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Background Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics. Methods In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. Results A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. Conclusions Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. Trial registration NCT01766830 at ClinicalTrials.gov.
Test & Treat Project offers universal HIV testing and access to antiretroviral treatment in Northern Tanzania. The current cross-sectional study provides midterm results on HIV testing and counseling activities through community outreaches and facility-based services. A total 255,329 HIV tests were performed: 198,451 (77.7%) during testing campaigns in the villages, 12,592 (4.9%) during special events outreach and 44,286 (17.4%) in the health facilities. Females represented 53.8% (23,809) among those tested in the health facilities, while males were the majority in the community (54.4%, 114,835). Over one third of tests (n = 104,605, 41%) were performed among first-time testers. The overall HIV positivity rate was 1.2%, ranging from 0.7% in the community to 3.8% in the health facilities and decreased over time. Using a multivariable analysis, a positive test result was associated with age ≥ 50 years (PR 1.22, 95% CI 1.11 to 1.34), with female gender (PR 1.61, 95% CI 1.50 to 1.73), being tested in health facilities (PR 5.00, 95% CI 4.65 to 5.36) and for the first time (PR 1.86, 95% CI 1.73 to 2.00). The estimated proportion of PLHIV who knew their status of the project area increased by 28.6% (from 35.7% to 64.3%) and 11.1% (from 57.7% to 68.8%) in the project areas of Shinyanga and Simiyu regions respectively. Reaching the first UNAIDS 90 target by the end of this project seems possible. Future strategies should focus on improving PITC coverage, implementing more targeted testing modalities, together with current universal community-based approach.
Background In low-resource settings, inflammatory biomarkers can help identify patients with acute febrile illness who do not require antibiotics. Their use has not been studied in persistent fever (defined as fever lasting for ≥7 days at presentation). Methods C-reactive protein (CRP) and procalcitonin (PCT) levels were measured in stored serum samples of patients with persistent fever prospectively enrolled in Cambodia, the Democratic Republic of Congo, Nepal and Sudan. Diagnostic accuracy was assessed for identifying all bacterial infections, and the subcategory of severe infections judged to require immediate antibiotics. Results Among 1838 participants, CRP and PCT levels were determined in 1777 (96.7%) and 1711 (93.1%) samples respectively, while white blood cell (WBC) count was available for 1762 (95.9%). Areas under the receiver operating characteristic curves for bacterial infections were higher for CRP (0.669) and WBC count (0.651) as compared to PCT (0.600; P <0.001). Sensitivity for overall and severe bacterial infections was 76.3% (469/615) and 88.2% (194/220) for CRP >10 mg/L, 62.4% (380/609) and 76.8% (169/220) for PCT >0.1 µg/L, and 30.5% (184/604) and 43.7% (94/215) for WBC >11,000/µL, respectively. Initial CRP level was below 10 mg/L in 45% of the participants who received antibiotics at first presentation. Conclusions In patients with persistent fever; CRP and PCT showed higher sensitivity for bacterial infections than WBC count, applying commonly used cutoffs for normal values. A normal CRP value excluded the vast majority of severe infections and could therefore assist in deciding whether to withhold empiric antibiotics, after cautious clinical assessment.
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