Centre for Infectious Disease Research in Zambia
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Recent Submissions
Hepatitis B and C Prevention, Screening and Diagnostic Services at HIV Treatment Sites: International epidemiology Databases to Evaluate AIDS.
(2026-May-05) Kuniholm MH; Murenzi G; Samala N; Yunihastuti E; Wandeler G; Kim HN; Plaisy MK; Perazzo H; Twizere C; Odhiambo F; Bopage R; Muula G; Lo Re V; Minga A; López-Iñiguez A; Nsonde DM; Kasozi C; Wati DK; Fox MP; Kirk GD; Messou E; Cesar C; Ebasone PV; Byakwaga H; Ross J; Chimbetete C; Yendewa GA; Jaquet A; Succi RCM; Maruri F; Brazier E
BACKGROUND: Prevention, screening and diagnostic services for hepatitis B virus (HBV) and hepatitis C virus (HCV) can prevent morbidity and mortality in people receiving HIV care. However, there is limited information about the availability of HBV and HCV services at HIV clinics globally.
METHODS: The International epidemiology Databases to Evaluate AIDS (IeDEA) conducted surveys of service delivery and practices at participating HIV treatment centers from seven regions. We used 2023 survey data to measure availability of HBV vaccination, HBV and HCV screening, HBV surface antigen (HBsAg), HBV DNA, HCV antibody, HCV RNA testing. Multivariable logistic regression models were used to test associations of site characteristics with HBV and HCV services.
RESULTS: HBV vaccination was available on-site at 67.7% of 204 HIV treatment sites. Screening for HBV and HCV at HIV care enrollment was reported by 72.1% and 50% of sites, respectively. HBsAg, HBV DNA, HCV antibody and HCV RNA testing were available on-site at 77%, 47.6%, 61.8% and 44.6% of sites, respectively. Sites serving predominately rural (vs. urban) populations were less likely to report on-site availability of HBV DNA (odds ratio (OR):0.07; 95% confidence interval (CI):0.01-0.68;P=0.02), HCV antibody (OR=0.18; 95% CI:0.04-0.92;P=0.04) and HCV RNA (OR=0.10; 95% CI:0.01-0.90;P=0.04) testing.
CONCLUSION: Life-saving services such as HBV vaccination, HBsAg and HCV antibody testing were available on-site at most HIV treatment sites participating in the IeDEA network. Lower availability at rural sites suggests that expansion of services is important to eliminate HBV and HCV as public health problems in people receiving HIV care.
Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study.
(2026-May-14) de Vos M; Le H; Marcelo D; Ajide B; Alí-Francia KG; Borkman AL; Desravines R; Chang HT; Dowling W; Kamulegeya L; Marconi S; Moe CA; Rockman L; Shuma B; Christopher DJ; Hapeela N; Muyoyeta M; Nakiyingi L; Theron G; Ugarte-Gil C; Hung NV; Luong DV; Yu C; Alland D; Denkinger CM; Ellner J; Dorman SE; Kremer K; Manabe YC; Nahid P; Ruhwald M; Shah M; Penn-Nicholson A; Cattamanchi A; Bimba JS
BACKGROUND: Despite advancements in tuberculosis diagnostics, many cases remain unconfirmed because of challenges in conventional sputum-based testing. This study aimed to evaluate the diagnostic accuracy of tongue swab sampling as a non-invasive alternative for tuberculosis diagnosis using Xpert MTB/RIF Ultra (Ultra).
METHODS: We conducted a large-scale, multicountry, prospective diagnostic accuracy study of Ultra using tongue swabs in people with presumptive pulmonary tuberculosis. Participants were enrolled consecutively at primary health centres and hospitals across eight countries from June 26, 2023, to Feb 15, 2024, and the study was coordinated by three consortia. Eligible participants were individuals aged 12 years or older or 18 years or older, according to the consortium involved, with presumptive pulmonary tuberculosis or at least one risk factor for tuberculosis and a positive tuberculosis screening test at the select consortia. Standardised tongue swab collection and processing protocols were used in all countries. Sensitivity and specificity with 95% CI values were calculated against sputum liquid or solid culture (primary) and sputum Ultra (secondary) reference standards using Wilson's score method. Fisher's exact tests were used for subgroup comparisons, with p values < 0·05 considered statistically significant.
