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.

Reactivation of Plasmodium infection during a treatment with infliximab: A case report.

We describe a symptomatic Plasmodium falciparum infection in a 29-year-old Guinean man receiving Infliximab for one year and without recent travel. The reactivation of submicroscopic malaria following the inhibition of TNF-alpha by infliximab is suspected.

A population-based study of the prevalence and risk factors of low-grade Plasmodium falciparum malaria infection in children aged 0-15 years old in northern Tanzania.

OBJECTIVES: Northern Tanzania experiences significant malaria-related morbidity and mortality, but accurate data are scarce. We update the data on patterns of low-grade Plasmodium falciparum malaria infection among children in northern Tanzania. METHODS: Plasmodium falciparum malaria prevalence (pfPR) was assessed in a representative sample of 819 children enrolled in 94 villages in northern Tanzania between October 2015 and August 2016, using a complex survey design. Individual- and household-level risk factors for pfPR were elicited using structured questionnaires. pfPR was assessed using rapid diagnostic tests (RDTs) and thick film microscopy (TFM). Associations with pfPR, based on RDT, were assessed using adjusted odds ratios (aOR) and confidence intervals (CI) from weighted survey logistic regression models. RESULTS: Plasmodium falciparum malaria prevalence (pfPR) was 39.5% (95% CI: 31.5, 47.5) by RDT and 33.4% (26.0, 40.6) by TFM. pfPR by RDT was inversely associated with higher-education parents, especially mothers (5-7 years of education: aOR 0.55; 95% CI: 0.31, 0.96, senior secondary education: aOR 0.10; 95% CI: 0.02, 0.55), living in a house near the main road (aOR 0.34; 95% CI: 0.15, 0.76), in a larger household (two rooms: aOR 0.40; 95% CI: 0.21, 0.79, more than two rooms OR 0.35; 95% CI: 0.20, 0.62). Keeping a dog near or inside the house was positively associated with pfPR (aOR 2.01; 95% CI: 1.26, 3.21). pfPR was not associated with bed-net use or indoor residual spraying. CONCLUSIONS: Nearly 40% of children in northern Tanzania had low-grade malaria antigenaemia. Higher parental education and household metrics but not mosquito bed-net use were inversely associated with pfPR.

OBJECTIFS: La Tanzanie connaît une morbidité et une mortalité importantes liées au paludisme, mais les données précises sont rares. Nous mettons à jour les données sur les profils en matière d'infection par le paludisme à Plasmodium falciparum de faible grade chez les enfants dans le nord de la Tanzanie. MÉTHODES: La prévalence du paludisme à P. falciparum (pfPR) a été évaluée sur un échantillon représentatif de 819 enfants inscrits dans 94 villages dans le nord de la Tanzanie entre octobre 2015 et août 2016, à l'aide d'un plan d'enquête complexe. Des facteurs de risque de pfPR au niveau individuel et au niveau du ménage ont été déterminés à l'aide de questionnaires structurés. La pfPR a été évaluée à l'aide de tests de diagnostic rapides (TDR) et de microscopie à film épais (TFM). Les associations avec la pfPR, sur la base des TDR, ont été évaluées à l'aide des rapports de cotes ajustés (aOR) et des intervalles de confiance (IC) de modèles de régression logistique de surveillances pondérées. RÉSULTATS: La pfPR était de 39,5% (IC95%: 31,5-47,5) avec les TDR et de 33,4% (26,0-40,6) avec la TFM. La pfPR par les TDR était inversement associée aux parents avec un niveau d'éducation plus élevé, en particulier les mères (5-7 ans d'études: aOR: 0,55; IC95%: 0,31-0,96, enseignement secondaire supérieur: aOR: 0,10; IC95%: 0,02-0,55), vivre dans une maison proche de la route principale (aOR: 0,34; IC95%: 0,15-0,76), dans un ménage plus grand (2 chambres: aOR: 0,40; IC95%: 0,21-0,79, plus de 2 pièces aOR: 0,35; IC95%: 0,20-0,62). Garder un chien près ou à l'intérieur de la maison était positivement associé à la pfPR (aOR: 2,01; IC95%: 1,26-3,21). La pfPR n'était pas associée à l'utilisation de moustiquaire ou à la pulvérisation de résidus à l'intérieur. CONCLUSIONS: Près de 40% des enfants dans nord de la Tanzanie présentaient une antigénémie paludéenne de faible grade. Un niveau d'éducation parentale plus élevé et les indicateurs du ménage, mais pas l'utilisation de moustiquaires, étaient inversement associés à la pfPR.

