Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi: a modelling study.

BACKGROUND: In November 2011, Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant schedule. Four to 7 years after introduction (2015-2018), rolling prospective nasopharyngeal carriage surveys were performed in the city of Blantyre. Carriage of Streptococcus pneumoniae vaccine serotypes (VT) remained higher than reported in high-income countries, and impact was asymmetric across age groups. METHODS: A dynamic transmission model was fit to survey data using a Bayesian Markov-chain Monte Carlo approach, to obtain insights into the determinants of post-PCV13 age-specific VT carriage. RESULTS: Accumulation of naturally acquired immunity with age and age-specific transmission potential were both key to reproducing the observed data. VT carriage reduction peaked sequentially over time, earlier in younger and later in older age groups. Estimated vaccine efficacy (protection against carriage) was 66.87% (95% CI 50.49-82.26%), similar to previous estimates. Ten-year projected vaccine impact (VT carriage reduction) among 0-9 years old was lower than observed in other settings, at 76.23% (CI 95% 68.02-81.96%), with sensitivity analyses demonstrating this to be mainly driven by a high local force of infection. CONCLUSIONS: There are both vaccine-related and host-related determinants of post-PCV13 pneumococcal VT transmission in Blantyre with vaccine impact determined by an age-specific, local force of infection. These findings are likely to be generalisable to other Sub-Saharan African countries in which PCV impact on carriage (and therefore herd protection) has been lower than desired, and have implications for the interpretation of post-PCV carriage studies and future vaccination programs.

Direct and possible indirect effects of vaccination on rotavirus hospitalisations among children in Malawi four years after programmatic introduction.

INTRODUCTION: Despite increased use of vaccine in routine immunisation, rotavirus remains a major cause of acute gastroenteritis (AGE) in low-income countries. We describe rotavirus prevalence and hospitalisation in Malawi pre and four years post vaccine introduction; provide updated vaccine effectiveness (VE) estimates; and assess rotavirus vaccine indirect effects. METHODS: Children under five years of age presenting to a referral hospital in Blantyre with AGE were recruited. Stool samples were tested for rotavirus using Enzyme Immunoassay. The change in rotavirus prevalence was evaluated using Poisson regression. Time series analysis was used to further investigate trends in prevalence over time. VE against rotavirus diarrhoea of any severity was estimated using logistic regression. Indirect effects were estimated by evaluating rotavirus prevalence in unvaccinated children over time, and by comparing observed reductions in incidence of rotavirus hospitalisation to those expected based on vaccine coverage and trial efficacy estimates. RESULTS: 2320 children were included. Prevalence of rotavirus in hospitalised infants (<12 months) with AGE decreased from 69/139(49.64%) prior to vaccine introduction to 197/607(32.45%) post-vaccine introduction (adjusted RR 0.67[95% CI 0.55, 0.82]). Prevalence in children aged 12-23 months demonstrated a less substantial decline: 15/37(40.54%) pre- and 122/352(34.66%) post-vaccine introduction (adjusted RR 0.85, 95% CI 0.57, 1.28). Adjusted VE was 61.89%(95% CI 28.04-79.82), but lower in children aged 12-23 months (31.69% [95% CI -139.03 to 80.48]). In hospitalised infants with rotavirus disease, the observed overall effect of the vaccine was 9% greater than expected according to vaccine coverage and efficacy estimates. Rotavirus prevalence among unvaccinated infants declined post-vaccine introduction (RR 0.70[95% CI 0.55-0.80]). CONCLUSIONS: Following rotavirus vaccine introduction in Malawi, prevalence of rotavirus in hospitalised children with AGE has declined significantly, with some evidence of an indirect effect in infants. Despite this, rotavirus remains an important cause of severe diarrhoea in Malawian children, particularly in the second year of life.

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality.

Knowledge and perceptions of quality of obstetric and newborn care of local health providers: a cross-sectional study in three districts in Malawi.

