The aim was to assess the efficacy of ivermectin vs moxidectin for treating Strongyloides stercoralis infection. Ovid MEDLINE, Embase and Web of Science databases were searched for studies comparing ivermectin and moxidectin from inception to February 2024. The outcomes: elimination of infection or parasitological cure, mortality and serious adverse events. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data. Heterogeneity was assessed using Chi2 test for statistical heterogeneity and results of the I2 statistic. Two trials met the inclusion criteria that included 821 adult participants. Both studies were conducted in southeast Asia (Cambodia and Laos). Neither trial included immunocompromised patients. The mean age of the participants ranged from 40 to 45 years old, with a similar distribution of males and females. For all participants, S. stercoralis infection was confirmed by Baermann method. The evidence was moderate for parasitological cure rate. Certainty was downgraded by 1 level because of imprecision. Moxidectin was not inferior to ivermectin: OR 0.67, 95% CI 0.36–1.25 (P = 0.21), I2 = 0%, 821 participants. No deaths were reported in either trial. One trial reported mild adverse events. In total, 153/726 (21%) participants had an adverse event. The most reported symptoms were abdominal pain and headache. There is evidence for moderate quality that moxidectin is non-inferior to, and as safe as ivermectin; however, more high-quality and well-designed trials are needed. For patients with some underlying immunosuppressive disorder, or in patients who are very young or very old, current data are insufficient to be recommended.

Strongyloidiasis is a neglected tropical disease caused primarily by the roundworm Strongyloides stercoralis. Strongyloidiasis is most prevalent in Southeast Asia and the Western Pacific. Although cases have been documented worldwide, global prevalence is largely unknown due to limited surveillance. Infection of the definitive human host occurs via direct skin penetration of the infective filariform larvae. Parasitic females reside in the small intestine and reproduce via parthenogenesis, where eggs hatch inside the host before rhabditiform larvae are excreted in faeces to begin the single generation free-living life cycle. Rhabditiform larvae can also develop directly into infectious filariform larvae in the gut and cause autoinfection. Although many are asymptomatic, infected individuals may report a range of non-specific gastrointestinal, respiratory or skin symptoms. Autoinfection may cause hyperinfection and disseminated strongyloidiasis in immunocompromised individuals, which is often fatal. Diagnosis requires direct examination of larvae in clinical specimens, positive serology or nucleic acid detection. However, there is a lack of standardization of techniques for all diagnostic types. Ivermectin is the treatment of choice. Control and elimination of strongyloidiasis will require a multifaceted, integrated approach, including highly sensitive and standardized diagnostics, active surveillance, health information, education and communication strategies, improved water, sanitation and hygiene, access to efficacious treatment, vaccine development and better integration and acknowledgement in current helminth control programmes.

Primates are an important source of infectious disease in humans. Strongyloidiasis affects an estimated 600 million people worldwide, with a global distribution and hotspots of infection in tropical and subtropical regions. Recently added to the list of neglected tropical diseases, global attention has been demanded in the drive for its control. Through a literature review of Strongyloides in humans and non-human primates (NHP), we analysed the most common identification methods and gaps in knowledge about this nematode genus. The rise of molecular-based methods for Strongyloides detection is evident in both humans and NHP and provides an opportunity to analyse all data available from primates. Dogs were also included as an important host species of Strongyloides and a potential bridge host between humans and NHP. This review highlights the lack of molecular data across all hosts-humans, NHP and dogs-with the latter highly underrepresented in the database. Despite the cosmopolitan nature of Strongyloides, there are still large gaps in our knowledge for certain species when considering transmission and pathogenicity. We suggest that a unified approach to Strongyloides detection be taken, with an optimized, repeatable molecular-based method to improve our understanding of this parasitic infection. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'.

Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by Strongyloides stercoralis, a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.

Ivermectin and moxidectin, two macrocyclic lactones, are potent antiparasitic drugs currently registered and mainly used against filarial diseases; however, their potential value for improved soil-transmitted helminth (STH) control has been acknowledged. This review provides insights on recent studies evaluating the efficacy of ivermectin and moxidectin as single or coadministered therapy against human soil-transmitted helminthiases (including Strongyloides stercoralis infections) and on pharmacokinetic/pharmacodynamic parameters measured in treated populations. Furthermore, we discuss current gaps for research, highlight advantages - but also existing challenges - for uptake of ivermectin and/or moxidectin treatment schemes into routine STH control in endemic countries.

The World Health Organization 'Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021-2030' outlines the targets for control and elimination of neglected tropical diseases (NTDs). New drugs are needed to achieve some of them. We are providing an overview of the pipeline for new anti-infective drugs for regulatory registration and steps to effective use for NTD control and elimination. Considering drugs approved for an NTD by at least one stringent regulatory authority: fexinidazole, included in WHO guidelines for Trypanosoma brucei gambiense African trypanosomiasis, is in development for Chagas disease. Moxidectin, registered in 2018 for treatment of individuals ≥ 12 years old with onchocerciasis, is undergoing studies to extend the indication to 4-11-year-old children and obtain additional data to inform WHO and endemic countries' decisions on moxidectin inclusion in guidelines and policies. Moxidectin is also being evaluated for other NTDs. Considering drugs in at least Phase 2 clinical development, a submission is being prepared for registration of acoziborole as an oral treatment for first and second stage T.b. gambiense African trypanosomiasis. Bedaquiline, registered for tuberculosis, is being evaluated for multibacillary leprosy. Phase 2 studies of emodepside and flubentylosin in O. volvulus-infected individuals are ongoing; studies for Trichuris trichuria and hookworm are planned. A trial of fosravuconazole in Madurella mycetomatis-infected patients is ongoing. JNJ-64281802 is undergoing Phase 2 trials for reducing dengue viral load. Studies are ongoing or planned to evaluate oxantel pamoate for onchocerciasis and soil-transmitted helminths, including Trichuris, and oxfendazole for onchocerciasis, Fasciola hepatica, Taenia solium cysticercosis, Echinococcus granulosus and soil-transmitted helminths, including Trichuris. Additional steps from first registration to effective use for NTD control and elimination include country registrations, possibly additional studies to inform WHO guidelines and country policies, and implementation research to address barriers to effective use of new drugs. Relative to the number of people suffering from NTDs, the pipeline is small. Close collaboration and exchange of experience among all stakeholders developing drugs for NTDs may increase the probability that the current pipeline will translate into new drugs effectively implemented in affected countries.

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.

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.

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.