Effect of dietary intervention on the prevalence of asymptomatic malaria among 6-18-month-old children in rural Malawi.

BACKGROUND: The complex interaction between malaria and undernutrition leads to increased mortality and morbidity rate among young children in malaria-endemic regions. Results from previous interventions suggest that improving nutritional status of young children may reduce the burden of malaria. This study tested a hypothesis that provision of lipid-based nutrient supplements (LNS) or corn-soy blend (CSB) supplementation to 6-18-month-old children in Malawi would reduce the prevalence of asymptomatic malaria among them. METHODS: A total of 840 6-month-old children were enrolled in a randomized trial. The participants received 12-month supplementation with three different daily dietary supplementations: CSB, soy-LNS, or milk-LNS, and one control group without supplementation. The prevalence rate of asymptomatic Plasmodium falciparum was determined by real-time PCR from the participant's dried blood spots (DBS) collected at the baseline and every 3 months. The global null hypothesis was tested using modified Poisson regression to estimate the prevalence ratio (PR) between the control group and three intervention groups at all ages combined. All the models were adjusted for malaria at baseline, season of DBS sample collection, site of enrolment, and household asset Z-score. RESULTS: All children combined, the prevalence of P. falciparum was 14.1% at enrollment, 8.7% at 9 months, 11.2% at 12 months, 13.0% at 15 months and 22.4% at 18 months of age. Among all samples that were taken after enrolment, the prevalence was 12.1% in control group, 12.2% in milk-LNS, 14.0% in soy-LNS, and 17.2% in CSB group. Compared to children in the control group the prevalence ratio of positive malaria tests was 1.19 (95% CI 0.81-1.74; P = 0.372) in the milk-LNS group, 1.32 (95% CI 0.88-1.96; P = 0.177) in the soy-LNS group and 1.72 (95% CI 1.19-2.49; P = 0.004) in the CSB group. CONCLUSION: The study findings do not support a hypothesis that LNS or CSB supplementation would reduce the prevalence of asymptomatic malaria among Malawian children. In contrast, there was a signal of a possible increase in malaria prevalence among children supplemented with CSB.

Non-falciparum species and submicroscopic infections in three epidemiological malaria facets in Cameroon.

BACKGROUND: There are growing reports on the prevalence of non-falciparum species and submicroscopic infections in sub-Saharan African countries but little information is available from Cameroon. METHODS: A hospital-based cross-sectional study was carried out in four towns (Douala, Maroua, Mayo-Oulo, and Pette) from three malaria epidemiological strata (Forest, Sahelian, and Soudanian) of Cameroon. Malaria parasites were detected by Giemsa light microscopy and polymerase chain reaction (PCR) assay. Non-falciparum isolates were characterized and their 18S gene sequences were BLASTed for confirmatory diagnosis. RESULTS: PCR assay detected malaria parasites in 82.4% (98/119) patients, among them 12.2% (12/98) were asymptomatic cases. Three Plasmodium species viz. P. falciparum, P. ovale curtisi and P. vivax, and two co-infection types (P. falciparum + P. vivax and P. falciparum + P. ovale curtisi) were found. The remaining infections were mono-infections with either P. falciparum or P. ovale curtisi. All non-falciparum infections were symptomatic and microscopic. The overall proportion of submicroscopic infections was 11.8% (14/119). Most asymptomatic and submicroscopic infection cases were self-medicated with antimalarial drugs and/or medicinal plants. On analysis, P. ovale curtisi sequences were found to be phylogenetically closer to sequences from India while P. vivax isolates appeared closer to those from Nigeria, India, and Cameroon. No G6PD-d case was found among non-falciparum infections. CONCLUSIONS: This study confirms our previous work on circulation of P. vivax and P. ovale curtisi and the absence of P. knowlesi in Cameroon. More studies are needed to address non-falciparum malaria along with submicroscopic infections for effective malaria management and control in Cameroon.

Prevalence and association of malaria with ABO blood group and hemoglobin level in individuals visiting Mekaneeyesus Primary Hospital, Estie District, northwest Ethiopia: a cross-sectional study.

