High SARS-CoV-2 incidence and asymptomatic fraction during Delta and Omicron BA.1 waves in The Gambia.

Little is known about SARS-CoV-2 infection risk in African countries with high levels of infection-driven immunity and low vaccine coverage. We conducted a prospective cohort study of 349 participants from 52 households in The Gambia between March 2021 and June 2022, with routine weekly SARS-CoV-2 RT-PCR and 6-monthly SARS-CoV-2 serology. Attack rates of 45% and 57% were seen during Delta and Omicron BA.1 waves respectively. Eighty-four percent of RT-PCR-positive infections were asymptomatic. Children under 5-years had a lower incidence of infection than 18-49-year-olds. One prior SARS-CoV-2 infection reduced infection risk during the Delta wave only, with immunity from ≥2 prior infections required to reduce the risk of infection with early Omicron lineage viruses. In an African population with high levels of infection-driven immunity and low vaccine coverage, we find high attack rates during SARS-CoV-2 waves, with a high proportion of asymptomatic infections and young children remaining relatively protected from infection.

Histoplasma Seropositivity in TB Patients in The Gambia: Evidence to Drive Research on a High-Priority Fungal Pathogen.

Background: Inclusion of Histoplasma in the World Health Organization's first Fungal Priority Pathogens List under "high-priority" fungal species highlights the need for robust surveillance of Histoplasma spp. in endemic and underrepresented regions. Despite increasing reports of histoplasmosis in Africa, data on the burden of this fungal disease are sparse in The Gambia. This baseline study examined the human seroprevalence of anti-Histoplasma antibody in a TB patient group in The Gambia, explored associations between seropositivity and demographic and clinical variables, and proposes future research directions. Methods: Biobanked plasma samples were selected from active TB cases with variable HIV infection status. Latex agglutination tests were performed on samples from 52 study participants to detect the presence of anti-Histoplasma antibodies. Potential risk factors for Histoplasma exposure were explored using logistic regression analysis. Results: The sample seroprevalence of anti-Histoplasma antibody was 28.8% (n = 15/52; 95% CI, 17.1%-43.1%). Multivariable logistic regression analysis identified a statistically significant association between Histoplasma seropositivity and age (odds ratio, 0.91; 95% CI, 0.84-0.98; P = .008). Conclusions: This baseline study provides evidence of Histoplasma seropositivity in TB patients in The Gambia and explores risk factors for exposure. The small sample size and use of the LAT in TB and HIV-positive patient groups are significant study limitations. Future research directions are proposed to ascertain the burden of Histoplasma in general and patient populations and explore the context-specific risk factors for exposure and infection in The Gambia.

Comparing accuracy of lipoarabinomannan urine tests for diagnosis of pulmonary tuberculosis in children from four African countries: a cross-sectional study.

BACKGROUND: A sensitive and specific non-sputum-based test would be groundbreaking for the diagnosis of childhood tuberculosis. We assessed side by side the diagnostic accuracy of the urine-based lipoarabinomannan assays Fujifilm SILVAMP TB LAM (FujiLAM) and Alere Determine TB LAM Ag (AlereLAM) for detection of childhood tuberculosis. METHODS: In this cross-sectional study, we tested urine samples from children younger than 15 years with presumed pulmonary tuberculosis. Children were consecutively recruited from four dedicated outpatient childhood tuberculosis clinics in The Gambia, Mali, Nigeria, and Tanzania. Biobanked urine samples were thawed and tested using FujiLAM and AlereLAM assays. We measured diagnostic performance against a microbiological reference standard (confirmed tuberculosis) and a composite reference standard (confirmed and unconfirmed tuberculosis). Sensitivity and specificity were estimated with bivariate random-effects meta-analyses. FINDINGS: Between July 1, 2017, and Dec 1, 2018, we obtained and stored urine samples from 415 children. 63 (15%) children had confirmed tuberculosis, 113 (27%) had unconfirmed tuberculosis, and 239 (58%) were unlikely to have tuberculosis. 61 children were HIV-positive (prevalence 15%). Using the microbiological reference standard, the sensitivity of FujiLAM was 64·9% (95% CI 43·7-85·2; positive in 40 of 63 confirmed samples) and the sensitivity of AlereLAM was 30·7% (8·6-61·6; 19 of 63). The specificity of FujiLAM was 83·8% (95% CI 76·5-89·4; negative in 297 of 352 unconfirmed and unlikely samples) and the specificity of AlereLAM was 87·8% (79·0-93·7; 312 of 352). Against the composite reference standard, both assays had decreased sensitivity; the sensitivity of FujiLAM was 32·9% (95% CI 24·6-41·9; positive in 58 of 176 confirmed and unconfirmed samples) and the sensitivity of AlereLAM was 20·2% (12·3-29·4; 36 of 176). The specificity of FujiLAM was 83·3% (95% CI 71·8-91·7; negative in 202 of 239 unlikely samples) and the specificity of AlereLAM was 90·0% (81·6-95·6; 216 of 239). INTERPRETATION: By comparison with AlereLAM, FujiLAM showed higher sensitivity and similar specificity. FujiLAM could potentially add value to the rapid diagnosis of tuberculosis in children. FUNDING: German Federal Ministry of Education and Research, the Global Health Innovative Technology Fund, the UK Research and Innovation Global Challenges Research Fund, and the UK Medical Research Council.

ULBP1 Is Elevated in Human Hepatocellular Carcinoma and Predicts Outcome.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer death worldwide, and despite recent immunotherapeutic advances there remains a need for improved diagnostic, prognostic, and therapeutic tools. UL-16 binding protein 1 (ULBP1) is a ligand of the activatory receptor Natural Killer cell Group 2 receptor D (NKG2D) and is found as a cell-surface protein on some malignant cells including on human hepatocellular carcinomas. We aimed to explore the biological and clinical significance of NKG2D ligands in the circulation of patients with HCC. We measured ULBP1 in the serum of two retrospective cohorts of patients with HCC from the PROLIFICA cohort in The Gambia (n = 43) and from a tertiary care setting in the UK (n = 72) by sandwich ELISA. Exosome isolation by size exclusion was used to compare ULBP1 concentration in exosomes and as free protein. Survival analysis was performed and multiple linear regression and Poisson regression were used to assess the independent effect of ULBP1 concentration. ULBP1 was raised in both cohorts with HCC regardless of the underlying liver disease, and was not associated with markers of cirrhosis such as platelet count or serum albumin. ULBP1 was present predominantly as free protein rather than bound to exosomes. Serum ULBP1 > 2000 pg/ml was associated with a significantly reduced survival in both cohorts (hazard ratios in Gambian and UK cohorts 2.37 and 2.1, respectively). The effect remained significant after adjustment for BCLC staging (p = 0.03). These data suggest that ULBP1 merits further investigation as a prognostic marker in HCC in diverse settings and should also be explored as a therapeutic target.