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A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania.

ABSTRACT: In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment.We conducted a year-long exploratory study of fever syndrome among patients ? 1 year if age, presenting to clinical settings with an axillary temperature of ?37.5°C and symptomatic onset of ?5 days. Blood and naso-pharyngeal/oral-pharyngeal (NP/OP) specimens were collected and analyzed, respectively, using AFI and respiratory TaqMan Array Cards (TAC) for multi-pathogen detection of 57 potential causative agents. Furthermore, we examined numerous epidemiologic correlates of febrile illness, and conducted demographic, clinical, and behavioral domain-specific multivariate regression to statistically establish associations with agent detection.From 15 September 2014-13 September 2015, 1007 febrile patients were enrolled, and 997 contributed an epidemiologic survey, including: 14% (n = 139) 1<5yrs, 19% (n = 186) 5-14yrs, and 67% (n = 672) ?15yrs. AFI TAC and respiratory TAC were performed on 842 whole blood specimens and 385 NP/OP specimens, respectively. Of the 57 agents surveyed, Plasmodium was the most common agent detected. AFI TAC detected nucleic acid for one or more of seven microbial agents in 49% of AFI blood samples, including: Plasmodium (47%), Leptospira (3%), Bartonella (1%), Salmonella enterica (1%), Coxiella burnetii (1%), Rickettsia (1%), and West Nile virus (1%). Respiratory TAC detected nucleic acid for 24 different microbial agents, including 12 viruses and 12 bacteria. The most common agents detected among our surveyed population were: Haemophilus influenzae (67%), Streptococcus pneumoniae (55%), Moraxella catarrhalis (39%), Staphylococcus aureus (37%), Pseudomonas aeruginosa (36%), Human Rhinovirus (25%), influenza A (24%), Klebsiella pneumoniae (14%), Enterovirus (15%) and group A Streptococcus (12%). Our epidemiologic investigation demonstrated both age and symptomatic presentation to be associated with a number of detected agents, including, but not limited to, influenza A and Plasmodium. Linear regression of fully-adjusted mean cycle threshold (Ct) values for Plasmodium also identified statistically significant lower mean Ct values for older children (20.8), patients presenting with severe fever (21.1) and headache (21.5), as well as patients admitted for in-patient care and treatment (22.4).This study is the first to employ two syndromic TaqMan Array Cards for the simultaneous survey of 57 different organisms to better characterize the type and prevalence of detected agents among febrile patients. Additionally, we provide an analysis of the association between adjusted mean Ct values for Plasmodium and key clinical and demographic variables, which may further inform clinical decision-making based upon intensity of infection, as observed across endemic settings of sub-Saharan Africa.

SUBMITTER: Hercik C

PROVIDER: S-EPMC5747442 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania.

Hercik Christine C Cosmas Leonard L Mogeni Ondari D OD Wamola Newton N Kohi Wanze W Omballa Victor V Ochieng Melvin M Lidechi Shirley S Bonventure Juma J Ochieng Caroline C Onyango Clayton C Fields Barry S BS Mfinanga Sayoki S Montgomery Joel M JM

PloS one 20171229 12

<h4>Introduction</h4>In low-resource settings, empiric case management of febrile illness is routine as a result of limited access to laboratory diagnostics. The use of comprehensive fever syndromic surveillance, with enhanced clinical microbiology, advanced diagnostics and more robust epidemiologic investigation, could enable healthcare providers to offer a differential diagnosis of fever syndrome and more appropriate care and treatment.<h4>Methods</h4>We conducted a year-long exploratory study ...[more]

PMID: 29287070

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Project description:BackgroundFebrile diseases in Sub-Saharan Africa cause acute and chronic illness. Co-infections are common and these diseases have a complex etiology that includes zoonoses. For the implementation of appropriate treatment and control strategies, determinants of lay treatment-seeking behavior by the affected communities need to be understood. The objective of this study was to explore, using the socio-ecological model, the determinants of treatment-seeking actions among self-identified febrile illness cases in the Kilombero District of Tanzania.MethodsThirty-nine in-depth interviews were conducted with 28 men and 11 women in three villages in Kilombero district. These villages were purposively selected due to malaria endemicity in the area, animal husbandry practices, and proximity to livestock-wildlife interaction, all risk factors for contracting febrile zoonotic infections. Thematic analysis was conducted on the interviews to identify the key determinants of treatment-seeking actions.ResultsStudy participants attributed febrile illnesses to malaria, typhoid and urinary tract infections. Treatment-seeking behavior was an iterative process, influenced by individual, socio-cultural, ecological and policy factors. Age, expendable income, previous history with a febrile illness, perceptions on disease severity, seasonal livelihood activities and access to timely healthcare were some of the determinants. Self-treatment with pharmaceutical drugs and herbs was usually the initial course of action. Formal healthcare was sought only when self-treatment failed and traditional healers were consulted after the perceived failure of conventional treatment. Delays in seeking appropriate health care and the consultation of medically unqualified individuals was very common.ConclusionThe results imply that treatment-seeking behavior is shaped by multiple factors across all levels of the socio-ecological model. Public policy efforts need to focus on facilitating prompt health care seeking through community education on the complicated etiology of febrile illnesses. Improved access to timely treatment and better differential diagnostics by health professionals are essential to ensure correct and appropriate treatment and to reduce reliance of patients on unqualified persons.

