Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatment.

BACKGROUND: Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date. METHODS: Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy. RESULTS: Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively. CONCLUSIONS: Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections. TRIAL REGISTRATION: NCT03527732.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

Safety and tolerability of moxidectin and ivermectin combination treatments for lymphatic filariasis in Côte d'Ivoire: A randomized controlled superiority study.

BACKGROUND: Moxidectin is a macrocyclic lactone registered for the treatment of human onchocerciasis. The drug has a good safety profile, large volume of distribution and a long elimination half-life. This paper reports tolerability data from the first use of moxidectin in persons with Wuchereria bancrofti infection. METHODS: In this randomized, open-label, masked-observer superiority trial, adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to 1 of 4 treatment arms: ivermectin + albendazole (IA), moxidectin + albendazole (MoxA), ivermectin + diethylcarbamazine (DEC) + albendazole (IDA), or moxidectin + DEC + albendazole (MoxDA). As part of a larger efficacy trial, all participants were closely monitored for 7 days after treatment. RESULTS: One hundred sixty-four individuals were treated, and monitored for treatment emergent adverse events (TEAE). Eighty-seven participants (53%) experienced one or more mild (grade 1) or moderate (grade 2) TEAE. Four participants had transient Grade 3 hematuria after treatment (3 after IDA and 1 after IA). There were no serious adverse events. There were no significant differences in frequency or types of TEAE between treatment groups (IA = 22/41 (53%), MoxA = 24/40 (60%), IDA = 18/41 (44%), MoxDA = 15/42 (36%), p = 0.530). Fifty-nine participants (36%) had multiple TEAE, and 8.5% had a one or more grade 2 (moderate) TEAE. Grade 2 TEAE were more frequent after triple drug treatments (IDA, 14.6%; MoxDA, 9.5%) than after two-drug treatments (IA, 7.3%; MoxA, 2.5%). There was no difference in TEAEs based on baseline Mf counts (OR 0.69 (0.33, 1.43), p-value 0.319). CONCLUSION: All treatment regimens were well tolerated. We observed no difference in safety parameters between regimens that contained ivermectin or moxidectin. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04410406.

Efficacy, safety, and tolerability of albendazole and ivermectin based regimens for the treatment of microfilaraemic loiasis in adult patients in Gabon: A randomized controlled assessor blinded clinical trial.

BACKGROUND: There is a lack of systematic evidence for strategies to control loiasis transmission in highly endemic regions. Here we assessed albendazole and ivermectin based treatment regimens to reduce Loa loa microfilaraemia in Gabon. METHODS: Eligible adult patients with L. loa microfilaraemia between 5,000 and 50,000 microfilariae/ml were randomized to either a control or one of three intervention groups (1:2:2:2 allocation ratio) consisting of three-week twice daily 400mg oral albendazole followed by 1) no treatment, 2) two further weeks of twice daily 400mg albendazole, or 3) a single dose of ivermectin in this open label randomized assessor blinded controlled clinical trial. The primary outcome was the proportion of participants with L. loa microfilaraemia ≤ 100 mf/ml at Day 168. RESULTS: In the efficacy-population of 42 patients 0 (0%; control group), 1 (9%; 3-week albendazole), 5 (39%; 5-weeks albendazole) and 2 (22%; 3-week albendazole plus single dose ivermectin) participants met the primary outcome of microfilaraemia below 100/ml at day 168. A 80-90% reduction of microfilaraemia was observed in the active treatment groups. CONCLUSION: The 5-week regimen of albendazole or a 3-week regimen of albendazole followed by ivermectin were most efficacious to reduce microfilaraemia. All therapeutic regimens were well tolerated and safe. TRIAL REGISTRATION: Trial registered at the Pan-African Clinical Trials Registry: PACTR201807197019027.

Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study.

