Background A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. Methods Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. Results us-RDT identified few additional P. falciparum –positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. Conclusion There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT.

BackgroundThe 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.MethodsPlasma 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).ResultsOf 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).ConclusionsMeasuring 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.

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

BackgroundAlthough the incidence of dengue across Africa is high, severe dengue is reported infrequently. We describe the clinical features and the outcome of dengue according to raceduring an outbreak in Dar es Salaam, Tanzania that occurred in both native and expatriate populations.MethodsAdults with confirmed dengue (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) were included between December 2013 and July 2014 in outpatient clinics. Seven-day outcome was assessed by a visit or a call. Association between black race and clinical presentation, including warning signs, was assessed by logistic regression adjusted for age, malaria coinfection, secondary dengue and duration of symptoms at inclusion. The independent association between demographic and comorbidities characteristics of the patients and severe dengue was evaluated by multivariate logistic regression that included potential confounders.ResultsAfter exclusion of 3 patients of mixed race, 431 patients with dengue (serotype 2, genotype Cosmopolitan) were included: 241 of black and 190 of non-black race. Black patients were younger (median age 30 versus 41 years; p < 0.001) and attended care after a slightly longer duration of symptoms (median of 2.9 versus 2.7 days; p = 0.01). Malaria coinfection was not significantly different between black (5%) and non-black (1.6%) patients (p = 0.06). The same proportion of patients in both group had secondary dengue (13 and 14%; p = 0.78). Among warning signs, only mucosal bleed was associated with race, black race being protective (adjusted OR 0.44; 95% CI 0.21–0.92). Overall, 20 patients (4.7%) presented with severe dengue. Non-black race (adjusted OR 3.9; 95% CI 1.3–12) and previously known diabetes (adjusted OR 43; 95% CI 5.2–361) were independently associated with severe dengue.ConclusionsAlthough all patients were infected with the same dengue virus genotype, black race was independently protective against a severe course of dengue, suggesting the presence of protective genetic or environmental host factors among people of African ancestry. The milder clinical presentation of dengue in black patients might partly explain why dengue outbreaks are under-reported in Africa and often mistaken for malaria. These results highlight the need to introduce point-of-care tests, beside the one for malaria, to detect outbreaks and orientate diagnosis.Trial registrationClinicaltrials.gov Identifier: NCT01947075, retrospectively registered on the 13 of September 2014.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3549-z) contains supplementary material, which is available to authorized users.

Characterization of the viruses found in the blood of febrile patients provides information pertinent to public health and diagnostic medicine. PCR and culture have historically played an important role in clinical microbiology; however, these methods require a targeted approach and may lack the capacity to identify novel or mixed viral infections. High-throughput sequencing can overcome these constraints. As the cost of running multiple samples continues to decrease, the implementation of high-throughput sequencing for diagnostic purposes is becoming more feasible. Here we present a comparative analysis of findings from an investigation of unexplained febrile illness using two strategies: unbiased high-throughput sequencing and VirCapSeq-VERT, a positive selection high-throughput sequencing system.