Effect of mass deworming with antihelminthics for soil-transmitted helminths during pregnancy.

BACKGROUND: Helminthiasis is an infestation of the human body with parasitic worms. It is estimated to affect 44 million pregnancies, globally, each year. Intestinal helminthiasis (hookworm infestation) is associated with blood loss and decreased supply of nutrients for erythropoiesis, resulting in iron-deficiency anaemia. Over 50% of the pregnant women in low- and middle-income countries (LMIC) suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hookworm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious, but evidence of their beneficial effect and safety when given during pregnancy has not been established. This is an update of a Cochrane Review last published in 2015. OBJECTIVES: To determine the effects of mass deworming with antihelminthics for soil-transmitted helminths (STH) during the second or third trimester of pregnancy on maternal and pregnancy outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) (8 March 2021) and reference lists of retrieved studies. SELECTION CRITERIA: We included all prospective randomised controlled trials evaluating the effect of administration of antihelminthics versus placebo or no treatment during the second or third trimester of pregnancy; both individual-randomised and cluster-randomised trials were eligible. We excluded quasi-randomised trials and studies that were only available as abstracts with insufficient information. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, checked accuracy and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included a total of six trials (24 reports) that randomised 7873 pregnant women. All of the included trials were conducted in antenatal clinics within hospitals in LMICs (Uganda, Nigeria, Peru, India, Sierra Leone and Tanzania). Among primary outcomes, five trials reported maternal anaemia, one trial reported preterm birth and three trials reported perinatal mortality. Among secondary outcomes, included trials reported maternal worm prevalence, low birthweight (LBW) and birthweight. None of the included studies reported maternal anthropometric measures or infant survival at six months. Overall, we judged the included trials to be generally at low risk of bias for most domains, while the certainty of evidence ranged from low to moderate. Analysis suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia by 15% (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.72 to 1.00; I²= 86%; 5 trials, 5745 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on preterm birth (RR 0.84, 95% CI 0.38 to 1.86; 1 trial, 1042 participants; low-certainty evidence) or perinatal mortality (RR 1.01, 95% CI 0.67 to 1.52; 3 trials, 3356 participants; low-certainty evidence). We are uncertain of the effect of antihelminthics during pregnancy on hookworm (average RR 0.31, 95% CI 0.05 to 1.93; Tau² = 1.76, I² = 99%; 2 trials, 2488 participants; low-certainty evidence). Among other secondary outcomes, findings suggest that administration of antihelminthics during pregnancy may reduce the prevalence of trichuris (average RR 0.68, 95% CI 0.48 to 0.98; I²=75%; 2 trials, 2488 participants; low-certainty evidence) and ascaris (RR 0.24, 95% CI 0.19 to 0.29; I²= 0%; 2 trials, 2488 participants; moderate-certainty evidence). Antihelminthics during pregnancy probably make little or no difference to LBW (RR 0.89, 95% CI 0.69 to 1.16; 3 trials, 2960 participants; moderate-certainty evidence) and birthweight (mean difference 0.00 kg, 95% CI -0.03 kg to 0.04 kg; 3 trials, 2960 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence suggests that administration of a single dose of antihelminthics in the second trimester of pregnancy may reduce maternal anaemia and worm prevalence when used in settings with high prevalence of maternal helminthiasis. Further data is needed to establish the benefit of antihelminthic treatment on other maternal and pregnancy outcomes. Future research should focus on evaluating the effect of these antihelminthics among various subgroups in order to assess whether the effect varies. Future studies could also assess the effectiveness of co-interventions and health education along with antihelminthics for maternal and pregnancy outcomes.

Bayesian Methods for Exposure Misclassification Adjustment in a Mediation Analysis: Hemoglobin and Malnutrition in the Association Between Ascaris and IQ.