Malaria is a serious and sometimes fatal mosquito-borne disease caused by protozoan parasite of the genus Plasmodium. ABO blood group antigens represent polymorphic traits inherited among individuals and populations. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. This study was undertaken to determine the prevalence of malaria and its possible association with ABO blood group and hemoglobin level among individuals attending Mekaneeyesus Primary Hospital, Estie District, northwestern Ethiopia. Sociodemographic variables and relevant data were collected from 390 randomly selected individuals through structured questionnaire. Then, thick and thin smears were prepared from finger pricked blood samples, stained, and examined microscopically for detection and identification of malaria parasites. ABO blood group and hemoglobin levels of the same subjects were also determined. The data generated were analyzed for descriptive and logistic regression models. Variables with p value < 0.05 in multivariable logistic regression were considered explanatory variables. The overall prevalence of malaria was 8.5%; Plasmodium vivax (5.6%) was the most predominant, followed by P. falciparum (2.3%), and mixed infection of the two species (0.5%). In our study, being male (AOR = 3.48), under-five years of age (AOR = 72.84), rural residence (AOR = 2.64), and failing to use bed net (AOR =4.65) were significantly associated with the risk of malaria. Most (14.6%) of malaria-positive cases were among individuals with blood group "A," while the least numbers of cases were among subjects with blood group "O." Individuals with blood group "A" were about four times at risk of malaria as compared to individuals with blood group "O" (AOR= 3.74). The prevalence of anemia was 23.1% and significantly associated with malaria (p<0.05). Prevalence of malaria in this study is still higher compared to some of previous reports from Ethiopia. Thus, there is a need to intensify effort in malaria prevention among potentially at risk segments of population, including males, rural residents, and under-five children, and promotion of ITNs use in the community. Supplementation of iron-rich diet for iron-deficient anemia people is needed. Further in-depth investigation is also necessary to clearly establish the role that ABO blood group plays in malaria.

Sulfadoxine-pyrimethamine parasitological efficacy against Plasmodium falciparum among pregnant women and molecular markers of resistance in Zambia: an observational cohort study.

BACKGROUND: The World Health Organization recommends the provision of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) at 4-week intervals from gestational week 13 to delivery in areas of moderate to high malaria transmission intensity. However, the effect of IPTp-SP has been compromised in some areas due to parasite resistance, raising the importance of parasitological and chemoprophylactic surveillance, and monitoring SP-resistance markers in the Plasmodium falciparum population. METHODS: Between November 2013 and April 2014 in Nchelenge, Zambia, 1086 pregnant women received IPTp-SP at antenatal-care bookings. Blood samples were collected on day 0, and on day 28 post-treatment to test for malaria parasites and to estimate SP parasitological efficacy in the treatment and prevention of parasitaemia. A random sample of 96, day 0 malaria-positive samples were analysed to estimate the prevalence of SP-resistance markers in the P. falciparum population. RESULTS: The overall parasitological and prophylactic failure among women who had paired day 0 and day 28 blood slides was 18.6% (95% CI 15.5, 21.8; 109 of 590). Among pregnant women who had asymptomatic parasitaemia on day 0, the day 28 PCR-uncorrected parasitological failure was 30.0% (95% CI 23.7, 36.2; 62 of 207) and the day 28 PCR-corrected parasitological failure was 15.6% (95% CI: 10.6, 20.6; 32 of 205). Among women who tested negative at day 0, 12.3% (95% CI: 9.0, 15.6; 47 of 383) developed parasitaemia at day 28. Among the 96 malaria-positive samples assayed from day 0, 70.8% (95% CI: 60.8, 79.2) contained the DHPS double (Gly-437 + Glu-540) mutation and 92.7% (95% CI: 85.3, 96.5) had the DHFR triple (Asn-108 + Ile-51 + Arg-59) mutation. The quintuple mutation (DHFR triple + DHPS double) and the sextuple mutant (DHFR triple + DHPS double + Arg-581) were found among 68.8% (95% CI: 58.6, 77.3) and 9.4% (95% CI: 4.2, 16.0) of samples, respectively. CONCLUSION: The parasitological and chemoprophylactic failure of SP, and the prevalence of resistance markers in Nchelenge is alarmingly high. Alternative therapies are urgently needed to safeguard pregnant women against malarial infection.

Iron Status of Burkinabé Adolescent Girls Predicts Malaria Risk in the Following Rainy Season.

