Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages

BackgroundThe association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women.MethodsWe sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated.FindingsHousehold and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001).ConclusionCommunity-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes.     

Two-stage lot quality assurance sampling framework for monitoring and evaluation of neglected tropical diseases,allowing for imperfect diagnostics and spatial heterogeneity

BackgroundMonitoring and evaluation (M&E) is a key component of large-scale neglected tropical diseases (NTD) control programs. Diagnostic tests deployed in these M&E surveys are often imperfect, and it remains unclear how this affects the population-based program decision-making.MethodologyWe developed a 2-stage lot quality assurance sampling (LQAS) framework for decision-making that allows for both imperfect diagnostics and spatial heterogeneity of infections. We applied the framework to M&E of soil-transmitted helminth control programs as a case study. For this, we explored the impact of the diagnostic performance (sensitivity and specificity), spatial heterogeneity (intra-cluster correlation), and survey design on program decision-making around the prevalence decisions thresholds recommended by WHO (2%, 10%, 20% and 50%) and the associated total survey costs.Principal findingsThe survey design currently recommended by WHO (5 clusters and 50 subjects per cluster) may lead to incorrect program decisions around the 2% and 10% prevalence thresholds, even when perfect diagnostic tests are deployed. To reduce the risk of incorrect decisions around the 2% prevalence threshold, including more clusters (≥10) and deploying highly specific diagnostic methods (≥98%) are the most-cost saving strategies when spatial heterogeneity is moderate-to-high (intra-cluster correlation >0.017). The higher cost and lower throughput of improved diagnostic tests are compensated by lower required sample sizes, though only when the cost per test is <6.50 US$ and sample throughput is ≥3 per hour.Conclusion/SignificanceOur framework provides a means to assess and update M&E guidelines and guide product development choices for NTD. Using soil-transmitted helminths as a case study, we show that current M&E guidelines may severely fall short, particularly in low-endemic and post-control settings. Furthermore, specificity rather than sensitivity is a critical parameter to consider. When the geographical distribution of an NTD within a district is highly heterogeneous, sampling more clusters (≥10) may be required.     

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     

Soil-transmitted helminthiasis in China: A national survey in 2014-2015

BackgroundBased on two national surveys, the prevalence of soil-transmitted helminthiasis (STH) in China had decreased from 53.58% in 1988–1992 to 19.56% in 2001–2004. To update the epidemiology and characteristics of STH in China, a third national survey was implemented in 2014–2015.Methodology/Principal findingsThis survey covered rural areas in 31 provinces in mainland of China. Multiple-stage stratified cluster sampling was employed, which included three levels (provinces, ecozones and economical levels). Stool samples were collected and the Kato-Katz method was applied for helminth eggs detection. Samples with hookworm eggs were selected and hatched to differentiate the species based on larval morphology. Between June 2014 and May 2015, a total of 484,210 participants from 604 counties were enrolled. The weighted prevalence of STH overall was 4.49% (95% confidential interval (CI): 2.45%-6.53%), including 2.62% (95% CI: 0.86%-4.38%) hookworm infections, 1.36% (95% CI: 0.49%-2.23%) ascariasis, and 1.02% (95% CI: 0.15%-1.89%) trichuriasis. The estimated population infected was 29.12 million (95% CI: 15.88 million-42.32 million) for all STH; 16.97 million (95% CI: 5.57 million-28.39 million) for hookworm infections; 8.83 million (95% CI: 3.18 million-14.45 million) for ascariasis; and 6.60 million (95% CI: 0.97 million-12.25 million) for trichuriasis. Overall, the prevalence of ascariasis and trichuriasis was relatively high in children, while hookworm infections were more common in the older population, especially those over 60. STH was highly prevalent in western China, and moderately in central areas, but low in eastern and northern regions. Out of 3,579 hookworm cases with species differentiation, 479 cases (13.38%) were infected with only Ancylostoma spp., 2,808 cases (78.46%) with only Necator americanus, and another 292 cases (8.16%) with both species.Conclusions/SignificanceThis survey demonstrated the continuous decrease of STH in rural China. However, endemicity still prevails in the western areas of the country. Hookworm, especially N. americanus, is becoming the predominant species. Older farmers in western China should be prioritized for control due to the high prevalence of hookworm.     

