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.     

High prevalence of malaria in Zambezia, Mozambique: the protective effect of IRS versus increased risks due to pig-keeping and house construction

Background

African countries are scaling up malaria interventions, especially insecticide treated nets (ITN) and indoor residual spraying (IRS), for which ambitious coverage targets have been set. In spite of these efforts infection prevalence remains high in many parts of the continent. This study investigated risk factors for malaria infection in children using three malaria indicator surveys from Zambezia province, Mozambique. The impact of IRS and ITNs, the effects of keeping farm animals and of the construction material of roofs of houses and other potential risk factors associated with malaria infection in children were assessed.

Methods

Cross-sectional community-based surveys were conducted in October of 2006, 2007 and 2008. A total of 8338 children (ages 1–15 years) from 2748 households were included in the study. All children were screened for malaria by rapid diagnostic tests. Caregiver interviews were used to assess household demographic and wealth characteristics and ITN and IRS coverage. Associations between malaria infection, vector control interventions and potential risk factors were assessed.

Results

Overall, the prevalence of malaria infection was 47.8% (95%CI: 38.7%–57.1%) in children 1–15 years of age, less than a quarter of children (23.1%, 95%CI: 19.1%–27.6%) were sleeping under ITN and almost two thirds were living in IRS treated houses (coverage 65.4%, 95%CI: 51.5%–77.0%). Protective factors that were independently associated with malaria infection were: sleeping in an IRS house without sleeping under ITN (Odds Ratio (OR)  = 0.6; 95%CI: 0.4–0.9); additional protection due to sleeping under ITN in an IRS treated house (OR = 0.5; 95%CI: 0.3–0.7) versus sleeping in an unsprayed house without a ITN; and parental education (primary/secondary: OR = 0.6; 95%CI: 0.5–0.7) versus parents with no education. Increased risk of infection was associated with: current fever (OR = 1.2; 95%CI: 1.0–1.5) versus no fever; pig keeping (OR = 3.2; 95%CI: 2.1–4.9) versus not keeping pigs; living in houses with a grass roof (OR = 1.7; 95%CI: 1.3–2.4) versus other roofing materials and bigger household size (8–15 people: OR = 1.6; 95%CI: 1.3–2.1) versus small households (1–4 persons).

Conclusion

Malaria infection among children under 15 years of age in Zambezia remained high but conventional malaria vector control methods, in particular IRS, provided effective means of protection. Household ownership of farm animals, particularly pigs, and living in houses with a grass roof were independently associated with increased risk of infection, even after allowing for household wealth. To reduce the burden of malaria, national control programs need to ensure high coverage of effective IRS and promote the use of ITNs, particularly in households with elevated risks of infection, such as those keeping farm animals, and those with grass roofs.     

Species Shifts in the Anopheles gambiae Complex: Do LLINs Successfully Control Anopheles arabiensis?

Introduction

High coverage of conventional and long-lasting insecticide treated nets (ITNs and LLINs) in parts of E Africa are associated with reductions in local malaria burdens. Shifts in malaria vector species ratio have coincided with the scale-up suggesting that some species are being controlled by ITNs/LLINs better than others.

Methods

Between 2005–2006 six experimental hut trials of ITNs and LLINs were conducted in parallel at two field stations in northeastern Tanzania; the first station was in Lower Moshi Rice Irrigation Zone, an area where An. arabiensis predominates, and the second was in coastal Muheza, where An. gambiae and An. funestus predominate. Five pyrethroids and one carbamate insecticide were evaluated on nets in terms of insecticide-induced mortality, blood-feeding inhibition and exiting rates.

