Background Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed. MethodsIn this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A. Results From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P = 0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P = 0.003). ConclusionsThe 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731.)

There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with highincome settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.

BackgroundAntiretroviral therapy (ART) has led to increased survival of children with vertically acquired human immunodeficiency virus infection. Significant morbidity arises from respiratory symptoms, but aetiology and pulmonary function abnormalities have not been systematically studied.MethodsHuman immunodeficiency virus-positive children aged 8–16 years were systematically recruited within clinics in Blantyre, Malawi. Clinical review, quality of life assessment, spirometry, and chest radiography were performed.ResultsOne hundred sixty participants had a mean of age 11.1 (range, 8–16) years and 50.0% were female. Cough was present in 60 (37.5%) participants, and 55 (34.4%) had moderate or severe dyspnoea. Thirty-four (22.1%) participants had digital clubbing. Thirty-three (20.6%) participants were hypoxic at rest. One hundred eighteen (73.8%) of the children were receiving ART; median CD4 count was 698 cells/µL in these compared with 406 cells/µL in ART-naive individuals (P < .001). From 145 spirometry traces (90.6%), mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were 1.06 and 0.89 standard deviations below predicted mean, respectively. Twenty-one (14.5%) traces demonstrated obstructive defects and 26 (17.9%) reduced FVC. Lung function abnormality was not associated with any clinical findings. Of the 51 individuals with abnormal lung function, the mean increase in FEV1 after salbutamol was 3.8% (95% confidence interval, 0.02–7.53). “Tramlines” and ring shadows were seen on chest radiographs in over half of cases.ConclusionsSymptoms of chronic lung disease were highly prevalent with 2 main clinical phenotypes: “cough” and “hypoxia”. Lung function abnormalities are common, poorly responsive to bronchodilators, and apparent throughout the age range of our cohort. Pathological causes remain to be elucidated. Cough and hypoxic phenotypes could be a useful part of diagnostic algorithms if further validated.

BackgroundIn November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015–2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups.MethodsA dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage.ResultsAccumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49–82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0–9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02–81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection.ConclusionsThere are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.