INTRODUCTION: Dual diethylcarbamazine and albendazole (DA) therapy is the standard mass drug administration (MDA) regimen for lymphatic filariasis in Kenya. Following the recent World Health Organization recommendation, Kenya piloted triple therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in MDA. OBJECTIVE: We conducted a community-based, observational, cohort event monitoring study to compare the types, frequency, severity, and predictors of adverse events following dual versus triple therapy in 20,421 eligible residents. METHODS: Residents in Kilifi (n = 10,010) and Mombasa counties (n = 10,411) received DA and IDA through MDA campaigns, respectively. Adverse events were actively monitored through house-to-house visits on days 1, 2, and 7 after MDA. Any clinical events reported before and after MDA were cross-checked and verified to differentiate pre-existing events from MDA-associated adverse events. RESULTS: Overall, 5807 and 3102 adverse events were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more adverse events was significantly higher (p < 0.0001) in the IDA group (27.3%; 95% confidence interval [CI] 26.4-28.2) than in the DA group (16.2%; 95% CI 15.5-16.9). Dizziness (15.9% vs 5.9%) and drowsiness (10.1% vs 2.6%) were the most common adverse events and significantly higher in the IDA group compared with the DA group (p < 0.0001). Most adverse events were mild or moderate with a few severe cases (IDA = 0.05%; 95% CI 0.35-0.78, DA = 0.03%; 95% CI 0.14-0.60). Female sex, obesity, taking three or more diethylcarbamazine or ivermectin tablets, and having pre-existing clinical symptoms were significant predictors of adverse events following IDA treatment. CONCLUSIONS: Ivermectin, diethylcarbamazine, and albendazole as a combination is as safe and well tolerated as DA to use in MDA campaigns with no serious life-threatening adverse events. Systemic mild-to-moderate adverse events with a few severe cases and transient adverse events are more common with IDA treatment than with DA treatment. Hence, integrating pharmacovigilance into a MDA program is recommended for the timely detection and management of adverse events.

Albendazole Monotherapy for Pediatric Cystic Echinococcosis: A Case Series.

BACKGROUND: Data regarding albendazole monotherapy for cystic echinococcosis (CE) are scarce, especially in children. We report our experience treating CE in children with albendazole monotherapy. METHODS: A retrospective case series, 2005-2021, assessing factors leading to albendazole monotherapy, demographic, clinical, duration of treatment and follow-up, and outcome (changes in cyst size and side effects) characteristics. RESULTS: Overall, we identified 18 patients with 31 cysts; liver: 68% (n = 21), lungs: 29% (n = 9), and kidney: 3% (n = 1). Mean cyst size was 4.5 ± 2.6 cm. Reasons for administrating albendazole monotherapy were small (< 4 cm) cyst size (56%), difficulty to operate (33%) and comorbidity (22%). Duration of treatment (range 1-32 months) was 1, 2-3, 4-6 and > 6 months in 28% (n = 5), 39% (n = 7), 17% (n = 3) and 17% (n = 3) of children, respectively. Duration of follow up (range 1-87 months) was 1, 2-3, 4-6 and > 6 months in 11% (n = 2), 11% (n = 2), 17% (n = 3) and 61% (n = 11) of children, respectively. Overall, 83% (n = 15) of patients experienced lack of cyst growth, and 72% (n = 13) experienced reduction in cyst size, while 44% (n = 8) experienced reduction larger than 50%. Full resolution was noted in 22% (n = 4) of patients. In three cases (17%) treatment failure was recorded: one (6%) recurrence, and two cases (11%) of cyst growth. Neutropenia was recorded in two patients (11%), and liver enzymes elevation was recorded in six patients (33%). CONCLUSIONS: Albendazole monotherapy may be an adequate treatment for selected cases of CE disease in children, especially in CE with small, hepatic cysts.

Pharmacokinetics, feasibility and safety of co-administering azithromycin, albendazole, and ivermectin during mass drug administration: A review.

