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     

Diagnosis of soil-transmitted helminths in the era of preventive chemotherapy: effect of multiple stool sampling and use of different diagnostic techniques

Background

Soil-transmitted helminth infections are common throughout the tropics and subtropics and they disproportionately affect the poorest of the poor. In view of a growing global commitment to control soil-transmitted helminthiasis, there is a need to elucidate the effect of repeated stool sampling and the use of different diagnostic methods in areas targeted for preventive chemotherapy that are characterized by low-infection intensities. In this study, we focused on schoolchildren on Unguja Island, Zanzibar, an area where anthelminthic drugs have been repeatedly administered over the past decade.

Methodology/Principal Findings

Three serial stool samples from each of 342 schoolchildren were examined using the Kato-Katz (K-K), Koga agar plate (KAP), and Baermann (BM) techniques. These methods were used individually or in combination for the diagnosis of Ascaris lumbricoides (K-K), Trichuris trichiura (K-K), hookworm (K-K and KAP), and Strongyloides stercoralis (KAP and BM). The examination of multiple stool samples instead of a single one resulted in an increase of the observed prevalence; e.g., an increase of 161% for hookworm using the K-K method. The diagnostic sensitivity of single stool sampling ranged between 20.7% for BM to detect S. stercoralis and 84.2% for K-K to diagnose A. lumbricoides. Highest sensitivities were observed when different diagnostic approaches were combined. The observed prevalences for T. trichiura, hookworm, A. lumbricoides, and S. stercoralis were 47.9%, 22.5%, 16.5%, and 10.8% after examining 3 stool samples. These values are close to the ‘true’ prevalences predicted by a mathematical model.

Conclusion/Significance

Rigorous epidemiologic surveillance of soil-transmitted helminthiasis in the era of preventive chemotherapy is facilitated by multiple stool sampling bolstered by different diagnostic techniques.     

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.     

Effect of Sanitation on Soil-Transmitted Helminth Infection: Systematic Review and Meta-Analysis

Background

In countries of high endemicity of the soil-transmitted helminth parasites Ascaris lumbricoides, Trichuris trichiura, and hookworm, preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations) is the main strategy to control morbidity. However, rapid reinfection of humans occurs after successful deworming, and therefore effective preventive measures are required to achieve public health goals with optimal efficiency and sustainability.

Methods and Findings

We conducted a systematic review and meta-analysis to assess the effect of sanitation (i.e., access and use of facilities for the safe disposal of human urine and feces) on infection with soil-transmitted helminths. PubMed, Embase, ISI Web of Science, and the World Health Organization Library Database were searched without language restrictions and year of publication (search performed until December 31, 2010). Bibliographies of identified articles were hand-searched. All types of studies reporting data on sanitation availability (i.e., having access at own household or living in close proximity to sanitation facility), or usage, and soil-transmitted helminth infections at the individual level were considered. Reported odds ratios (ORs) of the protective effect of sanitation on soil-transmitted helminth infections were extracted from the papers or calculated from reported numbers. The quality of published studies was assessed with a panel of criteria developed by the authors. Random effects meta-analyses were used to account for observed heterogeneity. Thirty-six publications, consisting of 39 datasets, met our inclusion criteria. Availability of sanitation facilities was associated with significant protection against infection with soil-transmitted helminths (OR  =  0.46 to 0.58). Regarding the use of sanitation, ORs of 0.54 (95% confidence interval [CI] 0.28–1.02), 0.63 (95% CI 0.37–1.05), and 0.78 (95% CI 0.60–1.00) were determined for T. trichiura, hookworm, and A. lumbricoides, respectively. The overall ORs, combining sanitation availability and use, were 0.51 (95% CI 0.44–0.61) for the three soil-transmitted helminths combined, 0.54 (95% CI 0.43–0.69) for A. lumbricoides, 0.58 (95% CI 0.45–0.75) for T. trichiura, and 0.60 (95% CI 0.48–0.75) for hookworm.

Conclusions

Despite a number of limitations (e.g., most studies used a cross-sectional design and were of low quality, with potential biases and considerable heterogeneity), our results reveal that sanitation is associated with a reduced risk of transmission of helminthiases to humans. Access to improved sanitation should be prioritized alongside preventive chemotherapy and health education to achieve a durable reduction of the burden of helminthiases. Please see later in the article for the Editors'' Summary     

Comparing Diagnostic Accuracy of Kato-Katz,Koga Agar Plate,Ether-Concentration,and FLOTAC for Schistosoma mansoni and Soil-Transmitted Helminths

Background

Infections with schistosomes and soil-transmitted helminths exert a considerable yet underappreciated economic and public health burden on afflicted populations. Accurate diagnosis is crucial for patient management, drug efficacy evaluations, and monitoring of large-scale community-based control programs.

