Phylogeographic analysis of dengue virus serotype 1 and cosmopolitan serotype 2 in Africa.

OBJECTIVES: The origin and spread of dengue virus (DENV) circulating in Africa remain poorly characterized, with African sequences representing <1% of global sequence data. METHODS: Whole genome sequencing was performed on serum samples (n = 29) from an undifferentiated fever study in 2016 in the Democratic Republic of Congo (DRC), and from febrile travelers returning from Africa. The evolutionary history of the newly acquired African DENV-1 (n = 1) and cosmopolitan genotype DENV-2 (n = 18) genomes was reconstructed using a phylogeographic, time-scaled Bayesian analysis on a curated DENV panel including all known African sequences. RESULTS: A minimum of 10 and eight introductions could be identified into Africa for DENV-1 and cosmopolitan DENV-2, respectively, almost all originating from Asia. Three introductions were previously unknown. The currently circulating virus comprises mainly the recently introduced clades and one long-established African clade. Robust geographical clustering suggests limited spread of DENV after each introduction. Our data identified the DRC as the source of the 2018 Angolan DENV-2 epidemic, and similarly, the 2013 Angolan DENV-1 outbreak as the origin of our DRC study. CONCLUSION: Active genomic surveillance of DENV in Africa at the portals of entry might help early outbreak response and limit sero- and genotype spread and human disease burden.

Accuracy of C-reactive Protein and Procalcitonin for Diagnosing Bacterial Infections Among Subjects With Persistent Fever in the Tropics.

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 curve for bacterial infections were higher for CRP (0.669) and WBC count (0.651) as compared with PCT (0.600; P <.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 <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.

Potential usefulness of C-reactive protein and procalcitonin determination in patients admitted for neurological disorders in rural Democratic Republic of Congo.

In low-resource hospitals of central Africa, neurological disorders are frequent and etiologies very diverse. The difficulty to identify invasive bacterial infections in this setting results in major antibiotic overuse. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may help discriminate these conditions. We retrospectively determined the concentrations of CRP and PCT in the sera of patients consecutively enrolled from 2012 to 2015 in an etiological study on neurological disorders at the rural hospital of Mosango, Democratic Republic of Congo. Invasive bacterial infection had been diagnosed by the demonstration of a bacterial pathogen in cerebrospinal fluid or blood cultures or the presence of radiological pneumonia. Sera of 313 (89.2%) and 317 (90.3%) of the 351 enrolled participants were available for determination of CRP and PCT concentrations respectively. Areas under the receiver operating characteristic curves for invasive bacterial infection, diagnosed in 19 tested cases, were 94.3% for CRP and 91.7% for PCT. No single case had a normal CRP concentration (<10 mg/L). Our data, although limited, suggest that CRP or PCT concentrations may help discriminate invasive bacterial infections in patients with neurological disorders in tropical settings and that normal CRP values could assist in withholding antibiotics.