Factors associated with soil-transmitted helminths infection in Benin: Findings from the DeWorm3 study

BackgroundDespite several years of school-based MDA implementation, STH infections remain an important public health problem in Benin, with a country-wide prevalence of 20% in 2015. The DeWorm3 study is designed to assess the feasibility of using community-based MDA with albendazole to interrupt the transmission of STH, through a series of cluster-randomized trials in Benin, India and Malawi. We used the pre-treatment baseline survey data to describe and analyze the factors associated with STH infection in Comé, the study site of the DeWorm3 project in Benin. These data will improve understanding of the challenges that need to be addressed in order to eliminate STH as a public health problem in Benin.MethodsBetween March and April 2018, the prevalence of STH (hookworm spp., Ascaris and Trichuris trichiura) was assessed by Kato-Katz in stool samples collected from 6,153 residents in the community of Comé, Benin using a stratified random sampling procedure. A standardized survey questionnaire was used to collect information from individual households concerning factors potentially associated with the presence and intensity of STH infections in pre-school (PSAC, aged 1–4), school-aged children (SAC, aged 5–14) and adults (aged 15 and above). Multilevel mixed-effects models were used to assess associations between these factors and STH infection.ResultsThe overall prevalence of STH infection was 5.3%; 3.2% hookworm spp., 2.1% Ascaris lumbricoides and 0.1% Trichuris. Hookworm spp. were more prevalent in adults than in SAC (4.4% versus 2.0%, respectively; p = 0.0001) and PSAC (4.4% versus 1.0%, respectively; p<0.0001), whilst Ascaris lumbricoides was more prevalent in SAC than in adults (3.0% versus 1.7%, respectively; p = 0.004). Being PSAC (adjusted Odds Ratio (aOR) = 0.2, p< 0.001; adjusted Infection Intensity Ratio (aIIR) = 0.1, p<0.001) or SAC (aOR = 0.5, p = 0.008; aIIR = 0.3, p = 0.01), being a female (aOR = 0.6, p = 0.004; aIIR = 0.3, p = 0.001), and having received deworming treatment the previous year (aOR = 0.4, p< 0.002; aIIR = 0.2, p<0.001) were associated with a lower prevalence and intensity of hookworm infection. Lower income (lowest quintile: aOR = 5.0, p<0.001, 2^nd quintile aOR = 3.6, p = 0.001 and 3^rd quintile aOR = 2.5, p = 0.02), being a farmer (aOR = 1.8, p = 0.02), medium population density (aOR = 2.6, p = 0.01), and open defecation (aOR = 0.5, p = 0.04) were associated with a higher prevalence of hookworm infection. Lower education—no education, primary or secondary school- (aIIR = 40.1, p = 0.01; aIIR = 30.9, p = 0.02; aIIR = 19.3, p = 0.04, respectively), farming (aIIR = 3.9, p = 0.002), natural flooring (aIIR = 0.2, p = 0.06), peri-urban settings (aIIR = 6.2, 95%CI 1.82–20.90, p = 0.003), and unimproved water source more than 30 minutes from the household (aIIR = 13.5, p = 0.02) were associated with a higher intensity of hookworm infection. Improved and unshared toilet was associated with lower intensity of hookworm infections (aIIR = 0.2, p = 0.01). SAC had a higher odds of Ascaris lumbricoides infection than adults (aOR = 2.0, p = 0.01) and females had a lower odds of infection (aOR = 0.5, p = 0.02).ConclusionHookworm spp. are the most prevalent STH in Comé, with a persistent reservoir in adults that is not addressed by current control measures based on school MDA. Expanding MDA to target adults and PSAC is necessary to substantially impact population prevalence, particularly for hookworm.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03014167","term_id":"NCT03014167"}}NCT03014167.     

