Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999–2010

Background

Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM) tracked with malaria control intensification during this period.

Methods

Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL) prevalence (SAP) among children 6–59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition) likely to influence U5CM were also assessed. Population attributable risk percentage (PAR%) estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM.

Results

Household ownership of insecticide-treated nets (ITNs) rose from near zero in 1999 to 64% (95% CI, 61.7–65.2) in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6–28.0) by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6–59 months declined 50% between 2005 (11.1%; 95% CI, 10.0–12.3%) and 2010 (5.5%; 95% CI, 4.7–6.4%) and U5CM declined by 45% between baseline (1995–9) and endpoint (2005–9), from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1–23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11) with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains.

Conclusion

Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1–24 months of age in high malaria endemicity) experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate progress in child survival.     

The Impact of Integrated Community Case Management of Childhood Diseases Interventions to Prevent Malaria Fever in Children Less than Five Years Old in Bauchi State of Nigeria

Background

Malaria accounts for about 300,000 childhood deaths and 30% of under-five year old mortality in Nigeria annually. We assessed the impact of intervention strategies that integrated Patent Medicines Vendors into community case management of childhood-diseases, improved access to artemisinin combination therapy (ACT) and distributed bed nets to households. We explored the influence of household socioeconomic characteristics on the impact of the interventions on fever in the under-five year olds in Bauchi State Nigeria.

Methods

A cross-sectional case-controlled, interventional study, which sampled 3077 and 2737 under-5 year olds from 1,588 and 1601 households in pre- and post-intervention periods respectively, was conducted from 2013 to 2015. Difference-in-differences and logistic regression analyses were performed to estimate the impact attributable to the interventions: integrated community case management of childhood illness which introduced trained public and private sector health providers and the possession of nets on the prevalence of fever.

Results

Two-week prevalence of fever among under-fives declined from 56.6% at pre-intervention to 42.5% at post-intervention. Fever-prevention fraction attributable to nets was statistically significant (OR = 0.217, 95% CI: 0.08–0.33). Children in the intervention group had significantly fewer incidence of fever than children in the control group had (OR = 0.765, 95% CI: 0.67–0.87). Although being in the intervention group significantly provided 23.5% protection against fever (95% CI: 0.13–0.33), the post-intervention likelihood of fever was also significantly less than at pre-intervention (OR = 0.57, 95% CI: 0.50–0.65). The intervention protection fraction against fever was statistically significant at 43.4% (OR = 0.434, 95% CI: 0.36–0.50). Logistic regression showed that the odds of fever were lower in households with nets (OR = 0.72, 95% CI: 0.60–0.88), among children whose mothers had higher education, in the post-intervention period (OR = 0.39, 95% CI: 0.33–0.46) and in the intervention group (OR = 0.52, 95% CI: 0.48–0.66). The odds of fever increased with higher socio-economic status of households (17.9%-19.5%). Difference-in-differences showed that the interventions significantly reduced occurrence of fever in the intervention group (OR = 1.70, 95% CI: 1.36–2.14).

Conclusion

The interventions were effective in reducing the prevalence and the likelihood of childhood malaria fever. Taken to scale, these can significantly reduce the burden of malaria fever in the under-five year old children.     

Modelling the Contributions of Malaria,HIV, Malnutrition and Rainfall to the Decline in Paediatric Invasive Non-typhoidal Salmonella Disease in Malawi

Introduction

Nontyphoidal Salmonellae (NTS) are responsible for a huge burden of bloodstream infection in Sub-Saharan African children. Recent reports of a decline in invasive NTS (iNTS) disease from Kenya and The Gambia have emphasised an association with malaria control. Following a similar decline in iNTS disease in Malawi, we have used 9 years of continuous longitudinal data to model the interrelationships between iNTS disease, malaria, HIV and malnutrition.

Methods

Trends in monthly numbers of childhood iNTS disease presenting at Queen’s Hospital, Blantyre, Malawi from 2002 to 2010 were reviewed in the context of longitudinal monthly data describing malaria slide-positivity among paediatric febrile admissions, paediatric HIV prevalence, nutritional rehabilitation unit admissions and monthly rainfall over the same 9 years, using structural equation models (SEM).

Results

Analysis of 3,105 iNTS episodes identified from 49,093 blood cultures, showed an 11.8% annual decline in iNTS (p < 0.001). SEM analysis produced a stable model with good fit, revealing direct and statistically significant seasonal effects of malaria and malnutrition on the prevalence of iNTS disease. When these data were smoothed to eliminate seasonal cyclic changes, these associations remained strong and there were additional significant effects of HIV prevalence.

