Efficacy and Safety of Adding 6 Weeks of Doxycycline to the Essential Package of Care to Treat Filarial Lymphedema: A Double-Blind, Randomized, Controlled Trial in Southern India.

Finding additional ways to manage lymphedema due to lymphatic filariasis (LF) is a primary concern for the Global Program to Eliminate Lymphatic Filariasis. The WHO-recommended Essential Package of Care (EPC) consists of skin hygiene, elevation of affected limbs, exercise, protective shoe ware, wound care, and supportive therapy for acute phases. The care program has been successful but often hard to maintain. A double-blind study reexamined previous findings that doxycycline treatment could improve the lymphedematous changes in LF patients. The present study was carried out in a semi-urban location of Kerala, southern India, where Brugia sp. is the predominant parasite, and LF mass drug administration had ceased in many areas. Two hundred individuals (aged 14-65 years; 142 females and 58 males) with lymphedema of stages 1-3 were instructed in the EPC and were randomly administered either 200 mg doxycycline or an identical-appearing placebo daily for 6 weeks. Data were collected at 0, 3, 6, 12, 18, and 24 months and included the state of the lymphedema (size, cleanliness, skin thickness and changes), occurrence of adenolymphangitis (ADL) attacks, and patients' quality of life (QOL). The results demonstrated no difference over time between the two arms of the study; virtually all patients of both groups showed either improvement or "no worsening" in the parameters during the 2-year study period. Importantly, this rigorous trial confirmed that the EPC is of substantial benefit to lymphedema patients by reducing acute ADL and improving their QOL and clinical condition.

Managing Lymphedema Induced by Lymphatic Filariasis: Implementing and Improving Care at the Individual and Programmatic Levels.

Providing and improving the care of patients suffering from lymphedema remains an essential goal for the clinical management of populations affected by lymphatic filariasis. Although the Essential Package of Care (EPC) recommended by the WHO leads to important positive benefits for many of these lymphedema patients, it is important to continue to address the challenges that remain both in quantifying these effects and in ensuring optimal care. This report, based on the authors' scientific and field experience, focuses on the impact and significance of lymphedema, its clinical presentation, current treatment approaches, and the importance of lymphedema care to the Global Program to Eliminate Lymphatic Filariasis. It emphasizes specific practical issues related to managing lymphedema, such as the importance of beginning treatment in the condition's early stages and the development of effective approaches to assess patients' progress toward improving both their clinical status and their overall quality of life. Priorities for research are also examined, particularly the need for tools to identify patients and to assess disease burden in endemic communities, the creation of EPC accessibility to as many patients as possible (i.e., targeting 100% "geographic coverage" of care), and the empowerment of patients to ensure the sustainability, and ultimately the provision of care from sectors of the national public health systems of endemic countries.

Elimination of lymphatic filariasis as a public health problem in Malawi.