Prevalence,risk factors and health consequences of soil-transmitted helminth infection on the Bijagos Islands,Guinea Bissau: A community-wide cross-sectional study

Soil-transmitted helminths (STH) are endemic and widespread across Sub-Saharan Africa. A community wide soil-transmitted helminth (STH) prevalence survey was performed on the island of Bubaque in Guinea-Bissau using both Kato-katz microscopy and qPCR methodology. Predictors of infection and morbidity indicators were identified using multivariable logistic regression, and diagnostic methods were compared using k statistics. Among 396 participants, prevalence of STH by microscopy was 23.2%, hookworm was the only species identified by this method and the mean infection intensity was 312 eggs per gram. qPCR analysis revealed an overall prevalence of any STH infection of 47.3%, with the majority A. duodenale (32.3%), followed by N. americanus (15.01%) and S. stercoralis (13.2%). A. lumbricoides, and T. trichiura infections were negligible, with a prevalence of 0.25% each. Agreement between diagnostic tests was k = 0.22, interpreted as fair agreement, and infection intensity measured by both methods was only minimally correlated (R_s = -0.03). STH infection overall was more common in females and adults aged 31–40. STH infection was associated with open defaecation, low socio-economic status and further distance to a water-source. The prevalence of anaemia (defined as a binary outcome by the WHO standards for age and sex) was 69.1%, and 44.2% of children were malnourished according to WHO child growth standards. Hookworm infection intensity by faecal egg count showed no statistically significant association with age (R_s 0.06) but S. Stercoralis infection intensity by qPCR cycle threshold was higher in pre-school aged children (R_s = 0.30, p-value 0.03) There was no statistically significant association between STH infection and anaemia (OR 1.0 p = 0.8), stunting (OR 1.9, p-value 0.5) and wasting (OR 2.0, p-value 0.2) in children. This study reveals a persistent reservoir of STH infection across the community, with high rates of anaemia and malnutrition, despite high-coverage of mebendazole mass-drug administration in pre-school children. This reflects the need for a new strategy to soil-transmitted helminth control, to reduce infections and ultimately eliminate transmission.     

Comparison of the Kato-Katz and FLOTAC techniques for the diagnosis of soil-transmitted helminth infections

Decisions on individual or community treatment and evaluation of chemotherapy based control programs depend on parasitological diagnostic techniques. The aim of this study was to compare the accuracy of a single Kato-Katz thick smear and a single FLOTAC for the determination of the prevalence and intensity of soil-transmitted helminth infections. A total of 271 faecal specimens were collected from schoolchildren in Ethiopia, and microscopically examined using the Kato-Katz method (41.7 mg stool per slide) and the FLOTAC technique. The combined results from the Kato-Katz and FLOTAC methods were used as diagnostic 'gold' standard for reference in the analysis. Agreement between the two methods showed kappa values of 0.74, 0.73 and 0.28 for Ascaris lumbricoides, Trichuris trichiura and hookworm, respectively. A single FLOTAC revealed significantly more infections than a single Kato-Katz for each of the three soil-transmitted helminths (p<0.01). The sensitivities of a single Kato-Katz for diagnosis of T. trichiura, A. lumbricoides and hookworm infections were 76.6%, 67.8% and 19.6%, respectively, while the sensitivity of FLOTAC was 100% for all the three soil-transmitted helminth species. A single Kato-Katz yielded considerably higher mean faecal egg counts (FECs) (729.1, 145.2 and 60.7 eggs per gram of stool (EPG) for A. lumbricoides, T. trichiura and hookworm, respectively) compared with a single FLOTAC (142.5, 54.5 and 14.6 EPG, respectively) (p<0.05). Our study confirms that a single FLOTAC is more sensitive than a single Kato-Katz for the diagnosis of soil-transmitted helminth infections, but results in lower FECs. Further standardization and validation are still required in different epidemiological settings with varying levels of intensity of infections before recommending FLOTAC for large-scale community diagnosis.     

