Plasmodium falciparum remains a relevant global health pathogen with high levels of genomic variation and gene flow that could undermine malaria elimination strategies, especially in the high burden regions of Africa. Infections with P. falciparum remain complex across most of sub-Saharan Africa. SNP variants from 2263 isolates from 24 malaria endemic settings within 15 African countries classified into western, central and eastern ancestry, plus a divergent Ethiopian population. The parasite populations are interbred and share genomic haplotypes especially across drug resistance loci. Haplotypes across drug resistance associated loci showed the strongest recent identity-by-descent between populations and endogenous haplotypes have spread to and from all populations. A recent signature of selection on chromosome 12 with candidate resistance loci against artemisinin derivatives is evident in Ghana and Malawi. Such selection and emerging sub-structure may affect intervention strategies and the efficacy of drugs and vaccines for malaria elimination. Formatted: Font: +Body (Calibri) Formatted: Line spacing: Multiple 1.15 li

We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from GuineaBissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P ¼ 0.03 for DC-SIGN and P ¼ 0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63-0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.

Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged ≥6 months (4,194 individuals) and then in April (dry season). Entomological data were collected monthly throughout the malaria transmission season. Ownership of Long-Lasting Insecticidal Nets was 71.5% (2766/3869). Incidence of malaria infection and clinical disease varied significantly across the country, with the highest values in eastern (1.7/PYAR) than in central (0.2 /PYAR) and western (0.1/PYAR) Gambia. Malaria infection at the beginning of the transmission season was significantly higher in individuals who slept outdoors (HR = 1.51, 95% CI: 1.02–2.23, p = 0.04) and in those who had travelled outside the village (HR = 2.47, 95% CI: 1.83–3.34, p <0.01). Sub-patent infections were more common in older children (HR = 1.35, 95% CI: 1.04–1.6, p <0.01) and adults (HR = 1.53, 95% CI: 1.23–1.89, p<0.01) than in younger children. The risk of clinical malaria was significantly higher in households with at least one infected individual at the beginning of the transmission season (HR = 1.76, p<0.01). Vector parity was significantly higher in the eastern part of the country, both in the south (90.7%, 117/129, p<0.01) and the north bank (81.1%, 227/280, p<0.01), than in the western region (41.2%, 341/826), indicating higher vector survival. There is still significant residual malaria transmission across The Gambia, particularly in the eastern region. Additional interventions able to target vectors escaping Long-Lasting Insecticidal Nets and indoor residual spraying are needed to achieve malaria elimination.

BackgroundVaccination has been shown to reduce mortality and morbidity due to vaccine-preventable diseases. However, these diseases are still responsible for majority of childhood deaths worldwide especially in the developing countries. This may be due to low vaccine coverage or delay in receipt of age-appropriate vaccines. We studied the timeliness of routine vaccinations among children aged 12–59 months attending infant welfare clinics in semi-urban areas of The Gambia, a country with high vaccine coverage.MethodsA cross-sectional survey was conducted in four health centres in the Western Region of the Gambia. Vaccination dates were obtained from health cards and timeliness assessed based on the recommended age ranges for BCG (birth–8 weeks), Diphtheria-Pertussis–Tetanus (6 weeks–4 months; 10 weeks–5 months; 14 weeks–6 months) and measles vaccines (38 weeks–12 months). Risk factors for delay in age-appropriate vaccinations were determined using logistic regression. Analysis was limited to BCG, third dose of Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines.ResultsVaccination records of 1154 children were studied. Overall, 63.3 % (95 % CI 60.6–66.1 %) of the children had a delay in the recommended time to receiving at least one of the studied vaccines. The proportion of children with delayed vaccinations increased from BCG [5.8 % (95 % CI 4.5–7.0 %)] to DPT3 [60.4 % (95 % CI 57.9 %-63.0 %)] but was comparatively low for the measles vaccine [10.8 % (95 % CI 9.1 %–12.5 %)]. Mothers of affected children gave reasons for the delay, and their profile correlated with type of occupation, place of birth and mode of transportation to the health facilities.ConclusionDespite high vaccination coverage reported in The Gambia, a significant proportion of the children’s vaccines were delayed for reasons related to health services as well as profile of mothers. These findings are likely to obtain in several countries and should be addressed by programme managers in order to improve and optimize the impact of the immunization coverage rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-1015-9) contains supplementary material, which is available to authorized users.