Conclusions

These data suggest that the overall decline in iNTS disease observed in Malawi is attributable to multiple public health interventions leading to reductions in malaria, HIV and acute malnutrition. Understanding the impacts of public health programmes on iNTS disease is essential to plan and evaluate interventions.     

How Effective is Integrated Vector Management Against Malaria and Lymphatic Filariasis Where the Diseases Are Transmitted by the Same Vector?

Background

The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF) control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account.

Methodology/Principal Findings

We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R₀) for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs) and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites) were sufficient to eliminate the disease. Malaria had a far greater R₀ and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control.

Conclusions/Significance

Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple) interventions required for malaria with the long duration predicted to be required for filariasis elimination.     

Monitoring Change in Child Mortality through Household Surveys

Background

Most low- and middle-income countries lack fully functional civil registration systems. Measures of under-five mortality are typically derived from periodic household surveys collecting detailed information from women on births and child deaths. However, such surveys are expensive and are not appropriate for monitoring short-term changes in child mortality. We explored and tested the validity of two new analysis methods for less-expensive summary histories of births and child deaths for such monitoring in five African countries.

Methods and Findings

The first method we explored uses individual-level survey data on births and child deaths to impute full birth histories from an earlier survey onto summary histories from a more recent survey. The second method uses cohort changes between two surveys in the average number of children born and the number of children dead by single year of age to estimate under-five mortality for the inter-survey period. The first method produces acceptable annual estimates of under-five mortality for two out of six applications to available data sets; the second method produced an acceptable estimate in only one of five applications, though none of the applications used ideal data sets.

Conclusions

The methods we tested were not able to produce consistently good quality estimates of annual under-five mortality from summary birth history data. The key problem we identified was not with the methods themselves, but with the underlying quality of the summary birth histories. If summary birth histories are to be included in general household surveys, considerable emphasis must be placed on quality control.     

Abolishing Fees at Health Centers in the Context of Community Case Management of Malaria: What Effects on Treatment-Seeking Practices for Febrile Children in Rural Burkina Faso?

Introduction

Burkina Faso started nationwide community case management of malaria (CCMm) in 2010. In 2011, health center user fees for children under five were abolished in some districts.

Objective

To assess the effects of concurrent implementation of CCMm and user fees abolition on treatment-seeking practices for febrile children.

Methods

This is a natural experiment conducted in the districts of Kaya (CCMm plus user fees abolition) and Zorgho (CCMm only). Registry data from 2005 to 2014 on visits for malaria were collected from all eight rural health centers in the study area. Annual household surveys were administered during malaria transmission season in 2011 and 2012 in 1,035 randomly selected rural households. Interrupted time series models were fitted for registry data and Fine and Gray’s competing risks models for survey data.

Results

User fees abolition in Kaya significantly increased health center use by eligible children with malaria (incidence rate ratio for intercept change = 2.1, p <0.001). In 2011, in Kaya, likelihood of health center use for febrile children was three times higher and CHW use three times lower when caregivers knew services were free. Among the 421 children with fever in 2012, the delay before visiting a health center was significantly shorter in Kaya than in Zorgho (1.46 versus 1.79 days, p <0.05). Likelihood of visiting a health center on the first day of fever among households <2.5km or <5 km from a health center was two and three times higher in Kaya than in Zorgho, respectively (p <0.001).

Conclusions

User fees abolition reduced visit delay for febrile children living close to health centers. It also increased demand for and use of health center for children with malaria. Concurrently, demand for CHWs’ services diminished. User fees abolition and CCMm should be coordinated to maximize prompt access to treatment in rural areas.     

Spatio-Temporal Variations in Malaria Incidence in Children Less than 10 Years Old,Health District of Sokone,Senegal, 2010–2013

Introduction

Malaria is a leading cause of morbidity and mortality in sub-Saharan Africa. Detailed characterization of the risks for malaria, among populations living in areas where the disease is endemic, is an important priority, especially for planning and evaluating future malaria-control tools. A prospective cohort study was implemented in children under ten years living in rural areas with high Plasmodium falciparum transmission in Senegal.

