Single Dose Of Albendazole Research Articles

Effect of intensive versus standard anthelminthic treatment on growth and cognition among children living in a high Schistosoma mansoni transmission setting: a study nested within a cluster-randomised trial

Background: Schistosomiasis and other worm infections have been associated with growth and cognitive impairments; however, whether treatment reverses these effects is uncertain. Moreover, mechanisms linking these infections to cognition are not clear. We aimed to compare growth and cognitive benefits of intensive versus standard anthelminthic treatment in school-aged-children and explore processes that might be involved. We hypothesised that intensive treatment would have greater benefits than standard treatment. Methods: The study was nested within a cluster-randomised trial of either quarterly single-dose praziquantel of 40mg/kg to treat Schistosoma mansoni plus triple dose albendazole of 400mg (intensive treatment) to treat soil-transmitted worms including Ascaris lumbricoides, hookworm and Trichuris trichiura, or annual single-dose praziquantel 40mg/kg plus six-monthly single-dose albendazole 400mg (standard treatment) conducted in the Koome islands in Lake Victoria, Uganda (ISRCTN47196031). Children aged 5-9 years (N=384) were assessed on primary outcomes (height, weight and eight measures of cognitive ability), worm infection, and proposed mediators of worm effects (cytokines, iron status, physical activity) at one year (intensive n=85; standard n=64) and at two years (intensive n=158; standard n=128) of the intervention. Linear regression was used to examine intervention effects on height, weight and cognitive performance. Linear mixed effects models were used to study changes in growth and cognitive performance between the two arms across the two time-points. Results: Intensive treatment resulted in lower Schistosoma mansoni prevalence than standard treatment (at one year, 41% versus 70%; adjusted odds ratio (aOR)=0.24, 95% CI: 0.12, 0.49; at two years, 39% versus 69%; aOR=0.27; 95% CI: 0.16, 0.43) but there were no significant differences in growth and cognitive outcomes at either time-point. Worms and treatment showed no consistent association with the proposed mediators of worm effects. Conclusion: Reduction in worm burden may not improve growth and cognitive outcomes in high S. mansoni transmission settings. Possible implications are discussed.

Anthelminthic treatment receipt and its predictors in Lake Victoria fishing communities, Uganda: Intervention coverage results from the LaVIISWA cluster randomised trial.

BackgroundMass drug administration (MDA) is a cornerstone of control of parasitic helminths. In schistosomiasis-endemic areas with >50% of school-aged children infected, community-wide MDA with praziquantel is recommended by the World Health Organisation (WHO), with target coverage of >75%. Using data from a cluster-randomised trial of MDA treatment strategies, we aimed to describe the proportion of eligible residents who received MDA and predictors of treatment receipt, and to assess associations with helminth prevalence.MethodsIn the Koome islands of Lake Victoria, Uganda, where baseline schistosomiasis prevalence (by single stool sample, Kato Katz) was 52% overall (all ages) and 67% among school-aged children, we conducted a cluster-randomised trial of community-wide, intensive MDA (quarterly single-dose praziquantel 40mg/kg; triple-dose albendazole 400mg) versus standard, Uganda government intervention (annual single-dose praziquantel 40mg/kg; 6-monthly single-dose albendazole). Twenty-six fishing villages were randomised, 13 per trial arm, for four years. At each treatment round, praziquantel treatment and the first dose of albendazole treatment were directly observed by the study team, registers of village residents were updated and the proportion receiving treatment among those eligible recorded.ResultsDuring the four-year MDA, at each treatment round an average of 13,382 people were registered in the 26 villages (7,153 and 6,229 in standard and intensive intervention villages, respectively). Overall, the proportion of those eligible receiving praziquantel was lower than for albendazole (60% versus 65%), particularly in the standard arm (61% versus 71%) compared to the intensive arm (60% versus 62%). Albendazole receipt was lower when given concurrently with praziquantel. Absence was the commonest reason for non-receipt of treatment (81% albendazole, 77% praziquantel), followed by refusal (14% albendazole, 18% praziquantel). Proportions receiving treatment were lowest among school-aged children, but did not differ by sex. Longitudinal analysis of a subgroup of residents who did not move during the study period found that persistent non-receipt of treatment in this subgroup was rare. Refusal to receive treatment was highest among adults and more common among females.ConclusionIn schistosomiasis high-risk communities, a combination of approaches to increasing treatment coverage, such as extended periods of treatment delivery, and the provision of incentives, may be required to achieve WHO targets.