High levels of storage iron may increase malaria susceptibility. This risk has not been investigated in semi-immune adolescents. We investigated whether baseline iron status of non-pregnant adolescent girls living in a high malaria transmission area in Burkina Faso affected malaria risk during the following rainy season. For this prospective study, we analysed data from an interim safety survey, conducted six months into a randomised iron supplementation trial. We used logistic regression to model the risk of P. falciparum infection prevalence by microscopy, the pre-specified interim safety outcome, in relation to iron status, nutritional indicators and menarche assessed at recruitment. The interim survey was attended by 1223 (82%) of 1486 eligible participants, 1084 (89%) of whom were <20 years at baseline and 242 (22%) were pre-menarcheal. At baseline, prevalence of low body iron stores was 10%. At follow-up, 38% of adolescents had predominantly asymptomatic malaria parasitaemias, with no difference by menarcheal status. Higher body iron stores at baseline predicted an increased malaria risk in the following rainy season (OR 1.18 (95% CI 1.05, 1.34, p = 0.007) after adjusting for bed net use, age, menarche, and body mass index. We conclude that routine iron supplementation should not be recommended without prior effective malaria control.

Malaria risk map for India based on climate, ecology and geographical modelling.

Mapping the malaria risk at various geographical levels is often undertaken considering climate suitability, infection rate and/or malaria vector distribution, while the ecological factors related to topography and vegetation cover are generally neglected. The present study abides a holistic approach to risk mapping by including topographic, climatic and vegetation components into the framework of malaria risk modelling. This work attempts to delineate the areas of Plasmodium falciparum and Plasmodium vivax malaria transmission risk in India using seven geo-ecological indicators: temperature, relative humidity, rainfall, forest cover, soil, slope, altitude and the normalized difference vegetation index using multi-criteria decision analysis based on geographical information system (GIS). The weight of the risk indicators was assigned by an analytical hierarchical process with the climate suitability (temperature and humidity) data generated using fuzzy logic. Model validation was done through both primary and secondary datasets. The spatio-ecological model was based on GIS to classify the country into five zones characterized by various levels of malaria transmission risk (very high; high; moderate; low; and very low. The study found that about 13% of the country is under very high malaria risk, which includes the malaria- endemic districts of the states of Chhattisgarh, Odisha, Jharkhand, Tripura, Assam, Meghalaya and Manipur. The study also showed that the transmission risk suitability for P. vivax is higher than that for P. falciparum in the Himalayan region. The field study corroborates the identified malaria risk zones and highlights that the low to moderate risk zones are outbreak-prone. It is expected that this information will help the National Vector Borne Disease Control Programme in India to undertake improved surveillance and conduct target based interventions.

The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children.

BACKGROUND: Antibodies targeting malaria blood-stage antigens are important targets of naturally acquired immunity, and may act as valuable biomarkers of malaria exposure. METHODS: Six-hundred and one young Malawian children from a randomized trial of prenatal nutrient supplementation with iron and folic acid or pre- and postnatal multiple micronutrients or lipid-based nutrient supplements were followed up weekly at home and febrile episodes were investigated for malaria from birth to 18 months of age. Antibodies were measured for 601 children against merozoite surface proteins (MSP1 19kD, MSP2), erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2 (Rh2A9), schizont extract and variant surface antigens expressed by Plasmodium falciparum-infected erythrocytes (IE) at 18 months of age. The antibody measurement data was related to concurrent malaria infection and to documented episodes of clinical malaria. RESULTS: At 18 months of age, antibodies were significantly higher among parasitaemic than aparasitaemic children. Antibody levels against MSP1 19kD, MSP2, schizont extract, and IE variant surface antigens were significantly higher in children who had documented episodes of malaria than in children who did not. Antibody levels did not differ between children with single or multiple malaria episodes before 18 months, nor between children who had malaria before 6 months of age or between 6 and 18 months. CONCLUSIONS: Antibodies to merozoite and IE surface antigens increased following infection in early childhood, but neither age at first infection nor number of malaria episodes substantially affected antibody acquisition. These findings have implications for malaria surveillance during early childhood in the context of elimination. Trials registration Clinical Trials Registration: NCT01239693 (Date of registration: 11-10-2010). URL: http://www.ilins.org.

Malaria causes long-term effects on markers of iron status in children: a critical assessment of existing clinical and epidemiological tools.

