Children In Malaria-endemic Areas Research Articles

Not all severe malaria cases are severe: Is it time to redefine severity criteria for malaria in non-endemic regions?

BACKGROUNDThe current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort. METHODSA cohort study of patients managed for malaria in a non-endemic setting(2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2% threshold was applied. Patients with SM were distinguished as very severe malaria(VSM) when presenting at least one of the following conditions: parasitemia >10%, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria(LSM) was defined by: 2-10% parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections. RESULTSAmong 506 patients with malaria, 176(34.8%) presented with SM. A total of 37(7.3%) patients developed a life-threatening condition, namely death (n=4) and/or the need for life-saving interventions(n=34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28(5.5%) patients had a community-acquired co-infection, with no differences between groups (p=0.763). CONCLUSIONSSeverity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics.

Clinico-epidemiological profiles & outcome of severe malaria in children under-five in the tribal area of Kalahandi, Odisha.

Severe malaria is a cause of excess mortality and morbidity in children in malaria-endemic areas where indigenous people live. Currently, available reports are all from secondary or tertiary care hospitals across India and some African countries. The objective of this study was to assess the clinical and epidemiological profiles of children under five years in two primary care health centres located in tribal-dominant Thuamul Rampur Block of Kalahandi district, Odisha. The outcome of management of severe malaria in these children was also assessed. A retrospective review of case records of children under five years of age diagnosed and admitted with severe malaria in two non-governmental primary care facilities between 2017 and 2022, was undertaken. There was a declining trend in malaria cases documented in primary care health facilities between January 2017 and June 2022. Of the 4858 cases recorded, 242 (4.9%) had severe malaria, of whom 70.7 per cent (n=171) were children under 5 yr. The median age of the study children was 24 months (16-36). Children aged 1-2 yr had a significantly higher risk of malaria. The majority were tribals (87%), more than half the children presented with neurological manifestations (64.4%), and 49.6 per cent had respiratory manifestations, while 20.5 per cent had severe anaemia (Hb <5 g/dl). Most, 167 (97.7%) severe malaria was due to Plasmodium falciparum. Thirty-two percent of children were severely wasted (WHZ < -3 SD) and 28 per cent were moderately wasted (WHZ <-2 SD). There was no fatality among the 171 children who were managed for severe malaria in the two primary care facilities. In high endemic areas severe malaria is predominantly a disease of under-five children and is caused by P. falciparum. Clinical manifestations of severe malaria in children can be varied and life-threatening. Primary health facilities can manage severe malaria successfully, thereby reducing child mortality. Effective collaboration between malaria control and nutrition intervention programmes is essential for appropriate case management.

The prevalence and density of asymptomatic plasmodium infections among children in a rural community of South- Western Nigeria.

Asymptomatic malaria is highly prevalent in endem ic areas of Africa and it is a new challenge for the malaria elimination agenda. In recent years, the number of hospitalizations due to malaria cases in sub-Saharan Africa has steadily decreased. However, there are indications that this positive trend could suffer a setback due to asymptomatic malaria cases, which may serve as reservoir of infections for vulnerable populations. This cross-sectional study examined the prevalence of asymptomatic malaria in school-aged children living in a rural community in South- West, Nigeria. The study was conducted from August to September 2020, involving 300 randomly selected school children. Histidine rich protein II rapid diagnostic test kits (HRP2) were used to screen participants for malaria. All blood samples were further examined microscopically using 3% Giemsa-stained blood smears for confirmation, speciation, and parasites. The anaemia status of the children was quantification of malaria determined by measuring the haematocrit. Statistical analysis of the data was done using the chi-square test, student t-test, Mann Whitney U test and Kruskal-Wallis rank sum tests to determine the association between variables and the difference in mean/median with a significance level p≤ 0.05. The results showed a high prevalence of asymptomatic malaria of 41% by microscopy. The prevalence of asymptomatic malaria was statistically significantly higher among children aged 6 to 11 years (52%), compared to children &gt;12years (37%), and &lt; 5years old (13%), (p=0.00001). Plasmodium falciparum was responsible for 96% of the infection while the remaining 4% had multiple infections with Plasmodium falciparum and Plasmodium ovale. This study confirms that the prevalence of asymptomatic cases of malaria among children in malaria endemic areas is high and they will benefit from malaria chemoprophylaxis.