Methods

Malaria incidence was prospectively evaluated over three year follow-up among a cohort of children aged less than 10 years old living in eight villages of the Sokone health district. The parents of 1316 children comprising a passive case detection cohort were encouraged to seek care from the study health centers at any time their child felt sick. In the event of reported history of fever within 24 hours or measured axillary temperature ≥ 37.5°C, a Rapid Diagnostic Test (RDT) was performed.

Results

From November 2010 to October 2013, among the 1468 reported febrile episodes, 264 were confirmed malaria episodes. Over the 3 years, 218 (16.9%) children experienced at least one clinical malaria episode. Cumulative malaria incidence was 7.3 episodes per 100 children-year at risk, with remarkably heterogeneous rates from 2.5 to 10.5 episodes per 100 children-year at risk. Clinical malaria prevalence ranged from 11.5 to 28.4% in the high transmission season versus from 9.6 to 21.2% in the low transmission season.

Conclusion

This longitudinal community-based study shows that occurrence of clinical malaria was not evenly distributed among all the cohort children in the eight villages. It demonstrates the complexity of spatial distribution of malaria incidence at a local level, even in a region of vegetation and altitudinal homogeneity.     

Correction: Overcoming Stagnation in the Levels and Distribution of Child Mortality: The Case of the Philippines

Background

Health-related within-country inequalities continue to be a matter of great interest and concern to both policy makers and researchers. This study aims to assess the level and the distribution of child mortality outcomes in the Philippines across geographical and socioeconomic indicators.

Methodology

Data on 159,130 children ever borne were analysed from five waves of the Philippine Demographic and Health Survey. Direct estimation was used to construct under-five and neonatal mortality rates for the period 1980–2013. Rate differences and ratios, and where possible, slope and relative indices of inequality were calculated to measure disparities on absolute and relative scales. Stratification was undertaken by levels of rural/urban location, island groups and household wealth.

Findings

National under-five and neonatal mortality rates have shown considerable albeit differential reductions since 1980. Recently released data suggests that neonatal mortality has declined following a period of stagnation. Declines in under-five mortality have been accompanied by decreases in wealth and geography-related absolute inequalities. However, relative inequalities for the same markers have remained stable over time. For neonates, mixed evidence suggests that absolute and relative inequalities have remained stable or may have risen.

Conclusion

In addition to continued reductions in under-five mortality, new data suggests that the Philippines have achieved success in addressing the commonly observed stagnated trend in neonatal mortality. This success has been driven by economic improvement since 2006 as well as efforts to implement a nationwide universal health care campaign. Yet, such patterns, nonetheless, accorded with persistent inequalities, particularly on a relative scale. A continued focus on addressing universal coverage, the influence of decentralisation and armed conflict, and issues along the continuum of care is advocated.     

Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002-2008

Background

Around 8.8 million children under-five die each year, mostly due to infectious diseases, including malaria that accounts for 16% of deaths in Africa, but the impact of international financing of malaria control on under-five mortality in sub-Saharan Africa has not been examined.

Methods and Findings

We combined multiple data sources and used panel data regression analysis to study the relationship among investment, service delivery/intervention coverage, and impact on child health by observing changes in 34 sub-Saharan African countries over 2002–2008. We used Lives Saved Tool to estimate the number of lives saved from coverage increase of insecticide-treated nets (ITNs)/indoor residual spraying (IRS). As an indicator of outcome, we also used under-five mortality rate. Global Fund investments comprised more than 70% of the Official Development Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for malaria enabled distribution of 50,478 ITNs [95%CI: 37,774–63,182] in the disbursement year. 1,000 additional ITNs distributed saved 0.625 lives [95%CI: 0.369–0.881]. Cumulatively Global Fund investments that increased ITN/IRS coverage in 2002–2008 prevented an estimated 240,000 deaths. Countries with higher malaria burden received less ODA disbursement per person-at-risk compared to lower-burden countries ($3.90 vs. $7.05). Increased ITN/IRS coverage in high-burden countries led to 3,575 lives saved per 1 million children, as compared with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under-five mortality was significant among major child health interventions such as immunisation showing that 10% increase in households with ITN/IRS would reduce 1.5 [95%CI: 0.3–2.8] child deaths per 1000 live births.

Conclusions

Along with other key child survival interventions, increased ITNs/IRS coverage has significantly contributed to child mortality reduction since 2002. ITN/IRS scale-up can be more efficiently prioritized to countries where malaria is a major cause of child deaths to save greater number of lives with available resources.     

