Biology subjects

Williams, T. N.

Publications and source records attributed to Williams, T. N..

3 recordsLinked to original sources

bioRxiv2018

The impact of 10-valent Pneumococcal Conjugate Vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children.

BackgroundPneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes but the burden of pneumococcal disease in developing countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the impact of PCV on pneumonia incidence.\n\nMethodsWe linked prospective hospital surveillance for clinically-defined WHO severe or very-severe pneumonia at Kilifi County Hospital from 2002-2015 to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45,000 children aged <5 years. Chest radiographs were read according to a WHO standard. A 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PCV10) was introduced in Kenya in January 2011. In Kilifi, there was a catch-up campaign for children aged <5 years. We estimated the impact of PCV10 on pneumonia incidence through interrupted time series analysis accounting for seasonal and temporal trends.\n\nFindingsThe incidence of admission with clinically-defined pneumonia in 2002/3 was 21{middle dot}7/1000/year in children aged 2-59 months. This declined progressively over 13 years. By the end of March 2011, 61{middle dot}1% of children aged 2-11 months received [≥]2 doses and 62{middle dot}3% of children aged 12-59 months received [≥]1 dose of PCV10. Adjusted incidence rate ratios for admissions with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated with PCV10 introduction, were 0{middle dot}52 (95% CI 0{middle dot}32-0{middle dot}86), 0{middle dot}73 (95% CI 0{middle dot}54-0{middle dot}97) and 0{middle dot}63, (95% CI 0{middle dot}31-1{middle dot}26), respectively. The annual incidence of clinically-defined pneumonia in December 2010 was 12{middle dot}2/1000; this was reduced by 3{middle dot}3/1000 with PCV10 introduction.\n\nInterpretationOver 13 years, hospitalisations for clinically-defined pneumonia declined progressively at Kilifi County Hospital but fell abruptly by 27% in association with PCV10 introduction. The incidence of radiologically-confirmed pneumonia fell by 48%. The burden of childhood pneumonia in Kilifi, Kenya, has been reduced substantially by PCV10.\n\nFundingGavi, Wellcome Trust

epidemiology↗

bioRxiv2018

Population Turnover in Remote Oceania Shortly After Initial Settlement

Ancient DNA analysis of three individuals dated to ~3000 years before present (BP) from Vanuatu and one ~2600 BP individual from Tonga has revealed that the first inhabitants of Remote Oceania (\"First Remote Oceanians\") were almost entirely of East Asian ancestry, and thus their ancestors passed New Guinea, the Bismarck Archipelago, and the Solomon Islands with minimal admixture with the Papuan groups they encountered [1]. However, all present-day populations in Near and Remote Oceania harbor 25-100% Papuan ancestry, implying that there must have been at least one later stream of migration eastward from Near Oceania. We generated genome-wide data for 14 ancient individuals from Efate and Epi Islands in Vanuatu ranging from 3,000-150 BP, along with 185 present-day Vanuatu individuals from 18 islands. We show that people of almost entirely Papuan ancestry had arrived in Vanuatu by 2400 BP, an event that coincided with the end of the Lapita cultural period, changes in skeletal morphology, and the cessation of long-distance trade between Near and Remote Oceania [2]. First Remote Oceanian ancestry subsequently increased via admixture but remains at 10-20% in most islands. Through a fine-grained comparison of ancestry profiles in Vanuatu and Polynesia with diverse groups in Near Oceania, we find that Papuan ancestry in Vanuatu is consistent with deriving from the Bismarck Archipelago instead of the geographically closer Solomon Islands. Papuan ancestry in Polynesia also shows connections to the ancestry profiles present in the Bismarck Archipelago but is more similar to Tolai from New Britain and Tutuba from Vanuatu than to the ancient Vanuatu individuals and the great majority of present-day Vanuatu populations. This suggests a third eastward stream of migration from Near to Remote Oceania bringing a different type of Papuan ancestry.

genetics↗

bioRxiv2016

A structural variant encoding hybrid glycophorins is associated with resistance to severe malaria

Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. Here we analyse whole genome sequence data from worldwide human populations, including 765 new genomes from across sub-Saharan Africa, and identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA and GYPB. We find that a nearby reported association with severe malaria is explained by a complex structural variant that involves the loss of GYPB and gain of two hybrid genes, each with a GYPB extracellular domain and GYPA intracellular domain. This variant reduces the risk of severe malaria by 40% and has recently risen in frequency in parts of Kenya. We show that the structural variant encodes the Dantu blood group antigen, and therefore a serologically distinct red cell phenotype. These findings demonstrate that structural variation of red blood cell invasion receptors is associated with natural resistance to P. falciparum malaria.

genomics↗