BACKGROUND: Soil-transmitted helminth infections have been found to be associated with child development. The objective was to investigate hemoglobin levels and malnutrition as mediators of the association between Ascaris infection and intelligence quotient (IQ) scores in children. METHODS: We conducted a longitudinal cohort study in Iquitos, Peru, between September 2011 and July 2016. A total of 1760 children were recruited at 1 year of age and followed up annually to 5 years. We measured Ascaris infection and malnutrition at each study visit, and hemoglobin levels were measured as of age 3. The exposure was defined as the number of detected Ascaris infections between age 1 and 5. We measured IQ scores at age 5 and used Bayesian models to correct exposure misclassification. RESULTS: We included a sample of 781 children in the analysis. In results adjusted for Ascaris misclassification, mean hemoglobin levels mediated the association between Ascaris infection and IQ scores. The natural direct effects (not mediated by hemoglobin) (95% CrI) and natural indirect effects (mediated by hemoglobin) (95% CrI) were compared with no or one infection: -0.9 (-4.6, 2.8) and -4.3 (-6.9, -1.6) for the effect of two infections; -1.4 (-3.8, 1.0) and -1.2 (-2.0, -0.4) for three infections; and -0.4 (-3.2, 2.4) and -2.7 (-4.3, -1.0) for four or five infections. CONCLUSION: Our results are consistent with the hypothesis that hemoglobin levels mediate the association between Ascaris infection and IQ scores. Additional research investigating the effect of including iron supplements in STH control programs is warranted.

Ascaris lumbricoides infection: Still a threat for iron deficiency anaemia in 2-year-old Bangladeshi slum-dwelling children.

INTRODUCTION: Although parasitic infections lead to extracorporeal iron loss resulting in iron deficiency anaemia (IDA), data associating IDA with parasitic infections in the first two years of life are limited. We sought to evaluate the prevalence and severity of anaemia and IDA during this period and to investigate the association between intestinal parasitic infections and IDA. METHODOLOGY: Data was collected under MAL-ED study protocol in Bauniabadh slum of Dhaka, Bangladesh. The presence of parasites in stool was detected using wet preparation microscopy at 7, 15, and 24 months. Anaemia was defined as serum haemoglobin < 11 g/dL and IDA was defined by serum haemoglobin < 11 g/dL, serum ferritin < 12 g/L and soluble transferrin receptor > 8.3 mg/L. Logistic regression was done to quantify the relation between stool parasite and IDA separately on samples collected at 7, 15 and 24 months. RESULTS: 265 children were enrolled after birth and samples were collected at 7, 15 and 24 months. Anaemia was detected at 7, 15 and 24 months in 117 (48.8%), 106 (44.2%) and 67 (27.9%) cases whereas IDA was found in 15 (6.3%), 47 (19.6%) and 39 (16.3%) cases, respectively. Iron deficiency anaemia at 24 months was significantly associated with Ascaris lumbricoides infection (OR 3.76; 95 % CI, 1.08-13.11). CONCLUSIONS: The prevalence of anaemia and IDA in slum dwelling children of Dhaka is high and Ascaris lumbricoides infection was found to have a strong association with IDA at 24 months of age.

Hookworm Infection: A Neglected Cause of Overt Obscure Gastrointestinal Bleeding.

Hookworm infections are widely prevalent in tropical and subtropical areas, especially in low income regions. In the body, hookworms parasitize the proximal small intestine, leading to chronic intestinal hemorrhage and iron deficiency anemia. Occasionally, hookworms can cause overt gastrointestinal bleeding, but this is often ignored in heavily burdened individuals from endemic infectious areas. A total of 424 patients with overt obscure gastrointestinal bleeding were diagnosed by numerous blood tests or stool examinations as well as esophagogastroduodenoscopy, colonoscopy, capsule endoscopy or double-balloon enteroscopy. All of the patients lived in hookworm endemic areas and were not screened for hookworm infection using sensitive tests before the final diagnosis. The patients recovered after albendazole treatment, blood transfusion, and iron replacement, and none of the patients experienced recurrent bleeding in the follow-up. All the 31 patients were diagnosed with hookworm infections without other concomitant bleeding lesions, a rate of 7.3% (31/424). Seventeen out of 227 patients were diagnosed with hookworm infections in the capsule endoscopy (CE), and 14 out of 197 patients were diagnosed with hookworm infections in the double balloon enteroscopy (DBE). Hookworm infections can cause overt gastrointestinal bleeding and should be screened in patients with overt obscure gastrointestinal bleeding (OGIB) in endemic infectious areas with sensitive methods. Specifically, the examination of stool specimens is clinically warranted for most patients, and the proper examination for stool eggs relies on staff's communication.

The Effects of an Oil and Wheat Flour Fortification Program on Pre-School Children and Women of Reproductive Age Living in Côte d'Ivoire, a Malaria-Endemic Area.