The Effect of Albendazole Administration and Iron-Folic Acid Supplementation on Hemoglobin Level in Primary Schoolchildren with Soil-transmitted Helminth Infections

BACKGROUND: Soil-transmitted helminth (STH) infections were the highest infection in children aged 5–15 years old. They lead to iron deficiency anemia and folic acid deficiency. One of the strategies to treat the issues is anthelmintic administration with iron-folic acid supplementation.
 AIM: This study aims to evaluate the effectiveness of single-dose albendazole and albendazole with iron-folic acid supplementation on hemoglobin (Hb) levels in children with STHs.
 METHODS: This was an open-label randomized clinical trial conducted in Batubara Regency from September to November 2018. Subjects were primary schoolchildren with STH infections. They were grouped into albendazole and albendazole with iron-folic acid supplementation groups. The data were analyzed by independent t-test and Mann–Whitney U-test.
 RESULTS: From 139 children, 72 children received albendazole single dose and 67 children received albendazole with 30 mg iron and 250 μg folic acid weekly for 3 months. The median of baseline hemoglobin level was 12.2 gr/dL, whereas after intervention was 12.7 gr/dL. The hemoglobin level increases did not differ significantly between the two groups (p > 0.05). However, clinical improvement was observed.
 CONCLUSION: Iron-folic acid supplementation in addition to albendazole did not show any benefit for primary schoolchildren with STH infection in Batubara Regency, North Sumatera, Indonesia.

The impact of Worms and Ladders, an innovative health educational board game on Soil-Transmitted Helminthiasis control in Abeokuta, Southwest Nigeria.

In most endemic sub-Saharan African countries, repeated infections with soil-transmitted helminth (STH) occur as early as six weeks after the end of mass drug administration (MDA) with albendazole. In this study, we designed a new health educational board game Worms and Ladders and evaluated its potential to complement MDA with albendazole and reduce reinfection rates through the promotion of good hygiene practices among school-aged children. The evaluation employed a randomized control trial (RCT) design. Baseline knowledge, attitude and practices (KAP) relating to STH were obtained using a questionnaire from 372 pupils across six schools in Abeokuta, Nigeria. Schools were randomly assigned into intervention and control group, with the former and latter receiving Worms and Ladders and the common Snake and Ladder board game respectively. Fresh stool samples were also collected at baseline for STH diagnosis before administering 400mg single dose albendazole. Follow-up assessments of STH burden and KAP were conducted three and six months' post-intervention. Data generated from the study were analyzed using SPSS 20.0 software, with confidence interval set at 95%. Prevalence of STH dropped from 25.0% to 10.4% in the intervention group and 49.4% to 33.3% in the control group at three months' post-intervention. The prevalence further dropped to 5.6% in the intervention group at six months' post-intervention. However, it increased to 37.2% in the control group at six months' post-intervention. There was a significant difference (p<0.05) in prevalence after intervention among the groups. KAP on transmission, control and prevention of STH significantly improved (p<0.05) from 5.2% to 97.9% in the intervention group compared to 6.2% to 7.1% in the control group. The Worms and Ladders board game shows the potential to teach and promote good hygiene behavior among SAC. These findings posit the newly developed game as a reliable tool to complement mass drug administration campaigns for STH control.

Efficacy of a single dose versus a multiple dose regimen of Mebendazole against hookworm infections among school children: a randomized open-label trial

BackgroundDespite the existence of a population-based control program using single dose albendazole or mebendazole as a preventive chemotherapy, hookworm transmission remains high. It causes a negative impact on the growth and school performance of children. In connection to this preventive chemotherapy, different studies produced conflicting results. This study aimed at evaluating the efficacy of single (500 mg) versus multiple doses (100 mg twice a day during three consecutive days) of mebendazole against hookworm infections among school-aged children.MethodsThis randomized open-label clinical trial took place among school-aged children (6–14 years old) in Burie and Debre Elias towns, Northwest Ethiopia. Using simple randomization, eligible hookworm-positive children were allocated (1:1) to either a single or multiple dose treatment arms. Stool samples were collected and processed using McMaster method at baseline and follow-up period (14–21 days after treatment). Only laboratory technicians were blinded. The cure and egg reduction rates were the primary and secondary therapeutic outcome measures against hookworm infections, respectively. An independent t-test was used to compare group means, and logistic regression was used to calculate odds ratio (OR). P-value < 0.05 at 95% CI was considered statistically significant.ResultOne hundred eight children, 54 in each treatment arm had completed baseline data and received allocated treatment. One hundred three children had completed follow-up data records and included for the final efficacy analysis. Cure rate against hookworm was significantly higher in the multiple dose (96.1%) than in the single dose (30.8%) with OR = 55.125; 95% CI: 11.92–254.9; P < 0.001. The egg reduction rate in the multiple dose treatment arm (99.5%) was also significantly higher than in the single dose arm (68.9%) with difference t (101) =5.38; 95% CI 230.95–505.36; P < 0.001.ConclusionThe single dose regimen of mebendazole for the treatment of hookworm infections showed poor cure and egg reduction rates, while the multiple doses revealed satisfactory. Although multiple dose regimen administration is a bit more complex than the single dose, we strongly encourage replacing it with multiple dose regimen during deworming programs in hookworm endemic areas.Trial registrationThis trial is retrospectively registered in www.pactr.org, number PACTR201911466695052 on November 26, 2019.