The Epidemiology of Soil-Transmitted Helminths in Bihar State,India

Background

Soil-transmitted helminths (STHs) infect over a billion individuals worldwide. In India, 241 million children are estimated to need deworming to avert the negative consequences STH infections can have on child health and development. In February-April 2011, 17 million children in Bihar State were dewormed during a government-led school-based deworming campaign. Prior to programme implementation, a study was conducted to assess STH prevalence in the school-age population to direct the programme. The study also investigated risk factors for STH infections, including caste, literacy, and defecation and hygiene practices, in order to inform the development of complementary interventions.

Methods

A cross-sectional survey was conducted among children in 20 schools in Bihar. In addition to providing stool samples for identification of STH infections, children completed a short questionnaire detailing their usual defecation and hand-hygiene practices. Risk factors for STH infections were explored.

Results

In January-February 2011, 1279 school children aged four to seventeen provided stool samples and 1157 children also completed the questionnaire. Overall, 68% of children (10-86% across schools) were infected with one or more soil-transmitted helminth species. The prevalence of ascariasis, hookworm and trichuriasis was 52%, 42% and 5% respectively. The majority of children (95%) practiced open defecation and reported most frequently cleansing hands with soil (61%). Increasing age, lack of maternal literacy and certain castes were independently associated with hookworm infection. Absence of a hand-washing station at the schools was also independently associated with A. lumbricoides infection.

Conclusions

STH prevalence in Bihar is high, and justifies mass deworming in school-aged children. Open defecation is common-place and hands are often cleansed using soil. The findings reported here can be used to help direct messaging appropriate to mothers with low levels of literacy and emphasise the importance of water and sanitation in the control of helminths and other diseases.     

Habitat Hydrology and Geomorphology Control the Distribution of Malaria Vector Larvae in Rural Africa

Background

Larval source management is a promising component of integrated malaria control and elimination. This requires development of a framework to target productive locations through process-based understanding of habitat hydrology and geomorphology.

Methods

We conducted the first catchment scale study of fine resolution spatial and temporal variation in Anopheles habitat and productivity in relation to rainfall, hydrology and geomorphology for a high malaria transmission area of Tanzania.

Results

Monthly aggregates of rainfall, river stage and water table were not significantly related to the abundance of vector larvae. However, these metrics showed strong explanatory power to predict mosquito larval abundances after stratification by water body type, with a clear seasonal trend for each, defined on the basis of its geomorphological setting and origin.

Conclusion

Hydrological and geomorphological processes governing the availability and productivity of Anopheles breeding habitat need to be understood at the local scale for which larval source management is implemented in order to effectively target larval source interventions. Mapping and monitoring these processes is a well-established practice providing a tractable way forward for developing important malaria management tools.     

Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar

Background

The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.

Methods and Findings

Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner''s Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.

Conclusions

Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.     

Bayesian latent class models in malaria diagnosis

Aims

The main focus of this study is to illustrate the importance of the statistical analysis in the evaluation of the accuracy of malaria diagnostic tests, without admitting a reference test, exploring a dataset (3317) collected in São Tomé and Príncipe.

Methods

Bayesian Latent Class Models (without and with constraints) are used to estimate the malaria infection prevalence, together with sensitivities, specificities, and predictive values of three diagnostic tests (RDT, Microscopy and PCR), in four subpopulations simultaneously based on a stratified analysis by age groups (, 5 years old) and fever status (febrile, afebrile).

Results

In the afebrile individuals with at least five years old, the posterior mean of the malaria infection prevalence is 3.2% with a highest posterior density interval of [2.3–4.1]. The other three subpopulations (febrile 5 years, afebrile or febrile children less than 5 years) present a higher prevalence around 10.3% [8.8–11.7]. In afebrile children under-five years old, the sensitivity of microscopy is 50.5% [37.7–63.2]. In children under-five, the estimated sensitivities/specificities of RDT are 95.4% [90.3–99.5]/93.8% [91.6–96.0] – afebrile – and 94.1% [87.5–99.4]/97.5% [95.5–99.3] – febrile. In individuals with at least five years old are 96.0% [91.5–99.7]/98.7% [98.1–99.2] – afebrile – and 97.9% [95.3–99.8]/97.7% [96.6–98.6] – febrile. The PCR yields the most reliable results in four subpopulations.