Evaluating the impact of COVID-19 pandemic on complicated malaria admissions and outcomes in the paediatric Ho Teaching Hospital of the Volta Region of Ghana.

Since Ghana recorded its first cases of COVID-19 in early March 2020, healthcare delivery in the country has been hugely affected by the pandemic. Malaria continues to be an important public health problem in terms of morbidity and mortality among children, and it is responsible for significant hospital visits and admission. It is likely that, as with other illnesses, the COVID-19 pandemic may have impacted health seeking behaviour, hospital visits, and admissions of malaria among the paediatric population in Ghana. The aim of this study was to evaluate the impact of COVID-19 pandemic on the admissions and outcome of complicated malaria in the Ho Teaching Hospital of the Volta Region of Ghana. The medical records of children admitted for complicated malaria (cerebral and severe malaria) from 2016 to 2020, were obtained from the admission records of the children. Both demographics and clinical details were collected, and data was analysed using SPSS version 25 statistical software. The yearly differences in the trend and proportions of complicated malaria admissions were performed using rate comparison analysis and Pearson chi-square was used to assess the association between the various demographic factors and yearly admission rates. Clopper-Pearson test statistic was employed to determine the 95% confidence intervals of outcome variables of interest. The year 2020 had the lowest admission for complicated malaria (149, 11.5%; 95% CI: 9.7-13.5) but proportionally had, more cases of cerebral malaria (25, 16.8%; 95% CI: 10.9-24.8), and more deaths (6, 4.0%; 95% CI: 1.5-8.8), compared to the years under review. Children admitted in 2020 had the shortest mean stay on admission (4.34 ±2.48, p<0.001). More studies are needed to further elucidate the impact of the COVID-19 pandemic on the health of children in malaria endemic areas.

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial.

BackgroundIron fortification and micronutrient initiatives, specifically, vitamin A, and zinc supplementation are the most cost-effective developmental strategies against malnutrition and health emergencies in pre-school children. Iron-deficiency among pre-school children have been documented, however, studies evaluating the impact of immunoglobulin G (IgG) isotype responses among iron-fortified pre-school children in malaria endemic communities has not been assessed. We evaluated the impact of iron fortification on the IgG responses to GLURP R0, GLURP R2 and MSP3 FVO malaria-specific antigens among pre-school children in malaria endemic areas.MethodsThis community-based, placebo-controlled, double-blinded, cluster-randomized trial study was conducted in Wenchi Municipal and Tain District of Bono Region. The trial was registered at ClinicalTrials.gov-registered trial (Identifier: NCT01001871). Ethical approval was obtained and informed consent were sought from each participant parents/guardian. For the current objective, 871 children aged 6–35 months were screened, from which 435 children received semi-liquid home-made meals mixed with 12.5 mg of iron daily (intervention group), and 436 received micronutrient powder without iron (placebo group) for 5 months. Standardized clinical and epidemiological questionnaires were administered and blood samples taken to measure IgG responses to GLURP R0, GLURP R2 and MSP3 FVO recombinant antigens using the Afro Immunoassay (AIA) protocol.ResultsBaseline anthropometry, malaria diagnosis, anaemia and iron status, demographic features and dietary intake were identical among the groups (p > 0.05). After the intervention, there was no significant difference in the IgG response against GLUP R0, GLUP R2 and MSP3 FVO between the iron-containing micronutrient and placebo groups (p > 0.05). The iron-containing micronutrient powder group who were iron-sufficient or iron replete had significantly higher IgG response to GLURP R0 and GLURP R2 compared to iron-deficient and iron-deficiency anaemia in the same group (p < 0.05). The IgG responses to all the three malaria specific antigens were low among children without malaria episode but high among those with two and four episodes due to exposure differences.ConclusionIron fortification did not influence antibody response against endogenous malaria specific antigens among pre-school children in malaria endemic areas, however, IgG response to malaria specific antigens were high among children with sufficient iron status.

Determinants of Malaria Protective Immunity in Mice Immunized with Live Sporozoites during Trimethoprim-Sulfamethoxazole Prophylaxis.