INTRODUCTION: Traditionally, health ministries implement mass drug administration programmes for each neglected tropical disease (NTD) as separate and distinct campaigns. Many NTDs have overlapping endemicity suggesting co-administration might improve programme reach and efficiency, helping accelerate progress towards 2030 targets. Safety data are required to support a recommendation to undertake co-administration. METHODOLOGY: We aimed to compile and summarize existing data on co-administration of ivermectin, albendazole and azithromycin, including both data on pharmacokinetic interactions and data from previous experimental and observational studies conducted in NTD-endemic populations. We searched PubMed, Google Scholar, research and conference abstracts, gray literature, and national policy documents. We limited the publication language to English and used a search period from January 1st, 1995 through October 1st, 2022. Search terms were: azithromycin and ivermectin and albendazole, mass drug administration co-administration trials, integrated mass drug administration, mass drug administration safety, pharmacokinetic dynamics, and azithromycin and ivermectin and albendazole. We excluded papers if they did not include data on co-administration of azithromycin and both albendazole and ivermectin, or azithromycin with either albendazole or ivermectin alone. RESULTS: We identified a total of 58 potentially relevant studies. Of these we identified 7 studies relevant to the research question and which met our inclusion criteria. Three papers analyzed pharmacokinetic and pharmacodynamic interactions. No study found evidence of clinically significant drug-drug interactions likely to impact safety or efficacy. Two papers and a conference presentation reported data on the safety of combinations of at least two of the drugs. A field study in Mali suggested the rates of adverse events were similar with combined or separate administration, but was underpowered. A further field study in Papua New Guinea used all three drugs as part of a four-drug regimen also including diethylcarbamazine; in this setting, co-administration appeared safe but there were issues with the consistency in how adverse events were recorded. CONCLUSION: There are relatively limited data on the safety profile of co-administering ivermectin, albendazole and azithromycin as an integrated regimen for NTDs. Despite the limited amount of data, available evidence suggests that such a strategy is safe with an absence of clinically important drug-drug interactions, no serious adverse events reported and little evidence for an increase in mild adverse events. Integrated MDA may be a viable strategy for national NTD programmes.

Efficacy and Safety of Moxidectin-Albendazole and Ivermectin-Albendazole Combination Therapy Compared to Albendazole Monotherapy in Adolescents and Adults Infected with Trichuris trichiura: A Randomized, Controlled Superiority Trial.

BACKGROUND: The currently recommended benzimidazole monotherapy is insufficiently effective to control infection with the soil-transmitted helminth Trichuris trichiura. Ivermectin-albendazole combination has shown promising, but setting-dependent efficacy, with therapeutic underperformance in Côte d'Ivoire. We evaluated whether moxidectin-albendazole could serve as an alternative to albendazole monotherapy in Côte d'Ivoire. METHODS: In this community-based, randomized, placebo-controlled, parallel-group superiority trial, individuals aged 12-60 years were screened for T. trichiura eggs in their stool using quadruplicate Kato-Katz thick smears. Diagnostically and clinically eligible participants were randomly assigned (1:1:1) to receive single oral doses of moxidectin (8 mg) and albendazole (400 mg), ivermectin (200 µg/kg) and albendazole (400 mg), or albendazole (400 mg) and placebo. The primary outcome was proportion cured, ie, cure rate (CR), assessed at 2-3 weeks post-treatment. Safety endpoints were assessed pre-treatment and at 3 and 24 hours post-treatment. RESULTS: For the 210 participants with primary outcome data, we observed CRs of 15.3% in the moxidectin-albendazole arm and 22.5% in the ivermectin-albendazole arm, which did not differ significantly from the CR of 13.4% in the albendazole arm (differences: 1.8%-points [95% confidence interval: -10.1 to 13.6] and 9.1%-points [-3.9 to 21.8], respectively). Most common adverse events were abdominal pain (range across arms: 11.9%-20.9%), headache (4.7%-14.3%), and itching (5.8%-13.1%), which were predominantly mild and transient. CONCLUSIONS: All therapies showed similar low efficacy in treating trichuriasis in Côte d'Ivoire. Alternative treatment options need to be evaluated, and further analyses should be conducted to understand the lack of enhanced activity of the combination therapies in Côte d'Ivoire. CLINICAL TRIALS REGISTRATION: NCT04726969.

Emodepside for Trichuris trichiura and Hookworm Infection.

BACKGROUND: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. METHODS: We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. RESULTS: A total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. CONCLUSIONS: Emodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).

Efficacy and safety of antiparasitic therapy for neurocysticercosis in rural Tanzania: a prospective cohort study.

