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Background Joint efforts by government and non-government organizations have helped to reduce malaria in Bangladesh and set the country on a clear path to eventual malaria elimination. However, achieving that goal would be challenging without a comprehensive understanding of vector bionomics. Methods Targeted capturing of Anopheles mosquitoes over a rainy season, utilizing specific sampling methods, including human landing catches (HLCs), CDC-light traps (CDC-LTs), and pyrethrum spray catches (PSCs) were aimed to characterize entomological drivers of transmission in four sites of Bandarban, Bangladesh. Results Molecular characterization of a subset of 4637 mosquitoes has demonstrated the presence of at least 17 species whose capture rates were representative of the rainy season. Species compositions and bionomic traits did not vary between sites with Anopheles maculatus having the highest landing rate by HLCs and Anopheles vagus having the highest capture rate with CDC-LTs. Interestingly, Anopheles species compositions and capture rates varied significantly (p < 0.05) for An. vagus , between HLCs and its often-used proxy—CDC-LTs- suggesting impacts on downstream analysis. CDC-LTs capture rates demonstrated differing compositions with indoor and outdoor biting rates. For example, Anopheles nigerrimus and Anopheles nivipes were more endophagic by HLCs and more exophagic by CDC-LTs. The use of a cow-baited CDC-LT also demonstrated significantly different results when compared to a human-baited CDC-LT considering the high degree of anthropophily in these species. The exception to both zoophily and indoor resting was An. vagus , which demonstrated both anthropophily and high resting rates indoors — pointing to this species being a possible primary vector at this site. Conclusion A diverse Anopheles fauna in Bandarban has been confirmed through molecular methods, highlighting the potential impact of sampling techniques. Given the complexity of the local ecosystem, a better understanding of mosquito behaviour and ecology is required to achieve the goal of malaria elimination in Bangladesh.

The high frequency of the sickle-cell haemoglobin (HbS) gene in malaria endemic regions is believed to be due to a heterozygote (HbASp) advantage against fatal malaria. Data to prospectively confirm the protection associated with HbAS against mortality are lacking. We show that HbAS provides significant protection against all-cause mortality, severe malarial anaemia, and high-density parasitaemia. This significant reduction in mortality was detected between the ages of 2 and 16 months, the highest risk period for severe malarial anaemia in this area. These data are important in understanding the role of malaria in the selection and maintenance of the sickle cell gene.

Background Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues. Methods This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997–1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-1 19 , and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR. Results Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-1 19 , correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997–1999 ITN trial. Conclusions In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.

Background. Sulfadoxine-pyrimethamine (SP) is among the most commonly used antimalarial drugs during pregnancy, yet the pharmacokinetics of SP are unknown in pregnant women. HIV-infected (HIV+) women require more frequent doses of intermittent preventive therapy with SP than do HIV-uninfected (HIV-) women. We investigated whether this reflects their impaired immunity or an HIV-associated alteration in the disposition of SP. Methods. Seventeen pregnant HIV- women and 16 pregnant HIV+ women received a dose of 1500 mg of sulfadoxine and 75 mg of pyrimethamine. Five HIV- and 6 HIV+ postpartum women returned 2–3 months after delivery for another dose. The pharmacokinetics of sulfadoxine and pyrimethamine were compared between these groups. Results. HIV status did not affect the area under the curve (AUC0→∞) or the half-lives of sulfadoxine or pyrimethamine in prepartum or postpartum women, although partum status did have a significant affect on sulfadoxine pharmacokinetics. Among prepartum women, the median half-life for sulfadoxine was significantly shorter than that observed in postpartum women (148 vs 256 h; P < .001), and the median AUC0→∞ was ∼40% lower (22,816 vs 40,106 μg/mL/h, P < .001). HIV status and partum status did not show any significant influence on pyrimethamine pharmacokinetics. Conclusion. Pregnancy significantly modifies the disposition of SP, whereas HIV status has little influence on pharmacokinetic parameters in pregnant women.