.HIV and malaria geographically overlap. Trimethoprim–sulfamethoxazole (TMP-SMX) is a drug widely used in HIV-exposed uninfected and infected children in malaria-endemic areas, and is known to have antimalarial effects. Further study in terms of antimalarial impact and effect on development of malaria-specific immunity is therefore essential. Using rodent malaria models, we previously showed that repeated Plasmodium exposure during TMP-SMX administration, or chemoprophylaxis vaccination (CVac), induces CD8 T-cell–dependent preerythrocytic immunity. However, humoral immune responses have been shown to be important in models of preerythrocytic immunity. Herein, we demonstrate that antibody-mediated responses contribute to protective immunity induced by CVac immune sera using TMP-SMX in models of homologous, but not heterologous, parasite species. Clinical studies must account for potential anti-Plasmodium antibody induced during TMP-SMX prophylaxis.

Predictors of Health-Seeking Behavior for Fever Cases among Caregivers of Under-Five Children in Malaria-Endemic Area of Imo State, Nigeria.

Fever is one of the most common symptoms of pediatric illnesses; it is an important early symptom of malaria. Fever had served as the entry point for presumptive treatment of malaria among children in Nigerian. Appropriate HSB is important when seeking treatment for fever among under-five children; this will help for better prognosis because treatment will be initiated early. This study attempted to identify caregiver’s HSB for under-five children with fever. A cross-sectional study was conducted in Imo-State, Nigeria. Appropriate HSB was operationally defined as seeking treatment from health facility within 24 h of fever. Data were obtained using pretested self-administered questionnaire. Data were analyzed using SPSS version 22. Simple and multiple logistic regression were used to determine predictors of appropriate HSB. A total of 559 eligible respondents were recruited; 103 (18.6%) caregivers had appropriate HSB. The predictors of HSB are being male child (aOR = 2.760; 95% CI:1.536–4.958), the age of child younger than 27 months (aOR = 2.804; 95% CI:1.485–5.295), employed caregivers (aOR = 1.882; 95% CI:1.014–3.493), number of household members (aOR = 2.504; 95% CI:1.464–4.283), and caregivers who decided to seek treatment at early stage (aOR = 7.060; 95% CI:1.616–30.852). Only 18.6% caregivers practiced appropriate HSB for fever cases among under-five children. It is essential to educate caregivers and emphasise on early treatment of fever and appropriate use of health facilities for fever. The findings will be used to improve intervention at the community level and will be compared with follow-up data to evaluate their effectiveness.

OC 8568 A RANDOMISED CONTROLLED TRIAL OF ORAL IRON FOR TREATMENT OF POST-MALARIA ANAEMIA IN MALAWIAN CHILDREN COMPARING IMMEDIATE VERSUS DELAYED ADMINISTRATION

BackgroundAlthough universal provision of iron supplements to children is recommended by the WHO, it is not yet clear whether the administration of the supplements poses a risk in children in malaria-endemic areas. We investigate the effects of iron supplementation in children with post-malaria anaemia and haematological response with immediate and delayed (2’weeks) iron administration.MethodsA randomised double-blind clinical trial was conducted in Zomba and Blantyre between 2009 and 2013. All children aged 4 to 36 months with uncomplicated malaria and with iron deficiency were enrolled into the study. Malaria treatment was administered to all the children and they were randomly assigned to 3 groups as follows: immediate iron administration, delayed iron administration, or placebo. The children were followed up for 10 weeks, with their haematological recovery indices and adverse effects being monitored at 2, 4, 8 and 10 weeks. The primary outcome of the study was the proportion of children without anaemia (defined as Hb &gt;10.9 g/dl) at the end of the iron supplementation period.ResultsA total of 538 participants were randomised to immediate iron administration (n=183), delayed iron administration (n=183), or placebo (n=172). The incidence rate ratio (IRR) of being non-anaemic at the end of the follow-up period (10 weeks post-malaria infection) was 1.51 (95% CI 1.17–1.94, p&lt;0.001) among immediate group versus the placebo group. There was no significant difference between delayed and placebo group (IRR 1.18, 95% CI 0.91–1.55). Secondary analysis of risk of malaria and bacterial infection and iron markers at the end of the intervention period is underway and shall be presented at the conference.ConclusionThe results so far support the administration of iron immediately after completing antimalarial treatment in anaemic children, however safety results will be needed to be reviewed before conclusive recommendations.