PURPOSE: Neurocysticercosis is common in regions endemic for Taenia solium. Active-stage neurocysticercosis can be treated with antiparasitic medication, but so far no study on efficacy and safety has been conducted in Africa. METHODS: We conducted a prospective cohort study on treatment of neurocysticercosis in Tanzania between August 2018 and January 2022. Patients were initially treated with albendazole (15 mg/kg/d) for 10 days and followed up for 6 months. Additionally in July 2021, all participants who then still had cysts were offered a combination therapy consisting of albendazole (15 mg/kg/d) and praziquantel (50 mg/kg/d). Antiparasitic treatment was accompanied by corticosteroid medication and anti-seizure medication if the patient had experienced epileptic seizures before treatment. RESULTS: Sixty-three patients were recruited for this study, of whom 17 had a complete follow-up after albendazole monotherapy. These patients had a total of 138 cysts at baseline, of which 58 (42%) had disappeared or calcified by the end of follow-up. The median cyst reduction was 40% (interquartile range 11-63%). Frequency of epileptic seizures reduced considerably (p < 0.001). Three patients had all active cysts resolved or calcified and of the remaining 14, eight received the combination therapy which resolved 63 of 66 cysts (95%). Adverse events were infrequent and mild to moderate during both treatment cycles. CONCLUSION: Cyst resolution was unsatisfactory with albendazole monotherapy but was very high when it was followed by a combination of albendazole and praziquantel.

Treatment of hydatid cyst with albendazole desensitization: A pediatric case report.

Albendazole is a benzimidazole group drug used alone or in combination with surgery in the treatment of many helminthiasis, especially hydatid cysts. Type 1 hypersensitivity reaction has been reported rarely. Treatment with desensitization has been successfully applied in a few adult patients, however literature information on pediatric patients was not available. Here, we present a pediatric case in which Type 1 reaction occurred due to the use of albendazole during hydatid cyst treatment and undergone desensitization.

Acute hepatitis in a paediatric patient: immune-mediated drug-induced liver injury or albendazole-induced autoimmune hepatitis?

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity. CASE REPORT: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up. CONCLUSIONS: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population.

Efficacy and safety of praziquantel in the treatment of neurocysticercosis in Vietnam.

Neurocysticercosis (NCC) is a parasitic infection of the nervous system and is responsible for considerable morbidity and mortality. Praziquantel (PZQ) is one of the antiparasitics mostly used in managing NCC, however, there have been only a few studies on the treatment outcome of this drug. The present study aimed to evaluate the efficacy and safety of PZQ in patients with NCC. Sixty patients with typical characteristics of NCC received three 10-day cycles of PZQ and the interruption between these cycles was 10 days. Additional treatment included antiinflammation (steroids), antiepileptics and analgesics. Clinical and imaging studies were done at baseline and six months after therapy to assess the efficacy of treatment. Laboratory evaluation was done before and after each cycle to investigate laboratory safety profiles. By six months after finishing therapy, all patients had clinical improvement and 75% of them were free of symptoms. The rates of complete, partial or no resolution of cysts on brain magnetic resonance imaging were 61.7%, 28.3% and 10% respectively. The efficacy of therapy was not associated with the number of cysts. There was no difference between the levels of aspartate aminotransferase, alanine aminotransferase, urea and creatinine before and after treatment. Conclusion: Praziquantel is effective and safe in the treatment of patients with neurocysticercosis.

Adverse drug effects among students following mass de-worming exercise involving administration of Praziquantel and Albendazole in KEEA Municipality, Ghana.

