Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

Everett, Dean; Mukaka, Mavuto; Denis, Brigitte; Gordon, Stephen B.; Carrol, Enitan D.; Oosterhout, Joep J. van; Molyneux, Elizabeth; Molyneux, Malcolm E.; French, Neil; Heyderman, Robert S.

doi:10.1371/journal.pone.0017765

Cited by 67 publications

(80 citation statements)

References 48 publications

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“…The skyline plot suggests that the population then remained stable until the last sampling point in 2010, but this must be treated with caution because of the possibility that in this more recent time period, the relatively scant data leads the analysis to recover the prior [66]. The decline in the population size in clade SC3-SEA coincided with the previously reported decline in IPD in Malawi after scale-up of anti-retroviral therapy and cotrimoxazole prophylaxis [67]. In the South African clade, the population size increased slowly from late 1990s and has consistently remained higher than in Malawi and Mozambique from mid-2000s until 2010, possibly reflecting the higher diversity of the South African population.…”

Section: Discussionmentioning

confidence: 70%

Understanding pneumococcal serotype 1 biology through population genomic analysis

et al. 2016

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BackgroundPneumococcus kills over one million children annually and over 90 % of these deaths occur in low-income countries especially in Sub-Saharan Africa (SSA) where HIV exacerbates the disease burden. In SSA, serotype 1 pneumococci particularly the endemic ST217 clone, causes majority of the pneumococcal disease burden. To understand the evolution of the virulent ST217 clone, we analysed ST217 whole genomes from isolates sampled from African and Asian countries.MethodsWe analysed 226 whole genome sequences from the ST217 lineage sampled from 9 African and 4 Asian countries. We constructed a whole genome alignment and used it for phylogenetic and coalescent analyses. We also screened the genomes to determine presence of antibiotic resistance conferring genes.ResultsPopulation structure analysis grouped the ST217 isolates into five sequence clusters (SCs), which were highly associated with different geographical regions and showed limited intracontinental and intercontinental spread. The SCs showed lower than expected genomic sequence, which suggested strong purifying selection and small population sizes caused by bottlenecks. Recombination rates varied between the SCs but were lower than in other successful clones such as PMEN1. African isolates showed higher prevalence of antibiotic resistance genes than Asian isolates. Interestingly, certain West African isolates harbored a defective chloramphenicol and tetracycline resistance-conferring element (Tn5253) with a deletion in the loci encoding the chloramphenicol resistance gene (cat pC194), which caused lower chloramphenicol than tetracycline resistance. Furthermore, certain genes that promote colonisation were absent in the isolates, which may contribute to serotype 1’s rarity in carriage and consequently its lower recombination rates.ConclusionsThe high phylogeographic diversity of the ST217 clone shows that this clone has been in circulation globally for a long time, which allowed its diversification and adaptation in different geographical regions. Such geographic adaptation reflects local variations in selection pressures in different locales. Further studies will be required to fully understand the biological mechanisms which makes the ST217 clone highly invasive but unable to successfully colonise the human nasopharynx for long durations which results in lower recombination rates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1987-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 70%

Understanding pneumococcal serotype 1 biology through population genomic analysis

et al. 2016

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“…CSF samples were taken from the adult patients where there was clinical suspicion of meningitis 18 . Blood or CSF samples were taken from children with febrile illness, but who were malaria slide negative and had no obvious focus of infection, or who were severely ill with sepsis or meningitis, and patients who failed initial malaria treatment and remained febrile 19 . Antimicrobial susceptibility tests were performed by the disc diffusion method using methods and breakpoints outlined by BSAC (www.bsac.org.uk).…”