Results

In the experimental hut trials mortality of An. arabiensis was consistently lower than that of An. gambiae and An. funestus. The mortality rates in trials with pyrethroid-treated nets ranged from 25–52% for An. arabiensis, 63–88% for An. gambiae s.s. and 53–78% for An. funestus. All pyrethroid-treated nets provided considerable protection for the occupants, despite being deliberately holed, with blood-feeding inhibition (percentage reduction in biting rates) being consistent between species. Veranda exiting rates did not differ between species. Percentage mortality of mosquitoes tested in cone bioassays on netting was similar for An. gambiae and An. arabiensis.

Conclusions

LLINs and ITNs treated with pyrethroids were more effective at killing An. gambiae and An. funestus than An. arabiensis. This could be a major contributing factor to the species shifts observed in East Africa following scale up of LLINs. With continued expansion of LLIN coverage in Africa An. arabiensis is likely to remain responsible for residual malaria transmission, and species shifts might be reported over larger areas. Supplementary control measures to LLINs may be necessary to control this vector species.     

The use of mosquito nets and the prevalence of Plasmodium falciparum infection in rural South Central Somalia

Background

There have been resurgent efforts in Africa to estimate the public health impact of malaria control interventions such as insecticide treated nets (ITNs) following substantial investments in scaling-up coverage in the last five years. Little is known, however, on the effectiveness of ITN in areas of Africa that support low transmission. This hinders the accurate estimation of impact of ITN use on disease burden and its cost-effectiveness in low transmission settings.

Methods and Principal Findings

Using a stratified two-stage cluster sample design, four cross-sectional studies were undertaken between March-June 2007 across three livelihood groups in an area of low intensity malaria transmission in South Central Somalia. Information on bed net use; age; and sex of all participants were recorded. A finger prick blood sample was taken from participants to examine for parasitaemia. Mantel-Haenzel methods were used to measure the effect of net use on parasitaemia adjusting for livelihood; age; and sex. A total of 10,587 individuals of all ages were seen of which 10,359 provided full information. Overall net use and parasite prevalence were 12.4% and 15.7% respectively. Age-specific protective effectiveness (PE) of bed net ranged from 39% among <5 years to 72% among 5–14 years old. Overall PE of bed nets was 54% (95% confidence interval 44%–63%) after adjusting for livelihood; sex; and age.

Conclusions and Significance

Bed nets confer high protection against parasite infection in South Central Somalia. In such areas where baseline transmission is low, however, the absolute reductions in parasitaemia due to wide-scale net use will be relatively small raising questions on the cost-effectiveness of covering millions of people living in such settings in Africa with nets. Further understanding of the progress of disease upon infection against the cost of averting its consequent burden in low transmission areas of Africa is therefore required.     

Changing patterns of malaria epidemiology between 2002 and 2010 in Western Kenya: the fall and rise of malaria

Background

The impact of insecticide treated nets (ITNs) on reducing malaria incidence is shown mainly through data collection from health facilities. Routine evaluation of long-term epidemiological and entomological dynamics is currently unavailable. In Kenya, new policies supporting the provision of free ITNs were implemented nationwide in June 2006. To evaluate the impacts of ITNs on malaria transmission, we conducted monthly surveys in three sentinel sites with different transmission intensities in western Kenya from 2002 to 2010.

Methods and Findings

Longitudinal samplings of malaria parasite prevalence in asymptomatic school children and vector abundance in randomly selected houses were undertaken monthly from February 2002. ITN ownership and usage surveys were conducted annually from 2004 to 2010. Asymptomatic malaria parasite prevalence and vector abundances gradually decreased in all three sites from 2002 to 2006, and parasite prevalence reached its lowest level from late 2006 to early 2007. The abundance of the major malaria vectors, Anopheles funestus and An. gambiae, increased about 5–10 folds in all study sites after 2007. However, the resurgence of vectors was highly variable between sites and species. By 2010, asymptomatic parasite prevalence in Kombewa had resurged to levels recorded in 2004/2005, but the resurgence was smaller in magnitude in the other sites. Household ITN ownership was at 50–70% in 2009, but the functional and effective bed net coverage in the population was estimated at 40.3%, 49.4% and 28.2% in 2010 in Iguhu, Kombewa, and Marani, respectively.

