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Background\ud Pneumococcal infections are major causes of morbidity and mortality worldwide. We use routine hospital admissions data and time-series modelling analysis to estimate the impact of the seven and thirteen valent pneumococcal conjugate vaccines (PCV7 and PCV13) on hospital admissions due to pneumococcal disease in England.\ud Methods\ud Hospital admissions for pneumococcal meningitis, bacteraemia and pneumonia between January 1, 2003 and December 31, 2015 were identified from the national Hospital Episode Statistics database for all age groups in England. We model the impact of pneumococcal vaccination using interrupted time series analysis. Hospital admissions prior to vaccine introduction were extrapolated to predict the expected number of admissions in the absence of pneumococcal vaccines. Admissions avoided over time were estimated by comparing the fitted interrupted time series and the expected model for no vaccination in a Bayesian framework.\ud Results\ud Overall, there were 43 531 (95% credible interval (CrI): 36 486 – 51 346) fewer hospital admissions due to bacteraemia, meningitis and pneumonia in England during the period from 2006 to 2015 than would have been expected if pneumococcal vaccines had not been implemented, with the majority of hospital admissions avoided due to pneumonia. Among young children reductions in meningitis were more common, while among adults reductions in pneumonia admissions were relatively more important, with no evidence for reduced bacteraemia and meningitis among older adults. We estimated that 981 (95% CrI: 391 – 2 018), 749 (95% CrI: 295 – 1 442) and 1 464 (95% CrI: 793 – 2 522) bacteraemia, meningitis and pneumonia related hospital admissions, respectively, were averted in children

Background The spread of resistance to chloroquine (CQ) led to its withdrawal from use in most countries in sub-Saharan Africa in the 1990s. In Malawi, this withdrawal was followed by a rapid reduction in the frequency of resistance to the point where the drug is now considered to be effective once again, just nine years after its withdrawal. In this report, the polymorphisms of markers associated with CQ-resistance against Plasmodium falciparum isolates from coastal Kenya (Kilifi) were investigated, from 1993, prior to the withdrawal of CQ, to 2006, seven years after its withdrawal. Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared. Methods Mutations associated with CQ resistance, at codons 76 of pfcrt, at 86 of pfmdr1, and at codons 51, 59 and 164 of dhfr were analysed using PCR-restriction enzyme methods. In total, 406, 240 and 323 isolates were genotyped for pfcrt-76, pfmdr1-86 and dhfr, respectively. Results From 1993 to 2006, the frequency of the pfcrt-76 mutant significantly decreased from around 95% to 60%, while the frequency of pfmdr1-86 did not decline, remaining around 75%. Though the frequency of dhfr mutants was already high (around 80%) at the start of the study, this frequency increased to above 95% during the study period. Mutation at codon 164 of dhf r was analysed in 2006 samples, and none of them had this mutation. Conclusion In accord with the study in Malawi, a reduction in resistance to CQ following official withdrawal in 1999 was found, but unlike Malawi, the decline of resistance to CQ in Kilifi was much slower. It is estimated that, at current rates of decline, it will take 13 more years for the clinical efficacy of CQ to be restored in Kilifi. In addition, CQ resistance was declining before the drug's official withdrawal, suggesting that, prior to the official ban, the use of CQ had decreased, probably due to its poor clinical effectiveness.

Effective population-level interventions against Plasmodium falciparum malaria lead to age-shifts, delayed morbidity or rebounds in morbidity and mortality whenever they are deployed in ways that do not permanently interrupt transmission. When long-term intervention programmes target specific age-groups of human hosts, the age-specific morbidity rates ultimately adjust to new steady-states, but it is very difficult to study these rates and the temporal dynamics leading up to them empirically because the changes occur over very long time periods. This study investigates the age and magnitude of age- and time- shifting of incidence induced by either pre-erythrocytic vaccination (PEV) programmes or seasonal malaria chemo-prevention (SMC), using an ensemble of individual-based stochastic simulation models of P. falciparum dynamics. The models made various assumptions about immunity decay, transmission heterogeneity and were parameterized with data on both age-specific infection and disease incidence at different levels of exposure, on the durations of different stages of the parasite life-cycle and on human demography. Effects of transmission intensity, and of levels of access to malaria treatment were considered. While both PEV and SMC programmes are predicted to have overall strongly positive health effects, a shift of morbidity into older children is predicted to be induced by either programme if transmission levels remain static and not reduced by other interventions. Predicted shifting of burden continue into the second decade of the programme. Even if long-term surveillance is maintained it will be difficult to avoid mis-attribution of such long-term changes in age-specific morbidity patterns to other factors. Conversely, short-lived transient changes in incidence measured soon after introduction of a new intervention may give over-positive views of future impacts. Complementary intervention strategies could be designed to specifically protect those age-groups at risk from burden shift.