Adam Bennett

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542–753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Malaria prevention in pregnancy, birthweight, and neonatal mortality: a meta-analysis of 32 national cross-sectional datasets in Africa

BACKGROUND Low birthweight is a significant risk factor for neonatal and infant death. A prominent cause of low birthweight is infection with Plasmodium falciparum during pregnancy. Antimalarial intermittent preventive therapy in pregnancy (IPTp) and insecticide-treated mosquito nets (ITNs) significantly reduce the risk of low birthweight in regions of stable malaria transmission. We aimed to assess the effectiveness of malaria prevention in pregnancy (IPTp or ITNs) at preventing low birthweight and neonatal mortality under routine programme conditions in malaria endemic countries of Africa. METHODS We used a retrospective birth cohort from national cross-sectional datasets in 25 African countries from 2000-10. We used all available datasets from multiple indicator cluster surveys, demographic and health surveys, malaria indicator surveys, and AIDS indicator surveys that were publically available as of 2011. We tried to limit confounding bias through exact matching on potential confounding factors associated with both exposure to malaria prevention (ITNs or IPTp with sulfadoxine-pyrimethamine) in pregnancy and birth outcomes, including local malaria transmission, neonatal tetanus vaccination, maternal age and education, and household wealth. We used a logistic regression model to test for associations between malaria prevention in pregnancy and low birthweight, and a Poisson model for the outcome of neonatal mortality. Both models incorporated the matched strata as a random effect, while accounting for additional potential confounding factors with fixed effect covariates. FINDINGS We analysed 32 national cross-sectional datasets. Exposure of women in their first or second pregnancy to full malaria prevention with IPTp or ITNs was significantly associated with decreased risk of neonatal mortality (protective efficacy [PE] 18%, 95% CI 4-30; incidence rate ratio [IRR] 0·820, 95% CI 0·698-0·962), compared with newborn babies of mothers with no protection, after exact matching and controlling for potential confounding factors. Compared with women with no protection, exposure of pregnant women during their first two pregnancies to full malaria prevention in pregnancy through IPTp or ITNs was significantly associated with reduced odds of low birthweight (PE 21%, 14-27; IRR 0·792, 0·732-0·857), as measured by a combination of weight and birth size perceived by the mother, after exact matching and controlling for potential confounding factors. INTERPRETATION Malaria prevention in pregnancy is associated with substantial reductions in neonatal mortality and low birthweight under routine malaria control programme conditions. Malaria control programmes should strive to achieve full protection in pregnant women by both IPTp and ITNs to maximise their benefits. Despite an attempt to mitigate bias and potential confounding by matching women on factors thought to be associated with access to malaria prevention in pregnancy and birth outcomes, some level of confounding bias possibly remains.

Household Possession and Use of Insecticide-Treated Mosquito Nets in Sierra Leone 6 Months after a National Mass-Distribution Campaign

Background In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. Methods We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. Results The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥1∶2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. Conclusions The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden.

The path to eradication: a progress report on the malaria-eliminating countries

In the past several years, as worldwide morbidity and mortality due to malaria have continued to decrease, the global malaria community has grown increasingly supportive of the idea of malaria eradication. In 2015, three noteworthy global documents were released-the WHOs Global Technical Strategy for Malaria 2016-2030, the Roll Back Malaria Partnerships Action and Investment to defeat Malaria 2016-2030, and From Aspiration to Action: What Will It Take to End Malaria?-that collectively advocate for malaria elimination and eradication and outline key operational, technical, and financial strategies to achieve progress toward malaria eradication. In light of this remarkable change in global attitudes toward malaria elimination and eradication, and as the malaria community debates how and when to embark on this ambitious goal, it is important to assess current progress along the path to eradication. Although low-income, high-burden countries are often the focus when discussing the substantial challenges of eradication, the progress toward elimination in middle-income, low-burden countries is a major driver of global progress and deserves better recognition. Additionally, although global support and guidance is essential for success, malaria elimination and eradication efforts will ultimately be driven at the country level and achieved in a collaborative manner, region by region. In this Review, we examine the present status of the 35 malaria-eliminating countries, summarise existing national and regional elimination goals and the regional frameworks that support them, and identify the most crucial enabling factors and potential barriers to achieving eradication by a theoretical end date of 2040.

