Naor Bar-Zeev

Respiratory risks from household air pollution in low and middle income countries

A third of the worlds population uses solid fuel derived from plant material (biomass) or coal for cooking, heating, or lighting. These fuels are smoky, often used in an open fire or simple stove with incomplete combustion, and result in a large amount of household air pollution when smoke is poorly vented. Air pollution is the biggest environmental cause of death worldwide, with household air pollution accounting for about 3·5-4 million deaths every year. Women and children living in severe poverty have the greatest exposures to household air pollution. In this Commission, we review evidence for the association between household air pollution and respiratory infections, respiratory tract cancers, and chronic lung diseases. Respiratory infections (comprising both upper and lower respiratory tract infections with viruses, bacteria, and mycobacteria) have all been associated with exposure to household air pollution. Respiratory tract cancers, including both nasopharyngeal cancer and lung cancer, are strongly associated with pollution from coal burning and further data are needed about other solid fuels. Chronic lung diseases, including chronic obstructive pulmonary disease and bronchiectasis in women, are associated with solid fuel use for cooking, and the damaging effects of exposure to household air pollution in early life on lung development are yet to be fully described. We also review appropriate ways to measure exposure to household air pollution, as well as study design issues and potential effective interventions to prevent these disease burdens. Measurement of household air pollution needs individual, rather than fixed in place, monitoring because exposure varies by age, gender, location, and household role. Women and children are particularly susceptible to the toxic effects of pollution and are exposed to the highest concentrations. Interventions should target these high-risk groups and be of sufficient quality to make the air clean. To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact.

Effectiveness of a monovalent rotavirus vaccine in infants in Malawi after programmatic roll-out: an observational and case-control study

Summary Background Rotavirus is the main cause of severe acute gastroenteritis in children in Africa. Monovalent human rotavirus vaccine (RV1) was added into Malawis infant immunisation schedule on Oct 29, 2012. We aimed to assess the impact and effectiveness of RV1 on rotavirus gastroenteritis in the 2 years after introduction. Methods From Jan 1, 2012, to June 30, 2014, we recruited children younger than 5 years who were admitted into Queen Elizabeth Central Hospital, Blantyre, Malawi, with acute gastroenteritis. We assessed stool samples from these children for presence of rotavirus with use of ELISA and we genotyped rotaviruses with use of RT-PCR. We compared rotavirus detection rates in stool samples and incidence of hospital admittance for rotavirus in children from Jan 1 to June 30, in the year before vaccination (2012) with the same months in the 2 years after vaccination was introduced (2013 and 2014). In the case-control portion of our study, we recruited eligible rotavirus-positive children from the surveillance platform and calculated vaccine effectiveness (one minus the odds ratio of vaccination) by comparing infants with rotavirus gastroenteritis with infants who tested negative for rotavirus, and with community age-matched and neighbourhood-matched controls. Findings We enrolled 1431 children, from whom we obtained 1417 stool samples (99%). We detected rotavirus in 79 of 157 infants (50%) before the vaccine, compared with 57 of 219 (40%) and 52 of 170 (31%) in successive calendar years after vaccine introduction (p=0·0002). In the first half of 2012, incidence of rotavirus hospital admission was 269 per 100 000 infants compared with 284 in the same months of 2013 (rise of 5·8%, 95% CI −23·1 to 45·4; p=0·73) and 153 in these months in 2014 (a reduction from the prevaccine period of 43·2%, 18·0–60·7; p=0·003). We recruited 118 vaccine-eligible rotavirus cases (median age 8·9 months; IQR 6·6–11·1), 317 rotavirus-test-negative controls (9·4 months; 6·9–11·9), and 380 community controls (8·8 months; 6·5–11·1). Vaccine effectiveness for two doses of RV1 in rotavirus-negative individuals was 64% (95% CI 24–83) and community controls was 63% (23–83). The point estimate of effectiveness was higher against genotype G1 than against G2 and G12. Interpretation Routine use of RV1 reduced hospital admissions for several genotypes of rotavirus in children younger than 5 years, especially in infants younger than 1 year. Our data support introduction of rotavirus vaccination at the WHO recommended schedule, with continuing surveillance in high-mortality countries. Funding Wellcome Trust, GlaxoSmithKline Biologicals.

