Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Does Deworming Improve Growth and School Performance in Children?

Background The World Bank ranks soil-transmitted helminth infection as causing more ill health in children aged 5–15 years than any other infection. In light of this ranking, global agencies recommend regular, mass treatment with deworming drugs to children in developing countries. The World Health Organization (WHO) argues that “deworming helps meet the Millennium Development Goals”, in particular the six health-related goals:eradicate extreme poverty and hunger;achieve universal primary education;promote gender equality and empower women;reduce child mortality and improve maternal health; and combat HIV/AIDS, malaria, and other diseases. However, deworming campaigns cost money to deliver, and so we must be clear that WHO statements about the impact of these programmes are based on reliable evidence. In 2000, we systematically reviewed the reliable evidence from relevant controlled trials about the effects of anthelminth drugs for soil-transmitted helminth infection on child growth and cognition. This systematic review, published in The Cochrane Database and the BMJ, demonstrated uncertainty around the assumed benefit and concluded that it may be a potentially important intervention, but needed better evaluation. The BMJ published a large number of letters that criticised the findings, including from authors at the World Bank, the WHO, the United States Centers for Disease Control and Prevention, and the Pan American Health Organization. We do not feel that these criticisms were scientifically substantive enough to undermine the method or the conclusion. For example, several critics commented on the fact that the systematic review could not make any conclusions about the long-term effects of treatment—but, as we argued in our reply to these criticisms, “we were unable to find any randomised controlled trials that evaluated long term benefit, and the evidence of short term benefit was not, for us, convincing.” The research community quite correctly carried out further randomised controlled trials (RCTs) of repeated doses in community trials with longer follow-up compared with no intervention or placebo. In light of this additional research, we have now updated the original Cochrane review. An author of one of the trials included in the 2000 review, Ed Cooper, criticised the review for not taking into account heterogeneity in parasite burdens. Therefore, in the recently updated review, we conducted an additional subgroup analysis at trial level stratified by worm intensity and prevalence

Early Exposure of Infants to GI Nematodes Induces Th2 Dominant Immune Responses Which Are Unaffected by Periodic Anthelminthic Treatment

We have previously shown a reduction in anaemia and wasting malnutrition in infants <3 years old in Pemba Island, Zanzibar, following repeated anthelminthic treatment for the endemic gastrointestinal (GI) nematodes Ascaris lumbricoides, hookworm and Trichuris trichiura. In view of the low intensity of worm infections in this age group, this was unexpected, and it was proposed that immune responses to the worms rather than their direct effects may play a significant role in morbidity in infants and that anthelminthic treatment may alleviate such effects. Therefore, the primary aims of this study were to characterise the immune response to initial/early GI nematode infections in infants and the effects of anthelminthic treatment on such immune responses. The frequency and levels of Th1/Th2 cytokines (IL-5, IL-13, IFN-γ and IL-10) induced by the worms were evaluated in 666 infants aged 6–24 months using the Whole Blood Assay. Ascaris and hookworm antigens induced predominantly Th2 cytokine responses, and levels of IL-5 and IL-13 were significantly correlated. The frequencies and levels of responses were higher for both Ascaris positive and hookworm positive infants compared with worm negative individuals, but very few infants made Trichuris-specific cytokine responses. Infants treated every 3 months with mebendazole showed a significantly lower prevalence of infection compared with placebo-treated controls at one year following baseline. At follow-up, cytokine responses to Ascaris and hookworm antigens, which remained Th2 biased, were increased compared with baseline but were not significantly affected by treatment. However, blood eosinophil levels, which were elevated in worm-infected children, were significantly lower in treated children. Thus the effect of deworming in this age group on anaemia and wasting malnutrition, which were replicated in this study, could not be explained by modification of cytokine responses but may be related to eosinophil function

