Hepatitis B Vaccination Impact and the Unmet Need for Antiviral Treatment in Blantyre, Malawi.

BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce mortality, antiviral treatment programs are needed. We estimated prevalence, vaccine impact, and need for antiviral treatment in Blantyre, Malawi. METHODS: We conducted a household study in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardized hepatitis B surface antigen (HBsAg) seroprevalence. Impact of infant hepatitis B vaccination was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97386 censused individuals, 6073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% confidence interval [CI], 4.3%-6.1%) among adults and 0.3% (95% CI, .1%-.6%) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (95% CI, 70.3%-99.4%). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6%, and 9% were eligible for hepatitis B treatment by WHO, European, and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy.

A clinical and molecular epidemiological survey of hepatitis C in Blantyre, Malawi, suggests a historic mechanism of transmission.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. There are no previous representative community HCV prevalence studies from Southern Africa, and limited genotypic data. Epidemiological data are required to inform an effective public health response. We conducted a household census-based random sampling serological survey, and a prospective hospital-based study of patients with cirrhosis and hepatocellular carcinoma (HCC) in Blantyre, Malawi. We tested participants with an HCV antigen/antibody ELISA (Monolisa, Bio-Rad), confirmed with PCR (GeneXpert, Cepheid) and used line immunoassay (Inno-LIA, Fujiribio) for RNA-negative participants. We did target-enrichment whole-genome HCV sequencing (NextSeq, Illumina). Among 96,386 censused individuals, we randomly selected 1661 people aged ≥16 years. Population-standardized HCV RNA prevalence was 0.2% (95% CI 0.1-0.5). Among 236 patients with cirrhosis and HCC, HCV RNA prevalence was 1.9% and 5.0%, respectively. Mapping showed that HCV RNA+ patients were from peri-urban areas surrounding Blantyre. Community and hospital HCV RNA+ participants were older than comparator HCV RNA-negative populations (median 53 vs 30 years for community, p = 0.01 and 68 vs 40 years for cirrhosis/HCC, p < 0.001). Endemic HCV genotypes (n = 10) were 4v (50%), 4r (30%) and 4w (10%). In this first census-based community serological study in Southern Africa, HCV was uncommon in the general population, was centred on peri-urban regions and was attributable for <5% of liver disease. HCV infection was observed only among older people, suggesting a historic mechanism of transmission. Genotype 4r, which has been associated with treatment failure with ledipasvir and daclatasvir, is endemic.

Diagnostic performance evaluation of hepatitis B e antigen rapid diagnostic tests in Malawi.

BACKGROUND: The World Health Organization (WHO) has targeted a reduction in viral hepatitis-related mortality by 65% and incidence by 90% by 2030, necessitating enhanced hepatitis B treatment and prevention programmes in low- and middle-income countries. Hepatitis B e antigen (HBeAg) status is used in the assessment of eligibility for antiviral treatment and for prevention of mother-to-child transmission (PMTCT). Accordingly, the WHO has classified HBeAg rapid diagnostic tests (RDTs) as essential medical devices. METHODS: We assessed the performance characteristics of three commercially available HBeAg RDTs (SD Bioline, Alere, South Africa; Creative Diagnostics, USA; and Biopanda Reagents, UK) in two hepatitis B surface antigen-positive cohorts in Blantyre, Malawi: participants of a community study (n = 100) and hospitalised patients with cirrhosis or hepatocellular carcinoma (n = 94). Two investigators, blinded to the reference test result, independently assessed each assay. We used an enzyme-linked immunoassay (Monolisa HBeAg, Bio-Rad, France) as a reference test and quantified HBeAg concentration using dilutions of the WHO HBeAg standard. We related the findings to HBV DNA levels, and evaluated treatment eligibility using the TREAT-B score. RESULTS: Among 194 HBsAg positive patients, median age was 37 years, 42% were femaleand 26% were HIV co-infected. HBeAg prevalence was 47/194 (24%). The three RDTs showed diagnostic sensitivity of 28% (95% CI 16-43), 53% (38-68) and 72% (57-84) and specificity of 96-100% for detection of HBeAg. Overall inter-rater agreement κ statistic was high at 0.9-1.0. Sensitivity for identifying patients at the threshold where antiviral treatment is recommended for PMTCT, with HBV DNA > 200,000 IU/ml (39/194; 20%), was 22, 49 and 54% respectively. Using the RDTs in place of the reference HBeAg assay resulted in 3/43 (9%), 5/43 (12%) and 8/43 (19%) of patients meeting the TREAT-B treatment criteria being misclassified as ineligible for treatment. A relationship between HBeAg concentration and HBeAg detection by RDT was observed. A minimum HBeAg concentration of 2.2-3.1 log10IU/ml was required to yield a reactive RDT. CONCLUSIONS: Commercially available HBeAg RDTs lack sufficient sensitivity to accurately classify hepatitis B patients in Malawi. This has implications for hepatitis B public health programs in sub-Saharan Africa. Alternative diagnostic assays are recommended.