The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden

Objective

To estimate the degree of synergism between helminth species in their combined effects on anemia.

Methods

Quantitative egg counts using the Kato–Katz method were determined for Ascaris lumbricoides, hookworm, Trichuris trichiura, and Schistosoma japonicum in 507 school-age children from helminth-endemic villages in The Philippines. Infection intensity was defined in three categories: uninfected, low, or moderate/high (M+). Anemia was defined as hemoglobin <11 g/dL. Logistic regression models were used to estimate odds ratios (OR), 95% confidence intervals (CI), and synergy index for pairs of concurrent infections.

Results

M+ co-infection of hookworm and S. japonicum (OR = 13.2, 95% CI: 3.82–45.5) and of hookworm and T. trichiura (OR = 5.34, 95% CI: 1.76–16.2) were associated with higher odds of anemia relative to children without respective M+ co-infections. For co-infections of hookworm and S. japonicum and of T. trichiura and hookworm, the estimated indices of synergy were 2.9 (95% CI: 1.1–4.6) and 1.4 (95% CI: 0.9–2.0), respectively.

Conclusion

Co-infections of hookworm and either S. japonicum or T. trichiura were associated with higher levels of anemia than would be expected if the effects of these species had only independent effects on anemia. This suggests that integrated anti-helminthic treatment programs with simultaneous deworming for S. japonicum and some geohelminths could yield a greater than additive benefit for reducing anemia in helminth-endemic regions.     

Iron status predicts malaria risk in malawian preschool children

Introduction

Iron deficiency is highly prevalent in pre-school children in developing countries and an important health problem in sub-Saharan Africa. A debate exists on the possible protective effect of iron deficiency against malaria and other infections; yet consensus is lacking due to limited data. Recent studies have focused on the risks of iron supplementation but the effect of an individual''s iron status on malaria risk remains unclear. Studies of iron status in areas with a high burden of infections often are exposed to bias. The aim of this study was to assess the predictive value of baseline iron status for malaria risk explicitly taking potential biases into account.

Methods and materials

We prospectively assessed the relationship between baseline iron deficiency (serum ferritin <30 µg/L) and malaria risk in a cohort of 727 Malawian preschool children during a year of follow-up. Data were analyzed using marginal structural Cox regression models and confounders were selected using causal graph theory. Sensitivity of results to bias resulting from misclassification of iron status by concurrent inflammation and to bias from unmeasured confounding were assessed using modern causal inference methods.

Results and Conclusions

The overall incidence of malaria parasitemia and clinical malaria was 1.9 (95% CI 1.8–2.0) and 0.7 (95% CI 0.6–0.8) events per person-year, respectively. Children with iron deficiency at baseline had a lower incidence of malaria parasitemia and clinical malaria during a year of follow-up; adjusted hazard ratio''s 0.55 (95%-CI:0.41–0.74) and 0.49 (95%-CI:0.33–0.73), respectively. Our results suggest that iron deficiency protects against malaria parasitemia and clinical malaria in young children. Therefore the clinical importance of treating iron deficiency in a pre-school child should be weighed carefully against potential harms. In malaria endemic areas treatment of iron deficiency in children requires sustained prevention of malaria.     

Epidemiological and genetic data supporting the transmission of Ancylostoma ceylanicum among human and domestic animals

Background

Currently, information on species-specific hookworm infection is unavailable in Malaysia and is restricted worldwide due to limited application of molecular diagnostic tools. Given the importance of accurate identification of hookworms, this study was conducted as part of an ongoing molecular epidemiological investigation aimed at providing the first documented data on species-specific hookworm infection, associated risk factors and the role of domestic animals as reservoirs for hookworm infections in endemic communities of Malaysia.