Mass drug administration for the control and elimination of Plasmodium vivax malaria: An ecological study from Jiangsu province, China

BackgroundRecent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited. China has extensive experience with MDA, but it is not well documented.MethodsAn ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence. Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties. All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described. Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models.ResultsFrom 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population). Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973–1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976–1983. Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973–1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated. From 2000–2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population). Although safety data were not collected systematically, there were rare reports of serious but non-fatal events.ConclusionsIn Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission. MDA should be considered a potential key strategy for malaria control and elimination.

Prevalence of Plasmodium falciparum Infection in Rainy Season, Artibonite Valley, Haiti, 2006

We conducted a population-based survey to estimate the prevalence of Plasmodium falciparum infection among persons older than 1 month in the Artibonite Valley of Haiti during the high malaria transmission season in 2006. Results from PCR for 714 persons showed a prevalence of 3.1% for P. falciparum infection.

Chloroquine-Resistant Haplotype Plasmodium falciparum Parasites, Haiti

Chloroquine resistance is now present in this country.

Plasmodium falciparum parasite infection prevalence from a household survey in Zambia using microscopy and a rapid diagnostic test: implications for monitoring and evaluation.

This paper presents estimates of P. falciparum infection prevalence in children under 5 years old in the context of a population-based household survey in Luangwa District (Lusaka Province), Zambia, an area where greater than 75% of households possess at least one insecticide-treated mosquito net (ITN). The sensitivity and specificity of an HRP-2 rapid diagnostic test (RDT) (ICT Malaria Pf((R))) compared to microscopy, as well as factors associated with discordant diagnostic results are also presented. P. falciparum infection prevalence was estimated at 7.0% (95% CI 4.9-9.0%) using microscopy. Using microscopy as the gold standard, the sensitivity of the HRP-2 RDT was 100% and specificity was 91.5%; positive predictive value was estimated to be 46.7% (95% CI 36.3-57.4%). RDT discordance, or HRP-2 false positivity, was highest among older children, those in the northern part of Luangwa District, and those with a reported history of antimalarial treatment. These data suggest microscopy should remain the gold standard for estimating malaria parasite point prevalence from household surveys for monitoring and evaluation purposes.

Reductions in artemisinin-based combination therapy consumption after the nationwide scale up of routine malaria rapid diagnostic testing in Zambia.

The National Malaria Control Center of Zambia introduced rapid diagnostic tests (RDTs) to detect Plasmodium falciparum as a pilot in some districts in 2005 and 2006; scale up at a national level was achieved in 2009. Data on RDT use, drug consumption, and diagnostic results were collected in three Zambian health districts to determine the impact RDTs had on malaria case management over the period 2004–2009. Reductions were seen in malaria diagnosis and antimalarial drug prescription (66.1 treatments per facility-month (95% confidence interval [CI] = 44.7–87.4) versus 26.6 treatments per facility-month (95% CI = 11.8–41.4)) pre- and post-RDT introduction. Results varied between districts, with significant reductions in low transmission areas but none in high areas. Rapid diagnostic tests may contribute to rationalization of treatment of febrile illness and reduce antimalarial drug consumption in Africa; however, their impact may be greater in lower transmission areas. National scale data will be necessary to confirm these findings.

Evidence that parent-of-origin affects birth-weight reductions at high altitude.

Hypoxia exerts a profound depressant effect on fetal growth, lowering birth weight, and raising mortality risk. Multigenerational high‐altitude populations are relatively protected from this birth‐weight decline, leading us to hypothesize that genetic factors were involved. We asked if the amount of high‐ versus low‐altitude ancestry influenced birth weight at high altitude and, specifically, whether such influences were affected by parent‐of‐origin effects (i.e., genomic imprinting). Medical records were reviewed from 1,343 consecutive, singleton deliveries in La Paz, Bolivia (3,600 m) of high‐ (Andean) or low‐ (European) altitude ancestry. Parental surnames were used to classify ancestry as Andean, European, Mestizo (“mixed”) or some combination thereof. The effects of population ancestry on birth weight were determined by categorical, conditional linear regression. Babies born at altitude with two Andean parents weighed 252 g more than their European counterparts, with the protective effect being proportional to the amount of Andean parentage and independent of maternal parity, body size, smoking, or socioeconomic status. Paternal compared with maternal transmission raised birth weight 81 g for a given ancestry group. We concluded that indigenous high‐altitude ancestry protected against hypoxia‐associated fetal growth reduction in a dose‐dependent fashion consistent with the involvement of genetic factors. Further, some of the genes involved appeared to be influenced by parent‐of‐origin effects, given that maternal transmission restricted and paternal transmission enhanced fetal growth. Am. J. Hum. Biol., 2008.