Testing the hypothesis that malaria-induced immune remodeling of monocytes plays a role in immunity to malaria

Abstract In malaria-naïve individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger the systemic inflammation and fever characteristic of malaria. But, individuals in endemic areas who are repeatedly infected with P. falciparum are often asymptomatic and have low levels of iRBCs, even young children who have yet to acquire fully protective antibodies. The molecular mechanisms underlying these clinical observations remain unclear. We earlier showed that PBMCs collected from uninfected Malian children before the malaria season responded to iRBCs by producing pro-inflammatory mediators such as IL-1β, IL-6. However, following febrile malaria there was a marked shift in the response to iRBCs with the same children’s PBMCs producing lower levels of those cytokines. Moreover, genome-wide expression analysis showed that genes involved in phagocytosis and intracellular killing were upregulated in PBMCs after malaria as compared to before. Together, these data suggest that malaria-induced remodeling of innate immune cells might play a role in immunity to malaria. In ongoing work we are dissecting the underlying molecular pathways involved in P. falciparum-induced changes in monocyte/macrophages. We are studying monocytes ex vivo from malaria-exposed children, as well as monocytes stimulated with iRBCs in vitro. Initial data support the hypothesis that malaria-induced immune-remodeling of monocytes dampens pathogenic inflammation while enhancing anti-parasite effector mechanisms, consistent with our observation that children in malaria endemic areas are often afebrile and tend to control parasite replication in the face of repeated P. falciparum exposures.

Effect of a short course of iron polymaltose on acquisition of malarial parasitaemia in anaemic Indonesian schoolchildren: a randomized trial

BackgroundConcern exists about the safety of iron supplementation given to individuals in malarious areas. The possible unfavourable impact of iron supplementation on malaria might be less when slow-release iron compounds are used instead of ferrous salts, because no toxic non-transferrin bound iron is formed. The aim of this study was to determine the effect of iron supplementation using the slow-release iron compound iron polymaltose (IPM) on the acquisition of malarial parasitaemia.MethodsA randomized, placebo-controlled trial was performed in schoolchildren aged 5–18 years with mild or moderate anaemia on the Indonesian island Flores. Microscopic malaria-negative children were randomized to receive 8 weeks of IPM (6 mg elemental iron/kg/day) or placebo . The primary outcomes were the occurrence of microscopically detectable malarial parasitaemia at week 4, 8, 12 and 16 after start of treatment and the proportion of participants with real-time (RT) PCR positive malarial parasitaemia at week 16.Results294 Children were assigned to the IPM group and 297 to the placebo group. Whereas IPM supplementation failed to increased haemoglobin or ferritin concentrations, the IPM group had a significantly higher rate of occurrence of microscopically detectable parasitaemia [hazard ratio 2.2, 95% C.I. 1.2–4.0; P = 0.01]. This higher rate was confined to iron-replete children. At the end of the study, 89% of the children in the IPM group had remained free from microscopically detectable parasitaemia vs 95% of children in the placebo group. The proportion of plasmodial RT-PCR positive children was similar in both groups at week 16 (IPM group 16.6% vs placebo group 14.3%; P = 0.47). When analysis was restricted to iron-replete children (serum ferritin ≥30 µg/l), there was a trend for a higher proportion being RT-PCR positive at week 16 in the IPM group compared with the placebo group (20 vs 13.3%; P = 0.07). Erythrocyte microcytosis was an independent risk factor for microscopically detectable malarial parasitaemia.ConclusionsA short course of IPM should be used cautiously in anaemic children in malaria endemic areas, as it has limited efficacy in treating iron deficiency, while it increases the rate of microscopic malarial parasitaemia in those with replete iron stores.Trial registration ISRCTN 83091970. Registered 16 May 2012 (retrospectively registered)

Is there randomized controlled trial evidence to support the use of oral iron supplements (with or without folic acid) in children in malaria-endemic areas?

Is there randomized controlled trial evidence to support the use of oral iron supplements (with or without folic acid) in children in malaria-endemic areas?