BACKGROUND: To manage the deleterious effects of parasitic infections such as lymphatic filariasis (LF) and schistosomiasis among school children, most countries including Ghana make use of mass drug administration (MDA). Although MDA has proven effective in reducing worm burden, unfortunately adverse drug effects (ADEs) post-MDA are derailing the gains and also remain poorly monitored. The study assessed incidence and factors associated with ADEs among students following a school-based mass de-worming exercise involving administration of Praziquantel (PZQT) and Albendazole (ADZ) against LF and SCH at Komenda-Edina-Eguafo-Abirem (KEEA) Municipal. METHODOLOGY: After fulfilling all ethical obligations, a total of 598 students aged 5-20 years who received PZQT or ADZ monotherapy or a combination of the two (PZQT + ADZ) as part of the mass de-worming exercise were recruited through quota and random sampling. Bodyweight and height of students were measured and body mass index (BMI) calculated. Students were orally interviewed to obtain information such as age, sex, intake of diet before taking drugs. Subsequently, students were monitored over 24 hours post-MDA for cases of ADEs. Descriptive statistics and logistic regression analysis using SPSS version 26 was used to describe data collected and to determine associations between incidence of ADEs and predictor variables. PRINCIPAL FINDINGS: Out of the 598 students, 243 (40.64%) represented by 124 males (51.03%) and 119 females (48.97%) with mean (SD) age of 13.43 (2.74) years experienced one or more forms of ADE. In decreasing order, the detected ADEs included headache (64.6%), Abdominal pain (48.6%), fever (30.0%), diarrhea (21.4%) and itching (12.8%). Multivariable statistical analysis showed that age 5-9 years (OR: 2.01, p = 0.041) and underweight (OR: 2.02, p = 0.038) were associated with incidence of ADEs. Compared with students who received combination therapy, students who received ADZ only (OR: 0.05, p < 0.001) and PZQT only (OR: 0.26, p < 0.001) had low cases of ADEs. Gender and diet intake before MDA were not associated with ADE incidence. CONCLUSION: ADE incidence was common among students in the KEEA municipality. Age, underweight, and double dosing were associated with increase in ADE incidence, while gender and food intake were not associated with increase in ADE incidence. The Disease Control Unit of the Ghana Health Service should incorporate stringent ADE monitoring in post-MDA surveillance in the National MDA program in order to be able to detect, manage and report ADEs to inform planning for future MDA programs. Such initiatives will help not only in improving effectiveness of MDA programs but also identify high risk groups and exact strategies to reduce negative influence of ADE on MDA coverage and anthelminthic drug compliance.

Current pharmacotherapeutic strategies for Strongyloidiasis and the complications in its treatment.

INTRODUCTION: Strongyloidiasis, an infection caused by the soil-transmitted helminth Strongyloides stercoralis, can lead immunocompromised people to a life-threatening syndrome. We highlight here current and emerging pharmacotherapeutic strategies for strongyloidiasis and discuss treatment protocols according to patient cohort. We searched PubMed and Embase for papers published on this topic between 1990 and May 2022. AREAS COVERED: Ivermectin is the first-line drug, with an estimated efficacy of about 86% and excellent tolerability. Albendazole has a lower efficacy, with usage advised when ivermectin is not available or not recommended. Moxidectin might be a valid alternative to ivermectin, with the advantage of being a dose-independent formulation. EXPERT OPINION: The standard dose of ivermectin is 200 µg/kg single dose orally, but multiple doses might be needed in immunosuppressed patients. In the case of hyperinfection, repeated doses are recommended up to 2 weeks after clearance of larvae from biological fluids, with close monitoring and further dosing based on review. Subcutaneous ivermectin is used where there is impaired intestinal absorption/paralytic ileus. In pregnant or lactating women, studies have not identified increased risk with ivermectin use. However, with limited available data, a risk-benefit assessment should be considered for each case.

Enteropathy and bone marrow hypoplasia associated with presumptive albendazole toxicosis in a juvenile Boer goat.

Albendazole is a widely used anthelmintic drug that is labeled for the treatment of specific nematodes and flukes in ruminants. Albendazole is approved for the treatment of liver flukes in goats (10 mg/kg PO for a single dose), but is commonly used extra-label in situations in which parasite resistance is an issue. Albendazole toxicosis has been reported in pigeons, doves, alpacas, humans, dogs, and cats. Here we report an adverse event in a 6-mo-old goat associated with extra-label use of albendazole (35.7 mg/kg PO daily for 3 d). Clinicopathologic findings included severe diarrhea and death, with small intestinal crypt necrosis and dysplasia, and severe bone marrow hypoplasia. Microbial and molecular testing and transmission electron microscopy ruled out infectious organisms. The described pathologic changes are similar to those reported in other species that have experienced toxicosis associated with albendazole. To our knowledge, bone marrow and intestinal lesions associated with albendazole use in the goat have not been reported previously. Veterinarians should be aware of potential adverse events and toxicoses associated with anthelmintic drugs, especially as parasite resistance increases, and extra-label usage, and the use of such drugs without veterinary supervision, becomes more common.

Step towards elimination of Wuchereria bancrofti in Southwest Tanzania 10 years after mass drug administration with Albendazole and Ivermectin.