Methods/Findings

A total of 634 human and 105 domestic canine and feline fecal samples were randomly collected. The overall prevalence of hookworm in humans and animals determined via microscopy was 9.1% (95% CI = 7.0–11.7%) and 61.9% (95% CI = 51.2–71.2%), respectively. Multivariate analysis indicated that participants without the provision of proper latrine systems (OR = 3.5; 95% CI = 1.53–8.00; p = 0.003), walking barefooted (OR = 5.6; 95% CI = 2.91–10.73; p<0.001) and in close contact with pets or livestock (OR = 2.9; 95% CI = 1.19–7.15; p = 0.009) were more likely to be infected with hookworms. Molecular analysis revealed that while most hookworm-positive individuals were infected with Necator americanus, Ancylostoma ceylanicum constituted 12.8% of single infections and 10.6% mixed infections with N. americanus. As for cats and dogs, 52.0% were positive for A. ceylanicum, 46.0% for Ancylostoma caninum and 2.0% for Ancylostoma braziliense and all were single infections.

Conclusion

This present study provided evidence based on the combination of epidemiological, conventional diagnostic and molecular tools that A. ceylanicum infection is common and that its transmission dynamic in endemic areas in Malaysia is heightened by the close contact of human and domestic animal (i.e., dogs and cats) populations.     

Mapping the risk of anaemia in preschool-age children: the contribution of malnutrition, malaria, and helminth infections in West Africa

Background

Childhood anaemia is considered a severe public health problem in most countries of sub-Saharan Africa. We investigated the geographical distribution of prevalence of anaemia and mean haemoglobin concentration (Hb) in children aged 1–4 y (preschool children) in West Africa. The aim was to estimate the geographical risk profile of anaemia accounting for malnutrition, malaria, and helminth infections, the risk of anaemia attributable to these factors, and the number of anaemia cases in preschool children for 2011.

Methods and Findings

National cross-sectional household-based demographic health surveys were conducted in 7,147 children aged 1–4 y in Burkina Faso, Ghana, and Mali in 2003–2006. Bayesian geostatistical models were developed to predict the geographical distribution of mean Hb and anaemia risk, adjusting for the nutritional status of preschool children, the location of their residence, predicted Plasmodium falciparum parasite rate in the 2- to 10-y age group (Pf PR_2–10), and predicted prevalence of Schistosoma haematobium and hookworm infections. In the four countries, prevalence of mild, moderate, and severe anaemia was 21%, 66%, and 13% in Burkina Faso; 28%, 65%, and 7% in Ghana, and 26%, 62%, and 12% in Mali. The mean Hb was lowest in Burkina Faso (89 g/l), in males (93 g/l), and for children 1–2 y (88 g/l). In West Africa, severe malnutrition, Pf PR_2–10, and biological synergisms between S. haematobium and hookworm infections were significantly associated with anaemia risk; an estimated 36.8%, 14.9%, 3.7%, 4.2%, and 0.9% of anaemia cases could be averted by treating malnutrition, malaria, S. haematobium infections, hookworm infections, and S. haematobium/hookworm coinfections, respectively. A large spatial cluster of low mean Hb (<80 g/l) and maximal risk of anaemia (>95%) was predicted for an area shared by Burkina Faso and Mali. We estimate that in 2011, approximately 6.7 million children aged 1–4 y are anaemic in the three study countries.

Conclusions

By mapping the distribution of anaemia risk in preschool children adjusted for malnutrition and parasitic infections, we provide a means to identify the geographical limits of anaemia burden and the contribution that malnutrition and parasites make to anaemia. Spatial targeting of ancillary micronutrient supplementation and control of other anaemia causes, such as malaria and helminth infection, can contribute to efficiently reducing the burden of anaemia in preschool children in Africa. Please see later in the article for the Editors'' Summary     

Association between anaemia, iron deficiency anaemia, neglected parasitic infections and socioeconomic factors in rural children of West Malaysia

Background

Given that micronutrient deficiency, neglected intestinal parasitic infections (IPIs) and poor socioeconomic status are closely linked, we conducted a cross-sectional study to assess the relationship between IPIs and nutritional status of children living in remote and rural areas in West Malaysia.