Conclusion

The resurgence in parasite prevalence and malaria vectors has been observed in two out of three sentinel sites in western Kenya despite a high ownership of ITNs. The likely factors contributing to malaria resurgence include reduced efficacy of ITNs, insecticide resistance in mosquitoes and lack of proper use of ITNs. These factors should be targeted to avoid further resurgence of malaria transmission.     

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic

Background

Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use.

Methods

1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.

Findings

Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN''s use was more than 90% in both groups.

Conclusions

Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

Net benefits: a multicountry analysis of observational data examining associations between insecticide-treated mosquito nets and health outcomes

Background

Several sub-Saharan African countries have rapidly scaled up the number of households that own insecticide-treated mosquito nets (ITNs). Although the efficacy of ITNs in trials has been shown, evidence on their impact under routine conditions is limited to a few countries and the extent to which the scale-up of ITNs has improved population health remains uncertain.

Methods and Findings

We used matched logistic regression to assess the individual-level association between household ITN ownership or use in children under 5 years of age and the prevalence of parasitemia among children using six malaria indicator surveys (MIS) and one demographic and health survey. We used Cox proportional hazards models to assess the relationship between ITN household ownership and child mortality using 29 demographic and health surveys. The pooled relative reduction in parasitemia prevalence from random effects meta-analysis associated with household ownership of at least one ITN was 20% (95% confidence interval [CI] 3%–35%; I ² = 73.5%, p<0.01 for I ² value). Sleeping under an ITN was associated with a pooled relative reduction in parasitemia prevalence in children of 24% (95% CI 1%–42%; I ² = 79.5%, p<0.001 for I ² value). Ownership of at least one ITN was associated with a pooled relative reduction in mortality between 1 month and 5 years of age of 23% (95% CI 13–31%; I ² = 25.6%, p>0.05 for I ² value).

Conclusions

Our findings across a number of sub-Saharan African countries were highly consistent with results from previous clinical trials. These findings suggest that the recent scale-up in ITN coverage has likely been accompanied by significant reductions in child mortality and that additional health gains could be achieved with further increases in ITN coverage in populations at risk of malaria. Please see later in the article for the Editors'' Summary     

Multiple insecticide resistance: an impediment to insecticide-based malaria vector control program

Background

Indoor Residual Spraying (IRS), insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are key components in malaria prevention and control strategy. However, the development of resistance by mosquitoes to insecticides recommended for IRS and/or ITNs/LLINs would affect insecticide-based malaria vector control. We assessed the susceptibility levels of Anopheles arabiensis to insecticides used in malaria control, characterized basic mechanisms underlying resistance, and evaluated the role of public health use of insecticides in resistance selection.

Methodology/Principal findings

Susceptibility status of An. arabiensis was assessed using WHO bioassay tests to DDT, permethrin, deltamethrin, malathion and propoxur in Ethiopia from August to September 2009. Mosquito specimens were screened for knockdown resistance (kdr) and insensitive acetylcholinesterase (ace-1^R) mutations using AS-PCR and PCR-RFLP, respectively. DDT residues level in soil from human dwellings and the surrounding environment were determined by Gas Chromatography with Electron Capture Detector. An. arabiensis was resistant to DDT, permethrin, deltamethrin and malathion, but susceptible to propoxur. The West African kdr allele was found in 280 specimens out of 284 with a frequency ranged from 95% to 100%. Ace-1^R mutation was not detected in all specimens scored for the allele. Moreover, DDT residues were found in soil samples from human dwellings but not in the surrounding environment.

Conclusion

The observed multiple-resistance coupled with the occurrence of high kdr frequency in populations of An. arabiensis could profoundly affect the malaria vector control programme in Ethiopia. This needs an urgent call for implementing rational resistance management strategies and integrated vector control intervention.     

Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015

Objective

The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.

