Anna Maria van Eijk

Coverage of intermittent preventive treatment and insecticide-treated nets for the control of malaria during pregnancy in sub-Saharan Africa: a synthesis and meta-analysis of national survey data 2009-11.

BACKGROUND Pregnant women in malaria-endemic countries in sub-Saharan Africa are especially vulnerable to malaria. Recommended prevention strategies include intermittent preventive treatment with two doses of sulfadoxine-pyrimethamine and the use of insecticide-treated nets. However, progress with implementation has been slow and the Roll Back Malaria Partnership target of 80% coverage of both interventions by 2010 has not been met. We aimed to review the coverage of intermittent preventive treatment, insecticide-treated nets, and antenatal care for pregnant women in sub-Saharan Africa and to explore associations between coverage and individual and country-level factors, including the role of funding for malaria prevention. METHODS We used data from nationally representative household surveys from 2009-11 to estimate coverage of intermittent preventive treatment, use of insecticide-treated nets, and attendance at antenatal clinics by pregnant women in sub-Saharan Africa. Using demographic data for births and published data for malaria exposure, we also estimated the number of malaria-exposed births (livebirths and stillbirths combined) for 2010 by country. We used meta-regression analysis to investigate the factors associated with coverage of intermittent preventive treatment and use of insecticide-treated nets. RESULTS Of the 21·4 million estimated malaria-exposed births across 27 countries in 2010, an estimated 4·6 million (21·5%, 95% CI 19·3-23·7) were born to mothers who received intermittent preventive treatment. Insecticide-treated nets were used during pregnancy for 10·5 million of 26·9 million births across 37 countries (38·8%, 34·6-43·0). Antenatal care was attended at least once by 16·3 of 20·8 million women in 2010 (78·3%, 75·2-81·4; n=26 countries) and at least twice by 14·7 of 19·6 million women (75·1%, 72·9-77·3; n=22 countries). For the countries with previous estimates for 2007, coverage of intermittent preventive treatment increased from 13·1% (11·9-14·3) to 21·2% (18·9-23·5; n=14 countries) and use of insecticide-treated nets increased from 17·9% (15·1-20·7) to 41·6% (37·2-46·0; n=24 countries) in 2010. A fall in coverage by more than 10% was seen in two of 24 countries for intermittent preventive treatment and in three of 30 countries for insecticide-treated nets. High disbursement of funds for malaria control and a long time interval since adoption of the relevant policy were associated with the highest coverage of intermittent preventive treatment. High disbursement of funds for malaria control and high total fertility rate were associated with the greatest use of insecticide-treated nets, whereas a high per-head gross domestic product (GDP) was associated with less use of nets than was a lower GDP. Coverage of intermittent preventive treatment showed greater inequity overall than use of insecticide-treated nets, with richer, educated, and urban women more likely to receive preventive treatment than their poorer, uneducated, rural counterparts. INTERPRETATION Although coverage of intermittent preventive treatment and use of insecticide-treated nets by pregnant women has increased in most countries, coverage remains far below international targets, despite fairly high rates of attendance at antenatal clinics. The effect of the implementation of WHOs 2012 policy update for intermittent preventive treatment, which aims to simplify the message and align preventive treatment with the focused antenatal care schedule, should be assessed to find out whether it leads to improvements in coverage. FUNDING Bill & Melinda Gates Foundation.

HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

Background As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.Background As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. Objective To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. Design Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. Results The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. Conclusions Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

Malaria Molecular Epidemiology: Lessons from the International Centers of Excellence for Malaria Research Network

Molecular epidemiology leverages genetic information to study the risk factors that affect the frequency and distribution of malaria cases. This article describes molecular epidemiologic investigations currently being carried out by the International Centers of Excellence for Malaria Research (ICEMR) network in a variety of malaria-endemic settings. First, we discuss various novel approaches to understand malaria incidence and gametocytemia, focusing on Plasmodium falciparum and Plasmodium vivax. Second, we describe and compare different parasite genotyping methods commonly used in malaria epidemiology and population genetics. Finally, we discuss potential applications of molecular epidemiological tools and methods toward malaria control and elimination efforts.