Methods/Principal Findings

The diagnostic accuracy of four copromicroscopic techniques (i.e., Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC) for the detection of Schistosoma mansoni and soil-transmitted helminth eggs was compared using stool samples from 112 school children in Côte d''Ivoire. Combined results of all four methods served as a diagnostic ‘gold’ standard and revealed prevalences of S. mansoni, hookworm, Trichuris trichiura, Strongyloides stercoralis and Ascaris lumbricoides of 83.0%, 55.4%, 40.2%, 33.9% and 28.6%, respectively. A single FLOTAC from stool samples preserved in sodium acetate-acetic acid-formalin for 30 or 83 days showed a higher sensitivity for S. mansoni diagnosis (91.4%) than the ether-concentration method on stool samples preserved for 40 days (85.0%) or triplicate Kato-Katz using fresh stool samples (77.4%). Moreover, a single FLOTAC detected hookworm, A. lumbricoides and T. trichiura infections with a higher sensitivity than any of the other methods used, but resulted in lower egg counts. The Koga agar plate method was the most accurate diagnostic assay for S. stercoralis.

Conclusion/Significance

We have shown that the FLOTAC method holds promise for the diagnosis of S. mansoni. Moreover, our study confirms that FLOTAC is a sensitive technique for detection of common soil-transmitted helminths. For the diagnosis of S. stercoralis, the Koga agar plate method remains the method of choice.     

Low efficacy of single-dose albendazole and mebendazole against hookworm and effect on concomitant helminth infection in Lao PDR

Background

Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections. We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR. Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke.

Methodology

We conducted a randomized, open-label, two-arm trial. In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100). Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21–23 days posttreatment were used as primary outcome measures. Adverse events were monitored 3 hours post treatment.

Principal Findings

Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2–0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively. In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively).

Conclusions/Significance

Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole. Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic.

Clinical Trial Registration

Current Controlled Trials ISRCTN29126001     

Assessment of Anthelmintic Efficacy of Mebendazole in School Children in Six Countries Where Soil-Transmitted Helminths Are Endemic

Background

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained for similarly conducted trials of a single oral dose of albendazole (ALB; 400 mg).

Methodology

The efficacy of MEB, as assessed by FECR, was determined in six trials involving 5,830 school children in Brazil, Cambodia, Cameroon, Ethiopia, United Republic of Tanzania, and Vietnam. The efficacy of MEB was compared to that of ALB as previously assessed in 8,841 school children in India and all the above-mentioned study sites, using identical methodologies.

Principal Findings

The estimated FECR rate [95% confidence interval] of MEB was highest for A. lumbricoides (97.6% [95.8; 99.5]), followed by hookworm (79.6% [71.0; 88.3]). For T. trichiura, the estimated FECR rate was 63.1% [51.6; 74.6]. Compared to MEB, ALB was significantly more efficacious against hookworm (96.2% [91.1; 100], p<0.001) and only marginally, although significantly, better against A. lumbricoides infections (99.9% [99.0; 100], p = 0.012), but equally efficacious for T. trichiura infections (64.5% [44.4; 84.7], p = 0.906).

Conclusions/Significance

A minimum FECR rate of 95% for A. lumbricoides, 70% for hookworm, and 50% for T. trichiura is expected in MEB-dependent PC programs. Lower FECR results may indicate the development of potential drug resistance.     

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.     

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.     

Efficacy and side effects of albendazole currently in use against Ascaris,Trichuris and hookworm among school children in Wondo Genet,southern Ethiopia