Burden of soil-transmitted helminth infection in pregnant refugees and migrants on the Thailand-Myanmar border: Results from a retrospective cohort

BackgroundSoil-transmitted helminth (STH) infections are widespread in tropical and subtropical regions. While many STH infections are asymptomatic, vulnerable populations such as pregnant women face repercussions such as aggravation of maternal anaemia. However, data on prevalence and the effect of STH infections in pregnancy are limited. The aim of this analysis was to describe the burden of STH infections within and between populations of pregnant women from a local refugee camp to a mobile migrant population, and to explore possible associations between STH infection and pregnancy outcomes.MethodologyThis is a retrospective review of records from pregnant refugee and migrant women who attended Shoklo Malaria Research Unit antenatal care (ANC) clinics along the Thailand-Myanmar border between July 2013 and December 2017. Inclusion was based on provision of a stool sample during routine antenatal screening. A semi-quantitative formalin concentration method was employed for examination of faecal samples. The associations between STH mono-infections and maternal anaemia and pregnancy outcomes (i.e., miscarriage, stillbirth, preterm birth, and small for gestational age) were estimated using regression analysis.Principal findingsOverall, 12,742 pregnant women were included, of whom 2,702 (21.2%) had a confirmed infection with either Ascaris lumbricoides, hookworm, Trichuris trichiura, or a combination of these. The occurrence of STH infections in the refugee population (30.8%; 1,246/4,041) was higher than in the migrant population (16.7%; 1,456/8,701). A. lumbricoides was the predominant STH species in refugees and hookworm in migrants. A. lumbricoides and hookworm infection were associated with maternal anaemia at the first ANC consultation with adjusted odds ratios of 1.37 (95% confidence interval (CI) 1.08–1.72) and 1.65 (95% CI 1.19–2.24), respectively. Pregnant women with A. lumbricoides infection were less likely to miscarry when compared to women with negative stool samples (adjusted hazard ratio 0.63, 95% CI 0.48–0.84). STH infections were not significantly associated with stillbirth, preterm birth or being born too small for gestational age. One in five pregnant women in this cohort had STH infection. Association of STH infection with maternal anaemia, in particular in the event of late ANC enrolment, underlines the importance of early detection and treatment of STH infection. A potential protective effect of A. lumbricoides infection on miscarriage needs confirmation in prospective studies.     

Morphological and Molecular Diagnosis of Necator americanus and Ancylostoma ceylanicum Recovered from Villagers in Northern Cambodia

Human hookworm infections caused by adult Ancylostoma spp. and Necator americanus are one of the most important tropical diseases. We performed a survey of intestinal helminths using the Kato-Katz fecal examination technique targeting 1,156 villagers residing in 2 northern provinces (Preah Vihear and Stung Treng) of Cambodia in 2018. The results revealed a high overall egg positive rate of intestinal helminths (61.9%), and the egg positive rate of hookworms was 11.6%. Nine of the hookworm egg positive cases in Preah Vihear Province were treated with 5–10 mg/kg pyrantel pamoate followed by purging with magnesium salts, and a total of 65 adult hookworms were expelled in diarrheic stools. The adult hookworms were analyzed morphologically and molecularly to confirm the species. The morphologies of the buccal cavity and dorsal rays on the costa were observed with a light microscope, and the nucleotide sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were analyzed. The majority of the hookworm adults (90.7%) were N. americanus, whereas the remaining 9.3% were Ancylostoma ceylanicum, a rare hookworm species infecting humans. The results revealed a high prevalence of hookworm infections among people in a northern part of Cambodia, suggesting the necessity of a sustained survey combined with control measures against hookworm infections.     

Diagnosis of soil-transmitted helminths using the Kato-Katz technique: What is the influence of stirring,storage time and storage temperature on stool sample egg counts?