Anemia and micronutrient deficiencies are widespread in sub-Saharan Africa, but the impact of food fortification is still debated. The objective of this study was to estimate the iron and vitamin A status of preschool children (PSC) and women of reproductive age (WRA) in households consuming fortified oil and wheat flour. The survey was cross-sectional in a rural and an urban area. Data on demographics, socioeconomic status, and fortified foods were collected at households. Hemoglobin (Hb), retinol binding protein (RBP), ferritin, soluble transferrin receptors (sTfR), subclinical inflammation, and Plasmodium spp. infection data were collected. In PSC, vitamin A deficiency (VAD) was prevalent, but for each 1 mg retinol equivalents (RE)/kg of oil consumed, RBP increased by 0.37 µmol/L (p = 0.03). In WRA, there was no significant VAD in the population (0.7%). Anemia was found in 92.2% of rural and 56.3% of urban PSC (p < 0.001). PSC with access to adequately fortified flour had Hb concentrations 15.7 g/L higher than those who did not (p < 0.001). Hb levels increased by +0.238 g/L per mg/kg increase in iron fortification levels (p < 0.001). The national program fortifying vegetable oil with vitamin A and wheat flour with iron and folic acid may have contributed to improved micronutrient status of PSC from two areas in Côte d'Ivoire.

Predominance of Giardia lamblia assemblage A among iron deficiency anaemic pre-school Egyptian children.

Intestinal parasites and nutritional deficiency can coexist and influence each other. This study aimed to clarify the association between Giardia genotypes and presence of iron deficiency anaemia (IDA) among pre-school Egyptian children. Two groups (IDA and non-anaemic) of giardiasis children (44/group) were selected according to their recovery response after treatment of giardiasis. Each group included 24 and 20 gastrointestinal symptomatic and asymptomatic, respectively. Giardia human genotypes were performed by intergenic spacer (IGS) gene based polymerase chain reaction (PCR) with high-resolution melting curve (HRM). PCR/HRM proved that Tms of assemblage A and B ranged from 79.31 ± 0.29 to 84.77 ± 0.31. In IDA patients, assemblages A and B were found among 40/44 (90.9 %) and 4/44 (9.1 %), respectively, while in non-anaemic patients, assemblages A and B were found in 10/44 (22.7 %) and 32/44 (72.7 %), respectively, beside two (4.6 %) cases had mixed infection. The difference was statistically significant. No significant relation was found between symptomatic or asymptomatic assemblages and IDA as assemblage A was found in 21/24 (87.5 %) and 19/20 (95 %) of symptomatic and asymptomatic, respectively, while 3/24 (12.5 %) and 1/20 (5 %) of assemblage B were symptomatic was asymptomatic, respectively. A significant relation was found between assemblage A subtypes distribution among IDA patients as AI and AII were detected on 23 (52.3 %) and 16 (36.4 %) of patients, respectively, while one case (2.3 %) had mixed infection. In conclusion, assemblage A is predominant among IDA giardiasis children suggesting its role in enhancing the occurrence of IDA while B has a protective role.

Severe iron deficiency anaemia associated with heavy lice infestation in a young woman.

Lice feed on human blood, and heavy and chronic lice infestation can lead to chronic blood loss with resultant iron deficiency anaemia. Although no definite relationship between lice infestation and iron deficiency anaemia has been described, the concurrent presence of these two conditions has been reported in children and adults, as well as in cattle. We present a case of a young woman with severe iron deficiency anaemia that could not be explained by the known causes of iron deficiency anaemia. However, the patient was found to have heavy and chronic head lice infestation.

Effect of administration of antihelminthics for soil-transmitted helminths during pregnancy.