BACKGROUND: Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, causing severe pain, disfiguring, and disabling clinical conditions such as lymphoedema and hydrocoele. LF is a global public health problem affecting 72 countries, primarily in Africa and Asia. Since 2000, the World Health Organization (WHO) has led the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support all endemic regions. This paper focuses on the achievements of the Malawi LF Elimination Programme between 2000 and 2020 to eliminate LF as a public health problem, making it the second sub-Saharan country to receive validation from the WHO. METHODOLOGY/PRINCIPAL FINDINGS: The Malawi LF Programme addressed the widespread prevalence of LF infection and disease across the country, using the recommended WHO GPELF strategies and operational research initiatives in collaboration with key national and international partners. First, to stop the spread of infection (i.e., interrupt transmission) and reduce the circulating filarial antigen prevalence from as high as 74.4% to below the critical threshold of 1-2% prevalence, mass drug administration (MDA) using a two-drug regime was implemented at high coverage rates (>65%) of the total population, with supplementary interventions from other programmes (e.g., malaria vector control). The decline in prevalence was monitored and confirmed over time using several impact assessment and post-treatment surveillance tools including the standard sentinel site, spot check, and transmission assessment surveys and alternative integrated, hotspot, and easy-access group surveys. Second, to alleviate suffering of the affected populations (i.e., control morbidity) the morbidity management and disability prevention (MMDP) package of care was implemented. Specifically, clinical case estimates were obtained via house-to-house patient searching activities; health personnel and patients were trained in self-care protocols for lymphoedema and/or referrals to hospitals for hydrocoele surgery; and the readiness and quality of treatment and services were assessed with new survey tools. CONCLUSIONS: Malawi's elimination of LF will ensure that future generations are not infected and suffer from the disfiguring and disabling disease. However, it will be critical that the Malawi LF Elimination programme remains vigilant, focussing on post-elimination surveillance and MMDP implementation and integration into routine health systems to support long-term sustainability and ongoing success. SUMMARY: Lymphatic filariasis, also known as elephantiasis, is a disabling, disfiguring, and painful disease caused by a parasite that infected mosquitoes transmit to millions of people worldwide. Since 2000, the Global Programme to Eliminate Lymphatic Filariasis (GPELF) has supported endemic countries such as Malawi in south-eastern Africa, to eliminate the disease as a public health problem. The Malawi National LF Elimination Programme has worked tirelessly over the past two decades to implement the GPELF recommended strategies to interrupt the transmission with a two-drug regime, and to alleviate suffering in patients with lymphoedema and/or hydrocoele through morbidity management and disability prevention. Additionally, the LF Programme has collaborated with national and international stakeholders to implement a range of supplementary operational research projects to address outstanding knowledge gaps and programmatic barriers. In 2020, the World Health Organisation validated that Malawi had successfully eliminated LF as a public health problem, making it the second country in sub-Saharan Africa to achieve this, which is remarkable given that Malawi previously had very high infection rates. The LF Programme now remains vigilant, putting its efforts towards post-elimination surveillance and the continued implementation of care for patients with chronic conditions. Malawi's elimination of LF will ensure that future generations are not affected by this devastating disease.

Successful completion of onchocerciasis elimination mapping (OEM) in Niger, West Africa.

BACKGROUND: By 1987, onchocerciasis in Niger had been successfully controlled in the six endemic river basins. In 2017, onchocerciasis elimination mapping (OEM) was carried out to determine if there was any ongoing transmission in the country as a whole. METHODS: The recommended OEM procedures were implemented. RESULTS: Ten districts, that included 35 villages, required field investigation as sites of possible transmission. None of these were found capable of supporting black fly breeding, nor was there any evidence of the presence of Simulium sp. flies. CONCLUSIONS: The implementation of OEM indicates that there is no transmission of onchocerciasis currently taking place in these newly assessed sites in Niger.

Investigating Flubendazole as an Anthelmintic Treatment for Guinea Worm (Dracunculus medinensis): Clinical Trials in Laboratory-Reared Ferrets and Domestic Dogs in Chad.

Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs.

Scaling-up filariasis lymphoedema management into the primary health care system in Kerala State, Southern India: a case study in healthcare equity.