Oral iron supplements for children in malaria-endemic areas

BackgroundIron‐deficiency anaemia is common during childhood. Iron administration has been claimed to increase the risk of malaria.ObjectivesTo evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, MEDLINE (up to August 2015) and LILACS (up to February 2015). We also checked the metaRegister of Controlled Trials (mRCT) and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2015. We contacted the primary investigators of all included trials, ongoing trials, and those awaiting assessment to ask for unpublished data and further trials. We scanned references of included trials, pertinent reviews, and previous meta‐analyses for additional references.Selection criteriaWe included individually randomized controlled trials (RCTs) and cluster RCTs conducted in hyperendemic and holoendemic malaria regions or that reported on any malaria‐related outcomes that included children younger than 18 years of age. We included trials that compared orally administered iron, iron with folic acid, and iron with antimalarial treatment versus placebo or no treatment. We included trials of iron supplementation or fortification interventions if they provided at least 80% of the Recommended Dietary Allowance (RDA) for prevention of anaemia by age. Antihelminthics could be administered to either group, and micronutrients had to be administered equally to both groups.Data collection and analysisThe primary outcomes were clinical malaria, severe malaria, and death from any cause. We assessed the risk of bias in included trials with domain‐based evaluation and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We performed a fixed‐effect meta‐analysis for all outcomes and random‐effects meta‐analysis for hematological outcomes, and adjusted analyses for cluster RCTs. We based the subgroup analyses for anaemia at baseline, age, and malaria prevention or management services on trial‐level data.Main resultsThirty‐five trials (31,955 children) met the inclusion criteria. Overall, iron does not cause an excess of clinical malaria (risk ratio (RR) 0.93, 95% confidence intervals (CI) 0.87 to 1.00; 14 trials, 7168 children, high quality evidence). Iron probably does not cause an excess of clinical malaria in both populations where anaemia is common and those in which anaemia is uncommon. In areas where there are prevention and management services for malaria, iron (with or without folic acid) may reduce clinical malaria (RR 0.91, 95% CI 0.84 to 0.97; seven trials, 5586 participants, low quality evidence), while in areas where such services are unavailable, iron (with or without folic acid) may increase the incidence of malaria, although the lower CIs indicate no difference (RR 1.16, 95% CI 1.02 to 1.31; nine trials, 19,086 participants, low quality evidence). Iron supplementation does not cause an excess of severe malaria (RR 0.90, 95% CI 0.81 to 0.98; 6 trials, 3421 children, high quality evidence). We did not observe any differences for deaths (control event rate 1%, low quality evidence). Iron and antimalarial treatment reduced clinical malaria (RR 0.54, 95% CI 0.43 to 0.67; three trials, 728 children, high quality evidence). Overall, iron resulted in fewer anaemic children at follow up, and the end average change in haemoglobin from base line was higher with iron.Authors' conclusionsIron treatment does not increase the risk of clinical malaria when regular malaria prevention or management services are provided. Where resources are limited, iron can be administered without screening for anaemia or for iron deficiency, as long as malaria prevention or management services are provided efficiently.12 April 2019No update plannedOtherThere is high‐certainty evidence that oral iron supplements do not adversely affect children living in malaria‐endemic areas, meaning further research is unlikely to change our confidence in the estimate of effect. All eligible published studies found in the last search (30 Aug, 2015) were included.

Evaluation of specific antibody responses to selected malaria vaccine candidates in Zimbabwean children

