Although the molecular basis of resistance to a number of common antimalarial drugs is well known, a geographic description of the emergence and dispersal of resistance mutations across Africa has not been attempted. To that end we have characterised the evolutionary origins of antifolate resistance mutations in the dihydropteroate synthase (dhps) gene and mapped their contemporary distribution. We used microsatellite polymorphism flanking the dhps gene to determine which resistance alleles shared common ancestry and found five major lineages each of which had a unique geographical distribution. The extent to which allelic lineages were shared among 20 African Plasmodium falciparum populations revealed five major geographical groupings. Resistance lineages were common to all sites within these regions. The most marked differentiation was between east and west African P. falciparum, in which resistance alleles were not only of different ancestry but also carried different resistance mutations. Resistant dhps has emerged independently in multiple sites in Africa during the past 10–20 years. Our data show the molecular basis of resistance differs between east and west Africa, which is likely to translate into differing antifolate sensitivity. We have also demonstrated that the dispersal patterns of resistance lineages give unique insights into recent parasite migration patterns.

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 high-income 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.

An assessment of the accuracy of Paracheck Pf®, a malaria rapid diagnostic test (RDT) detecting histidine rich protein 2 was undertaken amongst children aged 6–59 months in eastern Democratic Republic of Congo.

GBS is a leading cause of mortality in newborn babies in high- and low-income countries worldwide. Different strains of GBS are characterized by different degrees of virulence, where some are harmlessly carried by humans or animals and others are much more likely to cause disease. The genome sequences of almost 2,000 GBS samples isolated from both animals and humans in high- and low- income countries were analyzed using a pan-genome-wide association study approach. This allowed us to identify 279 genes which are associated with different lineages of GBS, characterized by a different virulence and preferred host. Additionally, we propose that the GBS now carried in humans may have first evolved in animals before expanding clonally once adapted to the human host. These findings are essential to help understand what is causing GBS disease and how the bacteria have evolved and are transmitted.

Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi in November 2011 and is offered to infants at 6, 10 and 14 weeks of age as part of routine immunisation. PCV13 is expected to reduce vaccine type (VT) nasopharyngeal carriage, leading to reduced transmission and herd protection. We compared pneumococcal carriage in rural Karonga District, Malawi, pre-vaccine in 2009-2011 and post-vaccine in 2014 using a combination of cross-sectional and longitudinal analyses. Nasopharyngeal swabs were collected from a cohort of mother-infant pairs and household members <16 years. Pneumococci from 2009 to 2011 were serogrouped using latex agglutination and serotyped by Quellung reaction. In 2014, latex agglutination was used for both steps. Carriage prevalence ratios using prevalence data from before and after vaccine introduction were calculated by log-binomial regression, adjusted for age, seasonality and household composition. Participating infants in 2014 received PCV13 as part of routine immunisation. VT carriage prior to PCV-13 introduction was 11.4%, 45.1%, 28.2%, 21.2% and 6.6% for 6-week old infants, 18-week old infants, children 1-4 years, children 5-15 years and mothers, respectively. After vaccine introduction, VT carriage decreased among vaccinated 18-week old infants (adjusted prevalence ratio 0.24 (95%CI 0.08-0.75)), vaccinated children 1-4 years (0.54 (0.33-0.88)), unvaccinated children 5-15 years (0.37 (0.17-0.78)) and mothers (0.34 (0.15-0.79)). No decrease in VT carriage was observed for 6-week old infants too young to be vaccinated (1.07 (0.38-3.02)) and PCV-13 ineligible children 1-4 years (0.84 (0.53-1.33)). Non-VT carriage increased only among vaccinated children 1-4 years (1.58 (1.21-2.06)). There is evidence of reduced VT pneumococcal carriage three years after vaccine introduction in this rural Malawian population with good vaccine coverage using a 3 + 0 schedule. However carriage was sustained among 6-week-old infants and PCV13 ineligible 1-4 year olds, and there was some indication of serotype replacement in vaccinated 1-4 year olds.

The population impact of pneumococcal conjugate vaccines (PCVs) depends on direct and indirect protection. Following Malawi's introduction of the 13-valent PCV (PCV13) in 2011, we examined its impact on vaccine and non-vaccine serotype invasive pneumococcal disease among vaccine-eligible-age and vaccine-ineligible-age children and adults. We did a prospective observational time-series analysis and a case-control study. We used data from between Jan 1, 2006, and Dec 31, 2018, from laboratory-based surveillance at a government hospital in Malawi. This period included 6 years before and 7 years after introduction of PCV13. By use of negative-binomial regression, we evaluated secular trend-adjusted incidence rate ratio (IRR) in vaccine serotype and non-vaccine serotype invasive pneumococcal disease before and after introduction of PCV. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. The case-control study assessed vaccine effectiveness, comparing PCV uptake among cases of vaccine-eligible-age invasive pneumococcal disease versus matched community controls. Surveillance covered 10 281 476 person-years of observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. A reduction in total (vaccine serotype plus non-vaccine serotype) invasive pneumococcal disease incidence preceded introduction of PCV: 19% (IRR 0·81, 95% CI 0·74 to 0·88, p<0·0001) among infants (<1 year old), 14% (0·86, 0·80 to 0·93, p<0·0001) among children aged 1-4 years, and 8% (0·92, 0·83 to 1·01, p=0·084) among adolescents and adults (≥15 years old). Among children aged 5-14 years there was a 2% increase in total invasive pneumococcal disease (1·02, 0·93 to 1·11, p=0·72). Compared with the counterfactually predicted incidence, incidence of post-PCV13 vaccine serotype invasive pneumococcal disease was 74% (95% CI 70 to 78) lower among children aged 1-4 years and 79% (76 to 83) lower among children aged 5-14 years, but only 38% (37 to 40) lower among infants and 47% (44 to 51) lower among adolescents and adults. Although non-vaccine serotype invasive pneumococcal disease has increased in incidence since 2015, observed incidence remains low. The case-control study (19 cases and 76 controls) showed vaccine effectiveness against vaccine serotype invasive pneumococcal disease of 80·7% (-73·7 to 97·9). In a high-mortality, high-HIV-prevalence setting in Africa, there were significant pre-vaccine reductions in the incidence of invasive pneumococcal disease. 7 years after PCV introduction, although vaccine-attributable impact among vaccine-eligible-age children was significant, indirect effects benefitting unvaccinated infants and adults were not. Policy decisions should consider multiple alternative strategies for reducing disease burden, including targeted vaccination outside infant Expanded Programme of Immunization to benefit vulnerable populations. Bill & Melinda Gates Foundation, Wellcome Trust, and National Institute for Health Research.