Siân E. Clarke

National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010

Summary Background National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Methods Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. Findings In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. Interpretation The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Funding Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group (CHERG).

Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial

Summary Background Malaria is a major cause of morbidity and mortality in early childhood, yet its consequences for health and education during the school-age years remain poorly understood. We examined the effect of intermittent preventive treatment (IPT) in reducing anaemia and improving classroom attention and educational achievement in semi-immune schoolchildren in an area of high perennial transmission. Methods A stratified, cluster-randomised, double-blind, placebo-controlled trial of IPT was done in 30 primary schools in western Kenya. Schools were randomly assigned to treatment (sulfadoxine-pyrimethamine in combination with amodiaquine or dual placebo) by use of a computer-generated list. Children aged 5–18 years received three treatments at 4-month intervals (IPT n=3535, placebo n=3223). The primary endpoint was the prevalence of anaemia, defined as a haemoglobin concentration below 110 g/L. This outcome was assessed through cross-sectional surveys 12 months post-intervention. Analysis was by both intention to treat, excluding children with missing data, and per protocol. This study is registered with ClinicalTrials.gov, number NCT00142246. Findings 2604 children in the IPT group and 2302 in the placebo group were included in the intention-to-treat analysis of the primary outcome; the main reason for exclusion was loss to follow-up. Prevalence of anaemia at 12 months averaged 6·3% in the IPT group and 12·6% in the placebo group (adjusted risk ratio 0·52, 95% CI 0·29–0·93; p=0·028). Significant improvements were also seen in two of the class-based tests of sustained attention, with a mean increase in code transmission test score of 6·05 (95% CI 2·83–9·27; p=0·0007) and counting sounds test score of 1·80 (0·19–3·41; p=0·03), compared with controls. No effect was shown for inattentive or hyperactive-compulsive behaviours or on educational achievement. The per-protocol analysis yielded similar results. 23 serious adverse events were reported within 28 days of any treatment (19 in the IPT group and four in the placebo group); the main side-effects were problems of balance, dizziness, feeling faint, nausea, and/or vomiting shortly after treatment. Interpretation IPT of malaria improves the health and cognitive ability of semi-immune schoolchildren. Effective malaria interventions could be a valuable addition to school health programmes. Funding Gates Malaria Partnership, the Norwegian Education Trust Fund and multidonor Education Development Programme Fund of the World Bank, DBL Centre for Health Research and Development, and the Wellcome Trust.

Do untreated bednets protect against malaria

Bednets are thought to offer little, if any, protection against malaria, unless treated with insecticide. There is also concern that the use of untreated nets will cause people sleeping without nets to receive more mosquito bites, and thus increase the malaria risk for other community members. Regular retreatment of nets is therefore viewed as critical for malaria control. However, despite good uptake of nets, many control programmes in Africa have reported low re-treatment rates. We investigated whether untreated bednets had any protective benefit (in October and November 1996) in The Gambia where nets, although widely used, are mostly untreated. Cross-sectional prevalence surveys were carried out in 48 villages and the risk of malaria parasitaemia was compared in young children sleeping with or without nets. Use of an untreated bednet in good condition was associated with a significantly lower prevalence of Plasmodium falciparum infection (51% protection [95% CI 34-64%], P < 0.001). This finding was only partly explained by differences in wealth between households, and children in the poorest households benefited most from sleeping under an untreated net (62% protection [14-83%], P = 0.018). There was no evidence that mosquitoes were diverted to feed on children sleeping without nets. These findings suggest that an untreated net, provided it is in relatively good condition, can protect against malaria. Control programmes should target the poorest households as they may have the most to gain from using nets.

Risk of malaria attacks in Gambian children is greater away from malaria vector breeding sites

The causes of local variation in the prevalence of malaria were investigated in rural Gambia. Cross-sectional prevalence surveys were carried out among 1184 young children (aged 6 months-5 years) in 48 villages, at the end of the transmission season in 1996. Villages were categorized according to distance from the nearest vector breeding sites, and the patterns of malaria transmission, infection and disease compared. Children living in villages within 3 km of breeding sites experienced more infective bites, and higher prevalences of parasitaemia and spleen enlargement than less-exposed children living further away. Clinical illness, in contrast, was more common among infected children who were less exposed. Infected children living 3 km or more from breeding sites were more likely to have high-density parasitaemia (odds ratio [OR] = 1.98), fever (OR = 2.60) and high-density parasitaemia together with fever (OR = 3.17). Clinical attacks did not decline in older children, as seen amongst children who were more exposed. These findings show that significant differences in the risk of infection and clinical attacks can occur over very short distances. The age at which protective immunity is acquired may be delayed in villages where transmission intensity is lower, thus increasing the risk of a clinical attack following infection. Communities with the lowest vector densities may be those at greatest risk of disease.