BackgroundSoil-transmitted helminths infect about one fifth of the world’s population and have a negative impact on health. The Kato-Katz technique is the recommended method to detect soil-transmitted helminth eggs in stool samples, particularly in programmatic settings. However, some questions in its procedure remain. Our study aimed to investigate the effect of storage time, storage temperature and stirring of stool samples on fecal egg counts (FECs).Methodology/Principal findingsIn the framework of a clinical trial on Pemba Island, United Republic of Tanzania, 488 stool samples were collected from schoolchildren. These samples were evaluated in three experiments. In the first experiment (n = 92), two Kato-Katz slides were prepared from the same stool sample, one was stored at room temperature, the other in a refrigerator for 50 hours, and each slide was analyzed at nine time points (20, 50, 80, 110, 140 minutes, 18, 26, 42 and 50 hours). In the second experiment (n = 340), whole stool samples were split into two, one part was stored at room temperature, and the other part was put in a refrigerator for 48 hours. From each part one Kato-Katz slide was prepared and analyzed at three time points over two days (0, 24 and 48 hours). In the third experiment (n = 56), whole stool samples where stirred for 15 seconds six times and at each time point a Kato-Katz slide was prepared and analyzed.Mean hookworm FECs of Kato-Katz slides stored at room temperature steadily decreased following slide preparation. After two hours, mean hookworm FECs decreased from 22 to 16, whereas no reduction was observed if Kato-Katz slides were stored in the refrigerator (19 vs 21). The time x storage interaction effect was statistically significant (coefficient 0.26, 95% CI: 0.17 to 0.35, p < 0.0001). After 24 hours mean hookworm FECs dropped close to zero, irrespective of the storage condition. Whole stool samples stored at room temperature for one day resulted in a mean hookworm FEC decrease of 23% (p < 0.0001), compared to a 13% reduction (p < 0.0001) if samples were stored in the refrigerator. Fecal egg counts of A. lumbricoides and T. trichiura remained stable over time regardless of storage temperature of whole stool samples. Finally, we found a significant reduction of the variation of hookworm and T. trichiura eggs with increasing rounds of stirring the sample, but not for A. lumbricoides. For hookworm we observed a simultaneous decrease in mean FECs, making it difficult to draw recommendations on stirring samples.Conclusions/SignificanceOur findings suggest that stool samples (i) should be analyzed on the day of collection and (ii) should be analyzed between 20–30 minutes after slide preparation; if that is not possible, Kato-Katz slides can be stored in a refrigerator for a maximum of 110 minutes.     

Ancylostoma ceylanicum infections in humans in Vietnam

Ancylostoma ceylanicum is recognized as the only zoonotic hookworm species that is able to mature into adult stage in the human intestine. While human infections caused by this hookworm species have been reported from neighboring countries and this hookworm is prevalent in dogs in Vietnam, human infection has never been reported in Vietnam. The present study, therefore, aimed to identify human infections with A. ceylanicum in Vietnam. A total of 526 fecal samples from the residents in Long An Province were collected and the presence of hookworm eggs was detected by the Kato-Katz method. The results indicated that the overall prevalence of human hookworm infection was 85/526 (16.2%). After filter paper culture, 3rd stage larvae were successfully obtained from 48 egg-positive samples. The larvae were identified for their species using semi-nested PCR-RLFP on the cox1 gene. As a result, two hookworm species were confirmed; single species infections with Necator americanus or A. ceylanicum, and mixed infections with both species were found in 47.9%, 31.3%, and 20.8% of the samples, respectively.     

Long-term weekly iron-folic acid and de-worming is associated with stabilised haemoglobin and increasing iron stores in non-pregnant women in Vietnam

Background

The prevalence of anaemia and iron deficiency in women remains high worldwide. WHO recommends weekly iron-folic acid supplementation where anaemia rates in non-pregnant women of reproductive age are higher than 20%. In 2006, a demonstration project consisting of weekly iron-folic acid supplementation and regular de-worming was set up in two districts in a northern province in Vietnam where anaemia and hookworm rates were 38% and 76% respectively. In 2008 the project was expanded to all districts in the province, targeting some 250,000 women. The objectives of this study were to: 1) examine changes in haemoglobin, iron stores and soil transmitted helminth infection prevalence over three years and 2) assess women''s access to and compliance with the intervention.

Methods and Findings

The study was a semi-cross-sectional, semi-longitudinal panel design with a baseline survey, three impact surveys at three-, twelve- and thirty months after commencement of the intervention, and three compliance surveys after ten weeks, eighteen and thirty six months.

Results

After thirty months, mean haemoglobin stabilised at 130.3 g/L, an increase of 8.2 g/L from baseline, and mean serum ferritin rose from 23.9 µg/L to 52 µg/L. Hookworm prevalence fell from 76% to 22% over the same period. After thirty six months, 81% of the target population were receiving supplements and 87% were taking 75% or more of the supplements they received.

Conclusions

Weekly iron-folic acid supplementation and regular de-worming was effective in significantly and sustainably reducing the prevalence of anaemia and soil transmitted helminth infections and high compliance rates were maintained over three years.     

