Febrile Adults Research Articles

Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: a genomic epidemiological study

Enteric fever is a serious public health concern. The causative agents, Salmonella enterica serovars Typhi and Paratyphi A, frequently have antimicrobial resistance (AMR), leading to limited treatment options and poorer clinical outcomes. We investigated the genomic epidemiology, resistance mechanisms, and transmission dynamics of these pathogens at three urban sites in Africa and Asia. S Typhi and SParatyphi Abacteria isolated from blood cultures of febrile children and adults at study sites in Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) during STRATAA surveillance were sequenced. Isolates were charactered in terms of their serotypes, genotypes (according to GenoTyphi and Paratype), molecular determinants of AMR, and population structure. We used phylogenomic analyses incorporating globally representative genomic data from previously published surveillance studies and ancestral state reconstruction to differentiatelocally circulating from imported pathogen AMR variants. Clusters of sequences without any single-nucleotide variants in their core genome were identified and used to explore spatiotemporal patterns and transmission dynamics. We sequenced 731genomes from isolates obtained during surveillance across the three sites between Oct 1, 2016, and Aug 31, 2019 (24 months in Dhaka and Kathmandu and 34months in Blantyre). SParatyphi Awas present in Dhaka and Kathmandu but not Blantyre. STyphi genotype 4.3.1 (H58) was common in all sites, but with different dominant variants (4.3.1.1.EA1 in Blantyre, 4.3.1.1in Dhaka, and 4.3.1.2in Kathmandu). Multidrug resistance (ie,resistance to chloramphenicol, co-trimoxazole, and ampicillin) was common in Blantyre (138 [98%] of 141cases) and Dhaka (143 [32%] of 452), but absent from Kathmandu. Quinolone-resistance mutations were common in Dhaka (451 [>99%] of 452) and Kathmandu (123 [89%] of 138), but not in Blantyre (three [2%] of 141). Azithromycin-resistance mutations in acrB were rare, appearing only in Dhaka (five [1%] of 452). Phylogenetic analyses showed that most cases derived from pre-existing, locally established pathogen variants; 702(98%) of 713 drug-resistant infections resulted from local circulation of AMR variants, not imported variants or recent de novo emergence; and pathogen variants circulated across age groups. 479(66%) of 731cases clustered with others that were indistinguishable by point mutations; individual clusters included multiple age groups and persisted for up to 2·3years, and AMR determinants were invariant within clusters. Enteric fever was associated with locally established pathogen variants that circulate across age groups. AMR infections resulted from local transmission of resistant strains. These results form a baseline against which to monitor the impacts of control measures. Wellcome Trust, Bill & Melinda Gates Foundation, EU Horizon 2020, and UK National Institute for Health and Care Research.

Magnitude of malaria and associated factors among febrile adults in Siraro District Public Health facilities, West Arsi Zone, Oromia, Ethiopia 2022: a facility-based cross-sectional study

BackgroundDespite significant efforts made to control malaria in Ethiopia, the disease remains one of the top public health problems in the country. Baseline malaria prevalence and associated factor at high malaria area is important to guide malaria control interventions, there was paucity of information regarding the study area. Therefore, the aim of this study was to determine prevalence of malaria and associated factors among febrile adults in Siraro district health facilities, West Arsi Zone, Oromia, Ethiopia.MethodsInstitution-based cross-sectional study was conducted among 317 febrile adult patients at Siraro district health facilities. Structured pre-tested questionnaires were used to collect data. Epi-data version 3.1 and SPSS version 23 were used for data entry and analysis respectively. In order to identify factors associated with malaria infection bivariable and multivariable binary logistic regression analysis was employed, The Adjusted Odds Ratio (AOR) with a 95% confidence interval (CI) and p-value of < 0.05 was computed to show the strength of the association.ResultsThe overall prevalence of malaria at the study area was 130 (41.0%) [(95% CI 35.3–46.7)]. Occupation (being farmer) [(AOR = 6.05; 95% CI 1.38, 26.49)], having poor knowledge on malaria transmission [(AOR = 2.95 95%; CI 1.48–5.88)], house with wood wall [(AOR = 2.71; 95% CI 1.34–5.49)], and number of windows (≥ 3) in the house [(AOR = 6.82; 95% CI 1.05, 44.40)] were identified to be significantly associated with magnitude of malaria in the study area.ConclusionThe prevalence of malaria at the study area was high as compared with the national wide figures. Being farmer, having poor knowledge on malaria transmission, and housing condition (house with wood wall and houses with three and above windows) were found to be significantly associated with malaria infection in the study area. Therefore, there has to be an emphasis on addressing the factors by providing sustainable health education for the communities to improve their housing condition and knowledge of community on the way of malaria prevention.

