Composition of Anopheles species and bionomic characteristics over the peak malaria transmission season in Bandarban, Bangladesh.

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.

Preliminary Report of Pyrethroid Resistance in Anopheles vagus, an Important Malaria Vector in Bangladesh.

According to the WHO, unmanaged insecticide resistance may lead to increases in malaria-related mortality and morbidity. Bangladesh, having made significant progress in malaria control efforts, has recently seen an upswing in malaria cases-58% of which occurred in Bandarban district. Toward identifying entomological drivers of increased malaria, an entomological survey including Anopheles susceptibility to the insecticides in use was conducted in Bandarban. Anopheles vagus, the primary vector of malaria, was found to be resistant to both permethrin and deltamethrin-with only 29% and 55% mortality at 30 minutes, respectively. Intervention strategies in this area-all based on pyrethroids, may need to be reevaluated toward closing this gap in protection and increasing intervention efficacy.

Serological markers for monitoring historical changes in malaria transmission intensity in a highly endemic region of Western Kenya, 1994-2009.

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-119, 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-119, 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.

Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs) on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP-1) and circumsporozoite (CSP) in western Kenya.

BACKGROUND: Although several studies have investigated the impact of reduced malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns of morbidity and mortality, there is limited information on their effect on parasite diversity. METHODS: Sequencing was used to investigate the effect of ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1 (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic stage circumsporozoite protein (CSP) in a large community-based ITN trial site in western Kenya. The number and frequency of haplotypes as well as nucleotide and haplotype diversity were compared among parasites obtained from children <5 years old prior to the introduction of ITNs (1996) and after 5 years of high coverage ITN use (2001). RESULTS: A total of 12 MSP-1(19kDa) haplotypes were detected in 1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and FUP strains of P. falciparum were the most prevalent (range 32-37%), with an overall haplotype diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes, respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less than 4% at both time points. There was no significant difference in nucleotide and haplotype diversity in parasite isolates collected at both time points. CONCLUSION: High diversity in these two genes has been maintained overtime despite marked reductions in malaria transmission due to ITNs use. The frequency of 3D7 sequence-types was very low in this area. These findings provide information that could be useful in the design of future malaria vaccines for deployment in endemic areas with high ITN coverage and in interpretation of efficacy data for malaria vaccines based on 3D7 parasite strains.

Lives saved by Global Fund-supported HIV/AIDS, tuberculosis and malaria programs: estimation approach and results between 2003 and end-2007.

BACKGROUND: Since 2003, the Global Fund has supported the scale-up of HIV/AIDS, tuberculosis and malaria control in low- and middle-income countries. This paper presents and discusses a methodology for estimating the lives saved through selected service deliveries reported to the Global Fund. METHODS: Global Fund-supported programs reported, by end-2007, 1.4 million HIV-infected persons on antiretroviral treatment (ARV), 3.3 million new smear-positive tuberculosis cases detected in DOTS (directly observed TB treatment, short course) programs, and 46 million insecticide-treated mosquito nets (ITNs) delivered. We estimated the corresponding lives saved using adaptations of existing epidemiological estimation models. RESULTS: By end-2007, an estimated 681,000 lives (95% uncertainty range 619,000-774,000) were saved and 1,097,000 (993,000-1,249,000) life-years gained by ARV. DOTS treatment would have saved 1.63 million lives (1.09-2.17 million) when compared against no treatment, or 408,000 lives (265,000-551,000) when compared against non-DOTS treatment. ITN distributions in countries with stable endemic falciparum malaria were estimated to have achieved protection from malaria for 26 million of child-years at risk cumulatively, resulting in 130,000 (27,000-232,000) under-5 deaths prevented. CONCLUSIONS: These results illustrate the scale of mortality effects that supported programs may have achieved in recent years, despite margins of uncertainty and covering only selected intervention components. Evidence-based evaluation of disease impact of the programs supported by the Global Fund with international and in-country partners must be strengthened using population-level data on intervention coverage and demographic outcomes, information on quality of services, and trends in disease burdens recorded in national health information systems.