BACKGROUND: Lymphatic filariasis (LF) remains one of the world's most debilitating parasitic infections and is a major contributor to poor health in many endemic countries. The provision of continuing care for all those affected by LF and its consequences is an important component of the United Nations' Sustainable Development Goals. The aim of this study is to integrate lymphedema care into the primary health care system of the State by developing lymphedema clinics at each district, through training of health personnel to fulfill WHO recommendation for morbidity management and disability prevention. METHODS: Selected health care providers from all the districts in Kerala State of India participated in intensive training sessions endorsed by the State's health administration. The six training sessions (from 5 June 2017 to 25 May 2018) included appropriate self-care information and development of individual plans for each participating institution to provide instruction and care for their lymphoedema patients. The learning achieved by attendees was assessed by pre- and post-training tests. The number of lymphoedema patients receiving care and instruction from the post-training activities of each participating institution was assessed from local records, 6 months after the conclusion of the training sessions. RESULTS: One hundred and eighty-four medical personnel (91 doctors and 93 nurses) from 82 medical institutions were trained which quickly led to the establishment of active lymphoedema clinics providing the essential package of care (EPC) for lymphoedema patients at all the participating institutions. Six months after the training sessions the number of previously unidentified lymphoedema patients registered and receiving care at these clinics ranged from 296 to almost 400 per clinic, with a total of 3,477 new patients receiving training in EPC. CONCLUSIONS: Generalist health personnel, when appropriately trained, can provide quality lymphoedema care in public health settings and patients when provided services close to their home, are willing to access them. This is a feasible strategy for integrating long term care for LF patients into the national health system, and is a clear example of moving towards equity in health care for the medically underserved, and thus successfully addresses a major goal of the global program to eliminate lymphatic filariasis.

Control of felinine-derived malodor in cat litter.

OBJECTIVES: Malodors stemming from soiled cat litter are a major frustration for cat owners, despite the widespread use of absorbent litters with claims of odor control. Technologies for effective litter odor control have not been rigorously evaluated. Here, we report on the effectiveness of a novel litter formulation of 1-monochlorodimethylhydantoin (MCDMH)-modified clinoptilolite zeolite (MCDMH-Z) to control the odors of 3-mercapto-3-methylbutanol (3M3MB) and ammonia, the principal products generated by the enzymatic breakdown of felinine and urea, respectively. METHODS: The efficacy of MCDMH-Z for the odor control of 3M3MB was determined by solid-phase microextraction and gas chromatography mass spectrometry analysis, colorimetric analysis and a sensory panel. Enzyme inhibition was monitored by a colorimetric coupled assay for ammonia. The antimicrobial properties were measured by a reduction in colony-forming units (CFUs). RESULTS: 3M3MB proved highly susceptible to modification by MCDMH-Z granules. Headspace above litter exposed to MCDMH-Z showed no detectable 3M3MB; levels >59 ng were detected in commercially available products. Urease activity decreased by >97% after incubation with MCDMH-Z to 0.14 mg/ml. Cat litter F showed comparable inhibition (0.13 mg/ml); others showed less inhibition, producing up to 4.8 mg/ml of ammonia. MCDMH-Z reduced the CFUs of Proteus vulgaris by six log reduction values in 30 mins; in the same amount of time, no reduction was seen with commercial products tested. The odor control capability of the MCDMH-Z granules was further supported by a sensory panel scoring 3M3MB-spiked litters. CONCLUSIONS AND RELEVANCE: Samples of commercially available litter products showed an effect on malodor, or inhibition of urease, or contained antimicrobial activity; no samples were capable of accomplishing these concurrently. In contrast, MCDMH-Z granules were effective in all three test categories. Control of felinine-derived odors, in particular, has the potential to improve cat owner satisfaction, and may beneficially affect cat behaviors provoked by pheromonally active sulfurous metabolites deposited in the litter.

A framework for scabies control.

Scabies is a neglected tropical disease (NTD) that causes a significant health burden, particularly in disadvantaged communities and where there is overcrowding. There is emerging evidence that ivermectin-based mass drug administration (MDA) can reduce the prevalence of scabies in some settings, but evidence remains limited, and there are no formal guidelines to inform control efforts. An informal World Health Organization (WHO) consultation was organized to find agreement on strategies for global control. The consultation resulted in a framework for scabies control and recommendations for mapping of disease burden, delivery of interventions, and establishing monitoring and evaluation. Key operational research priorities were identified. This framework will allow countries to set control targets for scabies as part of national NTD strategic plans and develop control strategies using MDA for high-prevalence regions and outbreak situations. As further evidence and experience are collected and strategies are refined over time, formal guidelines can be developed. The control of scabies and the reduction of the health burden of scabies and associated conditions will be vital to achieving the targets set in WHO Roadmap for NTDs for 2021 to 2030 and the Sustainable Development Goals.