Antibacterial Utilization for Febrile Illnesses and Laboratory-Confirmed Bloodstream Infections in Northern Tanzania.

We describe antibacterial use in light of microbiology data and treatment guidelines for common febrile syndromes in Moshi, Tanzania. We compared data from 2 hospital-based prospective cohort studies, cohort 1 (2011-2014) and cohort 2 (2016-2019), that enrolled febrile children and adults. A study team member administered a standardized questionnaire, performed a physical examination, and collected blood cultures. Participants with bloodstream infection (BSI) were categorized as receiving effective or ineffective therapy based upon antimicrobial susceptibility interpretations. Antibacterials prescribed for treatment of pneumonia, urinary tract infection (UTI), or presumed sepsis were compared with World Health Organization and Tanzania Standard Treatment Guidelines. We used descriptive statistics and logistic regression to describe antibacterial use. Among participants, 430 of 1043 (41.2%) and 501 of 1132 (44.3%) reported antibacterial use prior to admission in cohorts 1 and 2, respectively. During admission, 930 of 1043 (89.2%) received antibacterials in cohort 1 and 1060 of 1132 (93.6%) in cohort 2. Inpatient use of ceftriaxone, metronidazole, and ampicillin increased between cohorts (P ≤ .002 for each). BSI was detected in 38 (3.6%) participants in cohort 1 and 47 (4.2%) in cohort 2. Of 85 participants with BSI, 81 (95.3%) had complete data and 52 (64.2%) were prescribed effective antibacterials. Guideline-consistent therapy in cohort 1 and cohort 2 was as follows: pneumonia, 87.4% and 56.8%; UTI, 87.6% and 69.0%; sepsis, 84.4% and 61.2% (P ≤ .001 for each). Receipt of antibacterials for febrile illness was common. While guideline-consistent prescribing increased over time, more than one-third of participants with BSI received ineffective antibacterials.

Host test based on tumor necrosis factor-related apoptosis-inducing ligand, interferon gamma-induced protein-10 and C-reactive protein for differentiating bacterial and viral respiratory tract infections in adults: diagnostic accuracy study

ObjectivesTo assess the performance of a test (called BV), integrating the blood levels of three immune proteins into a score, to differentiate bacterial from viral infection among adults with suspected lower respiratory tract infection (LRTI). MethodsProspective diagnostic accuracy study, enrolling febrile adults >18 years with LRTI signs or symptoms for less than 7 days presenting to several hospitals' emergency departments in Israel. The main exclusion criterion was immunodeficiency. Reference standard diagnosis (bacterial/viral/indeterminate) was based on three experts independently reviewing comprehensive patient data including follow-up data. BV generated three results: viral infection or other nonbacterial condition (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65) and bacterial infection including co-infection (65 < score ≤ 100). BV performance was assessed against the reference standard with indeterminate reference standard and equivocal BV cases removed. ResultsOf 490 enrolled patients, 415 met eligibility criteria (median age 56 years, interquartile range 35). The reference standard classified 104 patients as bacterial, 210 as viral and 101 as indeterminate. BV was equivocal in 9.6% (30/314). Excluding indeterminate reference standard diagnoses and equivocal BV results, BV's sensitivity for bacterial infection was 98.1% (101/103; 95% confidence interval 95.4–100), specificity 88.4% (160/181; 83.7–93.1) and negative predictive value 98.8% (160/162; 97.1–100). DiscussionBV exhibited high diagnostic performance for febrile adults with suspected LRTI among patients with reference standard diagnoses of bacterial or viral LRTI.