[Plasmodium falciparum infection by blood transfusion：a case report].

This paper reported one acute lymphoblastic leukemia patient who infected with Plasmodium falciparum after blood transfusion. Through the epidemiological investigation on this patient and the related blood donors as well as laboratory detections, the source of infection was ascertained. This blood donor was an overseas student from Africa, whose blood sample was positive in the rapid diagnostic test, and the results of microscopic examination of peripheral blood smear and PCR both suggested P. falciparum positive.

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.

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.

Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial.

IMPORTANCE: Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. OBJECTIVE: To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. INTERVENTIONS: Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. MAIN OUTCOMES AND MEASURES: Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth. RESULTS: Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, -1.2%, 95% CI, -11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, -0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use. CONCLUSIONS AND RELEVANCE: Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308112.

The importance of a travel history in the preoperative assessment of an elective surgical patient.

The authors present the case of a 43-year-old gentleman who was admitted for an elective surgical removal of an eroded gastric band. The patient reported no medical concerns and other than a mild anaemia of haemoglobin of 10.6, his preoperative assessment was non-significant. Postoperatively, the patient spiked temperatures on multiple occasions. When a travel history was subsequently taken, the patient revealed he had returned from Nigeria the night before his elective surgery. The patient tested positive for Plasmodium falciparum malaria for which he was successfully managed with oral quinine and doxycycline, and recuperated well both from malaria and the surgery. P falciparum malaria is a medical emergency and increases the morbidity and mortality of anaesthesia and surgery. Travel histories are not currently routinely taken as part of the preoperative assessment for elective surgical admissions; the authors argue that it should become a mandatory part.

Casos notificados de malária no Estado do Pará, Amazônia Brasileira, de 1998 a 2006 / Notified Cases of Malaria in the State of Pará, Brazilian Amazon, from 1998 to 2006

Este estudo realizou um levantamento dos casos notificados de malária no Estado do Pará entre 1998 e 2006, com intuito de quantificar o risco de transmissão da doença, discriminar o número de casos por espécies de Plasmodium e destacar as áreas de maior incidência. Das 5.454.700 amostras sanguíneas examinadas, a positividade foi de 27,58 por cento (22,38 por cento Plasmodium falciparum; 76,11 por cento Plasmodium vivax; 0,31 por cento Plasmodium malariae e 1,20 por cento infecções mistas P. falciparum e P. vivax), sendo observada redução gradativa de notificações a partir de 2001. Além disso, constatou-se que sete municípios apresentaram incidência parasitária anual (IPA) alta entre 1998 e 2006 e outros 31 tiveram média dos nove anos de IPA≥50, sendo constatado aumento do número de municípios com IPA média e baixa. Em suma, o Estado do Pará apresentou redução significativa de casos notificados de malária, com tendência de aumento do número de municípios com IPA baixa e média, provavelmente reflexo das ações governamentais de controle e prevenção à malária na região.

The aim of this study was to carry out a survey of malaria cases reported in the state of Pará from 1998 to 2006 inorder to quantify the risk of disease transmission, to discriminate the number of cases by Plasmodium species and todetermine the areas of greater incidence. Among 5,454.700 blood samples examined, 27.58 per cent tested positive (22.38 per cent Plasmodium falciparum; 76.11 percent Plasmodium vivax; 0.31 percent Plasmodium malariae and 1.20 percent mixed infections of P. falciparum and P. vivax). A gradual reduction in notifications was observed, beginning in 2001. In seven cities there was ahigh Annual Parasite Incidence (API) between 1998 and 2006 and another 31 had average API of ≥50 over nine years.There was an increase in the number of cities with average or low API values. In summary, the state of Pará witnessed a significant reduction in the notification of malaria cases, with an increased trend in cities with low and average API values. This is probably a result of government actions for malaria control and prevention in that region.

