406 (24%) had no diagnosis. Vector-borne diseases were the most common cause of AFI in adults including dengue (N = 188, 19%), malaria (N = 74, 8%), chikungunya (N = 15, 2%), and concurrent mosquito-borne infections (N = 23, 2%) occurring most frequently in the 3 months after the monsoon. In children, pneumonia was the most common cause of AFI (N = 214, 28%) and death. Bacteremia was found in 68 (4%) participants. Central nervous system infections occurred in 58 (6%) adults and 64 (8%) children. Etiology of AFI in India is diverse, highly seasonal, and difficult to differentiate on clinical grounds alone. Diagnostic strategies adapted for season and age may reduce diagnostic uncertainty and identify causative organisms in treatable, fatal causes of AFI.