Efficacy of different strategies to treat anemia in children: a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Anemia continues to be a major public health problem among children in many regions of the world, and it is still not clear which strategy to treat it is most effective.</p> <p>Objective</p> <p>To evaluate the efficacy and children's acceptance of several recognized strategies to treat anemia.</p> <p>Methods</p> <p>Non-breastfed children (n = 577), 6 to 43 mo of age, were screened for the trial; 267 were anemic (hemoglobin < 11.7 g/dL), and 266 of those were randomized into 1 of 5 treatments to received daily either: an iron supplement (IS), an iron+folic acid supplement (IFS), a multiple micronutrient supplement (MMS), a micronutrient-fortified complementary food as porridge powder (FCF), or zinc+iron+ascorbic acid fortified water (FW). The iron content of each daily dose was 20, 12.5, 10, 10 and 6.7 mg respectively. Hemoglobin (Hb), ferritin, total iron, weight and height were measured at baseline and after 4 months of treatment. Morbidity, treatment acceptability and adherence were recorded during the intervention.</p> <p>Results</p> <p>All treatments significantly increased Hb and total iron concentration; ferritin did not change significantly. Groups MMS, IS and IFS increased Hb (g/dL) [1.50 (95%CI: 1.17, 1.83), 1.48 [(1.18, 1.78) and 1.57 (1.26, 1.88), respectively] and total iron ((μg/dL) [0.15 (0.01, 0.29), 0.19 (0.06, 0.31) and 0.12(-0.01, 0.25), respectively] significantly more than FCF [0.92 (0.64, 1.20)] but not to FW group [0.14 (0.04, 0.24)]. The prevalence of anemia was reduced to a greater extent in the MMS and IFS groups (72% and 69%, respectively) than in the FCF group (45%) (p < 0.05). There were no significant differences in anthropometry or in the number of episodes of diarrhea and respiratory infections among treatment groups. The supplements MMS and IS were less acceptable to children, than IFS, FCF and FW.</p> <p>Conclusion</p> <p>The three supplements IS, ISF and MMS increased Hb more than the FCF; the supplements that contained micronutrients (IFS and MMS) were more effective for reducing the prevalence of anemia. In general, fortified foods were better accepted by the study participants than supplements.</p> <p>ClinicalTrial.gov Identifier</p> <p>NCT00822380</p

Mapping the Risk of Anaemia in Preschool-Age Children: The Contribution of Malnutrition, Malaria, and Helminth Infections in West Africa

Ricardo Soares Magalhães and colleagues used national cross-sectional household-based demographic health surveys to map the distribution of anemia risk in preschool children in Burkina Faso, Ghana, and Mali

Can an Integrated Approach Reduce Child Vulnerability to Anaemia? Evidence from Three African Countries.

Addressing the complex, multi-factorial causes of childhood anaemia is best done through integrated packages of interventions. We hypothesized that due to reduced child vulnerability, a "buffering" of risk associated with known causes of anaemia would be observed among children living in areas benefiting from a community-based health and nutrition program intervention. Cross-sectional data on the nutrition and health status of children 24-59 mo (N = 2405) were obtained in 2000 and 2004 from program evaluation surveys in Ghana, Malawi and Tanzania. Linear regression models estimated the association between haemoglobin and immediate, underlying and basic causes of child anaemia and variation in this association between years. Lower haemoglobin levels were observed in children assessed in 2000 compared to 2004 (difference -3.30 g/L), children from Tanzania (-9.15 g/L) and Malawi (-2.96 g/L) compared to Ghana, and the youngest (24-35 mo) compared to oldest age group (48-59 mo; -5.43 g/L). Children who were stunted, malaria positive and recently ill also had lower haemoglobin, independent of age, sex and other underlying and basic causes of anaemia. Despite ongoing morbidity, risk of lower haemoglobin decreased for children with malaria and recent illness, suggesting decreased vulnerability to their anaemia-producing effects. Stunting remained an independent and unbuffered risk factor. Reducing chronic undernutrition is required in order to further reduce child vulnerability and ensure maximum impact of anaemia control programs. Buffering the impact of child morbidity on haemoglobin levels, including malaria, may be achieved in certain settings

Podoconiosis and soil-transmitted helminths (STHs): double burden of neglected tropical diseases in Wolaita zone, rural southern Ethiopia