BACKGROUND: Lymphatic filariasis is a mosquito transmitted parasitic infection in tropical regions. Annual mass treatment with ivermectin and albendazole is used for transmission control of Wuchereria bancrofti, the infective agent of lymphatic filariasis in many African countries, including Tanzania. METHODOLOGY: In a general population study in Southwest Tanzania, individuals were tested for circulating filarial antigen, an indicator of W. bancrofti adult worm burden in 2009 before mass drug administration commenced in that area. Seven annual rounds with ivermectin and albendazole were given between 2009 and 2015 with a population coverage of over 70%. Participants of the previous study took part in a follow-up activity in 2019 to measure the effect of this governmental activity. FINDINGS: One thousand two hundred and ninety nine inhabitants of Kyela district in Southwest Tanzania aged 14 to 65 years who had participated in the study activities in 2009 were revisited in 2010/11 and 2019. Among this group, the prevalence of lymphatic filariasis of the 14-65 years olds in 2009 was 35.1%. A follow-up evaluation in 2010/11 had shown a reduction to 27.7%. In 2019, after 7 years of annual treatment and an additional three years of surveillance, the prevalence had dropped to 1.7%, demonstrating successful treatment by the national control programme. Risk factors for W. bancrofti-infection were the occupation as farmer, male sex, and older age. Most infected individuals in the 2019 follow-up study already had a positive test for filarial antigen in 2009 and/or 2010/11. CONCLUSIONS: This data supports the findings of the Tanzanian Neglected Tropical Disease Control Programme (NTDCP), who conducted Transmission Assessment Surveys and found an impressive reduction in the prevalence of LF in children. Our results complement this data by showing a similar decrease in prevalence of LF in the adult population in the same area. The elimination of LF seems achievable in the near future.

Safety of Praziquantel and Albendazole Coadministration for the Control and Elimination of Schistosomiasis and Soil-Transmitted Helminths Among Children in Rwanda: An Active Surveillance Study.

INTRODUCTION: School-based preventive chemotherapy (Deworming) with praziquantel and albendazole to control and eliminate schistosomiasis and soil-transmitted helminths as public health problems is recommended by the World Health Organization (WHO). Safety monitoring during mass drug administration (MDA) is imperative but data from sub-Saharan Africa are scarce. OBJECTIVE: The aim of this active safety surveillance study was to identify the incidence, type, severity, and risk factors for adverse events (AEs) following mass administration of praziquantel and albendazole. METHODS: Overall, 8037 school children aged 5-15 years in Rwanda were enrolled. Baseline sociodemographic, medical history and any pre-existing clinical symptoms were recorded. Participants received a single dose of praziquantel and albendazole during MDA. AEs were actively monitored on days 1, 2, and 7 post MDA. RESULTS: Overall, 3196 AEs were reported by 1658 children; 91.3%, 8.4%, and 0.3% of the AEs were mild, moderate, and severe, respectively, and most resolved within 3 days. Headache (21%), dizziness or fainting (15.2 %), nausea (12.8%) and stomach pain (12.2%) were the most common AEs. The overall cumulative incidence of experiencing at least one type of AE was 20.6% (95% confidence interval [CI] 19.7-21.5%), being significantly higher (p < 0.001) in children with pre-MDA clinical events (27.5%, 95% CI 25.4-29.6%) than those without (18.7%, 95% CI 17.7-19.7%). Females, older age, having pre-MDA events, types of food taken before MDA and taking two or more praziquantel tablets were significant predictors of AEs. CONCLUSIONS: Praziquantel and albendazole MDA is safe and well-tolerated; however, one in five children experience transient mild to moderate, and in few cases severe, AEs. The incidence of AEs varies significantly between sex and age groups. Pharmacovigilance in the MDA program is recommended for timely detection and management of AEs.

Country Reports on Practical Aspects of Conducting Large-Scale Community Studies of the Tolerability of Mass Drug Administration with Ivermectin/Diethylcarbamazine/Albendazole for Lymphatic Filariasis.

This article is a compilation of summaries prepared by lead investigators for large-scale safety and efficacy studies on mass drug administration of IDA (ivermectin, diethylcarbamazine, and albendazole) for lymphatic filariasis. The summaries highlight the experiences of study teams that assessed the safety and efficacy of IDA in five countries: India, Indonesia, Haiti, Papua New Guinea, and Fiji. They also highlight significant challenges encountered during these community studies and responses to those challenges that contributed to success.