BACKGROUND: Helminthiasis is infestation of the human body with parasitic worms and it is estimated to affect 44 million pregnancies, globally, each year. Intestinal helminthiasis (hook worm) is associated with blood loss and decreased supply of nutrients for erythropoiesis, resulting in iron-deficiency anaemia. Over 50% of the pregnant women in low- and middle-income countries suffer from iron-deficiency anaemia. Though iron-deficiency anaemia is multifactorial, hook worm infestation is a major contributory cause in women of reproductive age in endemic areas. Antihelminthics are highly efficacious in treating hook worm but evidence of their beneficial effect and safety, when given during pregnancy, has not been established. OBJECTIVES: To determine the effects of administration of antihelminthics for soil-transmitted helminths during the second or third trimester of pregnancy on maternal anaemia and pregnancy outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: All prospective randomised controlled trials evaluating the effect of administration of antihelminthics during the second or third trimester of pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. MAIN RESULTS: A total of four trials including 4265 participants were included in this review. Two of the included trials were of high quality, while two were of relatively low quality with limitations and biases in design and conduct.Analysis showed that administration of a single dose of antihelminthic in the second trimester of pregnancy is not associated with any impact on maternal anaemia in the third trimester (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.81 to 1.10; 3266 participants; four trials; low quality evidence). Subgroup analysis on the basis of co-interventions other than antihelminthic, which included iron supplementation given to both groups was also not associated with any impact on maternal anaemia (RR 0.76; 95% CI 0.47 to 1.23; 1290 participants; three trials; moderate quality evidence). No impact was found for the outcomes of low birthweight (RR 1.00; 95% CI 0.79 to 1.27; 3255 participants; three trials; moderate quality evidence), preterm birth (RR 0.88; 95% CI 0.43 to 1.78; 1318 participants; two trials, moderate quality evidence) and perinatal mortality (RR 1.09; 95% CI 0.71 to 1.67; 3385 participants; two trials; moderate quality evidence). None of the included studies reported impact on infant survival at six months of age. AUTHORS' CONCLUSIONS: The evidence to date is insufficient to recommend use of antihelminthic for pregnant women after the first trimester of pregnancy. More well-designed, large scale randomised controlled trials are needed to establish the benefit of antihelminthic treatment during pregnancy.

Varón brasileño de 19 años con anemia ferropénica grave / A 19 year old Brazilian male with severe iron deficiency anemia

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Nutritional iron deficiency anemia: magnitude and its predictors among school age children, southwest Ethiopia: a community based cross-sectional study.

BACKGROUND: Iron deficiency anemia (IDA) is a global public health problem among school age children, which retards psychomotor development and impairs cognitive performance. There is limited data on prevalence and risk factors for IDA. OBJECTIVE: The aim of this study was to determine the prevalence, severity, and predictors of nutritional IDA in school age children in Southwest Ethiopia. METHODOLOGY: A community based cross-sectional study was conducted in Jimma Town, Southwest Ethiopia from April to July 2013. A total of 616 school children aged 6 to 12 years were included in the study using multistage sampling technique. A structured questionnaire was used to collect sociodemographic data. Five milliliter venous blood was collected from each child for hematological examinations. Anemia was defined as a hemoglobin level lower than 11.5 g/dl and 12 g/dl for age group of 5-11 years and 12-15 years, respectively. Iron deficiency anemia was defined when serum iron and ferritin levels are below 10 µmol/l and 15 µg/dl, respectively. Moreover, fresh stool specimen was collected for diagnosis of intestinal parasitic infection. Stained thick and thin blood films were examined for detection of Plasmodium infection and study of red blood cell morphology. Dietary patterns of the study subjects were assessed using food frequency questionnaire and anthropometric measurements were done. Data were analyzed using SPSS V-20.0 for windows. RESULT: Overall, prevalence of anemia was 43.7%, and that of IDA was 37.4%. Not-consuming protein source foods [AOR = 2.30, 95%CI(1.04,5.14)], not-consuming dairy products [AOR = 1.83, 95%CI(1.14,5.14)], not-consuming discretionary calories [AOR = 2.77, 95%CI(1.42,5.40)], low family income [AOR = 6.14, 95%CI(2.90,12.9)] and intestinal parasitic infections [AOR = 1.45, 95%CI(1.23, 5. 27)] were predictors of IDA. CONCLUSION: Iron deficiency anemia is a moderate public health problem in the study site. Dietary deficiencies and intestinal parasitic infections were predictors of IDA. Therefore, emphasis should be given to the strategies for the prevention of risk factors for IDA.

Severe iron deficiency anemia and marked eosinophilia in adolescent girls with the diagnosis of human fascioliasis.

Human fascioliasis (HF), caused by the common liver fluke Fasciola hepatica, is an endemic infection in many parts of tropical countries. HF can also be seen in some of the non-tropical countries. This report describes two girls with severe iron deficiency anemia and eosinophilia, who were diagnosed as HF. The infection was successfully eliminated with the administration of triclabendazole. No side effects or recurrence was observed after the treatment. It should be kept in mind that marked eosinophilia with severe iron deficiency anemia should alert pediatricians to the possibility of F. hepatica infection.