Design

Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.

Results

Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.

Conclusion

Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.     

Barriers to insecticide-treated mosquito net possession 2 years after a mass free distribution campaign in Luangwa District, Zambia

Background and Methods

Roll Back Malaria set the goal of 100% of households in malaria endemic countries in Africa owning an insecticide-treated mosquito net (ITN) by 2010. Zambia has used mass free distribution campaigns and distribution through antenatal care (ANC) clinics to achieve high coverage.

Methodology and Principal Findings

We conducted a probability survey of 801 households in 2008 to assess factors associated with households that lacked an ITN after mass distribution. Community perceptions of barriers to ITN access were also obtained from in-depth interviews with household heads that reported not owning an ITN. Nearly 74% of households in Luangwa district reported owning ≥1 ITN. Logistic regression showed households without a child <5 years old during the ITN distribution campaigns were twice as likely to not have an ITN as those with a child <5 during distribution (Adjusted odds ratio (AOR)  = 2.43; 95% confidence interval (CI): 1.67–3.55). Households without a woman who attended an ANC in the past 2 years were more likely to be without ITNs compared to households with a woman who attended an ANC in the past 2 years (AOR  = 1.52; 95% CI: 1.04–2.21). In-depth interviews with heads of households without an ITN revealed that old age was a perceived barrier to receiving an ITN during distribution, and that ITNs wore out before they could be replaced.

Conclusions and Significance

Delivery of a large number of ITNs does not translate directly into 100% household coverage. Due to their design, current ITN distribution strategies may miss households occupied by the elderly and those without children or ANC access. ITN distribution strategies targeting the elderly, those with limited access to distribution points, and others most likely to be missed are necessary if 100% ITN coverage of households is to be achieved.     

Findings from a rapid assessment of avoidable blindness (RAAB) in Southern Malawi

Background

Data on prevalence and causes of avoidable blindness in Malawi are not readily available. The purpose of this study was to determine the prevalence and causes of blindness in persons aged 50 and above in southern Malawi to plan eye care services for the community.

Methodology

A population-based survey was conducted in 7 districts in southern Malawi. Villages were selected by probability proportionate to size within each district. Clusters were further subdivided into segments. A predetermined number of segments were selected randomly in each cluster. The survey team moved from house to house in each segment until they had examined 50 people over the age of 50. Examination consisted of visual acuity measurement with tumbling “E” chart and ocular examination by an ophthalmologist. Participants were categorized by visual acuity. Those who were visually impaired (VA<6/18 in the better eye with available correction) were assigned a main cause of visual loss. Further information was sought from anyone who had received cataract surgery.

Results

A total number of 3,583 persons aged 50 and above were sampled; among these 3,430 (95.7%) were examined. The prevalence of blindness (presenting visual acuity <3/60 in the better eye) among persons aged 50 and above was 3.3% (95% CI 2.5–4.1). Cataract was the most common cause of blindness contributing to 48.2% of all cases, followed by glaucoma (15.8%) and cornea scarring (12.3%). The cataract surgical coverage in blind persons was 44.6%.

Conclusion

The prevalence of blindness and visual impairment in persons aged 50 and above was lower than the WHO estimate for Malawi. The majority of the causes were avoidable, with cataract accounting for approximately half of all cases of blindness. The data suggests that expansion of eye care programs to address avoidable causes of blindness is necessary in this area of southern Malawi.     

Targeting antibiotics to households for trachoma control

Background

Mass drug administration (MDA) is part of the current trachoma control strategy, but it can be costly and results in many uninfected individuals receiving treatment. Here we explore whether alternative, targeted approaches are effective antibiotic-sparing strategies.