Monitoring the efficacy of anthelminthic drugs is essential. The objective of this study was to assess the efficacy of a single oral dose of 400 mg albendazole (ABZ) against the major soil-transmitted helminth (STH) infection in school children, Wondo Genet, southern Ethiopia. A single fresh stool sample was collected from 298 school children and examined using a duplicate smear of the Kato–Katz method. Children positive for STH infections were treated with single oral dose of 400 mg ABZ and re-examined for intestinal helminth infections 21 days post-treatment. The participants were interviewed for symptoms related with the drug uptake 24 h after ABZ treatment. Children positive for Schistosoma mansoni infections were treated with Praziquantel (40 mg/kg of body weight) after an ABZ treatment follow up survey. 51.3%, 49.7%, 44.6% and 88.3% had hookworm, Ascaris lumbricoides, Trichuris trichiura and any intestinal helminth infection, respectively. Cure rates were 97.4% for hookworm, 96.6% for A. lumbricoides and 30.8% for T. trichiura infections. Egg reduction rates (ERRs) were 99.8% for hookworm, 99.9% for A. lumbricoides and 83.1% for T. trichiura infections. Mild and transient symptoms were observed among the participants which were quite frequent. In conclusion, a 400 mg single oral dose of ABZ was effective against hookworm and A. lumbricoides but less efficacious against T. trichiura infection. The drug resulted in high ERRs for hookworm, A. lumbricoides and T. trichiura. Administration of the drug in repeated doses or in combination with other drugs might be necessary.     

Efficacy and Safety of Praziquantel,Tribendimidine and Mebendazole in Patients with Co-infection of Clonorchis sinensis and Other Helminths

Background

Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.

Method

We performed a randomized open-label trial in Qiyang, People''s Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.

Results

156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.

Conclusion

Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.

Trial Registration

Controlled-Trials.com ISRCTN55086560     

A comparison of the sensitivity and fecal egg counts of the McMaster egg counting and Kato-Katz thick smear methods for soil-transmitted helminths

Background

The Kato-Katz thick smear (Kato-Katz) is the diagnostic method recommended for monitoring large-scale treatment programs implemented for the control of soil-transmitted helminths (STH) in public health, yet it is difficult to standardize. A promising alternative is the McMaster egg counting method (McMaster), commonly used in veterinary parasitology, but rarely so for the detection of STH in human stool.

Methodology/Principal Findings

The Kato-Katz and McMaster methods were compared for the detection of STH in 1,543 subjects resident in five countries across Africa, Asia and South America. The consistency of the performance of both methods in different trials, the validity of the fixed multiplication factor employed in the Kato-Katz method and the accuracy of these methods for estimating ‘true’ drug efficacies were assessed. The Kato-Katz method detected significantly more Ascaris lumbricoides infections (88.1% vs. 75.6%, p<0.001), whereas the difference in sensitivity between the two methods was non-significant for hookworm (78.3% vs. 72.4%) and Trichuris trichiura (82.6% vs. 80.3%). The sensitivity of the methods varied significantly across trials and magnitude of fecal egg counts (FEC). Quantitative comparison revealed a significant correlation (Rs >0.32) in FEC between both methods, and indicated no significant difference in FEC, except for A. lumbricoides, where the Kato-Katz resulted in significantly higher FEC (14,197 eggs per gram of stool (EPG) vs. 5,982 EPG). For the Kato-Katz, the fixed multiplication factor resulted in significantly higher FEC than the multiplication factor adjusted for mass of feces examined for A. lumbricoides (16,538 EPG vs. 15,396 EPG) and T. trichiura (1,490 EPG vs. 1,363 EPG), but not for hookworm. The McMaster provided more accurate efficacy results (absolute difference to ‘true’ drug efficacy: 1.7% vs. 4.5%).

Conclusions/Significance

The McMaster is an alternative method for monitoring large-scale treatment programs. It is a robust (accurate multiplication factor) and accurate (reliable efficacy results) method, which can be easily standardized.     

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.     

Effect of Deworming on Physical Fitness of School-Aged Children in Yunnan,China: A Double-Blind,Randomized, Placebo-Controlled Trial

Background

There is considerable debate on the health impacts of soil-transmitted helminth infections. We assessed effects of deworming on physical fitness and strength of children in an area in Yunnan, People''s Republic of China, where soil-transmitted helminthiasis is highly endemic.

Methodology

The double-blind, randomized, placebo-controlled trial was conducted between October 2011 and May 2012. Children, aged 9–12 years, were treated with either triple-dose albendazole or placebo, and monitored for 6 months post-treatment. The Kato-Katz and Baermann techniques were used for the diagnosis of soil-transmitted helminth infections. Physical fitness was assessed with a 20-m shuttle run test, where the maximum aerobic capacity within 1 min of exhaustive exercise (VO₂ max estimate) and the number of 20-m laps completed were recorded. Physical strength was determined with grip strength and standing broad jump tests. Body height and weight, the sum of skinfolds, and hemoglobin levels were recorded as secondary outcomes.