BACKGROUND: Most epidemiological studies on the interplay between iron deficiency and malaria risk classify individuals as iron-deficient or iron-replete based on inflammation-dependent iron markers and adjustment for inflammation by using C-reactive protein (CRP) or α-1-acid glycoprotein (AGP). The validity of this approach and the usefulness of fibroblast growth factor 23 (FGF23) as a proposed inflammation-independent iron marker were tested. METHODS: Conventional iron markers and FGF23 were measured in children with acute falciparum malaria and after 1, 2, 4, and 6 weeks. Children, who were transfused or received iron supplementation in the follow-up period, were excluded, and iron stores were considered to be stable throughout. Ferritin levels 6 weeks after admission were used as a reference for admission iron status and compared with iron markers at different time points. RESULTS: There were long-term perturbations in iron markers during convalescence from acute malaria. None of the tested iron parameters, including FGF23, were independent of inflammation. CRP and AGP normalized faster than ferritin after malaria episodes. CONCLUSION: Malaria may bias epidemiological studies based on inflammation-dependent iron markers. Better markers of iron status during and after inflammation are needed in order to test strategies for iron supplementation in populations at risk of malaria.

Major Threat to Malaria Control Programs by Plasmodium falciparum Lacking Histidine-Rich Protein 2, Eritrea.

False-negative results for Plasmodium falciparum histidine-rich protein (HRP) 2-based rapid diagnostic tests (RDTs) are increasing in Eritrea. We investigated HRP gene 2/3 (pfhrp2/pfhrp3) status in 50 infected patients at 2 hospitals. We showed that 80.8% (21/26) of patients at Ghindae Hospital and 41.7% (10/24) at Massawa Hospital were infected with pfhrp2-negative parasites and 92.3% (24/26) of patients at Ghindae Hospital and 70.8% (17/24) at Massawa Hospital were infected with pfhrp3-negative parasites. Parasite densities between pfhrp2-positive and pfhrp2-negative patients were comparable. All pfhrp2-negative samples had no detectable HRP2/3 antigen and showed negative results for HRP2-based RDTs. pfhrp2-negative parasites were genetically less diverse and formed 2 clusters with no close relationships to parasites from Peru. These parasites probably emerged independently by selection in Eritrea. High prevalence of pfhrp2-negative parasites caused a high rate of false-negative results for RDTs. Determining prevalence of pfhrp2-negative parasites is urgently needed in neighboring countries to assist case management policies.

Effect of nutrient supplementation on the acquisition of humoral immunity to Plasmodium falciparum in young Malawian children.

BACKGROUND: There is evidence that suggests that undernutrition has a detrimental effect on malarial immunity in children. The aim of the study was to discover whether nutrient supplementation improved development of malarial antibody immunity in children up to 18 months of age. METHODS: The study was conducted with a subset of 432 Malawian children from a randomized controlled trial of nutritional supplements. The arms included pre- and postnatal small-quantity lipid-based nutrient supplements for both mother and child; prenatal supplementation with iron and folic acid; and pre- and postnatal supplementation with multiple micronutrients. Paired plasma samples were collected at 6 and 18 months of age. The levels of antibodies against merozoite surface protein 1 (MSP1 19kD) and MSP2, erythrocyte binding antigen 175 (EBA175), reticulocyte binding protein homologue 2A (Rh2A9), schizont extract and variant antigens expressed on the surface of infected erythrocytes were measured. RESULTS: At 18 months of age, 5.4% of children were parasitaemic by microscopy and 49.1% were anaemic. Antibodies to the tested merozoite antigens and schizont extract increased between 6 and 18 months and this increase was statistically significant for MSP1, MSP2 and EBA175 (p < 0.0001) whereas IgG to variant surface antigens decreased with increasing age (p < 0.0001). However, the supplementation type did not have any impact on the prevalence or levels of antibodies at either 6 or 18 months of age to any of the tested malaria antigens in either univariate analysis or multivariate analysis after adjusting for covariates. CONCLUSIONS: Pre- and postnatal lipid-based nutrient supplementation did not alter malaria antibody acquisition during infancy, compared to prenatal supplementation with iron and folic acid or pre- and postnatal supplementation with multiple micronutrients. Trail registeration Clinicaltrials.gov registration number NCT01239693.

Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates.

Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum. This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC50) below 500 nM. The most active among the selected compounds was MMV006087 (average IC50 of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs.

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention (n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week (n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week (n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (PF < 30 µg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA (p = 0.028) and a borderline significant time by treatment interaction on iron deficiency with or without anemia (p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

High Iron Levels Are Associated with Increased Malaria Risk in Infants during the First Year of Life in Benin.