Project description:ObjectiveTo compare rapid diagnostic tests (RDTs) for malaria with routine microscopy in guiding treatment decisions for febrile patients.DesignRandomised trial.SettingOutpatient departments in northeast Tanzania at varying levels of malaria transmission.Participants2416 patients for whom a malaria test was requested.InterventionStaff received training on rapid diagnostic tests; patients sent for malaria tests were randomised to rapid diagnostic test or routine microscopyMain outcome measureProportion of patients with a negative test prescribed an antimalarial drug.ResultsOf 7589 outpatient consultations, 2425 (32%) had a malaria test requested. Of 1204 patients randomised to microscopy, 1030 (86%) tested negative for malaria; 523 (51%) of these were treated with an antimalarial drug. Of 1193 patients randomised to rapid diagnostic test, 1005 (84%) tested negative; 540 (54%) of these were treated for malaria (odds ratio 1.13, 95% confidence interval 0.95 to 1.34; P=0.18). Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides (P=0.003). Patients with a negative test by any method were more likely to be prescribed an antibiotic (odds ratio 6.42, 4.72 to 8.75; P<0.001). More than 90% of prescriptions for antimalarial drugs in low-moderate transmission settings were for patients for whom a test requested by a clinician was negative for malaria.ConclusionsAlthough many cases of malaria are missed outside the formal sector, within it malaria is massively over-diagnosed. This threatens the sustainability of deployment of artemisinin combination treatment, and treatable bacterial diseases are likely to be missed. Use of rapid diagnostic tests, with basic training for clinical staff, did not in itself lead to any reduction in over-treatment for malaria. Interventions to improve clinicians' management of febrile illness are essential but will not be easy.Trial registrationClinical trials NCT00146796 [ClinicalTrials.gov].

Project description:Identifying etiologies of acute febrile illnesses (AFI) is challenging due to non-specific presentation and limited availability of diagnostics. Prospective AFI studies provide a methodology to describe the syndrome by age and etiology, findings that can be used to develop case definitions and multiplexed diagnostics to optimize management. We conducted a 3-year prospective AFI study in Puerto Rico. Patients with fever ≤7 days were offered enrollment, and clinical data and specimens were collected at enrollment and upon discharge or follow-up. Blood and oro-nasopharyngeal specimens were tested by RT-PCR and immunodiagnostic methods for infection with dengue viruses (DENV) 1-4, chikungunya virus (CHIKV), influenza A and B viruses (FLU A/B), 12 other respiratory viruses (ORV), enterovirus, Leptospira spp., and Burkholderia pseudomallei. Clinical presentation and laboratory findings of participants infected with DENV were compared to those infected with CHIKV, FLU A/B, and ORV. Clinical predictors of laboratory-positive dengue compared to all other AFI etiologies were determined by age and day post-illness onset (DPO) at presentation. Of 8,996 participants enrolled from May 7, 2012 through May 6, 2015, more than half (54.8%, 4,930) had a pathogen detected. Pathogens most frequently detected were CHIKV (1,635, 18.2%), FLU A/B (1,074, 11.9%), DENV 1-4 (970, 10.8%), and ORV (904, 10.3%). Participants with DENV infection presented later and a higher proportion were hospitalized than those with other diagnoses (46.7% versus 27.3% with ORV, 18.8% with FLU A/B, and 11.2% with CHIKV). Predictors of dengue in participants presenting <3 DPO included leukopenia, thrombocytopenia, headache, eye pain, nausea, and dizziness, while negative predictors were irritability and rhinorrhea. Predictors of dengue in participants presenting 3-5 DPO were leukopenia, thrombocytopenia, facial/neck erythema, nausea, eye pain, signs of poor circulation, and diarrhea; presence of rhinorrhea, cough, and red conjunctiva predicted non-dengue AFI. By enrolling febrile patients at clinical presentation, we identified unbiased predictors of laboratory-positive dengue as compared to other common causes of AFI. These findings can be used to assist in early identification of dengue patients, as well as direct anticipatory guidance and timely initiation of correct clinical management.

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A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania.

Publications

A diagnostic and epidemiologic investigation of acute febrile illness (AFI) in Kilombero, Tanzania.

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