Principal Findings

Children receiving triple-dose albendazole scored slightly higher in the primary and secondary outcomes than placebo recipients, but the difference lacked statistical significance. Trichuris trichiura-infected children had 1.6 ml kg⁻¹ min⁻¹ (P = 0.02) less increase in their VO₂ max estimate and completed 4.6 (P = 0.04) fewer 20-m laps than at baseline compared to non-infected peers. Similar trends were detected in the VO₂ max estimate and grip strength of children infected with hookworm and Ascaris lumbricoides, respectively. In addition, the increase in the VO₂ max estimate from baseline was consistently higher in children with low-intensity T. trichiura and hookworm infections than in their peers with high-intensity infections of all soil-transmitted helminths (range: 1.9–2.1 ml kg⁻¹ min⁻¹; all P<0.05).

Conclusions/Significance

We found no strong evidence for significant improvements in physical fitness and anthropometric indicators due to deworming over a 6-month follow-up period. However, the negative effect of T. trichiura infections on physical fitness warrants further investigation.     

Efficacy and safety of nitazoxanide, albendazole, and nitazoxanide-albendazole against Trichuris trichiura infection: a randomized controlled trial

Background

The currently used anthelmintic drugs, in single oral application, have low efficacy against Trichuris trichiura infection, and hence novel anthelmintic drugs are needed. Nitazoxanide has been suggested as potential drug candidate.

Methodology

The efficacy and safety of a single oral dose of nitazoxanide (1,000 mg), or albendazole (400 mg), and a nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug administered separately on two consecutive days, were assessed in a double-blind, randomized, placebo-controlled trial in two schools on Pemba, Tanzania. Cure and egg reduction rates were calculated by per-protocol analysis and by available case analysis. Adverse events were assessed and graded before treatment and four times after treatment.

Principal Findings

Complete data for the per-protocol analysis were available from 533 T. trichiura-positive children. Cure rates against T. trichiura were low regardless of the treatment (nitazoxanide-albendazole, 16.0%; albendazole, 14.5%; and nitazoxanide, 6.6%). Egg reduction rates were 54.9% for the nitazoxanide-albendazole combination, 45.6% for single albendazole, and 13.4% for single nitazoxanide. Similar cure and egg reduction rates were calculated using the available case analysis. Children receiving nitazoxanide had significantly more adverse events compared to placebo recipients. Most of the adverse events were mild and had resolved within 24 hours posttreatment.

Conclusions/Significance

Nitazoxanide shows no effect on T. trichiura infection. The low efficacy of albendazole against T. trichiura in the current setting characterized by high anthelmintic drug pressure is confirmed. There is a pressing need to develop new anthelmintics against trichuriasis.

Trial Registration

Controlled-Trials.com ISRCTN08336605     

How Long Can Stool Samples Be Fixed for an Accurate Diagnosis of Soil-Transmitted Helminth Infection Using Mini-FLOTAC?

Background

Kato-Katz is a widely used method for the diagnosis of soil-transmitted helminth infection. Fecal samples cannot be preserved, and hence, should be processed on the day of collection and examined under a microscope within 60 min of slide preparation. Mini-FLOTAC is a technique that allows examining fixed fecal samples. We assessed the performance of Mini-FLOTAC using formalin-fixed stool samples compared to Kato-Katz and determined the dynamics of prevalence and intensity estimates of soil-transmitted helminth infection over a 31-day time period.

Methodology

The study was carried out in late 2013 on Pemba Island, Tanzania. Forty-one children were enrolled and stool samples were subjected on the day of collection to a single Kato-Katz thick smear and Mini-FLOTAC examination; 12 aliquots of stool were fixed in 5% formalin and subsequently examined by Mini-FLOTAC up to 31 days after collection.

Principal Findings

The combined results from Kato-Katz and Mini-FLOTAC revealed that 100% of children were positive for Trichuris trichiura, 85% for Ascaris lumbricoides, and 54% for hookworm. Kato-Katz and Mini-FLOTAC techniques found similar prevalence estimates for A. lumbricoides (85% versus 76%), T. trichiura (98% versus 100%), and hookworm (42% versus 51%). The mean eggs per gram of stool (EPG) according to Kato-Katz and Mini-FLOTAC was 12,075 and 11,679 for A. lumbricoides, 1,074 and 1,592 for T. trichiura, and 255 and 220 for hookworm, respectively. The mean EPG from day 1 to 31 of fixation was stable for A. lumbricoides and T. trichiura, but gradually declined for hookworm, starting at day 15.