Diarrhea in children less than two years of age with known HIV status in Kisumu, Kenya.

OBJECTIVE: To compare the frequency and etiology of diarrhea in children aged less than 2 years with known HIV status. METHODS: This was a nested cohort study, whereby children were followed during monthly routine and unscheduled visits. The HIV status of children was determined with PCR. A stool culture was obtained from children with diarrhea. A subset of stool samples was examined for parasites and tested for rotavirus. RESULTS: Between 1997 and 2001, 682 children (51.0% male) contributed observation periods with a mean of 47 weeks. Overall there were 198 episodes of diarrhea per 100 child-years of observation (CYO); diarrhea was more common among HIV-positive children than among HIV-negative children (321 vs. 183 episodes/100 CYO, respectively, p<0.01) and was not statistically different for HIV-negative children born to HIV-positive compared with HIV-negative mothers (182 vs. 187 episodes/100 CYO, respectively, p=0.36). For 66.5% of the acute episodes a stool culture was obtained; 27.8% of stool cultures yielded a bacterial pathogen. A positive stool culture was less likely among HIV-positive children compared to children of HIV-negative mothers (20.5% vs. 34.3%, p=0.01). Susceptibility of Salmonella and Shigella to commonly used antibiotics was low. Rotavirus was detected in 13.9% of 202 examined stool samples, and a stool parasite in 3.8% of 394 samples. Diarrhea was associated with 37.8% of child deaths. CONCLUSIONS: Diarrhea was more common among HIV-infected children, but was not associated with specific bacterial pathogens. Measures that reduce diarrhea will benefit all children, but may benefit HIV-infected children in particular.

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.

Viewpoint: evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa.

OBJECTIVE: To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS: Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS: All methods require a plausibility argument-i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS: Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added.

Pharmacokinetics of sulfadoxine-pyrimethamine in HIV-infected and uninfected pregnant women in Western Kenya.

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 (AUC(0-->infinity)) 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 AUC(0-->infinity) was ~40% lower (22,816 vs 40,106 microg/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.

HIV, malaria, and infant anemia as risk factors for postneonatal infant mortality among HIV-seropositive women in Kisumu, Kenya.

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 HIV-negative infants of HIV-seropositive women.

Estimating the number of insecticide-treated nets required by African households to reach continent-wide malaria coverage targets.

CONTEXT: African countries are scaling up malaria interventions, especially insecticide-treated nets (ITNs), for which ambitious coverage targets have been set. OBJECTIVE: To estimate how many ITNs are available in African households that are at risk of malaria and how many ITNs are needed to reach targets for use by children younger than 5 years and pregnant women. DATA SOURCES: Primary sources of data were the Multiple Indicator Cluster Surveys II, the Demographic and Health Surveys, or other nationally representative or large-scale household surveys that measured household possession and use of nets or ITNs among children younger than 5 years. DATA EXTRACTION: Data from 42 household surveys between 1999 and 2006 on net and ITN coverage (either household possession or use) and average numbers of nets and ITNs per household were compared with populations and households at risk. Data are included for 43 sub-Saharan African countries. DATA SYNTHESIS: For the median survey year 2003, the population-weighted mean proportion of households possessing at least 1 ITN was 6.7% (range among countries, 0.1%-71.0%) and was 23.8% (range, 5.0%-91.2%) for any type of net. Based on an average of 0.13 ITNs per household, we estimated that 53.6 million nets, of which 16.7 million were ITNs, were available in households at risk of malaria. Between 130 million and 264 million ITNs are required in 2007 to reach the 80% coverage target for about 133 million children younger than 5 years and pregnant women living in 123 million households in risk areas; the exact number depends on usage patterns (best estimate, assuming 55% of owned ITNs are used by the target groups, 192 million ITNs). CONCLUSION: To achieve the targeted ITN usage rates, numbers of ITNs available to African households must be dramatically increased.

Effect of haematinic supplementation and malaria prevention on maternal anaemia and malaria in western Kenya.

