%0 Journal Article %J PLoS One %D 2017 %T Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study. %A McCollum, Eric D %A Nambiar, Bejoy %A Deula, Rashid %A Zadutsa, Beatiwel %A Bondo, Austin %A King, Carina %A Beard, James %A Liyaya, Harry %A Mankhambo, Limangeni %A Lazzerini, Marzia %A Makwenda, Charles %A Masache, Gibson %A Bar-Zeev, Naor %A Kazembe, Peter N %A Mwansambo, Charles %A Lufesi, Norman %A Costello, Anthony %A Armstrong, Ben %A Colbourn, Tim %K Child %K Child Mortality %K Cost of Illness %K Dose-Response Relationship, Immunologic %K Geography %K Humans %K Hypoxia %K Malawi %K Pneumococcal Vaccines %K Pneumonia, Pneumococcal %K Time Factors %K Vaccines, Conjugate %X

BACKGROUND: The pneumococcal conjugate vaccine's (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia.

METHODS AND FINDINGS: Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children <5 years at seven hospitals, 18 health centres, and with 38 community health workers in two districts, central Malawi. Eligible children had clinical pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation <90% defined hypoxemic pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children <5 years. We observed a shift towards disease without danger signs, as the proportion of cases with danger signs decreased by 65% (-46%, -77%, p<0.0001). These results were generally robust to plausible alternative model specifications.

CONCLUSIONS: Thirty months after PCV13 introduction in Malawi, the health system burden and rates of the severest forms of childhood pneumonia, including hypoxemia and death, have markedly decreased.

%B PLoS One %V 12 %P e0168209 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/28052071?dopt=Abstract %R 10.1371/journal.pone.0168209 %0 Journal Article %J Lancet Glob Health %D 2016 %T Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study. %A Lazzerini, Marzia %A Seward, Nadine %A Lufesi, Norman %A Banda, Rosina %A Sinyeka, Sophie %A Masache, Gibson %A Nambiar, Bejoy %A Makwenda, Charles %A Costello, Anthony %A McCollum, Eric D %A Colbourn, Tim %X

BACKGROUND: Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012.

METHODS: Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed effects logistic regression models.

FINDINGS: Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92·7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6·6% (95% CI 6·4-6·7). The case fatality rate significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11·8%), severe undernutrition (15·4%), severe acute malnutrition (34·8%), and symptom duration of more than 21 days (9·0%).

INTERPRETATION: Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of effective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi.

FUNDING: Bill & Melinda Gates Foundation.

%B Lancet Glob Health %V 4 %P e57-68 %8 2016 Jan %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26718810?dopt=Abstract %R 10.1016/S2214-109X(15)00215-6