Conclusions/Significance

The findings of our study suggest that for a qualitative diagnosis of soil-transmitted helminth infection, stool samples can be fixed in 5% formalin for at least 30 days. However, for an accurate quantitative diagnosis of hookworm, we suggest a limit of 15 days of preservation. Our results have direct implication for integrating soil-transmitted helminthiasis into transmission assessment surveys for lymphatic filariasis.     

Soil-transmitted helminth reinfection after drug treatment: a systematic review and meta-analysis

Background

Soil-transmitted helminth (STH) infections (i.e., Ascaris lumbricoides, hookworm, and Trichuris trichiura) affect more than a billion people. Preventive chemotherapy (i.e., repeated administration of anthelmintic drugs to at-risk populations), is the mainstay of control. This strategy, however, does not prevent reinfection. We performed a systematic review and meta-analysis to assess patterns and dynamics of STH reinfection after drug treatment.

Methodology

We systematically searched PubMed, ISI Web of Science, EMBASE, Cochrane Database of Systematic Reviews, China National Knowledge Infrastructure, WanFang Database, Chinese Scientific Journal Database, and Google Scholar. Information on study year, country, sample size, age of participants, diagnostic method, drug administration strategy, prevalence and intensity of infection pre- and posttreatment, cure and egg reduction rate, evaluation period posttreatment, and adherence was extracted. Pooled risk ratios from random-effects models were used to assess the risk of STH reinfection after treatment. Our protocol is available on PROSPERO, registration number: CRD42011001678.

Principal Findings

From 154 studies identified, 51 were included and 24 provided STH infection rates pre- and posttreatment, whereas 42 reported determinants of predisposition to reinfection. At 3, 6, and 12 months posttreatment, A. lumbricoides prevalence reached 26% (95% confidence interval (CI): 16–43%), 68% (95% CI: 60–76%) and 94% (95% CI: 88–100%) of pretreatment levels, respectively. For T. trichiura, respective reinfection prevalence were 36% (95% CI: 28–47%), 67% (95% CI: 42–100%), and 82% (95% CI: 62–100%), and for hookworm, 30% (95% CI: 26–34%), 55% (95% CI: 34–87%), and 57% (95% CI: 49–67%). Prevalence and intensity of reinfection were positively correlated with pretreatment infection status.

Conclusion

STH reinfections occur rapidly after treatment, particularly for A. lumbricoides and T. trichiura. Hence, there is a need for frequent anthelmintic drug administrations to maximize the benefit of preventive chemotherapy. Integrated control approaches emphasizing health education and environmental sanitation are needed to interrupt transmission of STH.     

Soil-transmitted helminth infections among plantation sector schoolchildren in Sri Lanka: prevalence after ten years of preventive chemotherapy

Background

The plantation sector in Sri Lanka lags behind the rest of the country in terms of living conditions and health. In 1992, a sector-wide survey of children aged 3–12 years and women of reproductive age showed >90% prevalence of soil-transmitted helminth infections. Biannual mass de-worming targeting children aged 3–18 years started in 1994 and was continued until 2005. The present study was carried out to assess the status of infection four years after cessation of mass de-worming.

Methods/Findings

A school-based cross-sectional survey was carried out. Faecal samples from approximately 20 children from each of 114 schools in five districts were examined using the modified Kato-Katz technique. Data regarding the school, the child''s family and household sanitation were recorded after inspection of schools and households. Multivariate analysis was carried out using logistic regression, to identify risk factors for infection. Faecal samples were obtained from 1890 children. In 4/5 districts, >20% were infected with one or more helminth species. Overall combined prevalence was 29.0%; 11.6% had infections of moderate-heavy intensity. The commonest infection was Ascaris lumbricoides, present in all five districts, as was Trichuris trichiura. Hookworm was not detected in two districts. Multivariate analysis identified low altitude and maternal under-education as risk factors for all three infections. Poor household sanitation was identified as a risk factor for A. lumbricoides and hookworm, but not T. trichiura infections.

Conclusions/Significance

The results indicate that regular mass de-worming of plantation sector children should be resumed along with more emphasis on better sanitation and health education. They show that even after 10 years of mass chemotherapy, prevalence can bounce back after cessation of preventive chemotherapy, if the initial force of transmission is strong and other long-term control measures are not concomitantly implemented.     