Feasibility of Onchocerciasis Elimination Using a "Test-and-not-treat" Strategy in Loa loa Co-endemic Areas.

BACKGROUND: Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. METHODS: We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. RESULTS: In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months. CONCLUSIONS: Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

Caring for patients in the global programme to eliminate lymphatic filariasis.

Clinical lymphatic filariasis (LF) is a debilitating, disfiguring medical condition with severe psychosocial consequences for patients and their families. Addressing these patients' medical needs is a major component of the global programme to eliminate lymphatic filariasis (GPELF). In the 20 y of providing a minimal package of care many thousands of surgical operations to correct LF hydrocoeles been performed and national programmes in >90% of LF endemic countries have received the training needed to care for their patients. The creation of educational materials detailing appropriate patient care, together with increased funding, have been key catalysts in increasing awareness of clinical LF in recent years. Nevertheless, the implementation of care for these patients has often faced challenges that have led to delays in fully implementing the patient care component of GPELF; these include locating these often stigmatised individuals, maintaining provision of the necessary consumables (e.g. soaps and creams) and maintaining programme support within already overstretched national LF teams. As the LF global programme moves to achieve success by 2030 it will be vital to continue to focus efforts on the care and rehabilitation of those suffering from lymphoedema and hydrocoeles, learning from the experiences of the past 20 y.

Podoconiosis: key priorities for research and implementation.

Podoconiosis is a non-infectious tropical lymphoedema causing swelling of the lower legs. Podoconiosis is associated with stigma, depression and reduced productivity, resulting in significant socio-economic impacts for affected individuals, families and communities. It is caused by barefoot exposure to soils and affects disadvantaged populations. Evidence from the past 5 y suggests that podoconiosis is amenable to public health interventions, e.g. footwear and hygiene-based morbidity management, which reduce acute clinical episodes. Although much has been learned in recent years, advances in care for these patients and worldwide control requires further reliable and relevant research. To develop a comprehensive global control strategy, the following key research priorities are important: better understanding of the global burden of podoconiosis through extended worldwide mapping, development of new point-of-care diagnostic methods and approaches to define the presence of the environmental characteristics that contribute to the development of the condition, improving treatment through an increased understanding of the pathogenesis of dermal changes over time, improved understanding of optimal ways of providing patient care at the national level, including research to optimize behavioural change strategies, determine the optimum package of care and integrate approaches to deliver robust surveillance, monitoring and evaluation of control programmes.

Community-based door to door census of suspected people living with epilepsy: empowering community drug distributors to improve the provision of care to rural communities in Cameroon.

BACKGROUND: Epilepsy is a severe neurological disorder with huge psychological, social, and economic consequences, including premature deaths and loss of productivity. Sub-Saharan Africa carries the highest burden of epilepsy. The management of epilepsy in Cameroon remains unsatisfactory due to poor identification of cases and a limited knowledge of the distribution of the disease. The objective of this study was to determine whether community drug distributors (CDDs) - volunteers selected by their communities to distribute ivermectin against onchocerciasis and who have been proven efficient to deliver other health interventions such as insecticide-treated bed nets to prevent malaria, vitamin A tablets, and albendazole to treat soil transmitted helminthiasis - can be used to reliably identify people living with epilepsy to promote better management of cases. METHODS: This study was carried out in three health Districts in Cameroon. An exhaustive house to house census was carried out by trained CDDs under the supervision of local nurses. In each household, all suspected cases of epilepsy were identified. In each health district, five communities were randomly selected for a second census by trained health personnel (research team). The results of the two censuses were compared for verification purposes. RESULTS: A total of 53,005 people was registered in the 190 communities surveyed with 794 (1.4%) individuals identified as suspected cases of epilepsy (SCE) by the CDDs. In the 15 communities where the SCE census was verified, the average ratio between the number of suspected cases of epilepsy reported in a community by the research team and that reported by the CDDs was 1.1; this ratio was < 0.8 and > 1.2 in 6 communities. CONCLUSIONS: The results of this study suggest that CDDs, who are present in about 200,000 communities in 31 Sub Saharan African countries where onchocerciasis is endemic, can be successfully used to assess epilepsy prevalence, and therefore map epilepsy in many African countries.