Introduction: There is high malaria related morbidity and mortality amongst infants and children in malaria endemic areas. An In-depth understanding of protective immunity correlates enables the long due necessary development of an effective malaria vaccine. This study aimed at evaluating antibody responses to apical membrane antigen 1 (AMA 1) that helps P falciparum entry into red blood cells, Glutamate rich protein (GLURP), an antigen expressed in the whole life cycle of the malaria causing pathogen, merozoite surface protein-1 (MSP 1) coding for a major antigen in the asexual stage of P falciparum and merozoite surface protein 3 (MSP 3), a polymorphic blood stage malaria antigen in Zimbabwean children living in malaria endemic areas. Methods: We characterized humoral immune responses to malaria vaccine candidates in a two year longitudinal survey among 136 children (6-16 years) from Burma and Kariba in Zimbabwe. Blood samples were collected and analyzed for malaria parasites, plasma and antibody titers against malaria vaccine candidates [MSP1, MSP3, GLURP, AMA] by ELISA technique. The blood samples were also checked for potential confounders like anemia, bilharzia and HIV sero-status using the ELISA technique. Results: Ig levels were significantly different ( p < .0001) across the three time points, and against the different candidates ( p < .0001). MSP3 had the highest (13,552.2) and GLURP the least (4,741.6) IgM titers. However, IgG, IgG1, IgG3 and IgG4 levels were highest against AMA compared to other vaccine candidates, [anti-MSP3 IgG3 (15.3) and anti-GLURP IgG4 (58.7)]. Anemia burden was about 44% at baseline with a threefold decrease (-16%) over the 12 month follow up. Conclusions: This study highlights the need for robust evaluation of several malaria vaccine candidates in combination to understand correlates of protective immunity as suggested by the significant antibody levels against the four vaccine candidates. Longer follow up periods are needed to assess the impact of continuous malaria exposure on host immune responses. Multivalent malaria vaccine development offer a better chance towards an efficacious malaria vaccine compared to monovalent vaccine. Antibody levels against the four vaccine candidates were significant suggesting that an ideal malaria vaccine should target more than one antigen.

Decline in childhood iron deficiency after interruption of malaria transmission in highland Kenya , ,

Achieving optimal iron status in children in malaria-endemic areas may increase the risk of malaria. Malaria itself may contribute to iron deficiency, but the impact of an interruption in malaria transmission on the prevalence of iron deficiency is unknown. We aimed to determine whether 1) iron status improved in children living in 2 Kenyan villages with a documented cessation in malaria transmission and 2) changes in iron status correlated with changes in hemoglobin. We measured iron [hemoglobin, ferritin, soluble transferrin receptor (sTfR)] and inflammatory [C-reactive protein (CRP)] markers in paired plasma samples from 190 children aged 4-59 mo at the beginning (May 2007) and end (July 2008) of a documented 12-mo period of interruption in malaria transmission in 2 highland areas in Kenya with unstable malaria transmission and ongoing malaria surveillance. Between May 2007 and July 2008, mean (±SD) hemoglobin increased from 10.8 ± 1.6 to 11.6 ± 1.6 g/dL. Median (25th, 75th percentile) ferritin increased from 17.0 (9.7, 25.6) to 22.6 (13.4, 34.7) μg/L (P < 0.001), whereas median sTfR decreased from 32.4 (26.3, 43.2) to 27.7 (22.1, 36.0) nmol/L (P < 0.001). Median CRP was low (<1 mg/L in both years) and did not change significantly. Iron deficiency prevalence (ferritin <12 μg/L, or <30 μg/L if CRP ≥10 mg/L) decreased from 35.9% (95% CI: 28.9%, 43.0%) to 24.9% (18.5%, 31.2%) (P = 0.005). The prevalence of iron deficiency with anemia (hemoglobin <11.0 g/dL) declined from 27.2% (20.7%, 33.8%) to 12.2% (7.4%, 17.1%) (P < 0.001). Improvement in iron status correlated with an increase in hemoglobin and was greater than explained by physiologic changes expected with age. In this area of unstable malaria transmission, the prevalence of iron deficiency in children decreased significantly after the interruption of malaria transmission and was correlated with an increase in hemoglobin. These findings suggest that malaria elimination strategies themselves may be an effective way to address iron deficiency in malaria-endemic areas.

High Prevalence of Malaria Parasitemia and Anemia among Hospitalized Children in Rakai, Uganda