Occupational Plasmodium falciparum malaria following accidental blood exposure: a case, published reports and considerations for post-exposure prophylaxis.

A French nurse presented Plasmodium falciparum malaria 10 d after a needlestick while sampling blood in a source patient with malaria. As did the source patient, the nurse recovered fully although diagnosis was delayed and her malaria severe. We proceeded to a thorough description of the transmission profile of P. falciparum following occupational needlestick. A review of the literature found 21 published reports of occupational malaria including our own, documenting 22 P. falciparum infections. One of these was lethal. The mean incubation time to fever onset was documented in 21 reports including our own and is 11.60 +/- 3.38 d (median 12.0, range 4-17 d). The incubation period was compatible to that found in experimental anopheline bites or transfusion malaria. The transmission profile cites a pathogen which may be more easily transmissible by occupational exposure to blood than human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Undiagnosed malaria in non-immune health care workers can be lethal. Presumptive treatment of malaria is widely available and well tolerated. Clinicians should consider P. falciparum malaria when faced with a febrile patient who has or may have been exposed to biological fluids. Further research is needed in the field of P. falciparum prophylaxis following accidental exposure to a malaria patient's blood.

The use of the multi-organ-dysfunction score to discriminate different levels of severity in severe and complicated Plasmodium falciparum malaria.

Clinical presentation of Plasmodium falciparum malaria reflects a continuum from asymptomatic to multi-organ manifestation and death. Severe malaria is defined by the World Health Organization as a qualitative variable. We used the multi-organ dysfunction score (MODS) as a quantitative approach for severity in 29 patients with severe and complicated P. falciparum malaria to test its usefulness in discriminating different severity levels. The MODS on admission was highly correlated with the duration of symptoms after admission (r = 0.73, P < 0.001) and the serum level of tumor necrosis factor alpha (r = 0.41, P = 0.03). In addition, the simplified MODS, based mainly on clinical findings, was also correlated with liver and renal dysfunction during hospitalization (alanine transaminase, r = 0.42, P = 0.02; blood urea nitrogen, r = 0.45, P = 0.015). A score >or= 16 was associated with significantly longer disease duration (P = 0.018). Thus, this score might provide a predictive value for morbidity in P. falciparum malaria.

Experimental infection of immunomodulated NOD/LtSz-SCID mice as a new model for Plasmodium falciparum erythrocytic stages.

The main objective of this study was to determine whether a chemical immunomodulation protocol could reduce the resistance of NOD/LtSz-SCID mice to Plasmodium falciparum infection and provide an improved mouse model for screening the antimalarial activity of new compounds. This model was compared with the presently used immunodeficient Beige/Nude/Xid (BNX) mouse model, using the same protocol, in terms of percentage of infected mice, parasite development, leukocyte response and phagocytosis of P. falciparum infected cells in various organs. Our results show that the combination of the chemical immune modulation protocol with the genetic background of NOD/LtSz-SCID mice results in the development of long-lasting P. falciparum infection in a high percentage of mice. A comparison of the results obtained in the histological study for both mouse models suggests that the higher rate of success in NOD/LtSz-SCID mice could be related to the reduced macrophage recruitment developed in different tissues to remove the parasite from blood.

Cell-cell interaction in the pathogenesis of severe falciparum malaria.

One of the major unresolved questions in malaria is why some patients with Plasmodium falciparum infection become so sick and die. Cell-cell interactions between the parasite and the host involving adherence/invasion appear generally, but not exclusively, to correlate with severity. The most important of these interactions in the asexual blood cycle are: (i) the invasion of red cells by merozoites, (ii) the binding of parasitised red blood cells (PRBC) to uninfected red cells (rosetting), (iii) the binding of PRBC to endothelial cells in critical organs (cytoadherence) and (iv) the induction of pro-inflammatory cytokines by PRBC, notably tumour necrosis factor (TNFalpha). The resulting clinical manifestations are protean. Analysis of these cellular interactions has revealed marked heterogeneity in molecular specificity which highlights the complexity of pathogenesis, but also opens the way to new modalities for treating this deadly infection.

