br Bacterial glycoconjugate vaccines contain capsule derived

Bacterial glycoconjugate vaccines contain capsule-derived bacterial polysaccharides chemically conjugated to carrier proteins and are highly immunogenic in the infant population for whom they were originally designed. This class of vaccine has shown a profound impact on the incidence of both invasive disease, such as septicaemia and meningitis, as well as mucosal infections including pneumonia and otitis media, in individuals who receive the vaccine. Unlike purified polysaccharide vaccines, glycoconjugates have also shown a profound indirect impact, reducing the incidence of disease in the unvaccinated population of all ages. This indirect or herd effect is the result of the reduced spread of bacteria from those vaccinated, a consequence of vaccine-induced prevention of bacterial colonisation of the upper respiratory tract. The glycoconjugate vaccines that have shown the most profound indirect effect and which have been best studied are the pneumococcal conjugate vaccines (PCV) first licensed in 2000. The indirect effect of PCV is particularly relevant because the pneumococcus is an important cause of disease in older people and in adults with comorbidities. Most data for the indirect effect of PCV are from developed countries with mature surveillance systems where PCV was introduced into the infant immunisation programme relatively soon after licensure. Surveillance in these countries has revealed not only the reduction of invasive pneumococcal disease in older people but also a reduction in disease rates in adults with underlying comorbidities in whom direct protection might be suboptimal. In , Tinevimbo Shiri and colleagues present a meta-analysis of the indirect effect of PCV, using data from 34 different countries and assessing the reduction in invasive pneumococcal disease and the mean time to maximal impact. Analysis of the impact of the first licensed PCV, which was seven-valent (PCV7), confirmed the near-elimination of invasive pneumococcal disease due to serotypes in the vaccine in the unvaccinated in settings with a mature childhood PCV7 programme. A second-generation vaccine containing 13 serotypes (PCV13) was licensed and introduced in 2010. Shiri and colleagues\' meta-analysis predicts that the residual invasive pneumococcal disease due to the additional six serotypes contained in PCV13 will be halved after an average 3-Methyladenine manufacturer of 3·3 years (95% credible interval [CrI] 2·1–6·8) and nearly eradicated after about 9 years following the introduction of PCV13 (5·7–19·7). The predicted mean time to attaining the maximal indirect impact is relevant when considering adult vaccination with PCV. Most developed countries do not recommend PCV in adults, believing that with the high coverage in the infant programme, adult disease will (eventually) decline. The US vaccine decision-making body, the Advisory Committee on Immunization Practices, recommended PCV13 vaccination in adults despite high coverage of PCV13 in the infant programme. However, in recognition of the probable changing epidemiology of adult disease, the recommendation built in a review of the evidence, scheduled for 2018, to re-evaluate the decision. Questions remain over whether the indirect impact on invasive pneumococcal disease is mirrored by the same reduction in pneumonia. A US study of adults admitted to hospital with community-acquired pneumonia suggested a persistent burden of disease due to serotypes contained in PCV13; however, UK and Dutch studies suggest the magnitude of the decline in non-invasive pneumococcal pneumonia in adults mirrors the reduction seen in invasive pneumococcal disease.
Considerable effort has been made to meet the challenges posed by decreased effectiveness of the antimalarial artemisinin and its key partner drugs against in Cambodia and neighbouring countries. Despite the threat of resistance, malaria endemicity has actually been falling over the past decade in the Greater Mekong Subregion. But what if such phenomena began to unfold in Africa, in those countries where the daily incidence of symptomatic malaria cases can equal the annual burden in some Asian countries? Hypolite Mavoko and colleagues report in a study designed to compare current rescue treatment options for malaria in Africa, should front-line therapies fail. The authors set out to formally test whether, in the event of recurrence of malaria symptoms in children receiving the recommended artemisinin-based combination therapy (ACT), retreatment with that same regimen was inferior to either an alternative ACT, or the current WHO recommendation for rescue treatment, oral quinine plus an antibiotic (in this study, quinine plus clindamycin, QnC). The team recruited children aged 12–59 months who presented with laboratory-confirmed malaria to either of two clinics, in Kinshasa, DR Congo or Mbarara, Uganda. Both sites serve populations exposed to intense malaria transmission. First-line ACT differs between these countries, with artesunate-amodiaquine (ASAQ) used in DR Congo, and artemether-lumefantrine (AL) in Uganda. In an unusual design, passive follow-up identified treated participants with recurrent symptoms within 42 days; on second presentation with confirmed falciparum malaria, these children were then randomly assigned to one of three second treatments. The first group was retreated with the same ACT as used for the original malaria episode (retreatment ACT group), the second group with the alternative ACT (AL in DR Congo and ASAQ in Uganda) and the third group with the WHO recommendation, QnC. All treatment was fully observed, and 571 randomised children were actively followed up for 28 days.