Methods/Findings

A total of 550 children participated, comprising 520 (94.5%) school children aged 7 to 12 years old, 30 (5.5%) young children aged 1 to 6 years old, 254 (46.2%) boys and 296 (53.8%) girls. Of the 550 children, 26.2% were anaemic, 54.9% iron deficient and 16.9% had iron deficiency anaemia (IDA). The overall prevalence of helminths was 76.5% comprising Trichuris trichiura (71.5%), Ascaris lumbricoides (41.6%) and hookworm infection (13.5%). It was observed that iron deficiency was significantly higher in girls (p = 0.032) compared to boys. Univariate analysis demonstrated that low level of mother''s education (OR = 2.52; 95% CI = 1.38–4.60; p = 0.002), non working parents (OR = 2.18; 95% CI = 2.06–2.31; p = 0.013), low household income (OR = 2.02; 95% CI = 1.14–3.59; p = 0.015), T. trichiura (OR = 2.15; 95% CI = 1.21–3.81; p = 0.008) and A. lumbricoides infections (OR = 1.63; 95% CI = 1.04–2.55; p = 0.032) were significantly associated with the high prevalence of IDA. Multivariate analysis confirmed that low level of mother''s education (OR = 1.48; 95 CI% = 1.33–2.58; p<0.001) was a significant predictor for IDA in these children.

Conclusion

It is crucial that a comprehensive primary health care programme for these communities that includes periodic de-worming, nutrition supplement, improved household economy, education, sanitation status and personal hygiene are taken into consideration to improve the nutritional status of these children.     

Impact of long-term treatment with ivermectin on the prevalence and intensity of soil-transmitted helminth infections

Background

Control of soil-transmitted helminth (STH) infections relies on the periodic and long-term administration of anthelmintic drugs to high-risk groups, particularly school-age children living in endemic areas. There is limited data on the effectiveness of long-term periodic anthelmintic treatment on the prevalence of STHs, particularly from operational programmes. The current study investigated the impact of 15 to 17 years of treatment with the broad-spectrum anthelmintic ivermectin, used for the control of onchocerciasis, on STH prevalence and intensity in school-age and pre-school children.

Methods and Findings

A cross-sectional study was conducted in communities that had received annual or twice-annual ivermectin treatments and geographically adjacent communities that had not received treatment in two districts of Esmeraldas Province in Ecuador. Stool samples were collected from school-age children and examined for STH infection using the Kato-Katz and formol-ether concentration methods. Samples were collected also from pre-school children and examined by the formol-ether concentration method. Data on risk factors for STH infection were collected by parental questionnaire. We sampled a total of 3,705 school-age children (6–16 years) from 31 treated and 27 non-treated communities, and 1,701 pre-school children aged 0–5 years from 18 treated and 18 non-treated communities. Among school-age children, ivermectin treatment had significant effects on the prevalence (adjusted OR =  0.06, 95% CI 0.03–0.14) and intensity of Trichuris trichiura infection (adjusted RR = 0.28, 95% CI 0.11–0.70), but appeared to have no impact on Ascaris lumbricoides or hookworm infection. Reduced prevalence and intensities of T. trichiura infection were observed among children not eligible to receive ivermectina, providing some evidence of reduced transmission of T. trichiura infection in communities receiving mass ivermectin treatments.

Conclusion

Annual and twice-annual treatments with ivermectin over a period of up to 17 years may have had a significant impact on T. trichiura infection. The present data indicate that the long-term control of onchocerciasis with ivermectin may provide additional health benefits by reducing infections with trichuriasis. The addition of a second anthelmintic drug such as albendazole may be useful for a long-term effect on A. lumbricoides infection.     

Severity of Anemia among Children under 36 Months Old in Rural Western China

Objective

To describe severity of anemia and explore its determinants among children under 36 months old in rural western China.

Study Design

The family information of 6711 children was collected and their hemoglobin was measured in 2005. A generalized estimated equation (GEE) linear model was used to identify the determinants of severity of childhood anemia.

Results

The prevalence of mild, moderate and severe anemia among these children was 27.4%, 21.9% and 3.2% respectively. GEE model analysis showed that province-level region and severity of maternal anemia affected the severity of childhood anemia not only in 0–5 months but also beyond 5 months. In addition, children aged 0–5 months in families using iron pot (coefficient = −0.26 95%CI −0.41,−0.12) had seldom more severe anemia, and children aged 6–36 months in families more than 4 members (coefficient = −0.03 95%CI −0.06,−0.01) or of Han ethnicity (coefficient = −0.08 95%CI −0.13,−0.04) seldom had more severe anemia but boys (coefficient = 0.03 95%CI 0.01,0.06) or younger children (6–11 month vs 30–36 month: coefficient = 0.23 95%CI 0.17, 0.28; 12–17 month vs 30–36 month: coefficient = 0.19 95%CI 0.15,0.24; 18–23 vs 30–36 month: coefficient = 0.09 95%CI 0.04,0.13) had more severe anemia.