The Association between Malaria and Iron Status or Supplementation in Pregnancy: A Systematic Review and Meta-Analysis

Introduction Malaria prevention and iron supplementation are associated with improved maternal and infant outcomes. However, evidence from studies in children suggests iron may adversely modify the risk of malaria. We reviewed the evidence in pregnancy of the association between malaria and markers of iron status, iron supplementation or parenteral treatment. Methods and Findings We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Global Health Library, and the Malaria in Pregnancy library to identify studies that investigated the association between iron status, iron treatment or supplementation during pregnancy and malaria. Thirty one studies contributed to the analysis; 3 experimental and 28 observational studies. Iron supplementation was not associated with an increased risk of P. falciparum malaria during pregnancy or delivery in Africa (summary Relative Risk = 0.89, 95% Confidence Interval (CI) 0.66–1.20, I2 = 78.8%, 5 studies). One study in Asia reported an increased risk of P. vivax within 30 days of iron supplementation (e.g. adjusted Hazard Ratio = 1.75, 95% CI 1.14–2.70 for 1–15 days), but not after 60 days. Iron deficiency (based on ferritin and C-reactive protein) was associated with lower odds for malaria infection (summary Odds Ratio = 0.35, 0.24–0.51, I2 = 59.2%, 5 studies). With the exception of the acute phase protein ferritin, biomarkers of iron deficiency were generally not associated with malaria infection. Conclusions Iron supplementation was associated with a temporal increase in P vivax, but not with an increased risk of P. falciparum; however, data are insufficient to rule out the potential for an increased risk of P. falciparum. Iron deficiency was associated with a decreased malaria risk in pregnancy only when measured with ferritin. Until there is more evidence, it is prudent to provide iron in combination with malaria prevention during pregnancy.

Menstrual hygiene management among adolescent girls in India: a systematic review and meta-analysis

Objectives To assess the status of menstrual hygiene management (MHM) among adolescent girls in India to determine unmet needs. Design Systematic review and meta-analysis. We searched PubMed, The Global Health Database, Google Scholar and references for studies published from 2000 to September 2015 on girls’ MHM. Setting India. Participants Adolescent girls. Outcome measures Information on menarche awareness, type of absorbent used, disposal, hygiene, restrictions and school absenteeism was extracted from eligible materials; a quality score was applied. Meta-analysis was used to estimate pooled prevalence (PP), and meta-regression to examine the effect of setting, region and time. Results Data from 138 studies involving 193 subpopulations and 97 070 girls were extracted. In 88 studies, half of the girls reported being informed prior to menarche (PP 48%, 95% CI 43% to 53%, I2 98.6%). Commercial pad use was more common among urban (PP 67%, 57% to 76%, I2 99.3%, n=38) than rural girls (PP 32%, 25% to 38%, I2 98.6%, n=56, p<0.0001), with use increasing over time (p<0.0001). Inappropriate disposal was common (PP 23%, 16% to 31%, I2 99.0%, n=34). Menstruating girls experienced many restrictions, especially for religious activities (PP 0.77, 0.71 to 0.83, I2 99.1%, n=67). A quarter (PP 24%, 19% to 30%, I2 98.5%, n=64) reported missing school during periods. A lower prevalence of absenteeism was associated with higher commercial pad use in univariate (p=0.023) but not in multivariate analysis when adjusted for region (p=0.232, n=53). Approximately a third of girls changed their absorbents in school facilities (PP 37%, 29% to 46%, I2 97.8%, n=17). Half of the girls’ homes had a toilet (PP 51%, 36% to 67%, I2 99.4%, n=21). The quality of studies imposed limitations on analyses and the interpretation of results (mean score 3 on a scale of 0–7). Conclusions Strengthening of MHM programmes in India is needed. Education on awareness, access to hygienic absorbents and disposal of MHM items need to be addressed. Trial registration number CRD42015019197.