Anthelmintic drugs for treating ascariasis.

BackgroundAscaris lumbricoides is a common infection, and mainly affects children living in low‐income areas. Water and sanitation improvement, health education, and drug treatment may help break the cycle of transmission, and effective drugs will reduce morbidity.ObjectivesTo compare the efficacy and safety of anthelmintic drugs (albendazole, mebendazole, ivermectin) for treating people with Ascaris infection.Search methodsWe searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, three other databases, and reference lists of included studies, without language restrictions, up to 4 July 2019.Selection criteriaRandomized controlled trials (RCT) that compared albendazole, mebendazole, and ivermectin in children and adults with confirmed Ascaris infection.Data collection and analysisTwo review authors independently assessed studies for inclusion, assessed risk of bias, and extracted data from the included trials. A third review author checked the quality of data extraction. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) to compare dichotomous outcomes in treatment and control groups. We used the fixed‐effect model for studies with low heterogeneity and the random‐effects model for studies with moderate to high heterogeneity. We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative cure rates in the comparison groups.Main resultsWe included 30 parallel‐group RCTs, which enrolled 6442 participants from 17 countries across Africa, Asia, Central America and the Caribbean, and South America. Participants were from 28 days to 82 years of age, recruited from school, communities, and health facilities. Twenty studies were funded or co‐funded by manufacturers, while 10 studies were independent of manufacturer funding. Twenty‐two trials had a high risk of bias for one or two domains (blinding, incomplete outcome data, selective reporting).Single dose of albendazole (four trials), mebendazole (three trials) or ivermectin (one trial) was compared to placebo. Parasitological cure at 14 to 60 days was high in all the studies (illustrative cure of 93.0% in the anthelmintic group and 16.1% in the placebo group; RR 6.29, 95% CI 3.91 to 10.12; 8 trials, 1578 participants; moderate‐certainty evidence). Single dose of albendazole is as effective as multiple doses of albendazole (illustrative cure of 93.2% with single dose, 94.3% with multiple doses; RR 0.98, 95% CI 0.92 to 1.05; 3 trials, 307 participants; high‐certainty evidence); or as single dose of mebendazole (illustrative cure of 98.0% with albendazole, 96.9% with mebendazole; RR 1.01, 95% CI 1.00 to 1.02; 6 trials, 2131 participants; high‐certainty evidence). Studies did not detect a difference between a single dose of albendazole and a single dose of ivermectin (cure rates of 87.8% with albendazole, 90.2% with ivermectin; RR 0.99, 95% CI 0.91 to 1.08; 3 trials, 519 participants; moderate‐certainty evidence).Across all the studies, failure after single dose of albendazole ranged from 0.0% to 30.3%, mebendazole from 0.0% to 22.2%, and ivermectin from 0.0% to 21.6%.The egg reduction rate (ERR) measured up to 60 days after the treatment was high in all treated groups, regardless of the anthelmintic used (range 96% to 100%). It was not possible to evaluate parasitological cure by classes of infection intensity.No included trials reported complication or serious adverse events. Other adverse events were apparently similar among the compared anthelmintic groups (moderate‐ to low‐certainty evidence). The most commonly reported other adverse events were nausea, vomiting, abdominal pain, diarrhoea, headache, and fever.Authors' conclusionsSingle‐dose of albendazole, mebendazole, and ivermectin all appeared effective against Ascaris lumbricoides infection, yielding high parasitological cure and large reductions in eggs excreted, with no differences detected between them. The drugs appear to be safe to treat children and adults with confirmed Ascaris infection. There is little to choose between drugs and regimens in terms of cure or adverse events.