BackgroundAn outbreak of pneumococcal meningitis among non-infant children and adults occurred in the Brong-Ahafo region of Ghana between December 2015 and April 2016 despite the recent nationwide implementation of a vaccination programme for infants with the 13-valent pneumococcal conjugate vaccine (PCV13).MethodsCerebrospinal fluid (CSF) specimens were collected from patients with suspected meningitis in the Brong-Ahafo region. CSF specimens were subjected to Gram staining, culture and rapid antigen testing. Quantitative PCR was performed to identify pneumococcus, meningococcus and Haemophilus influenzae. Latex agglutination and molecular serotyping were performed on samples. Antibiogram and whole genome sequencing were performed on pneumococcal isolates.ResultsEight hundred eighty six patients were reported with suspected meningitis in the Brong-Ahafo region during the period of the outbreak. In the epicenter district, the prevalence was as high as 363 suspected cases per 100,000 people. Over 95 % of suspected cases occurred in non-infant children and adults, with a median age of 20 years. Bacterial meningitis was confirmed in just under a quarter of CSF specimens tested. Pneumococcus, meningococcus and Group B Streptococcus accounted for 77 %, 22 % and 1 % of confirmed cases respectively. The vast majority of serotyped pneumococci (80 %) belonged to serotype 1. Most of the pneumococcal isolates tested were susceptible to a broad range of antibiotics, with the exception of two pneumococcal serotype 1 strains that were resistant to both penicillin and trimethoprim-sulfamethoxazole. All sequenced pneumococcal serotype 1 strains belong to Sequence Type (ST) 303 in the hypervirulent ST217 clonal complex.ConclusionThe occurrence of a pneumococcal serotype 1 meningitis outbreak three years after the introduction of PCV13 is alarming and calls for strengthening of meningitis surveillance and a re-evaluation of the current vaccination programme in high risk countries.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1914-3) contains supplementary material, which is available to authorized users.

PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

Genomic evolution, transmission and pathogenesis of Streptococcus pneumoniae, an opportunistic human-adapted pathogen, is driven principally by nasopharyngeal carriage. However, little is known about genomic changes during natural colonisation. Here, we use wholegenome sequencing to investigate within-host microevolution of naturally carried pneumococci in ninety-eight infants intensively sampled sequentially from birth until twelve months in a high-carriage African setting. We show that neutral evolution and nucleotide substitution rates up to forty-fold faster than observed over longer timescales in S. pneumoniae and other bacteria drives high within-host pneumococcal genetic diversity. Highly divergent co-existing strain variants emerge during colonisation episodes through real-time intra-host homologous recombination while the rest are co-transmitted or acquired independently during multiple colonisation episodes. Genic and intergenic parallel evolution occur particularly in antibiotic resistance, immune evasion and epithelial adhesion genes. Our findings suggest that withinhost microevolution is rapid and adaptive during natural colonisation.

Iron deficiency and iron deficiency anemia are highly prevalent in low-income countries, especially among young children. Hepcidin is the major regulator of systemic iron homeostasis. It controls dietary iron absorption, dictates whether absorbed iron is made available in circulation for erythropoiesis and other iron-demanding processes, and predicts response to oral iron supplementation. Understanding how hepcidin is itself regulated is therefore important, especially in young children. We investigated how changes in iron-related parameters, inflammation and infection status, seasonality, and growth influenced plasma hepcidin and ferritin concentrations during infancy using longitudinal data from two birth cohorts of infants in rural Gambia (n=114 and n=193). This setting is characterized by extreme seasonality, prevalent childhood anemia, undernutrition, and frequent infection. Plasma was collected from infants at birth and at regular intervals, up to 12 months of age. Hepcidin, ferritin and plasma iron concentrations declined markedly during infancy, with reciprocal increases in soluble transferrin receptor and transferrin concentrations, indicating declining iron stores and increasing tissue iron demand. In cross-sectional analyses at 5 and 12 months of age, we identified expected relationships of hepcidin with iron and inflammatory markers, but also observed significant negative associations between hepcidin and antecedent weight gain. Correspondingly, longitudinal fixed effects modeling demonstrated weight gain to be the most notable dynamic predictor of decreasing hepcidin and ferritin through infancy across both cohorts. Infants who grow rapidly in this setting are at particular risk of depletion of iron stores, but since hepcidin concentrations decrease with weight gain, they may also be the most responsive to oral iron interventions.