OBJECTIVE: To evaluate the effect of routine antenatal haematinic supplementation programmes and intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP) in Kenya. METHODS: Anaemia [haemoglobin (Hb) <11 g/dl), severe anaemia (Hb <8 g/dl) and placental malaria were compared among women with known HIV status who delivered at a provincial hospital after study enrolment in the third trimester during three consecutive periods: period 1, no routine intervention (reference); period 2, routine haematinic supplementation (60 mg elementary iron three times/day, folic acid 5 mg once daily) and period 3, haematinics and IPT with SP. RESULTS: Among 3108 participants, prevalence of placental malaria, anaemia and severe anaemia postpartum was 16.7%, 53.6% and 12.7%, respectively. Compared with period 1, women in period 2 were less anaemic [adjusted odds ratio (AOR), 95% confidence interval anaemia: 0.56, 0.47-0.67; severe anaemia 0.37, 0.28-0.49] and shared a similar prevalence of placental malaria (AOR 1.07, 0.86-1.32). Women in period 3 were also less anaemic (AOR anaemia: 0.43, 0.35-0.53 and severe anaemia: 0.43, 0.31-0.59), and had less placental malaria (AOR 0.56, 0.42-0.73). The effect of intervention did not differ significantly by HIV status. CONCLUSION: The haematinic supplementation programme was associated with significant reductions in anaemia in HIV-seropositive and HIV-seronegative women. The subsequent introduction of IPT was associated with halving of malaria, but no additional haematological benefit over haematinics.

Building to collective impact: the Global Fund support for measuring reduction in the burden of malaria.

The Global Fund to Fight AIDS, Tuberculosis, and Malaria was established in 2002 to fund substantial scaling-up coverage of proven and effective interventions to reduce infection, illness, and deaths in those communities most at risk. As of December 2006 the Global Fund has committed $2.6 billion over 5 years to support malaria prevention and control in 85 countries. The Global Fund has worked closely with Roll Back Malaria partners to develop consensus on a set of outcome and impact indicators that have been incorporated into malaria grant agreements. Although the Global Fund has recommended that 5-10% of grant funds be invested in improving the capacity of the national monitoring and evaluation systems, an average of only 3.9% is invested in these systems. Several countries are already demonstrating reductions in the malaria burden. To sustain the scale-up in funding to support malaria interventions, countries must ensure that resources are used now to show robust, systematic, and regular measurement of impact on the burden of malaria.

Evaluation of various methods of maternal placental blood collection for immunology studies.

The collection of maternal placental intervillous blood (IVB), without contamination of fetal blood and with an accurate mononuclear cell profile, is essential for immunological studies of placental malaria and other infectious diseases of the placenta. We have compared five documented methods of IVB collection: perfusion, incision, biopsy, tissue grinding, and puncture (prick) for fetal blood contamination and mononuclear cell profiles using flow cytometry. Twenty-five placentas were obtained from Plasmodium falciparum and human immunodeficiency virus-negative primigravid and secundigravid women delivering at Nyanza Provincial Hospital in Kisumu, western Kenya. Each of the five methods was performed on the same placenta. Fetal red blood cell contamination was significantly lower for the prick and perfusion methods (4.1% and 8.3%, respectively) than for incision (59.5%), biopsy (42.6%), and tissue grinding (19.9%). Significant variation was noted among the five methods in the percentages of monocytes, total T cells, CD4+ and CD8+ T cells, B cells, and NK cells. Further, a pairwise comparison of prick and perfusion, the two methods with low fetal blood contamination, showed that they were not different for fetal red blood cell contamination levels; however, prick yielded significantly higher percentages of CD4 T cells and CD4 memory T cells than perfusion. Collection by prick was determined to be the best method of intervillous blood collection for immunology studies, and perfusion represented the next best method of choice due to high sample volume yield. Overall, in considering the advantages/disadvantages of the two methods with low fetal cell contamination, we conclude that a combination of prick and perfusion is most suitable for immunology studies.

The burden of malaria mortality among African children in the year 2000.

