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

Triple Co-Administration of Ivermectin, Albendazole and Praziquantel in Zanzibar: A Safety Study

This paper describes how the use of three drugs which are used separately in mass drug distribution programmes when given together appear safe for use in large populations which have been previously treated with the same drugs separately (Mectizan [ivermectin], albendazole and praziquantel). The target diseases—lymphatic filariasis, soil-transmitted worms and schistosomiasis—were prevalent in Zanzibar up to 2000 but have been largely controlled by mass drug administration. The Ministry of Health and Social Welfare, with the support of WHO, initiated a small scale trial in a population of triple therapy in over 5,000 people initially in two sites, and having found there were no severe adverse events associated with the combined treatment then upscaled to treat the whole of the eligible population of over 700,000. Similarly, there were no severe adverse events. This is the first time the three drugs have been used together at the same time at scale in Africa and provide a basis for expansion of integrated preventive chemotherapy of helminths (worms). The next steps need to be initiated in populations which have heavier worm loads and such interventions need to be subject to close monitoring and ethical review

Early helminth infections are inversely related to anemia, malnutrition, and malaria and are not associated with inflammation in 6- to 23-month-old Zanzibari children.

Helminths aggravate anemia and malnutrition among school children. We studied this association in a cross-sectional study of 6- to 23-month-old Zanzibari children (N = 2322) and a sub-sample of 690 children matched on age and helminth infection status. Ascaris, hookworm, and Trichuris infections were diagnosed along with recent fever, malaria infection, mid-upper arm circumference (MUAC) and hemoglobin concentration (Hb). Alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP), height, and weight were measured in the sub-sample. Infected children had higher Hb (beta = 5.44 g/L, P < 0.001) and MUAC-for-age Z score (beta = 0.30 Z, P < 0.001) compared with uninfected children after adjusting for covariates. Although helminths were not associated with inflammation, their association with Hb or MUAC-for-age Z score was modified by inflammation. Malaria-infected children were less likely to be infected with helminths (adjusted odds ratios 0.63 [95% confidence interval: 0.49, 0.81]). Non-anemic, better nourished, or non-malaria-infected children may be more exploratory of their environments and therefore increase their exposure to soil-transmitted helminths

A comparison of methods for detecting the eggs of Ascaris, Trichuris, and hookworm in infant stool, and the epidemiology of infection in Zanzibari infants.

This study compared five methods for detecting the eggs of the human parasitic geohelminths Ascaris, Trichuris, and hookworm in infant stool, and describes the epidemiology of infection in infants from a parasite-endemic area. A total of 424 infants 5-11 months old were enrolled from three villages on Pemba Island, Zanzibar. Methods used included the Kato-Katz technique, formol ethyl acetate sedimentation, modified formol ethyl acetate sedimentation, modified Wisconsin floatation, and simple gravity sedimentation. Of methods used alone, Wisconsin floatation and simple gravity sedimentation each provided the highest sensitivity for detecting eggs of these three geohelminths (89.6%). Of methods used in combination, the Kato-Katz technique/simple gravity sedimentation and Wisconsin floatation/simple gravity sedimentation each provided the highest sensitivity (99.0%). Prevalence of geohelminth infection was 26.5%. Between five and nine months of age the mean prevalence was 9.4%, while at 10 and 11 months of age the mean prevalence was 43.4%. Village prevalence varied from 3.6% to 43.8%. Infant geohelminth infection can occur at a high prevalence, and what method is best depends on research specifics

Adjusting for the acute phase response is essential to interpret iron status indicators among young Zanzibari children prone to chronic malaria and helminth infections.

The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population

Incidence and Risk Factors for Newborn Umbilical Cord Infections on Pemba Island, Zanzibar, Tanzania

BACKGROUND: Few community-based data exist on the frequency of cord infection signs in low resource settings, especially in Sub-Saharan Africa. We developed simple sign-based definitions of omphalitis and estimated incidence and risk factors for infection over a range of severity among neonates in Pemba, Zanzibar, Tanzania. METHODS: Infants\u27 umbilical stump was assessed on days 1, 3, 5, 7, 10, and 14 after birth for presence of pus, redness, swelling, and foul odor. Infection incidence and proportion of affected infants was estimated for 6 separate combinations of these signs. Two definitions were examined for associations between infection and selected potential risk factors using multivariate analysis. RESULTS: Nine thousand five hundred fifty cord assessments (in 1653 infants) were conducted. The proportion of affected infants ranged from 16 (1.0%, moderate to severe redness with pus discharge) to 199 (12.0%, pus and foul odor), while single signs were observed in \u3e20% of infants. Median time to onset of infection was 3 to 4 days; 90% of infections occurred by age 7 days. Breast-feeding within the first hour after birth was associated with lower risk of infection in multivariate analyses, while other maternal, and infant and care practices were generally not associated. CONCLUSIONS: Signs of omphalitis occur frequently and predominately in the first week of life among newborns in Pemba, Tanzania. Infection definitions relying on single signs without classifying severity level may overestimate burden. Redness with pus or redness at the moderate or severe level if pus is absent is more appropriate for estimating burden or during evaluation of interventions to reduce infection. © 2009 by Lippincott Williams & Wilkins

Population participating in the pilot intervention.

<p>Population participating in the pilot intervention.</p

Figure 1

<p>Population participating in the pilot intervention.</p

Evaluation of the efficacy of pyrantel-oxantel for the treatment of soil-transmitted nematode infections.

A randomized controlled trial comparing the efficacy of pyrantel-oxantel (10 mg/kg) with mebendazole (500 mg) was performed on 1329 schoolchildren aged 6-9 years on Pemba Island in September-October 2000 to evaluate alternative single-dose drugs for regular treatment of intestinal nematode infections. Both mebendazole and pyrantel-oxantel were very effective in eliminating Ascaris lumbricoides infection, inducing cure rates of more than 96% and reducing the mean egg counts by more than 95%. Both drugs had a moderate efficacy against Trichuris trichiura infection, but pyrantel-oxantel had a higher cure rate (31.5% vs. 23.3%, P < 0.01), though the reductions in egg counts did not differ significantly and were more than 80%. Pyrantel-oxantel and mebendazole had a similar, poor efficacy in curing hookworm infections and had a moderate effect in reducing the egg counts by 67% and 68%, respectively. Pyrantel-oxantel (10 mg/kg) offers a valuable alternative to mebendazole as a single-dose treatment for the control of intestinal nematode infections in children in endemic areas of sub-Saharan Africa, due to its comparable efficacy, its low cost and its suitability for use in young children