Egg excretion indicators for the measurement of soil-transmitted helminth response to treatment

BackgroundPeriodic administration of anthelmintic drugs is a cost-effective intervention for morbidity control of soil-transmitted helminth (STH) infections. However, with programs expanding, drug pressure potentially selecting for drug-resistant parasites increases. While monitoring anthelmintic drug efficacy is crucial to inform country control program strategies, different factors must be taken into consideration that influence drug efficacy and make it difficult to standardize treatment outcome measures. We aimed to identify suitable approaches to assess and compare the efficacy of different anthelmintic treatments.MethodologyWe built an individual participant-level database from 11 randomized controlled trials and two observational studies in which subjects received single-agent or combination therapy, or placebo. Eggs per gram of stool were calculated from egg counts at baseline and post-treatment. Egg reduction rates (ERR; based on mean group egg counts) and individual-patient ERR (iERR) were utilized to express drug efficacy and analyzed after log-transformation with a linear mixed effect model. The analyses were separated by follow-up duration (14–21 and 22–45 days) after drug administration.Principal findingsThe 13 studies enrolled 5,759 STH stool-positive individuals; 5,688 received active medication or placebo contributing a total of 11,103 STH infections (65% had two or three concurrent infections), of whom 3,904 (8,503 infections) and 1,784 (2,550 infections) had efficacy assessed at 14–21 days and 22–45 days post-treatment, respectively. Neither the number of helminth co-infections nor duration of follow-up affected ERR for any helminth species. The number of participants treated with single-dose albendazole was 689 (18%), with single-dose mebendazole 658 (17%), and with albendazole-based co-administrations 775 (23%). The overall mean ERR assessed by day 14–21 for albendazole and mebendazole was 94.5% and 87.4%, respectively on Ascaris lumbricoides, 86.8% and 40.8% on hookworm, and 44.9% and 23.8% on Trichuris trichiura. The World Health Organization (WHO) recommended criteria for efficacy were met in 50%, 62%, and 33% studies of albendazole for A. lumbricoides, T. trichiura, and hookworm, respectively and 25% of mebendazole studies. iERR analyses showed similar results, with cure achieved in 92% of A. lumbricoides-infected subjects treated with albendazole and 93% with mebendazole; corresponding figures for hookworm were 70% and 17%, and for T. trichiura 22% and 20%.Conclusions/significanceCombining the traditional efficacy assessment using group averages with individual responses provides a more complete picture of how anthelmintic treatments perform. Most treatments analyzed fail to meet the WHO minimal criteria for efficacy based on group means. Drug combinations (i.e., albendazole-ivermectin and albendazole-oxantel pamoate) are promising treatments for STH infections.     

Malaria and Helminth Co-Infections in School and Preschool Children: A Cross-Sectional Study in Magu District,North-Western Tanzania

Background

Malaria, schistosomiasis and soil transmitted helminth infections (STH) are important parasitic infections in Sub-Saharan Africa where a significant proportion of people are exposed to co-infections of more than one parasite. In Tanzania, these infections are a major public health problem particularly in school and pre-school children. The current study investigated malaria and helminth co-infections and anaemia in school and pre-school children in Magu district, Tanzania.

Methodology

School and pre-school children were enrolled in a cross-sectional study. Stool samples were examined for Schistosoma mansoni and STH infections using Kato Katz technique. Urine samples were examined for Schistosoma haematobium using the urine filtration method. Blood samples were examined for malaria parasites and haemoglobin concentrations using the Giemsa stain and Haemoque methods, respectively.

Principal Findings

Out of 1,546 children examined, 1,079 (69.8%) were infected with one or more parasites. Malaria-helminth co-infections were observed in 276 children (60% of all children with P. falciparum infection). Malaria parasites were significantly more prevalent in hookworm infected children than in hookworm free children (p = 0.046). However, this association was non-significant on multivariate logistic regression analysis (OR = 1.320, p = 0.064). Malaria parasite density decreased with increasing infection intensity of S. mansoni and with increasing number of co-infecting helminth species. Anaemia prevalence was 34.4% and was significantly associated with malaria infection, S. haematobium infection and with multiple parasite infections. Whereas S. mansoni infection was a significant predictor of malaria parasite density, P. falciparum and S. haematobium infections were significant predictors of anaemia.