Effect of Mass Drug Administration with a Single Dose of Albendazole on Ascaris lumbricoides and Trichuris trichiura Infection among Schoolchildren in Yangon Region, Myanmar

Soil-transmitted helminths, including Ascaris lumbricoides and Trichuris trichiura, are important intestinal parasites mostly affecting younger people in developing countries. In 2014–2015, we performed mass fecal examinations targeting a total of 2,227 schoolchildren in 3 districts (South Dagon, North Dagon, and Hlaing-thar-yar) of Yangon Region, Myanmar, using the Kato-Katz thick smear technique. The egg positive children were subjected to a mass drug administration (MDA) using a single oral dose of 400 mg albendazole. The pre-treatment egg positive rate (EPG/person) of A. lumbricoides averaged 17.2% (15,532); it was 25.2% (21,796), 14.2% (11,816), and 12.8% (12,983) in 3 districts, respectively, and that of T. trichiura averaged 19.4% (1,074), and was 24.1% (1,040), 12.3% (852), and 21.2% (1,330) in 3 districts, respectively. Follow-up fecal examinations performed 4 months post-MDA revealed considerable decreases of A. lumbricoides prevalence (EPG/person) to av. 8.3% (12,429), and 13.7% (17,640), 8.0% (7,797), and 4.5% (11,849) in 3 districts, respectively. However, T. trichiura did not show any recognizable decrease in the prevalence (EPG/person) remaining at av. 18.2% (862), and 18.5% (888), 11.5% (812), and 23.3% (887) in 3 districts, respectively. The results demonstrated difficulty in short-term control of T. trichiura by MDA using albendazole and suggested necessity of either a long-term MDA (>10 years) or changing the albendazole regimen into 2~3-day course (total 800 or 1,200 mg), or using an alternative drug/drug combination.

Two or Three Consecutive Days Albendazole Treatment Has Better Efficacy than Single-Dose Albendazole Treatment for Trichuriasis

BACKGROUND: Soil-transmitted helminth (STH) infection is endemic in Indonesia. Singledose albendazole is routinely used to control STH infections. Some studies found that repeated-dose of albendazole showed better efficacy. There is no study in Indonesia to compare single-dose and repeated-dose albendazole for against STH infections.METHODS: A randomized, open clinical trial was conducted in July-September 2018 among primary school children. Stool samples were collected before treatment and on day 7, 14, 21, and 28 after treatment then stained using the Kato-Katz method. Group I received three consecutive days, group II received two consecutive days, and Group III received single-dose of albendazole. Cure rate (CR) and egg reduction rate (ERR) were compared using Chi-square tests, and eggs per gram (EPG) was compared using the Kruskal Wallis test (p&lt;0.05).RESULTS: One hundred ninety-five subjects enrolled and divided into 65 subjects in each group. The CR and ERR of trichuriasis after three consecutive days (79.5% and 97.4%) and two consecutive days regimen (70.3% and 91.9%) were higher than single-dose regimen (32.2% and 74.6%) with p&lt;0.001, but not for ascariasis or hookworm infection. The highest efficacy was found in three consecutive days regimen group. Trichuris trichiura EPG was significantly different among the three groups on day 7, 14, 21, and 28 after treatment (p&lt;0.001).CONCLUSION: Three and two consecutive days albendazole have better efficacy than single-dose of albendazole for trichuriasis, but not for ascariasis or hookworm infection. Two consecutive days albendazole is better choice for treating trichuriasis with more adherence and less side effect than three consecutive days regimen.KEYWORDS: soil-transmitted helminth infection, albendazole, single-dose, repeated-dose

Systematic review of the effectiveness of selected drugs for preventive chemotherapy for Taenia solium taeniasis.

Preventive chemotherapy is a useful tool for the control of Taenia solium taeniasis and cysticercosis. The aim of this systematic review is to assess the scientific evidence concerning the effectiveness and safety of different drugs in preventive chemotherapy for T. solium taeniasis in endemic populations. A systematic review was conducted of controlled and uncontrolled studies, assessing the efficacy and adverse effects (among other outcomes) of albendazole, niclosamide and/or praziquantel for preventive chemotherapy of T. solium taeniasis. A comprehensive search was conducted for published and unpublished studies. Two reviewers screened articles, completed the data extraction and assessment of risk of bias. A meta-analysis of cure rate and relative reduction in prevalence was performed. The protocol for this review was registered on the International prospective register of systematic reviews (PROSPERO), number CRD42018112533. We identified 3555 records, of which we included 20 primary studies reported across 33 articles. Meta-analyses of drug and dose showed that a single dose of praziquantel 10mg/kg, albendazole 400mg per day for three consecutive days, or niclosamide 2g, resulted in better cure rates for T. solium taeniasis (99.5%, 96.4% and 84.3%, respectively) than praziquantel 5mg/kg or single dose albendazole 400mg (89.0% and 52.0%, respectively). These findings have a low certainty of evidence due to high risk of bias in individual studies and heterogeneity in combined estimates. In relation to side-effects, most studies reported either no or only mild and transient side-effects within the first three days following drug administration for all drugs and doses. Evidence indicated that praziquantel 10mg/kg, niclosamide 2g, and triple dose albendazole 400mg were effective as taenicides and could be considered for use in mass drug administration programs for the control of T. solium taeniasis. Evidence was not found that any of these drugs caused severe side effects at the indicated doses, although the extent of the available evidence was limited.

