Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

Background: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. Methods: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45000 children younger than 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 three-dose catch-up campaign for infants (aged \u3c1 \u3eyear) and a two-dose catch-up campaign for children aged 1–4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. Findings: Between May 1, 2002 and March 31, 2015, 44771 children aged 2–143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses’ strikes. In 2002–03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2–59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2–11 months had received at least two doses of PCV10 and 23298 (62·3%) of 37416 children aged 12–59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologicallyconfirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32–0·86), 0·73 (0·54–0·97), and 0·63 (0·31–1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100000; this value was reduced by 329 per 100000 at the point of PCV10 introduction. Interpretation: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10

Cohort profile : the Kilifi vaccine monitoring study

The Kilifi Vaccine Monitoring Study (KiVMS) is a long-term continuous cohort study set up to investigate effectiveness, impact, coverage, safety and indirect vaccine effects by recruiting birth cohorts and, where applicable, cohorts of older and adults. It is based in the area covered by the Kilifi Health and Demographic Surveillance System, Kilifi, Kenya, and currently has records of 33 962 children in the birth cohort database. A major strength of KiVMS is its unique integration of a vaccine registry, a morbidity surveillance system and the largest health and demographic surveillance system (HDSS) in Africa

Association between maternal factors and survival patterns of children, in rural Kwazulu-Natal, South Africa, 2004-2011

Globally, child mortality is a great concern, especially in resource-limited settings. The Millennium Development Goal (MDG) 4 was set with an aim to reduce under-5 child mortality by two-thirds between 1990 and 2015. This study examines mortality trends in infants, 1-4 and above 5-year-old children in rural KwaZulu-Natal, South Africa, the causes of death as well as the association of maternal HIV status and Antiretroviral Treatment (ART) usage to child mortality. We use a longitudinal birth cohort study design of children born between 1st January 2004 and 31st December 2010, in the Africa Centre Demographic Surveillance Area (DSA) in rural KwaZulu-Natal, South Africa. Children had to have been resident in the DSA at the time of birth. A total of 12,413 children born in the study period were eligible for this study. The main outcome measure was mortality either in infancy, the 1-4 year period or at 5 and above years of age, while assessing its association with maternal HIV and Antiretroviral Treatment uptake (ART) status on a time-varying basis. A total of 619 children died during the study period and mortality was observed to be highest in the infant group with 67% of the children dying in infancy. Fifteen percent of mothers were HIV positive at the time of birth of the child, about 59% were HIV negative while the HIV status of the rest was unknown. There was a three-fold increase in mortality observed for both infants and 1-4 year olds, who had mothers who were HIV infected compared to children whose mothers were HIV negative (p<0.05). Children whose mothers were on Antiretroviral Treatment (ART) however had a reduced mortality compared to those whose mothers were not on treatment. Infants and 1-4year olds whose mothers HIV status was not reported had a two-fold increase in mortality. Low maternal education, single motherhood, multiple births and parity of four or more children were also associated with increased child mortality. We concluded that although mortality varied by the age of the child, children born to mothers who were HIV positive had higher mortality rates than children born to HIV negative mothers but being on Anti Retroviral Treatment (ART) reduced children mortality. Interventions targeting HIV positive pregnant women and mothers should be carried out in the study area, with specific emphasis on reducing child mortality associated with maternal HIV status

Effect of 10-valent pneumococcal conjugate vaccine on the incidence of radiologically-confirmed pneumonia and clinically-defined pneumonia in Kenyan children: an interrupted time-series analysis

Summary: Background: Pneumococcal conjugate vaccines (PCV) are highly protective against invasive pneumococcal disease caused by vaccine serotypes, but the burden of pneumococcal disease in low-income and middle-income countries is dominated by pneumonia, most of which is non-bacteraemic. We examined the effect of 10-valent PCV on the incidence of pneumonia in Kenya. Methods: We linked prospective hospital surveillance for clinically-defined WHO severe or very severe pneumonia at Kilifi County Hospital, Kenya, from 2002 to 2015, to population surveillance at Kilifi Health and Demographic Surveillance System, comprising 45 000 children younger than 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 three-dose catch-up campaign for infants (aged <1 year) and a two-dose catch-up campaign for children aged 1–4 years, between January and March, 2011. We estimated the effect of PCV10 on the incidence of clinically-defined and radiologically-confirmed pneumonia through interrupted time-series analysis, accounting for seasonal and temporal trends. Findings: Between May 1, 2002 and March 31, 2015, 44 771 children aged 2–143 months were admitted to Kilifi County Hospital. We excluded 810 admissions between January and March, 2011, and 182 admissions during nurses' strikes. In 2002–03, the incidence of admission with clinically-defined pneumonia was 2170 per 100 000 in children aged 2–59 months. By the end of the catch-up campaign in 2011, 4997 (61·1%) of 8181 children aged 2–11 months had received at least two doses of PCV10 and 23 298 (62·3%) of 37 416 children aged 12–59 months had received at least one dose. Across the 13 years of surveillance, the incidence of clinically-defined pneumonia declined by 0·5% per month, independent of vaccine introduction. There was no secular trend in the incidence of radiologically-confirmed pneumonia over 8 years of study. After adjustment for secular trend and season, incidence rate ratios for admission with radiologically-confirmed pneumonia, clinically-defined pneumonia, and diarrhoea (control condition), associated temporally with PCV10 introduction and the catch-up campaign, were 0·52 (95% CI 0·32–0·86), 0·73 (0·54–0·97), and 0·63 (0·31–1·26), respectively. Immediately before PCV10 was introduced, the annual incidence of clinically-defined pneumonia was 1220 per 100 000; this value was reduced by 329 per 100 000 at the point of PCV10 introduction. Interpretation: Over 13 years, admissions to Kilifi County Hospital for clinically-defined pneumonia decreased sharply (by 27%) in association with the introduction of PCV10, as did the incidence of radiologically-confirmed pneumonia (by 48%). The burden of hospital admissions for childhood pneumonia in Kilifi, Kenya, has been reduced substantially by the introduction of PCV10. Funding: Gavi, The Vaccine Alliance and Wellcome Trust