Fever therapy in febrile adults: systematic review with meta-analyses and trial sequential analyses

ObjectiveTo investigate the effects of fever therapy compared with no fever therapy in a wide population of febrile adults.DesignSystematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data...

Clinical sign and biomarker-based algorithm to identify bacterial pneumonia among outpatients with lower respiratory tract infection in Tanzania

BackgroundInappropriate antibiotics use in lower respiratory tract infections (LRTI) is a major contributor to resistance. We aimed to design an algorithm based on clinical signs and host biomarkers to identify bacterial community-acquired pneumonia (CAP) among patients with LRTI.MethodsParticipants with LRTI were selected in a prospective cohort of febrile (≥ 38 °C) adults presenting to outpatient clinics in Dar es Salaam. Participants underwent chest X-ray, multiplex PCR for respiratory pathogens, and measurements of 13 biomarkers. We evaluated the predictive accuracy of clinical signs and biomarkers using logistic regression and classification and regression tree analysis.ResultsOf 110 patients with LRTI, 17 had bacterial CAP. Procalcitonin (PCT), interleukin-6 (IL-6) and soluble triggering receptor expressed by myeloid cells-1 (sTREM-1) showed an excellent predictive accuracy to identify bacterial CAP (AUROC 0.88, 95%CI 0.78–0.98; 0.84, 0.72–0.99; 0.83, 0.74–0.92, respectively). Combining respiratory rate with PCT or IL-6 significantly improved the model compared to respiratory rate alone (p = 0.006, p = 0.033, respectively). An algorithm with respiratory rate (≥ 32/min) and PCT (≥ 0.25 μg/L) had 94% sensitivity and 82% specificity.ConclusionsPCT, IL-6 and sTREM-1 had an excellent predictive accuracy in differentiating bacterial CAP from other LRTIs. An algorithm combining respiratory rate and PCT displayed even better performance in this sub-Sahara African setting.

Trends in fever case management for febrile inpatients in a low malaria incidence setting of Tanzania.

In 2010, WHO published guidelines emphasising parasitological confirmation of malaria before treatment. We present data on changes in fever case management in a low malaria transmission setting of northern Tanzania after 2010. We compared diagnoses, treatments and outcomes from two hospital-based prospective cohort studies, Cohort 1 (2011-2014) and Cohort 2 (2016-2019), that enrolled febrile children and adults. All participants underwent quality-assured malaria blood smear-microscopy. Participants who were malaria smear-microscopy negative but received a diagnosis of malaria or received an antimalarial were categorised as malaria over-diagnosis and over-treatment, respectively. We analysed data from 2098 participants. The median (IQR) age was 27 (3-43) years and 1047 (50.0%) were female. Malaria was detected in 23 (2.3%) participants in Cohort 1 and 42 (3.8%) in Cohort 2 (p=0.059). Malaria over-diagnosis occurred in 334 (35.0%) participants in Cohort 1 and 190 (17.7%) in Cohort 2 (p<0.001). Malaria over-treatment occurred in 528 (55.1%) participants in Cohort 1 and 196 (18.3%) in Cohort 2 (p<0.001). There were 30 (3.1%) deaths in Cohort 1 and 60 (5.4%) in Cohort 2 (p=0.007). All deaths occurred among smear-negative participants. We observed a substantial decline in malaria over-diagnosis and over-treatment among febrile inpatients in northern Tanzania between two time periods after 2010. Despite changes, some smear-negative participants were still diagnosed and treated for malaria. Our results highlight the need for continued monitoring of fever case management across different malaria epidemiological settings in sub-Saharan Africa.