Study on the prevalence of intestinal parasitic infections and the assessment of the efficacy of albendazole in soil-transmitted helminths in school-going children in East Sikkim.

Background:The problem of intestinal parasitic infections (IPIs) in children is one of the most worrisome problems worldwide. The latest estimates indicate that more than 880 million children are in the need of treatment for these parasites.Objective:The aim of this study was to measure the prevalence of IPIs in school-going children in East Sikkim, India, and to assess the efficacy of single-dose albendazole (ALB) in children infected with soil-transmitted helminths (STHs).Subjects and Methods:A total of 300 stool samples were collected from the schoolchildren of government schools of East Sikkim. Samples were processed for the identification of IPIs by direct microscopy and formalin-ether concentration method. Fecal egg counting was carried out for STH by Stoll's egg counting technique, pre- and posttreatment with single-dose ALB. The second stool samples were collected 10–14 days posttreatment of ALB. Cure rate (CR) and the fecal egg reduction rate (ERR), the two most widely used indicators for assessing the efficacy of an anthelmintic, were used in this study. The data were analyzed and the results were interpreted statistically.Results:The overall prevalence of the IPIs was 33.9%. Helminthic infection was 4.6% and protozoan infection was 29.3%. Among helminthes Ascaris lumbricoides and among protozoans Entamoeba spp. were the dominant intestinal parasites. For drug efficacy, A. lumbricoides had CR 55.5% and ERR 81.4%. Moreover, for Trichuris trichiura, CR and ERR was 100%. The study has shown less efficacy against A. lumbricoides infections compared to T. trichiura.Conclusion:The study provides useful insight into the current prevalence of IPIs in school-going children in government schools in East Sikkim region. Keeping in view of less efficacy of ALB, it is necessary to keep the monitoring of development of drug resistance simultaneously.

The Effect of Helminth Infections and Their Treatment on Metabolic Outcomes: Results of a Cluster-Randomized Trial.

BackgroundHelminths may protect against cardiometabolic risk through effects on inflammation and metabolism; their treatment may be detrimental to metabolic outcomes.MethodsIn a cluster-randomized trial in 26 Ugandan fishing communities we investigated effects of community-wide intensive (quarterly single-dose praziquantel, triple-dose albendazole) vs standard (annual single-dose praziquantel, biannual single-dose albendazole) anthelminthic treatment on metabolic outcomes, and observational associations between helminths and metabolic outcomes. The primary outcome, homeostatic model assessment of insulin resistance (HOMA-IR), and secondary outcomes (including blood pressure, fasting blood glucose, lipids) were assessed after 4 years' intervention among individuals aged ≥10 years.ResultsWe analyzed 1898 participants. Intensive treatment had no effect on HOMA-IR (adjusted geometric mean ratio, 0.96 [95% confidence interval {CI}, .86–1.07]; P = .42) but resulted in higher mean low-density lipoprotein cholesterol (LDL-c) (2.86 vs 2.60 mmol/L; adjusted mean difference, 0.26 [95% CI, −.03 to .56]; P = .08). Lower LDL-c levels were associated with Schistosoma mansoni (2.37 vs 2.80 mmol/L; −0.25 [95% CI, −.49 to −.02]; P = .04) or Strongyloides (2.34 vs 2.69 mmol/L; −0.32 [95% CI, −.53 to −.12]; P = .003) infection. Schistosoma mansoni was associated with lower total cholesterol (4.24 vs 4.64 mmol/L; −0.25 [95% CI, −.44 to −.07]; P = .01) and moderate to heavy S. mansoni infection with lower triglycerides, LDL-c, and diastolic blood pressure.ConclusionsHelminth infections improve lipid profiles and may lower blood pressure. Studies to confirm causality and investigate mechanisms may contribute to understanding the epidemiological transition and suggest new approaches to prevent cardiometabolic disease.Clinical Trials RegistrationISRCTN47196031.