Section: Methodsmentioning

confidence: 99%

Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting

Musicha¹,

Feasey

Cain

et al. 2017

Journal of Antimicrobial Chemotherapy

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Objectives: Efforts to treat Escherichia coli infections are increasingly being compromised by the rapid, global spread of antimicrobial resistance (AMR). Whilst AMR in E. coli has been extensively investigated in resource-rich settings, in sub-Saharan Africa molecular patterns of AMR are not well described. In this study, we have begun to explore the population structure and molecular determinants of AMR amongst E. coli isolates from Malawi. Methods: Ninety-four E. coli isolates from patients admitted to Queen’s Hospital, Malawi, were whole-genome sequenced. The isolates were selected on the basis of diversity of phenotypic resistance profiles and clinical source of isolation (blood, CSF and rectal swab). Sequence data were analysed using comparative genomics and phylogenetics. Results: Our results revealed the presence of five clades, which were strongly associated with E. coli phylogroups A, B1, B2, D and F. We identified 43 multilocus STs, of which ST131 (14.9%) and ST12 (9.6%) were the most common. We identified 25 AMR genes. The most common ESBL gene was blaCTX-M-15 and it was present in all five phylogroups and 11 STs, and most commonly detected in ST391 (4/4 isolates), ST648 (3/3 isolates) and ST131 [3/14 (21.4%) isolates]. Conclusions: This study has revealed a high diversity of lineages associated with AMR, including ESBL and fluoroquinolone resistance, in Malawi. The data highlight the value of longitudinal bacteraemia surveillance coupled with detailed molecular epidemiology in all settings, including low-income settings, in describing the global epidemiology of ESBL resistance.

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“…Clinically relevant groupings for continuous variables were created for the multivariate model to aid interpretation of the results. We have reported the seasonal nature of invasive pneumococcal disease in Malawi, and used this data to investigate if mortality was also seasonal [9], [20].…”

Section: Methodsmentioning

confidence: 99%

High Mortality amongst Adolescents and Adults with Bacterial Meningitis in Sub-Saharan Africa: An Analysis of 715 Cases from Malawi

et al. 2013

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Mortality from bacterial meningitis in African adults is significantly higher than those in better resourced settings and adjunctive therapeutic interventions such as dexamethasone and glycerol have been shown to be ineffective. We conducted a study analysing data from clinical trials of bacterial meningitis in Blantyre, Malawi to investigate the clinical parameters associated with this high mortality.MethodsWe searched for all clinical trials undertaken in Blantyre investigating bacterial meningitis from 1990 to the current time and combined the data from all included trial datasets into one database. We used logistic regression to relate individual clinical parameters to mortality. Adults with community acquired bacterial meningitis were included if the CSF culture isolate was consistent with meningitis or if the CSF white cell count was >100 cells/mm3 (>50% neutrophils) in HIV negative participants and >5 cells/mm3 in HIV positive participants. Outcome was measured by mortality at discharge from hospital (after 10 days of antibiotic therapy) and community follow up (day 40).ResultsSeven hundred and fifteen episodes of bacterial meningitis were evaluated. The mortality rate was 45% at day 10 and 54% at day 40. The most common pathogens were S.pneumoniae (84% of positive CSF isolates) and N.meningitidis (4%). 607/694 (87%) participants tested were HIV antibody positive. Treatment delays within the hospital system were marked. The median presenting GCS was 12/15, 17% had GCS<8 and 44.9% had a seizure during the illness. Coma, seizures, tachycardia and anaemia were all significantly associated with mortality on multivariate analysis. HIV status and pneumococcal culture positivity in the CSF were not associated with mortality. Adults with community acquired bacterial meningitis in Malawi present with a severe clinical phenotype. Predictors of high mortality are different to those seen in Western settings. Optimising in-hospital care and minimising treatment delays presents an opportunity to improve outcomes considerably.

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Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

Cited by 67 publications

References 48 publications

Understanding pneumococcal serotype 1 biology through population genomic analysis

Understanding pneumococcal serotype 1 biology through population genomic analysis

Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting

High Mortality amongst Adolescents and Adults with Bacterial Meningitis in Sub-Saharan Africa: An Analysis of 715 Cases from Malawi

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