Conclusions/Significance

These findings suggest that multiple parasite infections are common in school and pre-school children in Magu district. Concurrent P. falciparum, S. mansoni and S. haematobium infections increase the risk of lower Hb levels and anaemia, which in turn calls for integrated disease control interventions. The associations between malaria and helminth infections detected in this study need further investigation.     

Soil-transmitted helminth infections and nutritional indices among Filipino schoolchildren

BackgroundSoil-transmitted helminth (STH) infections are still prevalent among schoolchildren in the Philippines. We evaluated the risk factors associated with STH and the relationship between STH and nutritional indices among schoolchildren aged 9–10 years in Laguna province, the Philippines.MethodsWe used the baseline data from 40 schools enrolled in a randomised controlled trial of the Magic Glasses Philippines health education package. Data on demographic and socio-economic variables, and STH related knowledge, attitudes and practices, were obtained through a questionnaire. Stool samples were collected and assessed for STH egg presence using the Kato-Katz technique. Haemoglobin levels and height and weight of study participants were also determined. The generalized estimating equations approach was used to construct logistic regression models to assess STH-associated risk factors, and the association between any STH infection and anaemia, child stunting, wasting and being underweight. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000508471).FindingsAmong 1,689 schoolchildren, the prevalence of any STH was 23%. The prevalence of anaemia, stunting, being underweight and wasting was 13%, 20.2%, 19% and 9.5%, respectively. Age, socio-economic status, rural/urban classification of schools and knowledge of STH were significant risk factors for acquiring a STH infection. Moreover, infections with any STH were significantly associated with stunting (P = <0.001) and being underweight (P = <0.003), but not wasting (P = 0.375) or anaemia (P = 0.462) after controlling for confounding covariates.ConclusionThe study findings emphasise the need for sustainable deworming in tandem with other measures such as the provision of health education, improvements in sanitation and hygiene, and nutritional programs in order to control STH infections and improve morbidity outcomes in schoolchildren.Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12616000508471).     

Hookworm-related anaemia among pregnant women: a systematic review

Background and Objectives

Hookworm infection is among the major causes of anaemia in poor communities, but its importance in causing maternal anaemia is poorly understood, and this has hampered effective lobbying for the inclusion of anthelmintic treatment in maternal health packages. We sought to review existing evidence on the role of hookworm as a risk factor for anaemia among pregnant women. We also estimate the number of hookworm infections in pregnant women in sub-Saharan Africa (SSA).

Methods

Structured searches using MEDLINE and EMBASE as well as manual searches of reference lists were conducted, and unpublished data were obtained by contacting authors. Papers were independently reviewed by two authors, and relevant data were extracted. We compared haemoglobin concentration (Hb) according to intensity of hookworm infection and calculated standardised mean differences and 95% confidence intervals. To estimate the number of pregnant women, we used population surfaces and a spatial model of hookworm prevalence.

Findings

One hundred and five reports were screened and 19 were eligible for inclusion: 13 cross-sectional studies, 2 randomised controlled trials, 2 non-randomised treatment trials and 2 observational studies. Comparing uninfected women and women lightly (1–1,999 eggs/gram [epg]) infected with hookworm, the standardised mean difference (SMD) was −0.24 (95% CI: −0.36 to −0.13). The SMD between women heavily (4000+ epg) infected and those lightly infected was −0.57 (95% CI: −0.87 to −0.26). All identified intervention studies showed a benefit of deworming for maternal or child health, but since a variety of outcomes measures were employed, quantitative evaluation was not possible. We estimate that 37.7 million women of reproductive age in SSA are infected with hookworm in 2005 and that approximately 6.9 million pregnant women are infected.

Conclusions

Evidence indicates that increasing hookworm infection intensity is associated with lower haemoglobin levels in pregnant women in poor countries. There are insufficient data to quantify the benefits of deworming, and further studies are warranted. Given that between a quarter and a third of pregnant women in SSA are infected with hookworm and at risk of preventable hookworm-related anaemia, efforts should be made to increase the coverage of anthelmintic treatment among pregnant women.     