Co-circulation of dengue virus 1 and 2 several years after single serotype detection in Cross River State, Nigeria

Dengue is a mosquito-borne viral disease which affects over 390 million people annually around the world. High rates of unrecognized dengue infections have been observed in Nigeria through serological assays. This informed molecular investigation in some areas where previous reports were made. We screened individuals in a rural community in Nigeria for circulating dengue virus serotypes. Using a community based participatory approach, convenient sampling was employed to collect plasma from 17 febrile adults in Abia and Bendeghe wards within Etung Local Government Area of Cross River State, Nigeria. The area is forested with heavy mosquito presence. RNA extraction was carried out with viral RNA mini kit (QIAamp, QIAGEN GmbH, Hilden, Germany). Molecular detection of DENV serotypes was by Polymerase Chain Reaction using characterized DENV isolates as standard controls. Out of 17 participants, 3 (17.6%) tested positive to DENV. Two were infected with DENV-2 and one with DENV-1. All three were men in Abia ward while no person tested positive to the virus in Bendeghe. This present study highlights co-circulation of DENV-1 which demonstrates a change in the epidemiology of dengue in the area. It reinforces the need for public health professionals in the area to be vigilant, and signals the possibility of an increase in Dengue Hemorrhagic Fever. Sustained entomological surveillance is recommended.&#x0D; Keywords: Dengue, Cross River State, Molecular detection, Nigeria, Rain forest

Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study

ObjectivesExploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania. MethodsWe recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria. ResultsOf 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm3 and 25/52 (48%) if CD4 >200 cells/mm3, p 0.02). ConclusionsViral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.

A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar.

Data on causes of community-onset bloodstream infection in Myanmar are scarce. We aimed to identify etiological agents of bloodstream infections and patterns of antimicrobial resistance among febrile adolescents and adults attending Yangon General Hospital (YGH), Yangon, Myanmar. We recruited patients ≥12 years old with fever ≥38°C who attended YGH from 5 October 2015 through 4 October 2016. A standardized clinical history and physical examination was performed. Provisional diagnoses and vital status at discharge was recorded. Blood was collected for culture, bloodstream isolates were identified, and antimicrobial susceptibility testing was performed. Using whole-genome sequencing, we identified antimicrobial resistance mechanisms of Enterobacteriaceae and sequence types of Enterobacteriaceae and Streptococcus agalactiae. Among 947 participants, 90 (9.5%) had bloodstream infections (BSI) of which 82 (91.1%) were of community-onset. Of 91 pathogens isolated from 90 positive blood cultures, we identified 43 (47.3%) Salmonella enterica including 33 (76.7%) serovar Typhi and 10 (23.3%) serovar Paratyphi A; 20 (22.0%) Escherichia coli; 7 (7.7%) Klebsiella pneumoniae; 6 (6.6%), Staphylococcus aureus; 4 (4.4%) yeasts; and 1 (1.1%) each of Burkholderia pseudomallei and Streptococcus agalactiae. Of 70 Enterobacteriaceae, 62 (88.6%) were fluoroquinolone-resistant. Among 27 E. coli and K. pneumoniae, 18 (66.6%) were extended-spectrum beta-lactamase (ESBL)-producers, and 1 (3.7%) each were AmpC beta-lactamase- and carbapenemase-producers. Fluoroquinolone resistance was associated predominantly with mutations in the quinolone resistance-determining region. blaCTX-M-15 expression was common among ESBL-producers. Methicillin-resistant S. aureus was not detected. Fluoroquinolone-resistant, but not multiple drug-resistant, typhoidal S. enterica was the leading cause of community-onset BSI at a tertiary hospital in Yangon, Myanmar. Fluoroquinolone and extended-spectrum cephalosporin resistance was common among other Enterobactericeae. Our findings inform empiric management of severe febrile illness in Yangon and indicate that measures to prevent and control enteric fever are warranted. We suggest ongoing monitoring and efforts to mitigate antimicrobial resistance among community-onset pathogens.

Prognostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM-1)-based Algorithms in Febrile Adults Presenting to Tanzanian Outpatient Clinics.