Conclusions

The utility of this RDT in the field seems to be relevant. However, in all subpopulations, data provide enough evidence to suggest caution with the positive predictive values of the RDT. Microscopy has poor sensitivity compared to the other tests, particularly, in the afebrile children less than 5 years. This type of findings reveals the danger of statistical analysis based on microscopy as a reference test. Bayesian Latent Class Models provide a powerful tool to evaluate malaria diagnostic tests, taking into account different groups of interest.     

Knowledge,Attitudes, and Practices Concerning Malaria in Pregnancy: Results from a Qualitative Study in Madang,Papua New Guinea

Background

Malaria is the leading cause of illness and death in Papua New Guinea (PNG). Infection during pregnancy with falciparum or vivax malaria, as occurs in PNG, has health implications for mother and child, causing complications such as maternal anemia, low birth weight and miscarriage. This article explores knowledge, attitudes and practices concerning malaria during pregnancy and it’s prevention in Madang, PNG, a high prevalence area.

Methods

As part of a qualitative study in Madang, exploring MiP, participatory techniques (free-listing and sorting) were conducted along with focus group discussions, in-depth interviews (with pregnant women, health staff and other community members) and observations in the local community and health facilities.

Results

The main themes explored were attitudes towards and knowledge of MiP, its risks, and prevention. Although there was a general awareness of the term “malaria”, it was often conflated with general sickness or with pregnancy-related symptoms. Moreover, many preventive methods for MiP were related to practices of general healthy living. Indeed, varied messages from health staff about the risks of MiP were observed. In addition to ideas about the seriousness and risk of MiP, other factors influenced the uptake of interventions: availability and perceived comfort of sleeping under insecticide-treated mosquito nets were important determinants of usage, and women’s heavy workload influenced Chloroquine adherence.

Conclusion

The non-specific symptoms of MiP and its resultant conflation with symptoms of pregnancy that are perceived as normal have implications for MiP prevention and control. However, in Madang, PNG, this was compounded by the inadequacy of health staff’s message about MiP.     

Malaria parasitaemia among infants and its association with breastfeeding peer counselling and vitamin A supplementation: a secondary analysis of a cluster randomized trial

Background

Malaria is the second highest contributor to the disease burden in Africa and there is a need to identify low cost prevention strategies. The objectives of this study were to estimate the prevalence of malaria parasitaemia among infants and to measure the association between peer counselling for exclusive breastfeeding (EBF), vitamin A supplementation, anthropometric status (weight and length) and malaria parasitaemia.

Methods

A cluster randomized intervention trial was conducted between 2006 and 2008 where 12 of 24 clusters, each comprising one or two villages, in Eastern Uganda were allocated to receive peer counselling for EBF. Women in their third trimester of pregnancy (based on the last normal menstrual period) were recruited in all 24 clusters and followed up until their children''s first birthday. Blood was drawn from 483 infants between 3 and 12 months of age, to test for malaria parasitaemia.

Results

The prevalence of malaria parasitaemia was 11% in the intervention areas and 10% in the control areas. The intervention did not seem to decrease the prevalence of malaria (PR 1.7; 95% CI: 0.9, 3.3). After controlling for potential confounders, infants not supplemented with Vitamin A had a higher prevalence for malaria compared to those who had been supplemented (PR 6.1; 95% CI: 2.1, 17.6). Among children supplemented with vitamin A, every unit increase in length-for-age Z (LAZ) scores was associated with a reduced prevalence in malaria (PR 0.5; 95% CI:0.4, 0.6). There was no association between LAZ scores and malaria among children that had not been supplemented.

Conclusion

Peer counselling for exclusive breastfeeding did not decrease the prevalence of malaria parasitaemia. Children that had not received Vitamin A supplementation had a higher prevalence of malaria compared to children that had been supplemented.

Trial registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00397150","term_id":"NCT00397150"}}NCT00397150.     

Malaria morbidity in children in the year after they had received intermittent preventive treatment of malaria in Mali: a randomized control trial

Background

Intermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by >80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.

Methods

Morbidity from malaria and the prevalence of malaria parasitaemia and anaemia were measured in children who had previously received IPTc with SP and AQ using similar surveillance methods to those employed during the previous intervention period.

Results

1396 of 1508 children (93%) who had previously received IPTc and 1406 of 1508 children (93%) who had previously received placebos were followed up during the high malaria transmission season of the year following the intervention. Incidence rates of clinical malaria during the post-intervention transmission season (July –November 2009) were 1.87 (95% CI 1.76 –1.99) and 1.73 (95% CI; 1.62–1.85) episodes per child year in the previous intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09 (95% CI 0.99 –1.21) (P = 0.08). The prevalence of malaria infection was similar in the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73–1.33) (P = 0.95). At the end of post-intervention malaria transmission season, the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91 – 1.12]) (P = 0.84).