[The risk of malaria transmission by blood transfusion at Cotonou, Benin].

The risk of transmission of infectious agents by blood transfusion is a permanent preoccupation for diseases that we do not know how to cure, such as hepatitis B, hepatitis C and AIDS. However, few studies have been carried out concerning the risks of transmitting curable infectious diseases, such as malaria. We carried out a cross-sectional study of 355 healthy blood donors in the rainy season, in which we used thick and thin blood film smears to screen for malaria. We found that 33.5% of donors harbored trophozoites and were therefore capable of transmitting malaria via blood donation. There were 1,000 to 4,760 parasites per microliter of blood and there was no relationship between the load of parasitized red blood cells and clinical malaria. Plasmodium falciparum was the most common species identified (96.63% of cases). The results confirm that it is vital, in this age of resistance to anti-malaria drugs and HIV, to screen blood donations systematically. Patients receiving transfusions should be given anti-malaria treatment and donors should be encouraged to sleep under treated mosquito nets.

IgE and tumor necrosis factor in malaria infection.

IgE, the immunoglobulin instrumental in atopic diseases is also elevated in many infections. This paper reports on the occurrence and possible pathogenic role of IgE in human Plasmodium falciparum malaria, one of the most widely spread and severe infectious diseases world wide. Plasmodial infections induce IgE elevation in the blood of the majority of people living in malaria endemic areas and up to 5% of this IgE constitutes anti-malaria antibodies. Production of IgE is controlled by T cells and elevated IgE concentrations in the blood of malaria patients are the result of an increased ratio of T-helper 2 (Th2) over T-helper 1 (Th1) cells. The underlying Th1 to Th2 switch is controlled by a variety of environmental and genetic factors. The importance of the latter is demonstrated by the IgE levels occurring in monozygotic or dizygotic twins originating from malarious areas of Africa. While these levels were indistinguishable within monozygotic twin pairs, they were different within the dizygotic pairs. Comparison of the levels of total IgE or IgE anti-malaria antibodies in patients with uncomplicated malaria with those in patients with the severe form of the disease (cerebral malaria or severe malaria without cerebral involvement) indicate that these levels are significantly higher in the cases with severe disease. This is the reverse with IgG and suggests that IgE plays a role in malaria pathogenesis. An important pathogenic mediator causing malaria fever and tissue lesions is tumor necrosis factor (TNF), generally believed to be induced by toxins released from the parasite. However, sera from malaria patients can also cause TNF release from monocytes in a reaction dependent on the presence of IgE containing immune complexes or aggregates. This results in induction and cross-linking of Fcepsilon receptor II (CD23) and by binding to and activating these cells, IgE will contribute to a local over-production of TNF in capillaries and post-capillary venules where P. falciparum parasites or their products accumulate in the severe forms of this disease.

Malaria infection after allogeneic bone marrow transplantation in a child with thalassemia.

A 12-year-old girl with beta-thalassemia hemoglobin E disease received a marrow transplant from her HLA-identical elder brother in July 1995. She had previously been treated by repeated blood transfusions. Conditioning included busulfan 16 mg/kg for 2 days and cyclophosphamide 120 mg/kg for 2 days. Cyclosporine was used for graft-versus-host disease prophylaxis. Spiking fevers occurred on days 6 and 11. Plasmodium falciparum parasites, both trophozoites and gametocytes, were found on the peripheral blood smear. Quinine 30 mg/kg three times a day for 7 days followed by a single dose of mefloquine 25 mg/kg was given. The fever subsided within 2 days and parasitemia cleared in 4 days. After transplant, the girl autologously reconstituted and was followed-up over 15 months.