BackgroundThere is a paucity of data on malaria among hospitalized children in malaria endemic areas. We determined the prevalence, presentation and treatment outcomes of malaria and anemia among children in two hospitals in Rakai, Uganda.MethodsChildren under five years hospitalized in Kalisizo hospital or Bikira health center in Rakai district, Uganda between May 2011 and May 2012 were enrolled and followed-up until discharge, death or referral. Data were collected on social-demographic characteristics, current and past illnesses and clinical signs and symptoms. Blood smears, hemoglobin (Hgb) levels and HIV testing were performed from finger/heel prick blood. The associations between malaria infection and other factors were estimated using log-binomial regression to estimate adjusted prevalence risk ratios (aPRR) and 95% confidence intervals (CIs), controlling for clustering at health facilities.Results2471 children were enrolled. The most common medical presentations were fever (96.2%), cough (61.7%), vomiting (44.2%), diarrhea (20.8%), and seizures (16.0%). The prevalence of malaria parasitemia was 54.6%. Children with malaria were more likely to present with a history of fever (aPRR 2.23; CI 1.18–4.24) and seizures (aPRR 1.12; CI 1.09–1.16). Confirmed malaria was significantly lower among girls than boys (aPRR 0.92; CI 0.91–0.93), HIV infected children (aPRR 0.60 CI 0.52–0.71), and children with diarrhea (aPRR 0.76; CI 0.65–0.90). The overall prevalence of anemia (Hgb<10 g/dl) was 56.3% and severe anemia (Hgb<6 g/dL) was 17.8%. Among children with severe anemia 76.8% had malaria parasitemia, of whom 93.1% received blood transfusion. Malaria associated mortality was 0.6%.ConclusionThere was a high prevalence of malaria parasitemia and anemia among inpatient children under five years. Malaria prevention is a priority in this population.

Effect of Iron Fortification on Malaria Incidence in Infants and Young Children in Ghana

In sub-Saharan Africa, malaria is a leading cause of childhood morbidity and iron deficiency is among the most prevalent nutritional deficiencies. In 2006, the World Health Organization and the United Nations Children's Fund released a joint statement that recommended limiting use of iron supplements (tablets or liquids) among children in malaria-endemic areas because of concern about increased malaria risk. As a result, anemia control programs were either not initiated or stopped in these areas. To determine the effect of providing a micronutrient powder (MNP) with or without iron on the incidence of malaria among children living in a high malaria-burden area. Double-blind, cluster randomized trial of children aged 6 to 35 months (n = 1958 living in 1552 clusters) conducted over 6 months in 2010 in a rural community setting in central Ghana, West Africa. A cluster was defined as a compound including 1 or more households. Children were excluded if iron supplement use occurred within the past 6 months, they had severe anemia (hemoglobin level <7 g/dL), or severe wasting (weight-for-length z score <-3). Children were randomized by cluster to receive a MNP with iron (iron group; 12.5 mg/d of iron) or without iron (no iron group). The MNP with and without iron were added to semiliquid home-prepared foods daily for 5 months followed by 1-month of further monitoring. Insecticide-treated bed nets were provided at enrollment, as well as malaria treatment when indicated. Malaria episodes in the iron group compared with the no iron group during the 5-month intervention period. In intention-to-treat analyses, malaria incidence overall was significantly lower in the iron group compared with the no iron group (76.1 and 86.1 episodes/100 child-years, respectively; risk ratio (RR), 0.87 [95% CI, 0.79-0.97]), and during the intervention period (79.4 and 90.7 episodes/100 child-years, respectively; RR, 0.87 [95% CI, 0.78-0.96]). In secondary analyses, these differences were no longer statistically significant after adjusting for baseline iron deficiency and anemia status overall (adjusted RR, 0.87; 95% CI, 0.75-1.01) and during the intervention period (adjusted RR, 0.86; 95% CI, 0.74-1.00). In a malaria-endemic setting in which insecticide-treated bed nets were provided and appropriate malaria treatment was available, daily use of a MNP with iron did not result in an increased incidence of malaria among young children. clinicaltrials.gov Identifier: NCT01001871.

Editorial Commentary: Complex Interactions of HIV Infection, Malaria, and Iron Deficiency

children not infected with HIV [4]. Malaria and iron deficiency also have a complex relationship. Iron deficiency appears to be protective against clinical malaria in children in malaria-endemic areas [5], and iron supplementation in malaria-endemic areas, particularly in iron-replete children, has been associated with an increased risk of malaria and severe adverse events (hospitalization or death) [6].The relationship between HIV infection and iron deficiency is less well characterized. Some studies indicate that children infected with HIV have iron deficiency less frequently than children without HIV infection, but the chronic inflammation often seen during HIV infection might lead to underestimates of irondeficiencyinthispopulation,because

Haptoglobin phenotypes and iron status in children living in a malaria endemic area of Kenyan coast