Population Impact and Effectiveness of Monovalent Rotavirus Vaccination in Urban Malawian Children 3 Years After Vaccine Introduction: Ecological and Case-Control Analyses

Background. Rotavirus vaccines have been introduced in many low-income African countries including Malawi in 2012. Despite early evidence of vaccine impact, determining persistence of protection beyond infancy, the utility of the vaccine against specific rotavirus genotypes, and effectiveness in vulnerable subgroups is important. Methods. We compared rotavirus prevalence in diarrheal stool and hospitalization incidence before and following rotavirus vaccine introduction in Malawi. Using case-control analysis, we derived vaccine effectiveness (VE) in the second year of life and for human immunodeficiency virus (HIV)–exposed and stunted children. Results. Rotavirus prevalence declined concurrent with increasing vaccine coverage, and in 2015 was 24% compared with prevaccine mean baseline in 1997–2011 of 32%. Since vaccine introduction, population rotavirus hospitalization incidence declined in infants by 54.2% (95% confidence interval [CI], 32.8–68.8), but did not fall in older children. Comparing 241 rotavirus cases with 692 test-negative controls, VE was 70.6% (95% CI, 33.6%–87.0%) and 31.7% (95% CI, −140.6% to 80.6%) in the first and second year of life, respectively, whereas mean age of rotavirus cases increased from 9.3 to 11.8 months. Despite higher VE against G1P[8] than against other genotypes, no resurgence of nonvaccine genotypes has occurred. VE did not differ significantly by nutritional status (78.1% [95% CI, 5.6%–94.9%] in 257 well-nourished and 27.8% [95% CI, −99.5% to 73.9%] in 205 stunted children; P = .12), or by HIV exposure (60.5% [95% CI, 13.3%–82.0%] in 745 HIV-unexposed and 42.2% [95% CI, −106.9% to 83.8%] in 174 exposed children; P = .91). Conclusions. Rotavirus vaccination in Malawi has resulted in reductions in disease burden in infants <12 months, but not in older children. Despite differences in genotype-specific VE, no genotype has emerged to suggest vaccine escape. VE was not demonstrably affected by HIV exposure or stunting.

Income and child mortality in developing countries: a systematic review and meta-analysis:

Objective We aimed to quantify the relationship between national income and infant and under-five mortality in developing countries. Design We conducted a systematic literature search of studies that examined the relationship between income and child mortality (infant and/or under-five mortality) and meta-analysed their results. Setting Developing countries. Main outcome measures Child mortality (infant and /or under-five mortality). Results The systematic literature search identified 24 studies, which produced 38 estimates that examined the impact of income on the mortality rates. Using meta-analysis, we produced pooled estimates of the relationship between income and mortality. The pooled estimate of the relationship between income and infant mortality before adjusting for covariates is −0.95 (95% CI −1.34 to −0.57) and that for under-five mortality is −0.45 (95% CI −0.79 to −0.11). After adjusting for covariates, pooled estimate of the relationship between income and infant mortality is −0.33 (−0.39 to −0.26) while the estimate for under-five mortality is −0.28 (−0.37 to −0.19). If a country has an infant mortality of 50 per 1000 live births and the gross domestic product per capita purchasing power parity increases by 10%, the infant mortality will decrease to 45 per 1000 live births. Conclusion Income is an important determinant of child survival and this work provides a pooled estimate for the relationship.

Bacterial Meningitis in Malawian Adults, Adolescents, and Children During the Era of Antiretroviral Scale-up and Haemophilus influenzae Type b Vaccination, 2000–2012

Culture positive bacterial meningitis has fallen over a 12-year period in urban Malawi following Hib vaccination. Hib, NTS, and pneumococcal meningitis have fallen significantly in children. Pneumococcal meningitis has not fallen in adults; NTS and pneumococcal meningitis are seasonal.