FINDINGS: Among the 1844 participants included in the analysis, 389 tested positive and 1455 tested negative for pulmonary tuberculosis based on the primary sputum culture reference standard. 871 (47·2%) participants were female and 973 (52·7%) were male, with a mean age of 43 years (range 12-90). Among the 1844 participants, 399 (21·7%) were enrolled in Viet Nam, 166 (9·0%) in India, 427 (23·2%) in South Africa, 271 (14·7%) in the Philippines, 138 (7·5%) in Nigeria, 102 (5·5%) in Zambia, 175 (9·5%) in Uganda, and 166 (9·0%) in Peru. Tongue swab Ultra testing showed a sensitivity of 65·6% (95% CI 60·6-70·3) and specificity of 98·5% (95% CI 97·7-99·1) against the culture-based reference standard. Sensitivity estimates varied across collection centres and were higher in individuals without HIV than in those living with HIV (68·4% vs 50·0%; absolute difference 18·4 percentage points [95% CI 3·3-33·4]). When sputum Ultra was used as the reference standard, sensitivity was 75·4% (95% CI 69·0-78·8). Tongue swab Ultra showed higher sensitivity than sputum smear microscopy. Invalid or error result rates were variable and high at certain sites (range 0-16%).
INTERPRETATION: Tongue swabs are a promising sample type for rapid diagnostic tests for tuberculosis, with moderate sensitivity and high specificity when Ultra was used as the reference standard. However, further research is needed to optimise protocols for Ultra testing and develop assays tailored to tongue swab specimens. Adoption of tongue swab-based molecular testing could expand tuberculosis diagnostics access, especially for populations unable to produce sputum, thus supporting global tuberculosis elimination goals.
FUNDING: National Institute of Allergy and Infectious Diseases, United States Agency for International Development.
Global trends in norovirus genotype distribution among medically attended children with acute gastroenteritis, 2020-2025.
(2026-May-07) Cannon JL; Bonifacio J; Fumian TM; Pabbaraju K; Pietsch C; Gonzalez MD; Hossain ME; Selvarangan R; Buesa J; Pan CY; Sakon N; Chang JH; Hewitt J; Croucher D; White PA; Mercer LK; Chuchaona W; Martinez FJD; Moya ML; Trang NV; Hatyoka LM; Mans J; Niendorf S; Jacobsen S; Mendoza L; Alvarez CD; Gomes KA; Degiuseppe JI; Ingunza A; Varghese T; Lay MK; Santiago FG; Bartlett E; Relja B; Barclay L; Simuyandi M; Lanata CF; Rahman M; Poovorawan Y; Wu FT; Pang XL; Vinjé J
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis, with a broad diversity of genotypes infecting children. NoroSurv is an established global network for norovirus strain surveillance among medically attended children < 5 years of age.
METHODS: Participating laboratories uploaded norovirus sequences from stool specimens collected from 2020 to 2025 to a web portal, which assigned norovirus genotypes and strain data. Norovirus seasons were defined as September 1 to August 31.
RESULTS: Participants in 22 countries across 6 continental regions uploaded 4113 norovirus sequences, including 26 genotypes and 53 strains. GII.4 accounted for 53% (2167/4113), followed by GII.3 (12%), GII.17 (11%), GII.6 (7%), and GII.2 (5%). GII.4 Sydney was the most common variant (47%; 1912/4113), but new GII.4 variants/clusters emerged regionally, with GII.4 San Francisco, GII.4 Wichita and GII.4 Allegany more frequently detected than GII.4 Sydney in 2021-2022 in Africa, 2022-2023 in Central and South America and 2023-2024 in Central America. In 2023-2024, a dramatic rise in GII.17 detection was observed in most regions (32% of all 2024-2025 sequences). In North, Central and South America, Europe and Asia Pacific, GII.17 detection increased as GII.4 detection declined in 2024-2025. Other genotypes (GI.3, GII.1, GII.2, GII.3 and GII.6) had regional peaks, accounting for up to 37% of sequences during a specific season.
CONCLUSIONS: Our data may help guide norovirus vaccine development and provide a baseline of global norovirus strain distribution for evaluating the effectiveness of future vaccines in children. We continue to monitor the shifting distribution of norovirus genotypes through NoroSurv surveillance.