AIM: Quality of service delivery for maternal and newborn health in Malawi is influenced by human resource shortages and knowledge and care practices of the existing service providers. We assessed Malawian healthcare providers' knowledge of management of routine labour, emergency obstetric care and emergency newborn care; correlated knowledge with reported confidence and previous study or training; and measured perception of the care they provided. METHODS: This study formed part of a large-scale quality of care assessment in three districts (Kasungu, Lilongwe and Salima) of Malawi. Subjects were selected purposively by their role as providers of obstetric and newborn care during routine visits to health facilities by a research assistant. Research assistants introduced and supervised the self-completed questionnaire by the service providers. Respondents included 42 nurse midwives, 1 clinical officer, 4 medical assistants and 5 other staff. Of these, 37 were staff working in facilities providing Basic Emergency Obstetric Care (BEMoC) and 15 were from staff working in facilities providing Comprehensive Emergency Obstetric Care (CEMoC). RESULTS: Knowledge regarding management of routine labour was good (80% correct responses), but knowledge of correct monitoring during routine labour (35% correct) was not in keeping with internationally recognized good practice. Questions regarding emergency obstetric care were answered correctly by 70% of respondents with significant variation depending on clinicians' place of work. Knowledge of emergency newborn care was poor across all groups surveyed with 58% correct responses and high rates of potentially life-threatening responses from BEmOC facilities. Reported confidence and training had little impact on levels of knowledge. Staff in general reported perception of poor quality of care. CONCLUSION: Serious deficiencies in providers' knowledge regarding monitoring during routine labour and management of emergency newborn care were documented. These may contribute to maternal and neonatal deaths in Malawi. The knowledge gap cannot be overcome by simply providing more training.

Strategies developed and implemented by women's groups to improve mother and infant health and reduce mortality in rural Malawi.

We evaluated the strategies to tackle maternal and infant health problems developed by women's groups in rural Malawi. Quantitative data were analyzed on strategies developed by 184 groups at two of the meetings in the community action cycle (attended by 3365 and 3047 women). Data on strategies implemented was collected through a survey of the 197 groups active in January 2010. Qualitative data on the identification and implementation of strategies was collected through 17 focus group discussions and 12 interviews with men and women. To address the maternal and child health problems identified the five most common strategies identified were: health education sessions, bicycle ambulances, training of traditional birth attendants, wetland vegetable garden (dimba garden) cultivation and distribution of insecticide treated bednets (ITNs). The five most common strategies actually implemented were: dimba garden cultivation, health education sessions, ITN distribution, health programme radio listening clubs and clearing house surroundings. The rationale behind the strategies and the factors facilitating and hindering implementation are presented. The potential impact of the strategies on health is discussed. Women's groups help communities to take control of their health issues and have the potential to reduce neonatal, infant and maternal mortality and morbidity in the longer term.

Erratum to "Maternal, neonatal and child health interventions and services: moving from knowledge of what works to systems that deliver" [International Health 2 (2010) 87-98].

The Publisher regrets that an error occurred in the name of the 6th listed co-author for this paper. B. Matthias was listed in the original paper instead of M. Borchert; the correct listing can be seen above.

Women's groups' perceptions of neonatal and infant health problems in rural Malawi.

AIMS: To present the perceptions of women in rural Malawi regarding the health problems affecting neonates and infants and to explore the relevance of these perceptions for child health policy and strategy in Malawi. METHODS: Women's groups in Mchinji district identified newborn and infant health problems (204 groups, 3484 women), prioritised problems they considered most important (204 groups, 3338 women) and recorded these problems on monitoring forms. Qualitative data was obtained through 6 focus-group discussions with the women's groups and 22 interviews with individuals living in women's group communities but not attending groups. RESULTS: Women in Malawi do not define the neonatal period according to any epidemiological definition. In order of importance they identified and prioritised the following problems for newborns and infants: diarrhoea, infection, preterm birth, tetanus, malaria, asphyxia, respiratory tract infection, hypothermia, jaundice, convulsions and malnutrition. CONCLUSION: This study suggests that women in rural Malawi collectively have a developed understanding of neonatal and infant health problems. This makes a strong argument for the involvement of lay people in policy and strategy development and also suggests that this capacity, harnessed and strengthened through community mobilisation approaches, has the potential to improve neonatal and infant health and reduce mortality.