Methodology/Principal Findings

We analysed data on the prevalence of ocular infection with Chlamydia trachomatis and of active trachoma disease among 4,436 individuals from two communities in The Gambia (West Africa) and two communities in Tanzania (East Africa). An age- and household-structured mathematical model of transmission was fitted to these data using maximum likelihood. The presence of active inflammatory disease as a marker of infection in a household was, in general, significantly more sensitive (between 79% [95%CI: 60%–92%] and 86% [71%–95%] across the four communities) than as a marker of infection in an individual (24% [16%–33%]–66% [56%–76%]). Model simulations, under the best fit models for each community, showed that targeting treatment to households has the potential to be as effective as and significantly more cost-effective than mass treatment when antibiotics are not donated. The cost (2007US$) per incident infection averted ranged from 1.5 to 3.1 for MDA, from 1.0 to 1.7 for household-targeted treatment assuming equivalent coverage, and from 0.4 to 1.7 if household visits increased treatment coverage to 100% in selected households. Assuming antibiotics were donated, MDA was predicted to be more cost-effective unless opportunity costs incurred by individuals collecting antibiotics were included or household visits improved treatment uptake. Limiting MDA to children was not as effective in reducing infection as the other aforementioned distribution strategies.

Conclusions/Significance

Our model suggests that targeting antibiotics to households with active trachoma has the potential to be a cost-effective trachoma control measure, but further work is required to assess if costs can be reduced and to what extent the approach can increase the treatment coverage of infected individuals compared to MDA in different settings.     

Effect of Bednets and Indoor Residual Spraying on Spatio-Temporal Clustering of Malaria in a Village in South Ethiopia: A Longitudinal Study

Background

Understanding the spatio-temporal pattern of malaria transmission where prevention and control measures are in place will help to fine-tune strategies. The objective of this study was to assess the effect of mass distribution of bednets and indoor residual spraying (IRS) with insecticides on the spatio-temporal clustering of malaria in one malaria endemic village in south Ethiopia.

Methods

A longitudinal study was conducted from April 2009 to April 2011. The average population was 6631 in 1346 locations. We used active and passive searches for malaria cases for 101 weeks. SatScan v9.1.1 was used to identify statistically significant retrospective space–time clusters. A discrete Poisson based model was applied with the aim of identifying areas with high rates. PASW Statistics 18 was used to build generalized Poisson loglinear model.

Results

The total number of both types of malaria episodes was 622, giving 45.1 episodes per 1000 persons per year; among these, episodes of Plasmodium falciparum and vivax infection numbered 316 (22.9 per 1000 per year) and 306 (22.2 per 1000 per year), respectively. IRS with Dichlorodiphenyltrichloroethane (DDT) and later with Deltamethrin and free mass distribution of insecticide-treated nets (ITNs) were carried out during the study period. There was space–time clustering of malaria episodes at a household level. The spatio-temporal clustering of malaria was not influenced by free mass distribution of ITNs; however, the time-span of the spatio-temporal clustering of malaria cases ended after IRS with Deltamethrin. The presence of clusters on the south-east edge of the village was consistent with the finding of an increasing risk of acquiring malaria infection for individuals who lived closer to the identified vector breeding site.

Conclusion

The risk of getting malaria infection varied significantly within one village. Free mass distribution of ITNs did not influence the spatio-temporal clustering of malaria, but IRS might have eliminated malaria clustering.     

Ten years of surveillance for invasive Streptococcus pneumoniae during the era of antiretroviral scale-up and cotrimoxazole prophylaxis in Malawi

Objective

To document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis.

Methods

Between 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection.

Results

4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson''s correlation r = −0.91; p<0.001).

Conclusion

During 2004–2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes.     

Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania

Background

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone.

Methods and Findings

In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5–14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms.IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19–0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03–1.08).

Conclusions

This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.

Trial registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01697852","term_id":"NCT01697852"}}NCT01697852 Please see later in the article for the Editors'' Summary     

Are Long-Lasting Insecticidal Nets Effective for Preventing Childhood Deaths among Non-Net Users? A Community-Based Cohort Study in Western Kenya

Background

Increasing the distribution and use of insecticide-treated nets (ITNs) in Sub-Saharan Africa has made controlling malaria with ITNs more practical. We evaluated community effects induced by ITNs, specifically long-lasting insecticidal nets (LLINs), under ordinary conditions in an endemic malaria area of Western Kenya.