Efficacy of Albendazole and Mebendazole With or Without Levamisole for Ascariasis and Trichuriasis.

BACKGROUND:Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of helminthiasis in children.AIM:To investigated the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis and ascariasis.METHODS:This study was conducted as a double-blind, randomised clinical trial by comparing the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis. The sample of this study were 180 elementary school students at Deli Serdang Regency State Elementary School, Medan, Indonesia. The study was conducted from April to June 2015.RESULT:The cure rate of helminthiasis on the 7th day was 81.7% after albendazole therapy, 88.3% after albendazole levamisole therapy, and 83.3% after mebendazole combined with levamisole therapy (p = 0.577). Cure rate on the 14th day was 88.3%, 95%, and 91.7% for albendazole, albendazole combined with levamisole, and mebendazole combined with levamisole therapy, respectively (p = 0.418). On the 21th day, the cure rate was 88.3%, 96.7%, and 91.7% (p = 0.230). Combination of albendazole and levamisole showed the highest cure rate, despite the statistically insignificant difference for all groups (p > 0.05). Combination of albendazole combined with levamisole showed better cure rate for mild trichuriasis (95.8%) than albendazole therapy (46.2%) and mebendazole combined with levamisole (83.3%), (p < 0.05).CONCLUSION:Single-dose albendazole, a combination of albendazole and levamisole, and a combination of mebendazole and levamisole had similar efficacy in reducing egg count in helminthiasis. Combination of albendazole and levamisole showed better cure rate for mild trichuriasis and mixed infections. Side effects were similar in all treatment groups.

The Impact of Intensive Versus Standard Anthelminthic Treatment on Allergy-related Outcomes, Helminth Infection Intensity, and Helminth-related Morbidity in Lake Victoria Fishing Communities, Uganda: Results From the LaVIISWA Cluster-randomized Trial.

BackgroundThe prevalence of allergy-related diseases is increasing in low-income countries. Parasitic helminths, common in these settings, may be protective. We hypothesized that intensive, community-wide, anthelminthic mass drug administration (MDA) would increase allergy-related diseases, while reducing helminth-related morbidity.MethodsIn an open, cluster-randomized trial (ISRCTN47196031), we randomized 26 high-schistosomiasis-transmission fishing villages in Lake Victoria, Uganda, in a 1:1 ratio to receive community-wide intensive (quarterly single-dose praziquantel plus albendazole daily for 3 days) or standard (annual praziquantel plus 6 monthly single-dose albendazole) MDA. Primary outcomes were recent wheezing, skin prick test positivity (SPT), and allergen-specific immunoglobulin E (asIgE) after 3 years of intervention. Secondary outcomes included helminths, haemoglobin, and hepatosplenomegaly.ResultsThe outcome survey comprised 3350 individuals. Intensive MDA had no effect on wheezing (risk ratio [RR] 1.11, 95% confidence interval [CI] 0.64–1.93), SPT (RR 1.10, 95% CI 0.85–1.42), or asIgE (RR 0.96, 95% CI 0.82–1.12). Intensive MDA reduced Schistosoma mansoni infection intensity: the prevalence from Kato Katz examinations of single stool samples from each patient was 23% versus 39% (RR 0.70, 95% CI 0.55–0.88), but the urine circulating cathodic antigen test remained positive in 85% participants in both trial arms. Hookworm prevalence was 8% versus 11% (RR 0.55, 95% CI 0.31–1.00). There were no differences in anemia or hepatospenomegaly between trial arms.ConclusionsDespite reductions in S. mansoni intensity and hookworm prevalence, intensive MDA had no effect on atopy, allergy-related diseases, or helminth-related pathology. This could be due to sustained low-intensity infections; thus, a causal link between helminths and allergy outcomes cannot be discounted. Intensive community-based MDA has a limited impact in high-schistosomiasis-transmission fishing communities, in the absence of other interventions.Clinical Trials RegistrationISRCTN47196031.

Efficacy of single dose albendazole and praziquantel drugs among helminth-infected school children at Rural Bahir Dar, northwest Ethiopia.

The resistance of anthelminthic drugs makes helminth control difficult. The aim of our study was to assess the efficacy of single dose albendazole and praziquantel drugs among helminth-infected children. A cross-sectional study was conducted from April to June, 2017. Stool examination was done by the Formol-Ether concentration technique. Students infected with geohelminths and s chistosoma mansoni were treated with a single dose of albendazole and praziquantel, respectively. Post-treatment stool examination was performed after two weeks. The magnitude of parasite infection, percentage of egg count reduction and cure rate following treatment were calculated using descriptive statistics. A total of 409 Sebatamet primary school students were included. The total prevalence of intestinal parasitosis was 58%. The cure rate of albendazole against hookworm was only 76.8%. Praziquantel had a 91.4% cure rate against Schistosoma mansoni. Therefore, periodic evaluation of the efficacy of anthelminthic drugs is required.

Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis.

Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64]). There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present. CRD42016050739.

Elimination of lymphatic filariasis as a public health problem from the Cook Islands

BackgroundThe Cook Islands has a long history of high-endemicity lymphatic filariasis (LF) transmitted by Aedes vector mosquitoes. Though the infection prevalence had declined between 1975 and 1999 following episodic treatment activities, still infection was widespread with pockets of persistent infection. Beginning in 1999, the Cook Islands embarked on a national program, in partnership with Pacific Programme to Eliminate LF (PacELF), to eliminate LF as a public health problem.MethodsAll 12 inhabited islands were identified as endemic, and six rounds of mass drug administration (MDA) with once-yearly, single-dose albendazole plus diethylcarbamazine (DEC) were implemented during 2000–2006 to interrupt transmission of LF. Surveys carried out at the baseline, mid-term, stop-MDA, and post-MDA periods assessed LF antigen (Ag) prevalence in children and adults. Historical data, health workers’ observations, and hospital records were used to assess the trend and burden of chronic disease.ResultsThe baseline Ag prevalence (1999) ranged from 2.0% in Manihiki to > 18.0% in Aitutaki, Mitiaro, and Pukapuka, and the national average Ag prevalence was 8.6%. MDA, carried out with a national treatment coverage over six annual rounds of MDA ranging from 63.5 to 96.7% in different years, was stopped in 2007. By then, the national Ag prevalence had declined to 0.27%. The post-MDA surveillance survey results (2013–2014) showed that Ag prevalence had fallen to 0% in 11/12 islands, and the national prevalence was only 0.03%. Chronic filarial disease had almost entirely disappeared.ConclusionThe Cook Islands met all the criteria required for the World Health Organization (WHO) to acknowledge elimination of LF as a public health problem, as it did officially in 2016. This success also confirms that LF, even when transmitted by Aedes mosquitoes that are recognized to be more efficient than other vector species, can be eliminated as a public health problem by six rounds of MDA.

Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis.

BackgroundThe soil-transmitted helminths (STH), Ascaris lumbricoides, Trichuris trichiura and hookworms, infect 1.5 billion people worldwide and cause an estimated burden of 3.3 million disability-adjusted life years (DALYs). Current control strategies focus on morbidity reduction through preventive chemotherapy (PC) but the most commonly used recommended drugs (albendazole and mebendazole) are particularly inefficacious against T. trichiura. This, together with the threat of emerging drug resistance, calls for new control strategies, including co-administration with other anthelminthics. Ivermectin plus albendazole is widely used against lymphatic filariasis, but its efficacy and safety against STH infections has not yet been fully understood.Methods and findingsWe conducted a systematic literature review and meta-analysis on the efficacy and safety of ivermectin-albendazole co-administration in five different databases (i.e. PubMed, ISI Web of Science, ScienceDirect, CENTRAL and clinicaltrials.gov) from 1960 to January 2018. Four studies reporting efficacy of ivermectin-albendazole against STH infections and five studies on its safety met the selection criteria and were included for quantitative analysis. Ivermectin-albendazole was significantly associated with lower risk (risk ratio (RR) = 0.44, 95% confidence interval (CI) = 0.31–0.62) for T. trichiura infection after treatment compared to albendazole alone. The co-administration revealed no or only a marginal benefit on cure and egg reduction rates over albendazole alone for A. lumbricoides and hookworm infections. Adverse events (AEs) occurring after ivermectin-albendazole co-administration were mostly mild and transient. Overall, the number of individuals reporting any AE was not different (RR = 1.09, 95% CI = 0.87–1.36) in co-treated and albendazole-treated patients. However, although not statistically significant, sub-group analysis showed a tendency for slightly more AEs in patients with filariasis treated with ivermectin-albendazole compared to those treated with albendazole alone (RR = 1.29, 95% CI = 0.81–2.05).ConclusionsOur findings suggest a good tolerability and higher efficacy of ivermectin-albendazole against T. trichiura compared to the current standard single-dose albendazole treatment, which supports the use of this co-administration in PC programs. Large-scale definitive randomized controlled trials are required to confirm our results.

Causes and Timing of Mortality and Morbidity Among Late Presenters Starting Antiretroviral Therapy in the REALITY Trial.