Elimination of onchocerciasis in Africa by 2025: an ambitious target requires ambitious interventions.

To achieve the elimination of onchocerciasis transmission in all African countries will entail enormous challenges, as has been highlighted by the active discussion around onchocerciasis intervention strategies and evaluation procedures in this journal.Serological thresholds for onchocerciasis elimination, adapted for the African setting, need to be established. The Onchocerciasis Technical Advisory Subgroup of the World Health Organization is currently developing improved guidelines to allow country elimination committees to make evidence-based decisions. Importantly, onchocerciasis-related morbidity should not be forgotten when debating elimination prospects. A morbidity management and disease prevention (MMDP) strategy similar to that for lymphatic filariasis will need to be developed. This will require collaboration between the onchocerciasis elimination program, the community and other partners including primary health and mental health programs.In order to reach the goal of onchocerciasis elimination in most African countries by 2025, we should prioritize community participation and advocate for tailored interventions which are scientifically proven to be effective, but currently considered to be too expensive.

The public health control of scabies: priorities for research and action.

Scabies is a parasitic disease of the skin that disproportionately affects disadvantaged populations. The disease causes considerable morbidity and leads to severe bacterial infection and immune-mediated disease. Scientific advances from the past 5 years suggest that scabies is amenable to population-level control, particularly through mass drug administration. In recognition of these issues, WHO added scabies to the list of neglected tropical diseases in 2017. To develop a global control programme, key operational research questions must now be addressed. Standardised approaches to diagnosis and methods for mapping are required to further understand the burden of disease. The safety of treatments for young children, including with ivermectin and moxidectin, should be investigated. Studies are needed to inform optimum implementation of mass treatment, including the threshold for intervention, target, dosing, and frequency. Frameworks for surveillance, monitoring, and evaluation of control strategies are also necessary.

Loa loa Microfilariae in Skin Snips: Consequences for Onchocerciasis Monitoring and Evaluation in L. loa-Endemic Areas.

The specificity of skin snips for onchocerciasis diagnoses is considered to be almost 100%. Our molecular methods revealed that microfilariae emerging from skin snips collected from highly microfilaremic Loa loa-infected individuals were largely misidentified as Onchocerca volvulus. This has important implications for onchocerciasis diagnostic testing in Loa-endemic areas.

Macrofilaricidal efficacy of single and repeated oral and subcutaneous doses of flubendazole in Litomosoides sigmodontis infected jirds.

Flubendazole (FBZ) is highly efficacious against filarial nematodes after parenteral administration and presents a promising macrofilaricidal drug candidate for the elimination of onchocerciasis and other filariae. In the present study the efficacy of a newly developed bioavailable amorphous solid dispersion (ASD) oral formulation of FBZ was investigated in the Litomosoides sigmodontis jird model. FBZ was administered to chronically infected, microfilariae-positive jirds by single (40mg/kg), repeated (2, 6 or 15mg/kg for 5 or 10 days) oral (OR) doses or single subcutaneous (SC) injections (2 or 10mg/kg). Jirds treated with 5 SC injections at 10mg/kg served as positive controls, with untreated animals used as negative controls. After OR doses, FBZ is rapidly absorbed and cleared and the exposures increased dose proportionally. SC administered FBZ was slowly released from the injection site and plasma levels remained constant up to necropsy eight weeks after treatment end. Increasing single SC doses caused less than dose-proportional exposures. At necropsy, all animals receiving 1x or 5x 10mg/kg SC FBZ had cleared all adult worms and the 1x 2mg/kg SC treatment had reduced the adult worm burden by 98%. 10x 15mg/kg OR FBZ reduced the adult worm burden by 95%, whereas 1x 40mg/kg and 5x 15mg/kg OR reduced the worm burden by 85 and 84%, respectively. Microfilaremia was completely cleared at necropsy in all animals of the SC treatment regimens, while all oral FBZ treatment regimens reduced the microfilaremia by >90% in a dose and duration dependent manner. In accordance, embryograms from female worms revealed a FBZ dose and duration dependent inhibition of embryogenesis. Histological analysis of the remaining female adult worms showed that FBZ had damaged the body wall, intestine and most prominently the uterus and uterine content. Results of this study demonstrate that single and repeated SC injections and repeated oral administrations of FBZ have an excellent macrofilaricidal effect.