Malaria infection may be affected by host genetic factors as well as nutritional status. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant may be determinants of malaria parasitemia. A combination of cross sectional studies and longitudinal follow-up were used to describe the association between iron status, C-reactive protein, malaria infections and host genetic factors including; haptoglobin (Hp) phenotypes, in children below 9 years in a malaria endemic area in Coastal Kenya. The prevalence of 0.45 and 0.41, respectively for Hp 1-1 and Hp 2-1 phenotypes was significantly higher than 0.14 for Hp 2-2 phenotype (n=162). Children with Hp 2-2 phenotype showed significantly higher iron storage compared to those with Hp 1-1 and Hp 2-1 phenotypes when children with malaria parasites and high C-reactive protein (>9mg/L) were excluded from the analysis. There were no significant differences in malaria parasite densities among Hp phenotypes but children with Hp 2-2 had lower number of clinical malaria episodes (P=0.045). Taken together, this study shows that the presence of malaria may complicate the interpretation of iron status in children based on their Hp-phenotypes. Further studies will be required to address possible interactions among the various genetic factors and iron status in a malaria endemic setting.

Plasmodium falciparum Infection Patterns Since Birth and Risk of Severe Malaria: A Nested Case-Control Study in Children on the Coast of Kenya

Children in malaria endemic areas acquire immunity to severe malaria faster than to mild malaria. Only a minority of children suffers from severe malaria and it is not known what determines this. The aim of this study was to establish how P. falciparum infections during the first years of life affect the risk of severe malaria. A matched case-control study was nested within a large birth cohort set up to study the immunoepidemiology of pneumococci on the Kenyan coast. Infection patterns in three-monthly blood samples in cohort children admitted to hospital with severe malaria were compared to controls matched on age, residential location and time of sampling. P. falciparum detected at least once from birth conferred an increased risk of severe malaria and particularly if multiclonal infections, as characterized by genotyping of a polymorphic antigen gene, were ever detected. The results show for the first time that children with severe malaria have more infections early in life compared to community controls. These findings provide important insights on the immunity to severe disease, knowledge essential for the development of a vaccine against severe malaria.

Incidence and Characteristics of Bacteremia among Children in Rural Ghana

The objective of the study was to describe systemic bacterial infections occurring in acutely ill and hospitalized children in a rural region in Ghana, regarding frequency, incidence, antimicrobial susceptibility patterns and associations with anthropometrical data.Blood cultures were performed in all children below the age of five years, who were admitted to Agogo Presbyterian Hospital (APH), Asante Region, Ghana, between September 2007 and July 2009. Medical history and anthropometrical data were assessed using a standardized questionnaire at admission. Incidences were calculated after considering the coverage population adjusted for village-dependent health-seeking behavior.Among 1,196 hospitalized children, 19.9% (n = 238) were blood culture positive. The four most frequent isolated pathogens were nontyphoidal salmonellae (NTS) (53.3%; n = 129), Staphylococcus aureus (13.2%; n = 32), Streptococcus pneumoniae (9.1%; n = 22) and Salmonella ser. Typhi (7.0%; n = 17). Yearly cumulative incidence of bacteremia was 46.6 cases/1,000 (CI 40.9–52.2). Yearly cumulative incidences per 1,000 of the four most frequent isolates were 25.2 (CI 21.1–29.4) for NTS, 6.3 (CI 4.1–8.4) for S. aureus, 4.3 (CI 2.5–6.1) for S. pneumoniae and 3.3 (CI 1.8–4.9) for Salmonella ser. Typhi. Wasting was positively associated with bacteremia and systemic NTS bloodstream infection. Children older than three months had more often NTS bacteremia than younger children. Ninety-eight percent of NTS and 100% of Salmonella ser. Typhi isolates were susceptible to ciprofloxacin, whereas both tested 100% susceptible to ceftriaxone. Seventy-seven percent of NTS and 65% of Salmonella ser. Typhi isolates were multi-drug resistant (MDR). Systemic bacterial infections in nearly 20% of hospitalized children underline the need for microbiological diagnostics, to guide targeted antimicrobial treatment and prevention of bacteremia. If microbiological diagnostics are lacking, calculated antimicrobial treatment of severely ill children in malaria-endemic areas should be considered.