The World Health Organization (WHO) estimates that 40% of children in low-income countries are anemic. Therefore, iron supplements are recommended by WHO in areas with high anemia rates. However, some studies have set into question the benefits of iron supplementation in malaria-endemic regions. In Benin, a west African country with high prevalence of anemia and malaria, no iron supplements are given systematically to infants so far despite the WHO recommendations. In this context, we wanted to investigate the effect of iron levels during the first year of life on malarial risk in Benin considering complementary risk factors. We followed 400 women and their offspring between January 2010 and June 2012 in Allada (Benin). Environmental, obstetric, and numerous clinical, maternal, and infant risk factors were considered. In multilevel models, high iron levels were significantly associated with the risk of a positive blood smear (adjusted odds ratio = 2.90, P < 0.001) and Plasmodium falciparum parasitemia (beta estimate = 0.38, P < 0.001). Infants with iron levels in the lowest quartile were less likely to have a positive blood smear (P < 0.001), and the risk increased with higher iron levels. Our results appeal for additional evaluation of the effect of different doses of iron supplements on the infant health status, including malaria incidence. Thus, the health status of infants should be compared between cohorts where iron is given either for prevention or anemia treatment, to better understand the effect of iron supplements on infant health.

Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.

Plasmodium falciparum malaria in 1st-2nd century CE southern Italy.

The historical record attests to the devastation malaria exacted on ancient civilizations, particularly the Roman Empire [1]. However, evidence for the presence of malaria during the Imperial period in Italy (1st-5th century CE) is based on indirect sources, such as historical, epigraphic, or skeletal evidence. Although these sources are crucial for revealing the context of this disease, they cannot establish the causative species of Plasmodium. Importantly, definitive evidence for the presence of malaria is now possible through the implementation of ancient DNA technology. As malaria is presumed to have been at its zenith during the Imperial period [1], we selected first or second molars from 58 adults from three cemeteries from this time: Isola Sacra (associated with Portus Romae, 1st-3rd century CE), Velia (1st-2nd century CE), and Vagnari (1st-4th century CE). We performed hybridization capture using baits designed from the mitochondrial (mtDNA) genomes of Plasmodium spp. on a prioritized subset of 11 adults (informed by metagenomic sequencing). The mtDNA sequences generated provided compelling phylogenetic evidence for the presence of P. falciparum in two individuals. This is the first genomic data directly implicating P. falciparum in Imperial period southern Italy in adults.

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

BACKGROUND: Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. METHODS: This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. FINDINGS: Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. INTERPRETATION: These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. FUNDING: National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat.

Paleopathology and Paleomicrobiology of Malaria.

Malaria is a disease caused by parasites of the genus Plasmodium, transmitted through the bites of female anopheles flies. Plasmodium falciparum causes severe malaria with undulating high fever (malaria tropica). Literary evidence of malarial infection dates back to the early Greek period, when Hippocrates described the typical undulating fever highly suggestive of plasmodial infection. Recent immunological and molecular analyses describe the unambiguous identification of malarial infections in several ancient Egyptian mummies and a few isolated cases in Roman and Renaissance Europe. Although the numbers of cases are low, there is evidence that the overall infection rates may have been relatively high and that this infectious disease may have had a significant impact on historical populations.

Complicated malaria symptoms associated with Plasmodium vivax among patients visiting health facilities in Mendi town, Northwest Ethiopia.