Conclusion

The prevalence of moderate-to-severe anemia in these children was about 25%. Province-level region, iron pot use, family size, ethnicity, age and gender of children and severity of maternal anemia were important determinants of the severity of childhood anemia. These findings have some important implications for health policy decision for childhood anemia in rural western China.     

The Influence of Malnutrition and Micronutrient Status on Anemic Risk in Children under 3 Years Old in Poor Areas in China

Background

Malnutrition and anemia affect large numbers of young children living in poor areas of China. Multi-micronutrient deficiencies may be related to the prevalence of anemia in different populations, and identifying the risk factors that render children susceptible to anemia is the first step in combating anemia effectively.

Methods

In this cross-sectional study, a total of 1370 children under 3 years old were selected based on probability proportional to size sampling principles from poor counties of China. Basic characteristics data were collected by questionnaire; then anthropometrics and hemoglobin were measured in the field and anemia prevalence evaluated. Venous blood was drawn from children aged 12–35 months (N = 553) to evaluate micronutrient status. Logistic regression was used to identify the risk factors for children’s anemia.

Results

Among children aged 0–35 months, the prevalence of stunting, low body weight and wasting was 17.5%, 8.6% and 5.1%, respectively, and 25.6% of the children were affected by anemia, with more anemic infants and younger children than older children (P <0.01). There were 26.5%, 12.8%, 14.1% and 20.0% of the children aged 12–35 months affected by iron deficiency, vitamin D deficiency, folic acid deficiency and vitamin B₁₂ deficiency, respectively. For children aged 0–11 months who were breastfed, the mothers’ anemic status was the only factor associated with the child’s anemia (OR = 2.6; 95% CI: 1.2–5.4, P < 0.05). For children aged 12–35 months, multivariate logistic regression indicated that anemia was significantly associated with iron and vitamin B₁₂ deficiency (OR = 5.3; 95% CI: 1.9–14.5, P < 0.01) and monotonous diet (OR = 2.3; 95% CI: 1.1–4.7, P < 0.05) after adjusting for age and gender.

Conclusion

The prevalence of anemia was higher in children under 2 years old and requires urgent intervention. An effective intervention strategy should include iron and vitamin B₁₂ supplements_, improving dietary diversity and controlling breastfeeding mothers'' anemia.     

Determinants of Iron Deficiency Anemia in a Cohort of Children Aged 6-71 Months Living in the Northeast of Minas Gerais,Brazil

Iron deficiency anemia is one of the most common nutritional disorders worldwide. The aim was to identify the prevalence and incidence of anemia in children and to identify predictors of this condition, including intestinal parasites, social, nutritional and environmental factors, and comorbidities. A population-based cohort study was conducted in a sample of 414 children aged 6–71 months living in Novo Cruzeiro in the Minas Gerais State. Data were collected in 2008 and 2009 by interview and included socio-economic and demographic information about the children and their families. Blood samples were collected for testing of hemoglobin, ferritin and C-reactive protein. Anthropometric measurements and parasitological analyses of fecal samples were performed. To identify risk factors associated with anemia multivariate analyses were performed using the generalized estimating equations (GEE). In 2008 and 2009, respectively, the prevalence rates of anemia were 35.9% (95%CI 31.2–40.8) and 9.8% (95%CI 7.2–12.9), the prevalence rates of iron deficiency were 18.4% (95%CI 14.7–22.6) and 21.8% (95%CI 17.8–26.2), and the incidence rates of anemia and iron deficiency were 3.2% and 21.8%. The following risk factors associated with anemia were: iron deficiency (OR = 3.2; 95%CI 2.0-.5.3), parasitic infections (OR = 1.9; 95%CI 1.2–2.8), being of risk of or being a low length/height-for-age (OR = 2.1; 95%CI 1.4–3.2), and lower retinol intake (OR = 1.7; 95%CI 1.1–2.7), adjusted over time. Nutritional factors, parasitic infections and chronic malnutrition were identified as risk factors for anemia. These factors can be verified in a chronic process and have been classically described as risk factors for these conditions.     