Estimating true prevalence of Schistosoma mansoni from population summary measures based on the Kato-Katz diagnostic technique

BackgroundThe prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the ‘true’ prevalence in a population. However, application of these models is complex and there is a need for adjustments that can be done without modeling expertise. This study provides estimates of the ‘true’ S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa.MethodologyAn individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation.Principal findingsOverall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katz to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and ‘true’ prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity.Conclusions/significanceEstimation of ‘true’ S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the ‘true’ prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the ‘true’ 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.     

Risk factors for helminth infections in a rural and a peri-urban setting of the Dongting Lake area, People's Republic of China

Schistosomiasis japonica and soil-transmitted helminthiasis are endemic parasitic diseases in the People’s Republic of China (PR China). As very few studies have reported on the distribution and interaction of multiple species helminth infections, we carried out a comparative study of households in a rural village and a peri-urban setting in the Dongting Lake area of Hunan province in November and December 2006 to determine the extent of single and multiple species infections, the underlying risk factors for infection, and the relationships with clinical manifestations and self-reported morbidity. In each household, stool samples were collected and subjected to the Kato-Katz method for identifying Schistosoma japonicum, Ascaris lumbricoides, hookworm and Trichuris trichiura infections. Clinical examinations were performed and questionnaire surveys conducted at both household and individual subject levels. Complete parasitological, clinical and questionnaire data were obtained for 1,298 inhabitants of the two settings. The overall prevalences of single infections of S. japonicum, A. lumbricoides, hookworm and T. trichiura were 6.5%, 5.5%, 3.0% and 0.8%, respectively; the majority of the infections were of light intensity. We found significant negative associations between wealth and infections with S. japonicum and A. lumbricoides. Clinical manifestations of splenomegaly, hepatomegaly and anaemia were prevalent (9.0%, 3.7% and 10.9%, respectively), the latter two being significantly (P < 0.05) associated with schistosomiasis. Self-reported symptoms were more common among females but there was considerable under-reporting in both sexes when relying only on spontaneous recall. Our findings may guide the design and targeting of a more equitable, comprehensive and integrated parasitic disease control programme in Hunan province and in other areas of PR China.     

Mapping of schistosomiasis and soil-transmitted helminthiases across 15 provinces of Angola

IntroductionSchistosomiasis (SCH) and soil transmitted helminthiases (STH) have been historically recognized as a major public health problem in Angola. However, lack of reliable, country wide prevalence data on these diseases has been a major hurdle to plan and implement programme actions to target these diseases. This study aimed to characterize SCH and STH prevalence and distribution in Angola.MethodsA country wide mapping was conducted in October 2018 (1 province) and from July to December 2019 (14 provinces) in school aged (SAC) children in 15 (of 18) provinces in Angola, using WHO protocols and procedures. A total of 640 schools and an average of 50 students per school (N = 31,938 children) were sampled. Stool and urine samples were collected and processed using the Kato-Katz method and Urine Filtration. Prevalence estimates for SCH and STH infections were calculated for each province and district with 95% confidence intervals. Factors associated with SCH and STH infection, respectively, were explored using multivariable logistic regression accounting for clustering by school.ResultsOf the 131 districts surveyed, 112 (85.5%) are endemic for STH, 30 (22.9%) have a prevalence above 50%, 24 (18.3%) are at moderate risk (prevalence 20%-50%), and 58 (44.3%) are at low risk (<20% prevalence); similarly, 118 (90,1%) of surveyed districts are endemic for any SCH, 2 (1.5%) are at high risk (>50% prevalence), 59 (45.0%) are at moderate risk (10%-50% prevalence), and 57 (43.5%) are at low risk (<10% prevalence). There were higher STH infection rates in the northern provinces of Malanje and Lunda Norte, and higher SCH infection rates in the southern provinces of Benguela and Huila.ConclusionsThis mapping exercise provides essential information to Ministry of Health in Angola to accurately plan and implement SCH and STH control activities in the upcoming years. Data also provides a useful baseline contribution for Angola to track its progress towards the 2030 NTD roadmap targets set by WHO.