Effect of Passive Zooprophylaxis on Malaria Transmission in the Gambia

Abstract The effect of zooprophylaxis on malaria transmission has not been studied on the African continent despite that the World Health Organization has recommended this intervention method since 1982. The effect of passive zooprophylaxis on malaria vector abundance, mosquito feeding preferences, and infectivity was studied in an area of moderate seasonal transmission in The Gambia. A paired cohort of 204 children <7 yr of age was selected and matched in groups for presence or absence of cattle (Bos taurus) within 20 m of their bedroom. Comparisons were made between mosquitoes collected from the bedrooms of the two groups of children. Other ruminants and equines were present in both groups of compounds. Most of the anopheline mosquitoes (98.5%) collected were Anopheles gambiae sensu lato. There was no difference in the geometric mean number of An. gambiae s.l. mosquitoes caught in houses near or far from cattle. The species composition of the An. gambiae complex was similar in both groups. Blood meal analysis of specimens collected in houses without cattle showed a human blood index (HBI) of 82% for An. Arabiensis (Patton), 56% for An. gambiae sensu stricto (Giles), and 36% for Anopheles Melas (Theobald), indicating that each of these sibling species fed readily on animals. The presence of cattle reduced the HBI of An. arabiensis but did not significantly alter the HBI of An. gambiae s.s. or An. melas. There was no significant difference between the groups in the sporozoite rates of An. gambiae s.l. nor in the estimated malaria transmission risk. These findings suggest that passive zooprophylaxis using cattle does not alter the individual exposure to malaria parasites in The Gambia.

Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda

BackgroundEarly recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda.MethodsThe study had two components: 1) passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2) a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases.ResultsCases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment.ConclusionIn low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.

Introducing malaria rapid diagnostic tests at registered drug shops in Uganda: limitations of diagnostic testing in the reality of diagnosis.

In Uganda, around two thirds of medicines are procured from the private sector, mostly from drug shops. The introduction of malaria rapid diagnostic tests (RDTs) at drug shops therefore has the potential to make a significant contribution to targeting antimalarial drugs to those with malaria parasites. We undertook formative research in a district in Uganda in preparation for a randomised trial of RDTs in drug shops. In May to July 2009, we interviewed 9 drug shop workers, 5 health workers and 4 district health officials and carried out 10 focus group discussions with a total of 75 community members to investigate the role of drug shops and the potential for implementation of RDTs at these health care outlets. Drug shops were seen to provide an important service to community members, the nature of which is determined by responsiveness to client demands. However, drug shops hold a liminal status: in the eyes of different actors, these outlets are at once a shop and clinic; legitimate and illegitimate; and trusted and distrusted. Malaria treatment was found to be synonymous with diagnosis. Diagnostic testing was deemed useful in theory, and community members were curious about the results, with the expectation that a test would decrease uncertainty and help secure an end to illness. However, whether testing would be sought as a routine step in treatment decisions in practice is uncertain, since the appeal of the tests waned in light of their costs and potential for results to conflict with presumed diagnosis. Interventions that increase awareness of multiple causes and management of malaria-like illness will be needed to support the new rationalisation for malaria treatment represented by parasitological diagnosis.

Relationships between anaemia and parasitic infections in Kenyan schoolchildren: A Bayesian hierarchical modelling approach

Anaemia is multi-factorial in origin and disentangling its aetiology remains problematic, with surprisingly few studies investigating the relative contribution of different parasitic infections to anaemia amongst schoolchildren. We report cross-sectional data on haemoglobin, malaria parasitaemia, helminth infection and undernutrition among 1523 schoolchildren enrolled in classes 5 and 6 (aged 10–21 years) in 30 primary schools in western Kenya. Bayesian hierarchical modelling was used to investigate putative relationships. Children infected with Plasmodium falciparum or with a heavy Schistosoma mansoni infection, stunted children and girls were found to have lower haemoglobin concentrations. Children heavily infected with S. mansoni were also more likely to be anaemic compared with uninfected children. This study further highlights the importance of malaria and intestinal schistosomiasis as contributors to reduced haemoglobin levels among schoolchildren and helps guide the implementation of integrated school health programmes in areas of differing parasite transmission.

The feasibility of introducing rapid diagnostic tests for malaria in drug shops in Uganda

BackgroundNational malaria control programmes and international agencies are keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria. The high proportion of the Ugandan population seeking care at drug shops makes these outlets attractive as providers of malaria RDTs. However, there is no precedent for blood testing at drug shops and little is known about how such tests might be perceived and used. Understanding use of drug shops by communities in Uganda is essential to inform the design of interventions to introduce RDTs.MethodsWe conducted a qualitative study, with 10 community focus group discussions, and 18 in-depth interviews with drug shop attendants, health workers and district health officials. The formative study was carried out in Mukono district, central Uganda an area of high malaria endemicity from May-July 2009.ResultsDrug shops were perceived by the community as important in treating malaria and there was awareness among most drug sellers and the community that not all febrile illnesses were malaria. The idea of introducing RDTs for malaria diagnosis in drug shops was attractive to most respondents. It was anticipated that RDTs would improve access to effective treatment of malaria, offset high costs associated with poor treatment, and avoid irrational drug use. However, communities did express fear that drug shops would overprice RDTs, raising the overall treatment cost for malaria. Other fears included poor adherence to the RDT result, reuse of RDTs leading to infections and fear that RDTs would be used to test for human immune deficiency virus (HIV). All drug shops visited had no record on patient data and referral of cases to health units was noted to be poor.ConclusionThese results not only provide useful lessons for implementing the intervention study but have wide implications for scaling up malaria treatment in drug shops.

Neonatal Mortality Risk Associated with Preterm Birth in East Africa, Adjusted by Weight for Gestational Age: Individual Participant Level Meta-Analysis

In an analysis of four datasets from East Africa, Tanya Marchant and colleagues investigate the neonatal mortality risk associated with preterm birth and how this changes with weight for gestational age.