Methods

Using the database from Mbita Health and Demographic Surveillance System (HDSS), children younger than 5 years old were assessed over four survey periods. We analyzed the effect of bed net usage, LLIN density and population density of young people around a child on all-cause child mortality (ACCM) rates using Cox PH models.

Results

During the study, 14,554 children were followed and 250 deaths were recorded. The adjusted hazard ratios (HRs) for LLIN usage compared with no net usage were not significant among the models: 1.08 (95%CI 0.76–1.52), 1.19 (95%CI 0.69–2.08) and 0.92 (95%CI 0.42–2.02) for LLIN users, untreated net users, and any net users, respectively. A significant increasing linear trend in risk across LLIN density quartiles (HR = 1.25; 95%CI 1.03–1.51) and a decreasing linear trend in risk across young population density quartiles among non-net user children (HR = 0.77; 95%CI 0.63–0.94) were observed.

Conclusions

Although our data showed that current LLIN coverage level (about 35%) could induce a community effect to protect children sleeping without bed nets even in a malaria-endemic area, it appears that a better system is needed to monitor the current malaria situation globally in order to optimize malaria control programs with limited resources.     

Distribution systems of insecticide-treated bed nets for malaria control in rural Burkina Faso: cluster-randomized controlled trial

Background

Insecticide-impregnated bed nets (ITNs) have been shown to be a highly effective tool against malaria in the endemic regions of sub-Saharan Africa (SSA). There are however different opinions about the role of ITN social marketing and ITN free distribution in the roll-out of ITN programmes. The objective of this study was to evaluate the effects of free ITN distribution through antenatal care services in addition to an ITN social marketing programme in an area typical for rural SSA.

Methods

A cluster-randomised controlled ITN trial took place in the whole Kossi Province in north-western Burkina Faso, an area highly endemic for malaria. Twelve clusters were assigned to long-term ITN (Serena brand) social marketing plus free ITN (Serena brand) distribution to all pregnant women attending governmental antenatal care services (group A), and 13 clusters to ITN social marketing only (group B). The intervention took place during the rainy season of 2006 and thereafter. The trial was evaluated through a representative household survey at baseline and after one year. Serena ITN household ownership was the primary outcome measure.

Findings

A total of 1052 households were visited at baseline in February 2006 and 1050 at follow-up in February 2007. Overall Serena ITN household ownership increased from 16% to 28% over the study period, with a significantly higher increase in group A (13% to 35%) than in group B (18% to 23%) (p<0.001).

Interpretation

The free distribution of ITNs to pregnant women through governmental antenatal care services in addition to ITN social marketing substantially improved ITN household ownership in rural Burkina Faso.

Trial registration

Controlled-Trials.com ISRCTN07985309     

Is the Scale Up of Malaria Intervention Coverage Also Achieving Equity?

Background and Methods

Malaria in Africa is most severe in young children and pregnant women, particularly in rural and poor households. In many countries, malaria intervention coverage rates have increased as a result of scale up; but this may mask limited coverage in these highest-risk populations. Reports were reviewed from nationally representative surveys in African malaria-endemic countries from 2006 through 2008 to understand how reported intervention coverage rates reflect access by the most at-risk populations.