Determinants and Coverage of Vaccination in Children in Western Kenya from a 2003 Cross-Sectional Survey

This study assesses full and timely vaccination coverage and factors associated with full vaccination in children ages 12-23 months in Gem, Nyanza Province, Kenya in 2003. A simple random sample of 1,769 households was selected, and guardians were invited to bring children under 5 years of age to participate in a survey. Full vaccination coverage was 31.1% among 244 children. Only 2.2% received all vaccinations in the target month for each vaccination. In multivariate logistic regression, children of mothers of higher parity (odds ratio [OR] = 0.27, 95% confidence interval [95% CI] = 0.13-0.65, P ≤ 0.01), children of mothers with lower maternal education (OR = 0.35, 95% CI = 0.13-0.97, P ≤ 0.05), or children in households with the spouse absent versus present (OR = 0.40, 95% CI = 0.17-0.91, P ≤ 0.05) were less likely to be fully vaccinated. These data serve as a baseline from which changes in vaccination coverage will be measured as interventions to improve vaccination timeliness are introduced.

Effect of Placental Malaria and HIV Infection on the Antibody Responses to Plasmodium falciparum in Infants

BACKGROUND Placental malaria (PM) and maternal infection with human immunodeficiency virus (HIV) type 1 have been shown to affect infant morbidity and immune responses to Plasmodium falciparum. We studied the effects of PM and HIV infection on the antimalarial antibody responses and morbidity outcomes of infants throughout the first year of life. METHODS A total of 411 Kenyan infants who were born to mothers who were singly or dually infected with PM and/or HIV had their levels of immunoglobulin G antibody to 6 P. falciparum antigens/epitopes (apical membrane antigen-1, erythrocyte-binding antigen-175; liver-stage antigen-1 [LSA-1], circumsporozoite protein [CSP], merozoite surface protein-2, and rhoptry-associated protein-1 [RAP-1]) and to tetanus toxoid (TT) tested using enzyme-linked immunosorbent assay. RESULTS PM had little effect on the antibody responses of infants, whereas maternal HIV infection resulted in decreased levels of antibody to LSA-1, CSP, and RAP-1 epitopes at birth, compared with the absence of PM and maternal HIV infection (P = .0063). Levels of antibodies to TT were significantly reduced in infants born to mothers coinfected with HIV and PM, compared with the levels noted in infants born to HIV-negative mothers (P = .0003). In HIV-infected infants, levels of antibody to TT were reduced, but levels of antibody to malarial antigens were not. Antimalarial antibody levels were positively associated with malaria-related morbidity outcomes. CONCLUSION Infant HIV infection and maternal coinfection with HIV and PM negatively influence antibody responses to TT, but not those to malarial antigens, in infants. Antimalarial antibodies rarely showed protective associations with morbidity in infants and were more often a marker for malaria exposure and risk of infection.

Prevalence of malaria infection in pregnant women compared with children for tracking malaria transmission in sub-Saharan Africa: a systematic review and meta-analysis