Planning health care in developing countries.

The major challenge for health care planners lies in integrating health promotion and disease prevention on the one hand and treatment of acute illness and chronic care on the other. This has to be done at all levels of the health system with the aim of delivering quality services equitably and efficiently to the whole population. This is a particular problem as many governments spend less than US $10 per person per year on health. Acute sector healthcare, including anaesthesia, is often deficient under these circumstances.

Contextualising the paediatric HIV epidemic: a review.

OBJECTIVE: To draw attention to the sub-optimal care that HIV-infected children are receiving in Africa. DATA SOURCES: Relevant published literature. DATA SYNTHESIS: Sub-optimal response to paediatric HIV infection has aggravated the negative impact that the epidemic has had on child health in Africa. Recently the African Network for the Care of Children Affected by HIV/AIDS (ANNECA) released an advocacy statement that called for the optimisation of prevention, diagnosis, treatment and care for children affected by the AIDS pandemic. Effective prevention strategies if comprehensively implemented, could prevent more than 500 000 paediatric infections per annum at current antenatal HIV prevalence rates. Improved care that includes universal utilisation of early diagnostic testing systems, cotrimoxazole prophylaxis, nutritional support and the timely introduction of antiretroviral therapy could improve the quality of life and lifespan of most infected children. CONCLUSION: Political leaders, public health officials and fellow child health professionals are urged to redouble their efforts to reverse the magnitude of the paediatric epidemic in Africa.

Neonatal sepsis: an international perspective.

Neonatal infections currently cause about 1.6 million deaths annually in developing countries. Sepsis and meningitis are responsible for most of these deaths. Resistance to commonly used antibiotics is emerging and constitutes an important problem world wide. To reduce global neonatal mortality, strategies of proven efficacy, such as hand washing, barrier nursing, restriction of antibiotic use, and rationalisation of admission to neonatal units, need to be implemented. Different approaches require further research.

Childhood tuberculosis in Malawi: caseload, diagnostic practices and treatment outcomes.

There were 22,982 cases of TB registered in Malawi in 1998, of which 2739 (11.9%) were children. Children accounted for 11.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extrapulmonary TB (EPTB). A significantly higher proportion of TB cases were diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. In 2001, all 44 non-private hospitals in Malawi that register and treat children with tuberculosis (TB) were surveyed to determine actual diagnostic practice. This cross sectional study identified 150 children aged 14 years or below in hospital receiving anti-TB treatment, 98 with pulmonary TB (PTB) and 52 with extrapulmonary TB (EPTB). Median duration of illness was 8 weeks. Most patients had fever, no response to anti-malarial treatment and antibiotics, and 40% had a positive family history of TB. Nearly 45% had weight for age < 60%. Diagnosis was mainly based on clinical features and radiography, with less than 10% having tuberculin skin tests or HIV serology, and very few having other sophisticated investigations. Diagnostic difficulties make it difficult to accurately define the actual burden of childhood TB in Malawi. Diagnostic practices are poor and treatment outcomes unsatisfactory.

Detection of bloodstream pathogens in a bacille Calmette-Guérin (BCG)-vaccinated pediatric population in Malawi: a pilot study.

Children in Malawi receive bacille Calmette-Guérin (BCG) vaccination within the first 3 days of life. Thus, we hypothesized that Malawian children infected with the human immunodeficiency type 1 virus (HIV-1) might be particularly vulnerable to dissemination of the BCG Mycobacterium bovis strain with which they were vaccinated. Following informed consent by parents, we studied children admitted to a Malawi general hospital during the 1998 wet and dry seasons. Blood from cohorts of acutely ill children was cultured for bacteria, including mycobacteria, and fungi, and tested for anti-HIV-1 antibodies. It was shown that non-typhi Salmonella and Escherichia coli were the predominant bloodstream pathogens during the wet and dry seasons, and that bloodstream dissemination of the BCG M. bovis strain is uncommon in HIV-1-infected children who receive the BCG vaccine.

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.