Little is known about the epidemiology of malaria during pregnancy in areas of unstable (epidemic-prone) transmission (UT) in sub-Saharan Africa. In cross-sectional studies, peripheral malaria parasitemia was identified in 10.4% of women attending antenatal care clinics at 1 stable transmission (ST) site and in 1.8% of women at 3 UT sites; parasitemia was associated with anemia in both ST (relative risk [RR], 2.0; P<.001) and UT (RR, 4.4; P<.001) sites. Placental parasitemia was identified more frequently during deliveries at ST sites (12/185; 6.5%) than at UT sites (21/833; 2.5%; P=.006). Placental parasitemia was associated with low birth weight at the ST site (RR, 3.2; P=.01) and prematurity at ST (RR, 2.7; P=.04) and UT (RR, 3.9; P=.01) sites and with a 7-fold increased risk of stillbirths at UT sites. The effectiveness and efficiency in Ethiopia of standard preventive strategies used in high-transmission regions (such as intermittent preventive treatment) may require further evaluation; approaches such as insecticide-treated bednets and epidemic preparedness may be needed to prevent adverse pregnancy outcomes

Background. HIV and malaria in sub-Saharan Africa are associated with poor pregnancy outcome and infant survival. We studied the association of placental malaria, infant malaria and anemia, and infant HIV status with postneonatal infant mortality (PNIM) among infants of HIV-seropositive women. Methods. During 1996–2001, infants born to 570 HIV-seropositive mothers in Kisumu, Kenya were monitored monthly for malaria (parasitemia or clinical malaria) and anemia (hemoglobin level <8 g/dL) and vital status. Results. Thirty-nine deaths occurred among 112 HIV-positive infants (420/1000 live births [LBs] [95% confidence interval {CI}, 318–522 LBs]), and 36 occurred among 458 HIV-negative infants (99/1000 LBs [95% CI, 68–130 LBs]) (P<.001). In multivariate Cox regression analysis among HIV-negative infants, PNIM was associated with infant anemia (adjusted hazard ratio [AHR], 5.03 [95% CI, 1.97–12.81]) but not with placental malaria (AHR, 1.22 [95% CI, 0.50–2.95]) or infant malaria (AHR, 0.35 [95% CI, 0.10–1.21]). Among HIV-positive infants, neither placental malaria (AHR, 0.34 [95% CI, 0.10–1.10]) nor infant malaria (AHR, 0.31 [95% CI, 0.07–1.33]) or anemia (AHR, 1.07 [95% CI, 0.32–3.61]) was significantly associated with PNIM. Conclusion. In this study population, placental malaria and infant parasitemia were not risk factors for PNIM among infants of HIV-seropositive women. The prevention of infant anemia may decrease PNIM among HIVnegative infants of HIV-seropositive women.

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.

Macrophage migration inhibitory factor (MIF) may play a role in immune responses to malaria during pregnancy by virtue of its ability to activate macrophages and to overcome the immunosuppressive effect of glucocorticoids. The present study investigated whether plasma MIF levels are altered in pregnant women with placental malaria (PM) and/or human immunodeficiency virus (HIV) infection. For the first time it is demonstrated that MIF levels in the intervillous blood (IVB) plasma were significantly elevated, compared with that in both peripheral plasma (∼500-fold) and cord plasma (4.6-fold; P<.01). IVB mononuclear cells also produced significantly higher levels of MIF, compared with that of peripheral blood mononuclear cells. PM was associated with increased levels of MIF in the IVB plasma (P<.02). Primigravid and secundigravid women had significantly higher levels of MIF in their IVB plasma than did multigravid women (P<.05). HIV infection did not significantly alter MIF levels in any site examined

A randomized, placebo-controlled treatment trial was conducted among 546 anemic (hemoglobin concentration, 7–11 g/dL) children aged 2–36 months in an area with intense malaria transmission in western Kenya. All children used bednets and received a single dose of sulfadoxine-pyrimethamine (SP) on enrollment, followed by either intermittent preventive treatment (IPT) with SP at 4 and 8 weeks and daily iron for 12 weeks, daily iron and IPT with SP placebo, IPT and daily iron placebo, or daily iron placebo and IPT with SP placebo (double placebo). The mean hemoglobin concentration at 12 weeks, compared with that for the double-placebo group, was 1.14 g/dL (95% confidence interval [CI], 0.82–1.47 g/dL) greater for the IPT+iron group, 0.79 g/dL (95% CI, 0.46–1.10 g/dL) greater for the iron group, and 0.17 g/dL (95% CI, −0.15–0.49 g/dL) greater for the IPT group. IPT reduced the incidence of malaria parasitemia and clinic visits, but iron did not. The combination of IPT and iron supplementation was most effective in the treatment of mild anemia. Although IPT prevented malaria, the hematological benefit it added to that of a single dose of SP and bednet use was modest