The inability to identify individuals with acute fever at risk of death is a barrier to effective triage and management of severe infections, especially in low-resource settings. Since endothelial and immune activation contribute to the pathogenesis of various distinct life-threatening infections, we hypothesized that measuring mediators of these pathways at clinical presentation would identify febrile adults at risk of death. Plasma concentrations of markers of endothelial (angiopoetin-1/2, soluble fms-like tyrosine kinase-1, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1) and immune (soluble triggering receptor expressed on myeloid cells [sTREM-1], interleukin-6, interleukin-8, chitinase-3-like protein-1, soluble tumor necrosis factor receptor-1, procalcitonin [PCT], C-reactive protein [CRP]) activation pathways were determined in consecutive adults with acute fever (≥38°C) at presentation to outpatient clinics in Dar es Salaam, Tanzania. We evaluated the accuracy of these mediators in predicting all-cause mortality and examined whether markers could improve the prognostic accuracy of clinical scoring systems, including the quick sequential organ failure assessment (qSOFA) and Glasgow coma scale (GCS). Of 507 febrile adults, 32 died (6.3%) within 28 days of presentation. We found that sTREM-1 was the best prognostic marker for 28-day mortality (area under the receiver operating characteristic [AUROC] 0.87, 95% confidence interval [CI] 0.81-0.92) and was significantly better than CRP (P < .0001) and PCT (P = .0001). The prognostic accuracy of qSOFA and the GCS were significantly enhanced when sTREM-1 was added (0.80 [95% CI 0.76-0.83] to 0.91 [95% CI 0.88-0.94; P < .05] and 0.72 [95% CI 0.63-0.80] to 0.94 [95% CI 0.91-0.97; P < .05], respectively). Measuring sTREM-1 at clinical presentation can identify febrile individuals at risk of all-cause febrile mortality. Adding severity markers such as sTREM-1 to simple clinical scores could improve the recognition and triage of patients with life-threatening infections in resource-limited settings.

Complete Genome Sequences of Dengue Virus Type 2 Strains from Kilifi, Kenya.

Dengue infection remains poorly characterized in Africa and little is known regarding its associated viral genetic diversity. Here, we report dengue virus type 2 (DENV-2) sequence data from 10 clinical samples, including 5 complete genome sequences of the cosmopolitan genotype, obtained from febrile adults seeking outpatient care in coastal Kenya.

Detection of dicistroviruses RNA in blood of febrile Tanzanian children

ABSTRACT Fever is the leading cause of paediatric outpatient consultations in Sub-Saharan Africa. Although most are suspected to be of viral origin, a putative causative pathogen is not identified in over a quarter of these febrile episodes. Using a de novo assembly sequencing approach, we report the detection (15.4%) of dicistroviruses (DicV) RNA in sera collected from 692 febrile Tanzanian children. In contrast, DicV RNA was only detected in 1/77 (1.3%) plasma samples from febrile Tanzanian adults, suggesting that children could represent the primary susceptible population. Estimated viral load by specific quantitative real-time RT–PCR assay ranged from < 1.32E3 to 1.44E7 viral RNA copies/mL serum. Three DicV full-length genomes were obtained, and a phylogenetic analyse on the capsid region showed the presence of two clusters representing tentative novel genus. Although DicV-positive cases were detected throughout the year, a significantly higher positivity rate was observed during the rainy season. This study reveals that novel DicV RNA is frequently detected in the blood of Tanzanian children, paving the way for further investigations to determine if DicV possibly represent a new agent in humans.

Prognostic value of quickSOFA as a predictor of 28-day mortality among febrile adult patients presenting to emergency departments in Dar es Salaam, Tanzania.