Rapid Detection and Identification of Human Hookworm Infections through High Resolution Melting (HRM) Analysis

Background

Hookworm infections are still endemic in low and middle income tropical countries with greater impact on the socioeconomic and public health of the bottom billion of the world''s poorest people. In this study, a real-time polymerase chain reaction (PCR) coupled with high resolution melting-curve (HRM) analysis was evaluated for an accurate, rapid and sensitive tool for species identification focusing on the five human hookworm species.

Methods

Real-time PCR coupled with HRM analysis targeting the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA as the genetic marker was used to identify and distinguish hookworm species in human samples. Unique and distinct characteristics of HRM patterns were produced for each of the five hookworm species. The melting curves were characterized by peaks of 79.24±0.05°C and 83.00±0.04°C for Necator americanus, 79.12±0.10°C for Ancylostoma duodenale, 79.40±0.10°C for Ancylostoma ceylanicum, 79.63±0.05°C for Ancylostoma caninum and 79.70±0.14°C for Ancylostoma braziliense. An evaluation of the method''s sensitivity and specificity revealed that this assay was able to detect as low as 0.01 ng/µl hookworm DNA and amplification was only recorded for hookworm positive samples.

Conclusion

The HRM assay developed in this study is a rapid and straightforward method for the diagnosis, identification and discrimination of five human hookworms. This assay is simple compared to other probe-based genotyping methods as it does not require multiplexing, DNA sequencing or post-PCR processing. Therefore, this method offers a new alternative for rapid detection of human hookworm species.     

Molecular Detection of Ancylostoma duodenale,Ancylostoma ceylanicum,and Necator americanus in Humans in Northeastern and Southern Thailand

The 2 principal species of hookworms infecting humans are Necator americanus and Ancylostoma duodenale. Case studies on zoonotic hookworm infections with Ancylostoma ceylanicum and/or Ancylostoma caninum are known mainly from Asian countries. Of these 2 zoonotic species, only A. ceylanicum can develop to adulthood in humans. In the present study, we report a molecular-based survey of human hookworm infections present in southern and northeastern Thailand. Thirty larval hookworm samples were obtained from fecal agar plate cultures of 10 patients in northeastren Thailand and 20 in southern Thailand. Partial ITS1, 5.8S, and ITS2 regions of the ribosomal DNA genes were amplified using PCR. The amplicons were sequenced, aligned, and compared with other hookworm sequences in GenBank database. The results showed that, in Thailand, N. americanus is more prevalent than Ancylostoma spp. and is found in both study areas. Sporadic cases of A. ceylanicum and A. duodenale infection were seen in northeastern Thailand.     

Necator americanus and helminth co-infections: further down-modulation of hookworm-specific type 1 immune responses

Background

Helminth co-infection in humans is common in tropical regions of the world where transmission of soil-transmitted helminths such as Ascaris lumbricoides, Trichuris trichiura, and the hookworms Necator americanus and Ancylostoma duodenale as well as other helminths such as Schistosoma mansoni often occur simultaneously.

Methodology

We investigated whether co-infection with another helminth(s) altered the human immune response to crude antigen extracts from either different stages of N. americanus infection (infective third stage or adult) or different crude antigen extract preparations (adult somatic and adult excretory/secretory). Using these antigens, we compared the cellular and humoral immune responses of individuals mono-infected with hookworm (N. americanus) and individuals co-infected with hookworm and other helminth infections, namely co-infection with either A. lumbricoides, Schistosoma mansoni, or both. Immunological variables were compared between hookworm infection group (mono- versus co-infected) by bootstrap, and principal component analysis (PCA) was used as a data reduction method.

Conclusions

Contrary to several animal studies of helminth co-infection, we found that co-infected individuals had a further downmodulated Th1 cytokine response (e.g., reduced INF-γ), accompanied by a significant increase in the hookworm-specific humoral immune response (e.g. higher levels of IgE or IgG4 to crude antigen extracts) compared with mono- infected individuals. Neither of these changes was associated with a reduction of hookworm infection intensity in helminth co-infected individuals. From the standpoint of hookworm vaccine development, these results are relevant; i.e., the specific immune response to hookworm vaccine antigens might be altered by infection with another helminth.     