Host iron status and iron supplementation mediate susceptibility to erythrocytic stage Plasmodium falciparum.

Iron deficiency and malaria have similar global distributions, and frequently co-exist in pregnant women and young children. Where both conditions are prevalent, iron supplementation is complicated by observations that iron deficiency anaemia protects against falciparum malaria, and that iron supplements increase susceptibility to clinically significant malaria, but the mechanisms remain obscure. Here, using an in vitro parasite culture system with erythrocytes from iron-deficient and replete human donors, we demonstrate that Plasmodium falciparum infects iron-deficient erythrocytes less efficiently. In addition, owing to merozoite preference for young erythrocytes, iron supplementation of iron-deficient individuals reverses the protective effects of iron deficiency. Our results provide experimental validation of field observations reporting protective effects of iron deficiency and harmful effects of iron administration on human malaria susceptibility. Because recovery from anaemia requires transient reticulocytosis, our findings imply that in malarious regions iron supplementation should be accompanied by effective measures to prevent falciparum malaria.

[Hookworm as cause of iron deficiency anemia in the prison population]. / Uncinariasis como causa de anemia ferropénica en población penitenciaria.

We report a case of hookworm parasitosis in a Spanish patient who before imprisonment had lived in Brazil. The diagnosis was established from a progressive manifestation of asthenia, together with significant weight loss. Laboratory tests showed hypochromic microcytic anemia and eosinophilia. Consequently, the patient was admitted to hospital in order to complete the study, where several hookworm eggs were later found in feces. The patient was subsequently treated with Albendazole and iron,achieving clinical cure, normalization of biochemical parameters and eventual eradication of the parasite. We believe it is important for the prison doctor to bear this and other parasitosis in mind when facing the case of inmates who are originally from tropical countries, where these parasites are endemic. In addition, it might be appropriate to implement parasite screening programs in the immigrant population headed by the Prison Health Service, even when said population is asymptomatic.

Blastocystis spp.: frequency and subtype distribution in iron deficiency anemic versus non-anemic subjects from Egypt.

Many helminthic and protozoal infections have been implicated in iron deficiency anemia (IDA) but few reports have suggested a link between Blastocystis sp. infection and IDA. Herein, we investigated the frequency and the association of the Blastocystis sp. genotype with IDA. Two-hundred and six stool samples were examined for Blastocystis sp. Samples were obtained from 96 cases with a confirmed diagnosis of IDA and 110 matched non-anemic controls. The prevalence of the parasite was significantly higher in the IDA group (54.2%) when compared to controls (17.3%) and was 34.5% in all study subjects. Thus, a relationship between Blastocystis sp. infection and IDA was confirmed. PCR amplification of isolates from cases with IDA and controls using subtype-specific sequenced-tagged site primers found that subtype 3 was the most common (83.3%), followed by subtype 1 (16.7%), and both had similar prevalence in both groups. Therefore, there was no correlation found between the Blastocystis sp. genotype and the occurrence of IDA.

Iron metabolism and its relationship to anemia and immune system in Trypanosoma evansi infected rats.

The aim of this study was to evaluate biochemical parameters of iron metabolism in rats experimentally infected with Trypanosoma evansi. To this end, 20 rats (Wistar) were intraperitoneally inoculated with blood containing trypomastigotes 10(6) (Group T) and 12 animals were used as negative control (Group C) and received saline (0.2 mL) through same route. Blood samples were collected by cardiac puncture on day 5 (C5, T5) and 30 (C30, T30) post-inoculation (pi) to perform complete blood count and determination of serum iron, transferrin, ferritin, total and latent iron fixation capacity, transferrin saturation and prohepcidin concentration. Also, bone marrow samples were collected, to perform Pearls staining reaction. Levels of iron, total and latent iron binding capacity and prohepcidin concentration were lower (P<0.05) in infected rats (T5 and T30 groups) compared to controls. On the other hand, levels of transferrin and ferritin were higher when compared to controls (P<0.05). The transferrin saturation increased on day 5 pi, but decreased on day 30 pi. The Pearls reaction showed a higher accumulation of iron in the bone marrow of infected animals in day 5 pi (P<0.01). Infection with T. evansi in rats caused anemia and changes in iron metabolism associated to the peaks of parasitemia. These results suggest that changes in iron metabolism may be related to the host immune response to infection and anemic status of infected animals.