BackgroundQuick Sequential Organ Failure Assessment (qSOFA) is a three-item clinical instrument for bedside identification of sepsis patients at risk of poor outcome. qSOFA could be a valuable triage tool in emergency departments of low-income countries, yet its performance in resource-limited settings remains unknown. The prognostic accuracy of qSOFA for 28-day all-cause mortality in febrile adults treated at the EDs in a low-income country was evaluated.MethodsRetrospective analysis of a prospective cohort study of consecutive patients (≥18 years) with fever (tympanic temperature ≥38°C and fever ≤7 days) who presented between July 2013 and May 2014 at four emergency departments in Dar es Salaam, Tanzania. Medical history, clinical examination, laboratory and microbiological data were collected to document the cause of fever. Variables for the previous and new sepsis criteria were collected at inclusion and qSOFA, SOFA and SIRS were measured at inclusion. Patients were followed up by phone at day 28. The performance (sensitivity, specificity and area under the receiver operating curve [AUROC]) of qSOFA (score ≥2), SOFA (increase of ≥2 points) and SIRS (≥2 criteria) as predictors of 28-day all-cause mortality was evaluated.ResultsAmong the 519 patients (median age: 30 years) included in the analysis, 47% were female and 25% were HIV positive. Overall, 85% had a microbiologically and/or clinically documented infection and 15% a fever of unknown origin. The most common site and causes of infections were the respiratory tract (43%), dengue (26%), malaria (6%) and typhoid fever (5%). Twenty-eight-day all-cause mortality was 6%: 3% for patients with a qSOFA <2 and 24% for those with a score ≥2 (absolute difference, 21%; 95% CI 12%-31%). The prognostic accuracy of qSOFA (AUROC 0.80, 95% CI 0.73–0.87) for 28-day mortality was similar to SOFA (AUROC 0.79, 0.71–0.87; p = 0.1) and better than SIRS (AUROC 0.61, 0.52–0.71; p<0.001).ConclusionsAmong patients with fever at emergency departments in Tanzania, qSOFA had a prognostic accuracy for 28-day mortality comparable to SOFA and superior to SIRS. These results support the use of qSOFA as a triage tool to identify patients with sepsis and at risk of poor outcome in resource-limited countries.Trial registrationClinicaltrials.gov Identifier: NCT01947075

Prognostic Value of quickSOFA as a Predictor of 28-day Mortality Among Febrile Adult Patients Presenting to Emergency Departments in Dar es Salaam, Tanzania

Prognostic Value of quickSOFA as a Predictor of 28-day Mortality Among Febrile Adult Patients Presenting to Emergency Departments in Dar es Salaam, Tanzania

Antibiotic Utilization and the Role of Suspected and Diagnosed Mosquito-borne Illness Among Adults and Children With Acute Febrile Illness in Pune, India.

Antibiotic resistance mechanisms originating in low- and middle- income countries are among the most common worldwide. Reducing unnecessary antibiotic use in India, the world's largest antibiotic consumer, is crucial to control antimicrobial resistance globally. Limited data describing factors influencing Indian clinicians to start or stop antibiotics are available. Febrile adults and children admitted to a public tertiary care hospital in Pune, India, were enrolled. Antibiotic usage and clinical history were recorded. Immunoassays for mosquito-borne disease and bacterial cultures were performed by protocol and clinician-directed testing. Clinical factors were assessed for association with empiric antibiotic initiation and discontinuation by day 5 using multivariable logistic regression and propensity score-matched Cox proportional hazard models. Among 1486 participants, 683 (82%) adults and 614 (94%) children received empiric antibiotics. Participants suspected of having mosquito-borne disease were less likely to receive empiric antibiotics (adjusted odds ratio [AOR], 0.5; 95% confidence interval [CI], .4-.8). Empiric antibiotics were discontinued in 450 (35%) participants by day 5. Dengue or malaria testing performed before day 4 was positive in 162 (12%) participants, and was associated with antibiotic discontinuation (AOR, 1.7; 95% CI, 1.2-2.4). In a propensity score-matched model accounting for admission suspicion of mosquito-borne disease, positive dengue or malaria tests increased hazard of antibiotic discontinuation (hazard ratio, 1.6; 95% CI, 1.2-2.0). Most patients with acute febrile illness in an Indian public hospital setting receive empiric antibiotics. Mosquito-borne disease identification is associated with reduced empiric antibiotic use and faster antibiotic discontinuation.

Dengue and Chikungunya Virus Infections among Young Febrile Adults Evaluated for Acute HIV-1 Infection in Coastal Kenya.