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.     

Complex Interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border

Background

Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.

Methodology

Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed.

Principal Findings

Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23–0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11–0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06–2.60) and anaemia (AOR: 2.41, 95% CI: 1.18–4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02–3.23).

Conclusion/Significance

A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy.     

Diagnostic accuracy of Kato-Katz and FLOTAC for assessing anthelmintic drug efficacy

Background

Sensitive diagnostic tools are required for an accurate assessment of prevalence and intensity of helminth infections in areas undergoing regular deworming, and for monitoring anthelmintic drug efficacy. We compared the diagnostic accuracy of the Kato-Katz and FLOTAC techniques in the frame of a drug efficacy trial.

Methodology/Principal Findings

Stool samples from 343 Zanzibari children were subjected to duplicate Kato-Katz thick smears and the FLOTAC basic technique in a baseline screening in early 2009. The FLOTAC showed a higher sensitivity than the Kato-Katz method for the diagnosis of Trichuris trichiura (95% vs. 88%, p = 0.012) and Ascaris lumbricoides (88% vs. 68%, p = 0.098), but a lower sensitivity for hookworm diagnosis (54% vs. 81%, p = 0.006). Considering the combined results from both methods as ‘gold’ standard, the prevalences of T. trichiura, hookworm and A. lumbricoides were 71% (95% confidence interval (CI): 66–75%), 22% (95% CI: 17–26%) and 12% (95% CI: 8–15%), respectively. At follow-up, 3–5 weeks after 174 among the 269 re-examined children were administered anthelmintic drugs, we observed cure rates (CRs) against A. lumbricoides, hookworm and T. trichiura of 91% (95% CI: 80–100%), 61% (95% CI: 48–75%) and 41% (95% CI: 34–49%), respectively, when using the Kato-Katz method. FLOTAC revealed lower CRs against A. lumbricoides (83%, 95% CI: 67–98%) and T. trichiura (36%, 95% CI: 29–43%), but a higher CR against hookworm (69%, 95% CI: 57–82%). These differences, however, lacked statistical significance. Considerable differences were observed in the geometric mean fecal egg counts between the two methods with lower egg reduction rates (ERRs) determined by FLOTAC.

Conclusion/Significance

Our results suggest that the FLOTAC technique, following further optimization, might become a viable alternative to the Kato-Katz method for anthelmintic drug efficacy studies and for monitoring and evaluation of deworming programs. The lower CRs and ERRs determined by FLOTAC warrant consideration and could strategically impact future helminth control programs.     

The Association of Parasitic Infections in Pregnancy and Maternal and Fetal Anemia: A Cohort Study in Coastal Kenya

Background

Relative contribution of these infections on anemia in pregnancy is not certain. While measures to protect pregnant women against malaria have been scaling up, interventions against helminthes have received much less attention. In this study, we determine the relative impact of helminthes and malaria on maternal anemia.

Methods

A prospective observational study was conducted in coastal Kenya among a cohort of pregnant women who were recruited at their first antenatal care (ANC) visit and tested for malaria, hookworm, and other parasitic infections and anemia at enrollment. All women enrolled in the study received presumptive treatment with sulfadoxine-pyrimethamine, iron and multi-vitamins and women diagnosed with helminthic infections were treated with albendazole. Women delivering a live, term birth, were also tested for maternal anemia, fetal anemia and presence of infection at delivery.

Principal Findings

Of the 706 women studied, at the first ANC visit, 27% had moderate/severe anemia and 71% of women were anemic overall. The infections with highest prevalence were hookworm (24%), urogenital schistosomiasis (17%), trichuria (10%), and malaria (9%). In adjusted and unadjusted analyses, moderate/severe anemia at first ANC visit was associated with the higher intensities of hookworm and P. falciparum microscopy-malaria infections. At delivery, 34% of women had moderate/severe anemia and 18% of infants'' cord hemoglobin was consistent with fetal anemia. While none of the maternal infections were significantly associated with fetal anemia, moderate/severe maternal anemia was associated with fetal anemia.