BackgroundIn sub-Saharan Africa, 20%–25% of people starting antiretroviral therapy (ART) have severe immunosuppression; approximately 10% die within 3 months. In the Reduction of EArly mortaLITY (REALITY) randomized trial, a broad enhanced anti-infection prophylaxis bundle reduced mortality vs cotrimoxazole. We investigate the contribution and timing of different causes of mortality/morbidity.MethodsParticipants started ART with a CD4 count <100 cells/µL; enhanced prophylaxis comprised cotrimoxazole plus 12 weeks of isoniazid + fluconazole, single-dose albendazole, and 5 days of azithromycin. A blinded committee adjudicated events and causes of death as (non–mutually exclusively) tuberculosis, cryptococcosis, severe bacterial infection (SBI), other potentially azithromycin-responsive infections, other events, and unknown.ResultsMedian pre-ART CD4 count was 37 cells/µL. Among 1805 participants, 225 (12.7%) died by week 48. Fatal/nonfatal events occurred early (median 4 weeks); rates then declined exponentially. One hundred fifty-four deaths had single and 71 had multiple causes, including tuberculosis in 4.5% participants, cryptococcosis in 1.1%, SBI in 1.9%, other potentially azithromycin-responsive infections in 1.3%, other events in 3.6%, and unknown in 5.0%. Enhanced prophylaxis reduced deaths from cryptococcosis and unknown causes (P < .05) but not tuberculosis, SBI, potentially azithromycin-responsive infections, or other causes (P > .3); and reduced nonfatal/fatal tuberculosis and cryptococcosis (P < .05), but not SBI, other potentially azithromycin-responsive infections, or other events (P > .2).ConclusionsEnhanced prophylaxis reduced mortality from cryptococcosis and unknown causes and nonfatal tuberculosis and cryptococcosis. High early incidence of fatal/nonfatal events highlights the need for starting enhanced-prophylaxis with ART in advanced disease.Clinical Trials RegistrationISRCTN43622374.

Community-based trial of annual versus biannual single-dose ivermectin plus albendazole against Wuchereria bancrofti infection in human and mosquito populations: study protocol for a cluster randomised controlled trial

BackgroundThe Global Programme for the Elimination of Lymphatic Filariasis (GPELF) has been in operation since the year 2000, with the aim of eliminating the disease by the year 2020, following five to six rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). In Ghana, MDA has been undertaken since 2001. While the disease has been eliminated in many areas, transmission has persisted in some implementation units that had experienced 15 or more rounds of MDA. Thus, new intervention strategies could eliminate residual infection in areas of persistent transmission and speed up the lymphatic filariasis (LF)-elimination process. This study, therefore, seeks to test the hypothesis that biannual treatment of LF-endemic communities will accelerate the interruption of LF in areas of persistent transmission.MethodsA cluster randomised trial will be implemented in LF-endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM + ALB or (2) annual MDA with IVM + ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.DiscussionIt is expected that this study will add to the existing evidence on the need for alternative intervention strategies for the elimination of LF in Ghana and in other African countries that are facing similar challenges or are at the beginning of their LF-elimination programmes.Trial registrationClinicalTrials.gov, ID: NCT03036059. Registered on 26 January 2017.Pan African Clinical Trials Registry, ID: PACTR201702002012425. Registered on 23 February 2017.

Global deworming: moving past albendazole and mebendazole

Since the 2001 adoption of the World Health Assembly (WHA) resolution calling for the global deworming of children affected by soil-transmitted helminth (STH) infections and schistosomiasis, 1 WHOWHA54.19 Schistosomiasis and soil-transmitted helminth infections. http://www.who.int/neglected_diseases/mediacentre/WHA_54.19_Eng.pdf Google Scholar the world's public health leaders have gradually responded. Although we are still behind schedule in terms of the WHA's original 2010 targets, WHO continues to report progress—in 2015, approximately 59% of the world's children requiring treatment received access to deworming medicines for their STH infections, 2 WHOSchistosomiasis and soil transmitted helminthiases: number of people treated in 2015. Wkly Epidemiol Rec. 2016; 91: 585-600 PubMed Google Scholar mostly single-dose albendazole or mebendazole (each an anthelmintic drug in the benzimidazole drug class). Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a randomised, controlled, single-blinded, non-inferiority trialTribendimidine in combination with either ivermectin or oxantel pamoate had a similar, non-inferior efficacy profile as albendazole plus oxantel pamoate, hence tribendimidine will be a useful addition to the depleted anthelmintic drug armamentarium. Full-Text PDF