BackgroundFever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya.MethodsWe tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18–35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014–2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection.Results489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4–11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3–6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0–13.1) or research health facility (AOR = 25.6, 95% CI: 8.9–73.2) instead of a public health facility.ConclusionA high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya.

Utility of procalcitonin as a diagnostic biomarker for bacterial infections and its comparison with C reactive protein and total leucocyte count

Background: Distinguishing bacterial fever from other fevers is important for early treatment and the judicious use of antibiotics. This study aimed to evaluate the levels of procalcitonin (PCT) in febrile adults and compare it with C reactive protein (CRP) and total leukocyte count (TLC). Methods: 70 patients were classified clinically according to severity of infection into mild (Group A 30), moderate (Group B 23) and severe (Group C 17). 30 healthy controls were taken (Group D). After a detailed clinical history, their blood collected aseptically was sent for complete hemogram, culture, biochemistry, PCT and CRP. PCT was measured by immunochromatographic method (Result Range: 2, >10ng/ml). CRP was measured by immunoturbidometry. Chisquare, ANOVA, Pearson’s Correlation were used. Results: PCT was significantly elevated with higher degrees of infection (p value < 0.001). Sensitivity and specificity of PCT in Group 2 and 3 were both 100%. Group 1 had no rise in PCT proving that it is neither specific nor sensitive for mild infection. Mean CRP was significantly increased (p value <0.001) with severity of infection; sensitivity and specificity being 97.14% and 80%. TLC increased significantly (p value <0.001) with the severity of infection. However, it did not rise above the cut off, for mild infection. Conclusions: PCT was highly sensitive and specific for moderate to severe infection and also determined prognosis. It could not identify mild local infection. CRP was sensitive for any grade of infection but not specific for bacterial fever. TLC was specific for moderate to severe infection though less sensitive.

Bloodstream Infections and Frequency of Pretreatment Associated With Age and Hospitalization Status in Sub-Saharan Africa.

The clinical diagnosis of bacterial bloodstream infections (BSIs) in sub-Saharan Africa is routinely confused with malaria due to overlapping symptoms. The Typhoid Surveillance in Africa Program (TSAP) recruited febrile inpatients and outpatients of all ages using identical study procedures and enrollment criteria, thus providing an opportunity to assess disease etiology and pretreatment patterns among children and adults. Inpatients and outpatients of all ages with tympanic or axillary temperatures of ≥38.0 or ≥37.5°C, respectively, and inpatients only reporting fever within the previous 72 hours were eligible for recruitment. All recruited patients had one blood sample drawn and cultured for microorganisms. Data from 11 TSAP surveillance sites in nine different countries were used in the analysis. Bivariate analysis was used to compare frequencies of pretreatment and BSIs in febrile children (<15 years old) and adults (≥15 years old) in each country. Pooled Cochran Mantel-Haenszel odds ratios (ORs) were calculated for overall trends. There was no significant difference in the odds of a culture-proven BSI between children and adults among inpatients or outpatients. Among both inpatients and outpatients, children had significantly higher odds of having a contaminated blood culture compared with adults. Using country-pooled data, child outpatients had 66% higher odds of having Salmonella Typhi in their bloodstream than adults (OR, 1.66; 95% confidence interval [CI], 1.01-2.73). Overall, inpatient children had 59% higher odds of pretreatment with analgesics in comparison to inpatient adults (OR, 1.59; 95% CI, 1.28-1.97). The proportion of patients with culture-proven BSIs in children compared with adults was similar across the TSAP study population; however, outpatient children were more likely to have Salmonella Typhi infections than outpatient adults. This finding points to the importance of including outpatient facilities in surveillance efforts, particularly for the surveillance of typhoid fever. Strategies to reduce contamination among pediatric blood cultures are needed across the continent to prevent the misdiagnosis of BSI cases in children.

Acetaminophen: No Help (or Harm) for Critically Ill Patients with Fever

Is treatment of fever with acetaminophen a good thing for critically ill patients? Is cooling patients to reduce oxygen consumption and physiologic stress beneficial, or is fever a protective response to infection? To address these questions, investigators randomized 690 febrile adults in intensive …