BACKGROUND: Malaria is still a major health problem in some parts of the world. Plasmodium falciparum is the common pathogenic parasite and is responsible for majority of malaria associated deaths. Recently the other benign parasite, P. vivax, is reported to cause life threatening severe malaria complications. Thus, this study was aimed to assess incidence of severe malaria symptoms caused by P. vivax parasite in some malaria endemic areas of Ethiopia. MATERIALS AND METHODS: Presumptive malaria patients (all age groups) seeking medication at the selected health facilities in Mendi town, Northwest Ethiopia, were recruited for the study. Socio-demographic, clinical and parasitological characteristics were assessed following standard procedures. Data was analyzed using descriptive statistics, chi-square test and relative risk. RESULTS: Of the 384 patients enrolled in the study for P. vivax mono-infection, 55 (14.3 %) of them were fulfilled at least one of the WHO criteria for severe malaria indicators. Some of these clinical manifestations were: prostration 14 (25.45 %), persistent vomiting 9 (16.36 %), respiratory distress 6 (10.9 %), hypoglycemia 5 (9.1 %), hyperpyrexia 8 (14.5 %), and severe anemia 13 (23.63 %). Differences in parasite load did not affect the frequency of some severe malaria symptoms. However, severe anemia, prostration, and persistent vomiting were significantly affected (P < 0.05) by relatively higher load of parasitemia, (OR = 3.8, 95 % CI, 1.1-13.7; OR = 4.4, 95 % CI, 1.4-13.9; and OR = 7, 95 % CI, 1.8-27.4) respectively. CONCLUSION: P.vivax associated severe malaria symptoms observed in this study is supportive evidence for the notion that P.vivax is no longer benign parasite but rather virulent. Thus, to meet international and regional targets of malaria eradication, a holistic prevention and control approaches should be designed.

Iron and malaria: a dangerous liaison?

Malaria increases the burden of anemia in low-income countries, where, according to 2012 data from the World Health Organization, 40% of children are anemic. Moreover, iron is a cofactor for Plasmodium falciparum development, raising fears that iron supplementation might be harmful in patients with P. falciparum infection. The primary objective of this narrative review is to describe current knowledge on the iron-malaria association, including recent findings and substantive qualitative results. Between 2012 and 2016 the MEDLINE database was searched for literature published about malaria and iron levels. Observational studies reported some protection of iron supplementation against malaria among iron-deficient children, while older clinical trials reported increased susceptibility to malaria among iron-supplemented children. However, iron supplements were not significantly associated with increased malaria risk in recent clinical trials or in a 2016 Cochrane review. Evidence of an iron-malaria association is limited by the following factors: the protective effect of control interventions, the limited follow-up of children, and the lack of homogenous iron indicators. The effects of previous health status and possible thresholds in iron levels should be investigated using a gold-standard combination of iron markers. Moreover, the benefits of iron supplementation require further evaluation.

Prevalence of malaria in pregnancy in southern Laos: a cross-sectional survey.

BACKGROUND: There are no data on the burden of malaria in pregnancy (MiP) in Laos, where malaria still remains prevalent in the south. METHODS: Two cross-sectional surveys were conducted in 2014 to assess the prevalence of MiP in Vapi District, Salavan Province, southern Laos: the first consisted of screening 204 pregnant women during pregnancies [mean (95 % CI) gestational age: 23 (22-25) weeks] living in 30 randomly selected villages in Vapi District; the second was conducted among 331 pregnant women, who delivered during the study period in Vapi and Toumlane District Hospitals and in Salavan Provincial Hospital. Peripheral and placental malaria was detected using rapid diagnostic tests (RDT), thick blood smears (TBS) and real-time quantitative polymerase chain reactions (RT-qPCR). Factors associated with low birth weight (LBW) and maternal anaemia were assessed. RESULTS: In the villages, 12/204 women (5.9 %; 95 % CI 3.1-10.0) were infected with malaria as determined by RT-qPCR: 11 were Plasmodium vivax infections and 1 was mixed Plasmodium vivax/Plasmodium falciparum infection, among which 9 were sub-microscopic (as not detected by TBS). History of malaria during current pregnancy tended to be associated with a higher risk of MiP (aIRR 3.05; 95 % CI 0.94-9.88). At delivery, two Plasmodium falciparum sub-microscopic infections (one peripheral and one placental) were detected (4.5 %; 0.6-15.5) in Vapi District. In both surveys, all infected women stated they had slept under a bed net the night before the survey, and 86 % went to the forest for food-finding 1 week before the survey in median. The majority of infections (94 %) were asymptomatic and half of them were associated with anaemia. Overall, 24 % of women had LBW newborns. Factors associated with a higher risk of LBW were tobacco use (aIRR 2.43; 95 % CI 1.64-3.60) and pre-term delivery (aIRR 3.17; 95 % CI 2.19-4.57). Factors associated with a higher risk of maternal anaemia were no iron supplementation during pregnancy, Lao Theung ethnicity and place of living. CONCLUSIONS: The prevalence of MiP in this population was noticeable. Most infections were asymptomatic and sub-microscopic vivax malaria, which raises the question of reliability of recommended national strategies for the screening and prevention of MiP in Laos.