Background Both podoconiosis and soil-transmitted helminth (STH) infections occur among barefoot people in areas of extreme poverty; however, their co-morbidity has not previously been investigated. We explored the overlap of STH infection and podoconiosis in Southern Ethiopia and quantified their separate and combined effects on prevalent anemia and hemoglobin levels in podoconiosis patients and health controls from the same area. Methods and Principal Findings A two-part comparative cross-sectional study was conducted in Wolaita zone, southern Ethiopia. Data were collected from adult patients presenting with clinically confirmed podoconiosis, and unmatched adult neighborhood controls living in the same administrative area. Information on demographic and selected lifestyle factors was collected using interviewer-administered questionnaires. Stool samples were collected and examined qualitatively using the modified formalin-ether sedimentation method. Hemoglobin level was determined using two different methods: hemoglobinometer and automated hematology analyzer. A total of 913 study subjects (677 podoconiosis patients and 236 controls) participated. The prevalence of any STH infection was 47.6% among patients and 33.1% among controls (p<0.001). The prevalence of both hookworm and Trichuris trichiura infections was significantly higher in podoconiosis patients than in controls (AOR 1.74, 95% CI 1.25 to2.42, AOR 6.53, 95% CI 2.34 to 18.22, respectively). Not wearing shoes and being a farmer remained significant independent predictors of infection with any STH. There was a significant interaction between STH infection and podoconiosis on reduction of hemoglobin level (interaction p value = 0.002). Conclusions Prevalence of any STH and hookworm infection was higher among podoconiosis patients than among controls. A significant reduction in hemoglobin level was observed among podoconiosis patients co-infected with hookworm and ‘non-hookworm STH’. Promotion of consistent shoe-wearing practices may have double advantages in controlling both podoconiosis and hookworm infection in the study area

Hookworm-Related Anaemia among Pregnant Women: A Systematic Review

Anaemia affects large numbers of pregnant women in developing countries and increases their risk of dying during pregnancy and delivering low birth weight babies, who in turn are at increased risk of dying. Human hookworm infection has long been recognized among the major causes of anaemia in poor communities, but understanding of the benefits of the management of hookworm infection in pregnancy has lagged behind the other major causes of maternal anaemia. Low coverage of anthelmintic treatment in maternal health programmes in many countries has been the result. After systematically reviewing the available literature we observed that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women. We also estimate that between a quarter and a third of pregnant women in sub-Saharan Africa are infected with hookworm and at risk of preventable hookworm-related anaemia. However, all identified intervention studies showed a benefit of deworming for maternal or child health and we argue that increased efforts should be made to increase the coverage of anthelmintic treatment among pregnant women

Fecal occult blood and fecal calprotectin as point-of-care markers of intestinal morbidity in Ugandan children with Schistosoma mansoni infection.

BACKGROUND: Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). METHODS: 216 children (ages 3-9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. RESULTS: Fecal calprotectin concentrations of 150-300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. CONCLUSIONS: Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after treatment

Maternal fecal microbiome predicts gestational age, birth weight and neonatal growth in rural Zimbabwe.

BACKGROUND: Preterm birth and low birth weight (LBW) affect one in ten and one in seven livebirths, respectively, primarily in low-income and middle-income countries (LMIC) and are major predictors of poor child health outcomes. However, both have been recalcitrant to public health intervention. The maternal intestinal microbiome may undergo substantial changes during pregnancy and may influence fetal and neonatal health in LMIC populations. METHODS: Within a subgroup of 207 mothers and infants enrolled in the SHINE trial in rural Zimbabwe, we performed shotgun metagenomics on 351 fecal specimens provided during pregnancy and at 1-month post-partum to investigate the relationship between the pregnancy gut microbiome and infant gestational age, birth weight, 1-month length-, and weight-for-age z-scores using extreme gradient boosting machines. FINDINGS: Pregnancy gut microbiome taxa and metabolic functions predicted birth weight and WAZ at 1 month more accurately than gestational age and LAZ. Blastoscystis sp, Brachyspira sp and Treponeme carriage were high compared to Western populations. Resistant starch-degraders were important predictors of birth outcomes. Microbiome capacity for environmental sensing, vitamin B metabolism, and signalling predicted increased infant birth weight and neonatal growth; while functions involved in biofilm formation in response to nutrient starvation predicted reduced birth weight and growth. INTERPRETATION: The pregnancy gut microbiome in rural Zimbabwe is characterized by resistant starch-degraders and may be an important metabolic target to improve birth weight. FUNDING: Bill and Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Agency for Development and Cooperation, US National Institutes of Health, and UNICEF