Conclusion

IPTc with SP+AQ was not associated with an increase in incidence of malaria episodes, prevalence of malaria infection or anaemia in the subsequent malaria transmission season.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero,One and Five in India: A Decomposition Analysis

Objectives

Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover.

Methods

We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981–2009 for 16 Indian states by sex (comprising of India’s 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover.

Findings

India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women).

Conclusions

For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1–59 months in high child mortality areas can help India to attain this crossover early.     

Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

Background

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.

Methods and Findings

Between 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥18 mo with CD4 count > 350 cells/mm³ in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression.Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52–3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52–241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82–2.27, and IRR = 1.43, 95% CI 0.54–3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.

Conclusions

CTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01425073","term_id":"NCT01425073"}}NCT01425073     

Reduction in Malaria Incidence following Indoor Residual Spraying with Actellic 300 CS in a Setting with Pyrethroid Resistance: Mutasa District,Zimbabwe

Background

More than half of malaria cases in Zimbabwe are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. Recently, high levels of pyrethroid and carbamate resistance were detected in Anopheles funestus, the major malaria vector in eastern Zimbabwe. In response, a single round of indoor residual spraying (IRS) using pirimiphos-methyl (an organophosphate) was implemented in four high burden districts of Manicaland Province from November 1, 2014 to December 19, 2014. The objective of this study was to evaluate the effect of this programmatic switch in insecticides on malaria morbidity reported from health care facilities in Mutasa District, one of the worst affected districts in Manicaland Province.

Methods

The number of weekly malaria cases for each health facility 24 months prior to the 2014 IRS campaign and in the subsequent high transmission season were obtained from passive case surveillance. Environmental variables were extracted from remote-sensing data sources and linked to each health care facility. Negative binomial regression was used to model the weekly number of malaria cases, adjusted for seasonality and environmental variables.

Results

From December 2012 to May 2015, 124,206 malaria cases were reported from 42 health care facilities in Mutasa District. Based on a higher burden of malaria, 20 out of 31 municipal wards were sprayed in the district. Overall, 87.3% of target structures were sprayed and 92.1% of the target population protected. During the 6 months after the 2014 IRS campaign, a period when transmission would have otherwise peaked, the incidence of malaria was 38% lower than the preceding 24 months at health facilities in the sprayed wards.

Conclusions

Pirimiphos-methyl had a measurable impact on malaria incidence and is an effective insecticide for the control of An. funestus in eastern Zimbabwe.     

Mind the Gap: House Structure and the Risk of Malaria in Uganda

Background

Good house construction may reduce the risk of malaria by limiting the entry of mosquito vectors. We assessed how house design may affect mosquito house entry and malaria risk in Uganda.

Methods

100 households were enrolled in each of three sub-counties: Walukuba, Jinja district; Kihihi, Kanungu district; and Nagongera, Tororo district. CDC light trap collections of mosquitoes were done monthly in all homes. All children aged six months to ten years (n = 878) were followed prospectively for a total of 24 months to measure parasite prevalence every three months and malaria incidence. Homes were classified as modern (cement, wood or metal walls; and tiled or metal roof; and closed eaves) or traditional (all other homes).

Results

A total of 113,618 female Anopheles were collected over 6,765 nights. 6,816 routine blood smears were taken of which 1,061 (15.6%) were malaria parasite positive. 2,582 episodes of uncomplicated malaria were diagnosed after 1,569 person years of follow-up, giving an overall incidence of 1.6 episodes per person year at risk. The human biting rate was lower in modern homes than in traditional homes (adjusted incidence rate ratio (IRR) 0.48, 95% confidence interval (CI) 0.37–0.64, p<0.001). The odds of malaria infection were lower in modern homes across all the sub-counties (adjusted odds ratio 0.44, 95%CI 0.30–0.65, p<0.001), while malaria incidence was lower in modern homes in Kihihi (adjusted IRR 0.61, 95%CI 0.40–0.91, p = 0.02) but not in Walukuba or Nagongera.

Conclusions

House design is likely to explain some of the heterogeneity of malaria transmission in Uganda and represents a promising target for future interventions, even in highly endemic areas.