Summary Background In malarious areas, pregnant women are more likely to have detectable malaria than are their non-pregnant peers, and the excess risk of infection varies with gravidity. Pregnant women attending antenatal clinic for their first visit are a potential pragmatic sentinel group to track the intensity of malaria transmission; however, the relation between malaria prevalence in children, a standard measure to estimate malaria endemicity, and pregnant women has never been compared. Methods We obtained data on malaria prevalence in pregnancy from the Malaria in Pregnancy Library (January, 2015) and data for children (0–59 months) were obtained from recently published work on parasite prevalence in Africa and the Malaria in Pregnancy Library. We used random effects meta-analysis to obtain a pooled prevalence ratio (PPR) of malaria in children versus pregnant women (during pregnancy, not at delivery) and by gravidity, and we used meta-regression to assess factors affecting the prevalence ratio. Findings We used data from 18 sources that included 57 data points. There was a strong linear relation between the prevalence of malaria infection in pregnant women and children (r=0·87, p<0·0001). Prevalence was higher in children when compared with all gravidae (PPR=1·44, 95% CI 1·29–1·62; I2=80%, 57 studies), and against multigravidae (1·94, 1·68–2·24; I2=80%, 7 studies), and marginally higher against primigravidae (1·16, 1·05–1·29; I2=48%, 8 studies). PPR was higher in areas of higher transmission. Interpretation Malaria prevalence in pregnant women is strongly correlated with prevalence data in children obtained from household surveys, and could provide a pragmatic adjunct to survey strategies to track trends in malaria transmission in Africa. Funding The Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK; US Centers for Disease Control and Prevention; and Wellcome Trust, UK.

The Malaria in Pregnancy Library: a bibliometric review

BackgroundThe Malaria in Pregnancy (MiP) Library is a bibliographic database that was created by the MiP Consortium in 2005 and is updated every four months using a standardized search protocol. A bibliometric review was conducted of the contents of the Library to determine dynamics in the type, content and volume of literature on malaria in pregnancy over time.MethodsData on year of publication, type, language, country of first-author affiliation and content (topic) were extracted from entries in the MiP Library and plotted over time.ResultsBy January 2012, the MiP Library contained 5,346 entries, consisting of 3,721 journal articles (69.6%), 697 reports (13.0%), 219 academic theses (4.1%), 92 books or book chapters (1.7%), 487 conference proceedings (9.1%), 68 registered studies (1.3%) and 62 ‘other’ (1.2%). Most of the sources were in English language (87.3%), followed by French (7.5%) and Spanish (1.5%). Over 40% of source material was publicly available online (42.4%) and the remaining with restricted access (35.0%) or otherwise unavailable (22.7%). The number of journal articles related to malaria in pregnancy increased from 41 in the 1960s, to 708 in the 1990s, and 1,895 between 2000 and 2009, and the variety of themes has increased over time. English-language articles were sourced from 737 different journals. The top three journals were the American Journal of Tropical Medicine and Hygiene (184), Malaria Journal (158) and the Transactions of the Royal Society of Tropical Medicine and Hygiene (131).ConclusionThe last decade has seen a dramatic increase in publications related to malaria in pregnancy, and an increasing proportion of these are publically available online. The MiP Library is a useful, scholarly source for literature and systematic reviews related to malaria in pregnancy.

Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial.

Background In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). However, sulfadoxine-pyrimethamine (SP) efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP) as an alternative strategy to IPTp-SP. Methods and Findings This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the intermittent screening and treatment in pregnancy with DP (ISTp-DP) arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk]) in paucigravidae (first or second pregnancy) and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher). Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae). The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9%) and IPTp-SP (28.8%) arms (risk difference = 1.08% [95% CI −3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90–1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92–1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71–1.20], p = 0.543). The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3.07%–12.63%]; all women: RR = 1.19 [95% CI 1.07–1.33], p = 0.007; paucigravidae: RR = 1.16 [95% CI 1.04–1.31], p = 0.011; multigravidae: RR = 1.29 [95% CI 1.02–1.63], p = 0.037). Fetal loss was more common with ISTp-DP (2.6% versus 1.3%; RR = 2.06 [95% CI 1.01–4.21], p = 0.046) and highest among non-DP-recipients (3.1%) in the ISTp-DP arm. Limitations included the open-label design. Conclusions Scheduled screening for malaria parasites with the current generation of RDTs three to four times during pregnancy as part of focused antenatal care was not superior to IPTp-SP in this area with high malaria transmission and high SP resistance and was associated with higher fetal loss and more malaria at delivery. Trial Registration Pan African Clinical Trials Registry PACTR201103000280319; ISRCTN Registry ISRCTN69800930