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Background:Sustainable Development Goals set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Deployment of a robust prophylactic vaccine and enhanced interventions for prevention of mother to child transmission (PMTCT) are cornerstones of elimination strategy. However, in light of the estimated global burden of 290 million cases, enhanced efforts are required to underpin optimisation of public health strategy. Robust analysis of population epidemiology is particularly crucial for populations in Africa made vulnerable by HIV co-infection, poverty, stigma and poor access to prevention, diagnosis and treatment.Methods:We here set out to evaluate the current and future role of HBV vaccination and PMTCT as tools for elimination. We first investigated the current impact of paediatric vaccination in a cohort of children with and without HIV infection in Kimberley, South Africa. Second, we used these data to inform a new model to simulate the ongoing impact of preventive interventions. By applying these two approaches in parallel, we are able to determine both the current impact of interventions, and the future projected outcome of ongoing preventive strategies over time.Results:Existing efforts have been successful in reducing paediatric prevalence of HBV infection in this setting to Conclusions:Through extensive deployment of preventive strategies for HBV, significant positive public health impact is possible, although time to HBV elimination as a public health concern is likely to be substantially longer than that proposed by current goals.

Background: Reports of posttreatment control following antiretroviral therapy (ART) have prompted the question of how common immune control of HIV infection is in the absence of ART. In contrast to adult infection, where elite controllers have been very well characterized and constitute approximately 0.5% of infections, very few data exist to address this question in paediatric infection. Methods: We describe 11 ART-naive elite controllers from 10 cohorts of HIV-infected children being followed in South Africa, Brazil, Thailand, and Europe. Results: All but one of the elite controllers (91%) are females. The median age at which control of viraemia was achieved was 6.5 years. Five of these 11 (46%) children lost control of viraemia at a median age of 12.9 years. Children who maintained control of viraemia had significantly higher absolute CD4+ cell counts in the period of elite control than those who lost viraemic control. On the basis of data available from these cohorts, the prevalence of elite controllers in paediatric infection is estimated to be 5–10-fold lower than in adults. Conclusion: Although conclusions are limited by the study design, these data suggest that, whilst paediatric elite control can be achieved, compared with adult elite controllers, this occurs rarely, and takes some years after infection to achieve. Also, loss of immune control arises in a high proportion of children and often relatively rapidly. These findings are consistent with the more potent antiviral immune responses observed in adults and in females.

Background In South Africa, the first HBV vaccine dose is administered at age 6 weeks, leaving a potential window for vertical transmission. Insights into HBV seroprevalence in the vulnerable HIV-infected group are important to drive improvements in surveillance, treatment and prevention. Objectives We set out to implement a screening program for HBV among HIV-infected children and adolescents in Kimberley, South Africa. Our aims were to demonstrate that screening is feasible and sustainable, to establish the prevalence of HBV, to characterise the HBV cases we identified, and to inform discussion about the infant vaccination schedule. Study design We tested all HIV positive children (age 0–16) for Hepatitis B surface antigen (HBsAg), delivering this testing as part of routine state-funded care. We followed up HBsAg-positive cases with an extended panel of HBV serology tests, and HBV DNA viral load quantification. Results Our screening campaign was successfully incorporated into routine out-patient care. Among 625 patients tested, we found five positive for HBsAg (0.8%), of whom three were Hepatitis B e-antigen positive. Two additional children initially tested HBsAg-positive but were negative on repeat testing. Antiviral therapy in the HBsAg children was reviewed and adjusted if required. Conclusions The results testify to the overall success of the HBV vaccine campaign. However, we have demonstrated that ongoing vigilance is required to detect cases and prevent transmission events. Further evaluation of the optimum timing of the first vaccine HBV vaccine dose is required; a vaccine dose at birth could reduce prevalence further.

The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5 yrs were more frequently female (59%; p

Full model description and additional supplementary Figure S1-S6. This document includes a complete model description, including parameters, assumptions, mathematical expressions and fitting details, including further results and figures supporting the main text: Figure S1. Posteriors from the Bayesian Markov Chain Monte Carlo fitting to the Kimberley cohort data. Figure S2. Fitting HBV vaccine response according to HIV serostatus. Figure S3. Sensitivity of interventions with deterministic output. Figure S4. Post-intervention stochastic impact on HBV prevalence (HBsAg), with time to reach sustainable development goals when using routine neonatal vaccination and PMTCT independently. Figure S5. Sensitivity of mean intervention impact on HBV incidence (HBsAg) and HBeAg+ prevalence, with estimated mean year to reach sustainable development goals for combinations of routine + 6 years vaccination and PMTCT. Figure S6. Sensitivity of mean intervention impact on HBV incidence (HBsAg) and HBeAg+ prevalence, with estimated mean year to reach sustainable development goals for combinations of routine neonatal vaccination and PMTCT plus a complete catch-up campaign. (PDF 3606 kb)

Full model description and additional supplementary Figure S1-S6. This document includes a complete model description, including parameters, assumptions, mathematical expressions and fitting details, including further results and figures supporting the main text: Figure S1. Posteriors from the Bayesian Markov Chain Monte Carlo fitting to the Kimberley cohort data. Figure S2. Fitting HBV vaccine response according to HIV serostatus. Figure S3. Sensitivity of interventions with deterministic output. Figure S4. Post-intervention stochastic impact on HBV prevalence (HBsAg), with time to reach sustainable development goals when using routine neonatal vaccination and PMTCT independently. Figure S5. Sensitivity of mean intervention impact on HBV incidence (HBsAg) and HBeAg+ prevalence, with estimated mean year to reach sustainable development goals for combinations of routine + 6 years vaccination and PMTCT. Figure S6. Sensitivity of mean intervention impact on HBV incidence (HBsAg) and HBeAg+ prevalence, with estimated mean year to reach sustainable development goals for combinations of routine neonatal vaccination and PMTCT plus a complete catch-up campaign. (PDF 3606 kb)