Effect of Schistosomiasis and Soil-Transmitted Helminth Infections on Physical Fitness of School Children in C?te d'Ivoire

Background

Schistosomiasis and soil-transmitted helminthiasis are important public health problems in sub-Saharan Africa causing malnutrition, anemia, and retardation of physical and cognitive development. However, the effect of these diseases on physical fitness remains to be determined.

Methodology

We investigated the relationship between schistosomiasis, soil-transmitted helminthiasis and physical performance of children, controlling for potential confounding of Plasmodium spp. infections and environmental parameters (i.e., ambient air temperature and humidity). A cross-sectional survey was carried out among 156 school children aged 7–15 years from Côte d''Ivoire. Each child had two stool and two urine samples examined for helminth eggs by microscopy. Additionally, children underwent a clinical examination, were tested for Plasmodium spp. infection with a rapid diagnostic test, and performed a maximal multistage 20 m shuttle run test to assess their maximal oxygen uptake (VO₂ max) as a proxy for physical fitness.

Principal Findings

The prevalence of Schistosoma haematobium, Plasmodium spp., Schistosoma mansoni, hookworm and Ascaris lumbricoides infections was 85.3%, 71.2%, 53.8%, 13.5% and 1.3%, respectively. Children with single, dual, triple, quadruple and quintuple species infections showed VO₂ max of 52.7, 53.1, 52.2, 52.6 and 55.6 ml kg⁻¹ min⁻¹, respectively. The VO₂ max of children with no parasite infections was 53.5 ml kg⁻¹ min⁻¹. No statistically significant difference was detected between any groups. Multivariable analysis revealed that VO₂ max was influenced by sex (reference: female, coef. = 4.02, p<0.001) and age (years, coef. = −1.23, p<0.001), but not by helminth infection and intensity, Plasmodium spp. infection, and environmental parameters.

Conclusion/Significance

School-aged children in Côte d''Ivoire showed good physical fitness, irrespective of their helminth infection status. Future studies on children''s physical fitness in settings where helminthiasis and malaria co-exist should include pre- and post-intervention evaluations and the measurement of hemoglobin and hematocrit levels and nutritional parameters as potential co-factors to determine whether interventions further improve upon fitness.     

In vitro and in vivo efficacy of Monepantel (AAD 1566) against laboratory models of human intestinal nematode infections

Background

Few effective drugs are available for soil-transmitted helminthiases and drug resistance is of concern. In the present work, we tested the efficacy of the veterinary drug monepantel, a potential drug development candidate compared to standard drugs in vitro and in parasite-rodent models of relevance to human soil-transmitted helminthiases.

Methodology

A motility assay was used to assess the efficacy of monepantel, albendazole, levamisole, and pyrantel pamoate in vitro on third-stage larvae (L3) and adult worms of Ancylostoma ceylanicum, Necator americanus and Trichuris muris. Ancylostoma ceylanicum- or N. americanus-infected hamsters, T. muris- or Ascaris suum-infected mice, and Strongyloides ratti-infected rats were treated with single oral doses of monepantel or with one of the reference drugs.

Principal Findings

Monepantel showed excellent activity on A. ceylanicum adults (IC₅₀ = 1.7 µg/ml), a moderate effect on T. muris L3 (IC₅₀ = 78.7 µg/ml), whereas no effect was observed on A. ceylanicum L3, T. muris adults, and both stages of N. americanus. Of the standard drugs, levamisole showed the highest potency in vitro (IC₅₀ = 1.6 and 33.1 µg/ml on A. ceylanicum and T. muris L3, respectively). Complete elimination of worms was observed with monepantel (10 mg/kg) and albendazole (2.5 mg/kg) in A. ceylanicum-infected hamsters. In the N. americanus hamster model single 10 mg/kg oral doses of monepantel and albendazole resulted in worm burden reductions of 58.3% and 100%, respectively. Trichuris muris, S. ratti and A. suum were not affected by treatment with monepantel in vivo (following doses of 600 mg/kg, 32 mg/kg and 600 mg/kg, respectively). In contrast, worm burden reductions of 95.9% and 76.6% were observed following treatment of T. muris- and A. suum infected mice with levamisole (200 mg/kg) and albendazole (600 mg/kg), respectively.

Conclusions/Significance

Monepantel reveals low or no activities against N. americanus, T. muris, S. ratti and A. suum in vivo, hence does not qualify as drug development candidate for human soil-transmitted helminthiases.