Conclusions

More than one quarter of women receiving standard ANC with IPTp for malaria had moderate/severe anemia in pregnancy and high rates of parasitic infection. Thus, addressing the role of co-infections, such as hookworm, as well as under-nutrition, and their contribution to anemia is needed.     

Efficacy of single-dose and triple-dose albendazole and mebendazole against soil-transmitted helminths and Taenia spp.: a randomized controlled trial

Background

The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People''s Republic of China.

Methodology/Principal findings

The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed.Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them.

Conclusions/Significance

Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted.

Trial Registration

www.controlled-trials.com ISRCTN47375023     

Severe Anemia in Papua New Guinean Children from a Malaria-Endemic Area: A Case-Control Etiologic Study

Background

There are few detailed etiologic studies of severe anemia in children from malaria-endemic areas and none in those countries with holoendemic transmission of multiple Plasmodium species.

Methodology/Principal Findings

We examined associates of severe anemia in 143 well-characterized Papua New Guinean (PNG) children aged 0.5–10 years with hemoglobin concentration <50 g/L (median [inter-quartile range] 39 [33]–[44] g/L) and 120 matched healthy children (113 [107–119] g/L) in a case-control cross-sectional study. A range of socio-demographic, behavioural, anthropometric, clinical and laboratory (including genetic) variables were incorporated in multivariate models with severe anemia as dependent variable. Consistent with a likely trophic effect of chloroquine or amodiaquine on parvovirus B19 (B19V) replication, B19V PCR/IgM positivity had the highest odds ratio (95% confidence interval) of 75.8 (15.4–526), followed by P. falciparum infection (19.4 (6.7–62.6)), vitamin A deficiency (13.5 (5.4–37.7)), body mass index-for-age z-score <2.0 (8.4 (2.7–27.0)) and incomplete vaccination (2.94 (1.3–7.2)). P. vivax infection was inversely associated (0.12 (0.02–0.47), reflecting early acquisition of immunity and/or a lack of reticulocytes for parasite invasion. After imputation of missing data, iron deficiency was a weak positive predictor (6.4% of population attributable risk).

Conclusions/Significance

These data show that severe anemia is multifactorial in PNG children, strongly associated with under-nutrition and certain common infections, and potentially preventable through vitamin A supplementation and improved nutrition, completion of vaccination schedules, and intermittent preventive antimalarial treatment using non-chloroquine/amodiaquine-based regimens.     

Severe Infections in HIV-Exposed Uninfected Infants Born in a European Country

Background

Several studies indicate that HIV-exposed uninfected (HEU) children have a high infectious morbidity. We previously reported an increased incidence of group B streptococcus (GBS) infections in HEU infants born in Belgium.

Methods

This study was undertaken to evaluate the incidence and risk factors of all cause severe infections in HEU infants born in Belgium between 1985 and 2006, including the pre-antiretroviral (ARV) prophylaxis era (1985 to 1994). The medical charts of 537 HEU infants followed in a single center were reviewed.

Results

The incidence rate of severe infections during the first year of life was 16.8/100 HEU infant-years. The rates of invasive S. pneumoniae (0.62/100 infant-years) and GBS infections (1.05/100 infant-years) were, respectively, 4 and 13-fold higher in HEU infants than in the general infant population. Preterm birth was a risk factor for severe infections in the neonatal period (aOR = 21.34, 95%CI:7.12–63.93) and post-neonatal period (aHR = 3.00, 95%CI:1.53–5.88). As compared to the pre-ARV prophylaxis era, infants born in the ARV prophylaxis era (i.e., after April 1994) had a greater risk of severe infections (aHR = 2.93; 95%CI:1.07–8.05). This risk excess was present in those who received ARV prophylaxis (aHR 2.01, 95%CI 0.72–5.65) and also in those born in the ARV prophylaxis era who did not benefit from ARV prophylaxis as a result of poor access to antenatal care or lack of compliance (aHR 3.06, 95%CI 0.88–10.66).

Conclusions

In HEU infants born in an industrialized country, preterm birth and being born during the ARV prophylaxis era were risk factors of severe infections throughout the first year of life. These observations have important implications for the clinical management of HIV-infected mothers and their infants.