BACKGROUND: Although malaria is a leading cause of child deaths, few well-documented estimates of its direct and indirect burden exist. Our objective was to estimate the number of deaths directly attributable to malaria among children <5 years old in sub-Saharan Africa for the year 2000. METHODS: We divided the population into six sub-populations and, using results of studies identified in a literature review, estimated a malaria mortality rate for each sub-population. Malaria deaths were estimated by multiplying each sub-population by its corresponding rate. Sensitivity analyses were performed to assess the impact of varying key assumptions. RESULTS: The literature review identified 31 studies from 14 countries in middle Africa and 17 studies and reports from four countries in southern Africa. In 2000, we estimated that approximately 100 million children lived in areas where malaria transmission occurs and that 803 620 (precision estimate: 705 821-901 418) children died from the direct effects of malaria. For all of sub-Saharan Africa, including populations not exposed to malaria, malaria accounted for 18.0% (precision estimate: 15.8-20.2%) of child deaths. These estimates were sensitive to extreme assumptions about the causes of deaths with no known cause. CONCLUSIONS: These estimates, based on the best available data and methods, clearly demonstrate malaria's enormous mortality burden. We emphasize that these estimates are an approximation with many limitations and that the estimates do not account for malaria's large indirect burden. We describe information needs that, if filled, might improve the validity of future estimates.

Relationship of measles vaccination with anaemia and malaria in western Kenya.

OBJECTIVE: Mild viral illness, including that following immunization with live attenuated measles virus (LAMV), has been associated with transient decreases in haemoglobin (Hb) and cellular immune response that may persist for several weeks. In areas of intense malaria transmission, such as western Kenya, infants experience a progressive drop in Hb until age 9-10 months and one-third may have Hb < 8 g/dl. These children may be at risk of developing severe anaemia with further haematological insult. The objective of this paper was to determine if immunization with LAMV was associated with increased risk of transient anaemia and malaria infection. METHODS: Data from previous cross-sectional surveys (n = 5970) and one cohort study (n = 546) conducted among pre-school children were analyzed retrospectively. RESULTS: Measles vaccination coverage between 12 and 23 months of age ranged from 44.8% to 62.7%. Hb concentrations in children aged 6-23 months with documented measles immunization within the previous 14 or 30 days (n = 103) were similar to those with no history of measles immunization in the previous 90 days (n = 996); mean differences [95% confidence interval (CI)] by 30 days were: in cross-sectional surveys, -0.49 g/dl (-1.12, 0.14); in the cohort study, -0.032 g/dl (-0.52, 0.46). Similarly, the risk of malaria parasitemia or severe to moderate anaemia did not differ. CONCLUSION: These data do not suggest that the transient decrease in Hb and cellular immune response after immunization with LAMV results in clinically significant changes in the risk of subsequent severe to moderate anaemia or malaria in young children living in malaria-endemic regions.

Malaria and nutritional status among pre-school children: results from cross-sectional surveys in western Kenya.

Protein-energy malnutrition (PEM) affects millions of children in the developing world. The relationship between malaria and PEM is controversial. The goal of this study was to evaluate whether undernutrition is associated with increased or decreased malaria attributable morbidity. Three cross-sectional surveys were conducted using insecticide-treated bed nets (ITNs) among children aged 0-36 months living in an area with intense malaria transmission. Data were collected on nutritional status, recent history of clinical illness, socioeconomic status, current malaria infection status, and hemoglobin. In multivariate models, stunted children had more malaria parasitemia (odds ratio [OR] 1.98, P < 0.0001), high-density parasitemia (OR 1.84; P < 0.0001), clinical malaria (OR 1.77; P < 0.06), and severe malarial anemia (OR 2.65; P < 0.0001) than nonstunted children. The association was evident in children with mild-to-moderate (-3 < height-for-age Z-score [HAZ] < -2) and severe stunting (HAZ < -3). The cross-sectional nature of the study limits the interpretation of causality, but the data provide further observational support that the presence of undernutrition, in particular chronic undernutrition, places children at higher, not lower risk of malaria-related morbidity.