Design and feasibility considerations for a phase 3 efficacy trial of the M72/AS01
(2026-May-12) Dagnew AF; Noble R; Cinar A; Burhan E; Churchyard G; Fairlie L; Hanekom WA; Muyoyeta M; Mwandumba HC; Nduba V; Curran M; Schmidt AC
BACKGROUND: M72/AS01
METHODS: We conducted event-driven simulations using lower bound (LB) of the two-sided 95% confidence interval (CI) for VE(D). For IGRA-positive participants, assumptions included 1:1 randomization, 9000 participants/arm, 0.4% TB incidence/year, 55% true VE(D), 5% dropout/year, and two-year enrollment. Enrollment irrespective of baseline IGRA status (mixed IGRA-status population) and IGRA-negative-only scenarios were explored to estimate sample sizes and trial duration.
RESULTS: Simulations demonstrated that 110 events rule out a VE(D) 95% CI LB ≤10%, and 185 events rule out ≤25%, assuming ≥90% power and a true VE(D) of 55%. With 18,000 IGRA-positive participants, simulations projected a 90% probability of accruing 110 events within 3.5 to 4 years and 185 within 5.5 to 6 years. In the mixed IGRA-status population, few endpoints occurred among IGRA-negative participants, yielding insufficient power. Standalone VE(D) evaluation in IGRA-negative participants required large sample sizes (approximately 134,800) and prolonged timelines, indicating infeasibility. Accordingly, the selected primary objective of the phase 3 trial was to confirm VE(D) in IGRA-positive HIV-negative participants using LB of 95% CI for VE(D) > 10% after 110 events; secondary objectives include safety and immunogenicity in HIV-negative IGRA-positive; HIV-negative IGRA-negative; and HIV-positive individuals irrespective of IGRA status.
CONCLUSIONS: An IGRA-positive-enriched, event-driven phase 3 trial is feasible to confirm VE(D) of M72/AS01
Evaluation of plasma anti-CS3 and anti-LTB IgG avidity among Zambian children vaccinated with ETVAX.
(2026) Mubanga C; Mubanga M; Chilyabanyama ON; Phiri M; Chisenga CC; Glashoff RH; Chilengi R
BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheal disease in low- and middle-income countries (LMICs). To curb ETEC related diarrhoea, several candidate vaccines are in development, with ETVAX® being the most advanced. Although immunogenicity studies have primarily focused on measuring antibody titres, assessing antibody avidity offers additional valuable insight into antibody quality and immune maturity. This study assessed anti-CS3 and anti-LTB IgG avidity in Zambian children to better understand vaccine-induced antibody responses in an endemic setting.
METHODS: Children aged 6-23 months (n = 60) received three quarter-doses of ETVAX® with dmLT adjuvant on days 1, 14, and 90. Plasma samples collected at baseline prior to the first vaccination (Day 1; V1), seven days after the second dose (Day 22; V5), and seven days after the third dose (Day 97; V7) were analysed by limiting antigen dilution ELISA to calculate avidity indices (AI). Naïve classification was performed using titre-based thresholds (20th percentile of baseline titres) and avidity-defined naivety (AI < 0.5). Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of avidity indices against titre-defined naïve status.
RESULTS: Baseline avidity was detectable for both CS3 and LTB, consistent with prior natural exposure. Mean CS3 IgG avidity decreased from 0.7 at baseline to 0.6 after the third dose (p < 0.001), while LTB IgG avidity showed transient decreases but no net gain. Naïve classification at baseline revealed that 9/60 children had titres but low avidity (functional naivety), and 6/60 had waned titres but high avidity. Only one child was naïve by both criteria for CS3, and none for LTB. ROC analysis demonstrated moderate discrimination for CS3 (AUC = 0.65; optimal cut-off AI = 0.36) but poor discrimination for LTB (AUC = 0.30).
CONCLUSION: In this endemic population, ETVAX® induced strong antibody titres but minimal changes in avidity over time, with notable inter-individual variability. ROC analysis highlighted context-specific limitations in using avidity to discriminate immune maturity. Together, these findings suggest that while antibody avidity may provide complementary information on antibody quality, its interpretation should be cautious and considered alongside antibody titres in endemic settings.