Results

Reports were available from 27 Demographic and Health Surveys (DHSs), Multiple Indicator Cluster Surveys (MICSs), and Malaria Indicator Surveys (MISs) during this interval with data on household intervention coverage by urban or rural setting, wealth quintile, and sex. Household ownership of insecticide-treated mosquito nets (ITNs) varied from 5% to greater than 60%, and was equitable by urban/rural and wealth quintile status among 13 (52%) of 25 countries. Malaria treatment rates for febrile children under five years of age varied from less than 10% to greater than 70%, and while equitable coverage was achieved in 8 (30%) of 27 countries, rates were generally higher in urban and richest quintile households. Use of intermittent preventive treatment in pregnant women varied from 2% to more than 60%, and again tended to be higher in urban and richest quintile households. Across all countries, there were no significant male/female inequalities seen for children sleeping under ITNs or receiving antimalarial treatment for febrile illness. Parasitemia and anemia rates from eight national surveys showed predominance in poor and rural populations.

Conclusions/Significance

Recent efforts to scale up malaria intervention coverage have achieved equity in some countries (especially with ITNs), but delivery methods in other countries are not addressing the most at-risk populations. As countries seek universal malaria intervention coverage, their delivery systems must reach the rural and poor populations; this is not a small task, but it has been achieved in some countries.     

Quantifying child mortality reductions related to measles vaccination

Background

This study characterizes the historical relationship between coverage of measles containing vaccines (MCV) and mortality in children under 5 years, with a view toward ongoing global efforts to reduce child mortality.

Methodology/Principal Findings

Using country-level, longitudinal panel data, from 44 countries over the period 1960–2005, we analyzed the relationship between MCV coverage and measles mortality with (1) logistic regressions for no measles deaths in a country-year, and (2) linear regressions for the logarithm of the measles death rate. All regressions allowed a flexible, non-linear relationship between coverage and mortality. Covariates included birth rate, death rates from other causes, percent living in urban areas, population density, per-capita GDP, use of the two-dose MCV, year, and mortality coding system. Regressions used lagged covariates, country fixed effects, and robust standard errors clustered by country. The likelihood of no measles deaths increased nonlinearly with higher MCV coverage (ORs: 13.8 [1.6–122.7] for 80–89% to 40.7 [3.2–517.6] for ≥95%), compared to pre-vaccination risk levels. Measles death rates declined nonlinearly with higher MCV coverage, with benefits accruing more slowly above 90% coverage. Compared to no coverage, predicted average reductions in death rates were −79% at 70% coverage, −93% at 90%, and −95% at 95%.

Conclusions/Significance

40 years of experience with MCV vaccination suggests that extremely high levels of vaccination coverage are needed to produce sharp reductions in measles deaths. Achieving sustainable benefits likely requires a combination of extended vaccine programs and supplementary vaccine efforts.     

The co-distribution of Plasmodium falciparum and hookworm among African schoolchildren

Background

On the island of Bioko (Equatorial Guinea), insecticide-treated nets (ITNs) have been the main tool used to control malaria over the last 13 years. In 2004, started an indoor residual spraying (IRS) campaign to control malaria. The purpose of this study is to asses the impact of the two control strategies on the island of Bioko (Equatorial Guinea), with regards to Plasmodium infection and anaemia in the children under five years of age.

Methods

Two transversal studies, the first one prior to the start of the IRS campaign and the second one year later. Sampling was carried out by stratified clusters. Malaria infection was measured by means of thick and thin film, and the packed cell volume (PCV) percentage. Data related to ITN use and information regarding IRS were collected. The Pearson's chi-square and logistic regression statistical tests were used to calculate odds ratios (OR)

Results

In the first survey, 168 children were sampled and 433 children in the second one. The prevalence of infection was 40% in 2004, and significantly lower at 21.7% in 2005. PCV was 41% and 39%, respectively. 58% of the children surveyed in 2004 and 44.3% in 2005 had slept under an ITN. 78% of the dwellings studied in 2005 had been sprayed. In the 2005 survey, sleeping without a mosquito net meant a risk of infection 3 times greater than sleeping protected with a net hanged correctly and with no holes (p < 0.05).

Conclusion

IRS and ITNs have proven to be effective control strategies on the island of Bioko. The choice of one or other strategy is, above all, a question of operational feasibility and availability of local resources.