Sequential Acquisition of T Cells and Antibodies to Nontyphoidal Salmonella in Malawian Children

Background. Salmonella Typhimurium (STm) remain a prominent cause of bacteremia in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of age. We hypothesized that STm-specific CD4+ T cells develop alongside this process. Methods. Eighty healthy Malawian children aged 0–60 months were recruited. STm-specific CD4+ T cells producing interferon γ, tumor necrosis factor α, and interleukin 2 were quantified using intracellular cytokine staining. Antibodies to STm were measured by serum bactericidal activity (SBA) assay, and anti-STm immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Results. Between 2006 and 2011, STm bacteremias were detected in 449 children <5 years old. STm-specific CD4+ T cells were acquired in infancy, peaked at 14 months, and then declined. STm-specific SBA was detectable in newborns, declined in the first 8 months, and then increased to a peak at age 35 months. Acquisition of SBA correlated with acquisition of anti–STm–lipopolysaccharide (LPS) immunoglobulin G (r = 0.329 [95% confidence interval, .552–.062]; P = .01) but not anti–STm–outer membrane protein or anti–STm-flagellar protein (FliC). Conclusions. Acquisition of STm-specific CD4+ T cells in early childhood is consistent with early exposure to STm or cross-reactive protein antigens priming this T-cell development. STm-specific CD4+ T cells seem insufficient to protect against invasive nontyphoidal Salmonella disease, but sequential acquisition of SBA to STm LPS is associated with a decline in its incidence.

Determination of a Viral Load Threshold To Distinguish Symptomatic versus Asymptomatic Rotavirus Infection in a High-Disease-Burden African Population

ABSTRACT We evaluated quantitative real-time PCR to establish the diagnosis of rotavirus gastroenteritis in a high-disease-burden population in Malawi using enzyme immunoassay as the gold standard diagnostic test. In 146 children with acute gastroenteritis and 65 asymptomatic children, we defined a cutoff point in the threshold cycle value (26.7) that predicts rotavirus-attributable gastroenteritis in this population. These data will inform the evaluation of direct and indirect rotavirus vaccine effects in Africa.

Human Melioidosis, Malawi, 2011

A case of human melioidosis caused by a novel sequence type of Burkholderia pseudomallei occurred in a child in Malawi, southern Africa. A literature review showed that human cases reported from the continent have been increasing.

Use of health services by remote dwelling Aboriginal infants in tropical northern Australia : a retrospective cohort study

BackgroundAustralia is a wealthy developed country. However, there are significant disparities in health outcomes for Aboriginal infants compared with other Australian infants. Health outcomes tend to be worse for those living in remote areas. Little is known about the health service utilisation patterns of remote dwelling Aboriginal infants. This study describes health service utilisation patterns at the primary and referral level by remote dwelling Aboriginal infants from northern Australia.ResultsData on 413 infants were analysed. Following birth, one third of infants were admitted to the regional hospital neonatal nursery, primarily for preterm birth. Once home, most (98%) health service utilisation occurred at the remote primary health centre, infants presented to the centre about once a fortnight (mean 28 presentations per year, 95%CI 26.4-30.0). Half of the presentations were for new problems, most commonly for respiratory, skin and gastrointestinal symptoms. Remaining presentations were for reviews or routine health service provision. By one year of age 59% of infants were admitted to hospital at least once, the rate of hospitalisation per infant year was 1.1 (95%CI 0.9-1.2).ConclusionsThe hospitalisation rate is high and admissions commence early in life, visits to the remote primary health centre are frequent. Half of all presentations are for new problems. These findings have important implications for health service planning and delivery to remote dwelling Aboriginal families.

Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study

Summary Background Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance. Methods In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time. Findings Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016. Interpretation The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting. Funding Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).