Flubendazole as a macrofilaricide: History and background.

Benzimidazole anthelmintics have long been employed for the control of soil-transmitted helminth infections. Flubendazole (FBZ) was approved in 1980 for the treatment of gastrointestinal nematode infections in both veterinary and human medicine. It has also long been known that parenteral administration of FBZ can lead to high macrofilaricidal efficacy in a variety of preclinical models and in humans. As part of an effort to stimulate the discovery and development of new macrofilaricides, particularly for onchocerciasis, research has recently been devoted to the development of new formulations that would afford high oral bioavailability of FBZ, paving the way for potential clinical development of this repurposed drug for the treatment of human filariases. This review summarizes the background information that led to this program and summarizes some of the lessons learned from it.

Effect of flubendazole on developing stages of Loa loa in vitro and in vivo: a new approach for screening filaricidal agents.

BACKGROUND: Loiasis, an often-neglected tropical disease, is a threat to the success of lymphatic filariasis and onchocerciasis elimination programmes in rainforest areas of the central and western Africa. Its control and even its elimination might be possible through the use of a safe macrofilaricide, a prophylactic drug, or perhaps a vaccine. This present study evaluated the effect of flubendazole (FLBZ) on the development of Loa loa L3 in vitro and in vivo. METHODS: Infective stages of L. loa were isolated and co-cultured in Dulbecco's Modified Eagle's Medium in the presence of monkey kidney epithelial cells (LLC-MK2) feeder cells. FLBZ and its principal metabolites, reduced flubendazole (RFLBZ) and hydrolyzed flubendazole (HFLBZ), were screened in vitro at concentrations 0.05, 0.1, 0.5, 1 and 10 µg/ml. The viability of the parasites was assessed microscopically daily for 15 days. For in vivo study, a total of 48 CcR3 KO mice were infected subcutaneously with 200 L. loa L3 and treated with 10 mg/kg FLBZ once daily for 5 consecutive days. Twenty-four animals were used as control and received L3 and vehicle. They were dissected at 5, 10, 15 and 20 days post-treatment for worm recovery. RESULTS: The motility of L3 larvae in vitro was reduced from the second day of incubation with drugs at in vivo plasma concentration levels, with a strong correlation found between reduced motility and increased drug concentration (Spearman's rho = -0.9, P < 0.0001). Except for HFLBZ (0.05 µg/ml and 0.01 µg/ml), all concentrations of FLBZ, HFLBZ and RFLBZ interrupted the moulting of L. loa infective larvae to L4. In vivo, regardless of the experimental group, there was a decrease in parasite recovery with time. However, at each time point this reduction was more pronounced in the group of animals treated with FLBZ compared to equivalent control. Parasites were recovered from the flubendazole-treated groups only on day 5 post-inoculation at an average rate of 2.1%, a value significantly lower (Mann-Whitney U-test, U = 28, P = 0.0156) than the average of 31.1% recovered from the control group. CONCLUSIONS: This study reveals the ability of flubendazole to inhibit the development of L. loa L3 both in vitro and in vivo, and in addition validates the importance of in vitro and animal models of L. loa as tools for the development of drugs against loiasis.