An Updated Economic Assessment of Moxidectin Treatment Strategies for Onchocerciasis Elimination.

BACKGROUND: Concerns that annual mass administration of ivermectin, the predominant strategy for onchocerciasis control and elimination, may not lead to elimination of parasite transmission (EoT) in all endemic areas have increased interest in alternative treatment strategies. One such strategy is moxidectin. We performed an updated economic assessment of moxidectin- relative to ivermectin-based strategies. METHODS: We investigated annual and biannual community-directed treatment with ivermectin (aCDTI, bCDTI) and moxidectin (aCDTM, bCDTM) with minimal or enhanced coverage (65% or 80% of total population taking the drug, respectively) in intervention-naive areas with 30%, 50%, or 70% microfilarial baseline prevalence (representative of hypo-, meso-, and hyperendemic areas). We compared programmatic delivery costs for the number of treatments achieving 90% probability of EoT (EoT90), calculated with the individual-based stochastic transmission model EPIONCHO-IBM. We used the costs for 40 years of program delivery when EoT90 was not reached earlier. The delivery costs do not include drug costs. RESULTS: aCDTM and bCDTM achieved EoT90 with lower programmatic delivery costs than aCDTI with 1 exception: aCDTM with minimal coverage did not achieve EoT90 in hyperendemic areas within 40 years. With minimal coverage, bCDTI delivery costs as much or more than aCDTM and bCDTM. With enhanced coverage, programmatic delivery costs for aCDTM and bCDTM were lower than for aCDTI and bCDTI. CONCLUSIONS: Moxidectin-based strategies could accelerate progress toward EoT and reduce programmatic delivery costs compared with ivermectin-based strategies. The costs of moxidectin to national programs are needed to quantify whether delivery cost reductions will translate into overall program cost reduction.

Predictive Value of Microfilariae-Based Stop-MDA Thresholds After Triple Drug Therapy With IDA Against Lymphatic Filariasis in Treatment-Naive Indian Settings.

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low.

How Does the Proportion of Never Treatment Influence the Success of Mass Drug Administration Programs for the Elimination of Lymphatic Filariasis?

BACKGROUND: Mass drug administration (MDA) is the cornerstone for the elimination of lymphatic filariasis (LF). The proportion of the population that is never treated (NT) is a crucial determinant of whether this goal is achieved within reasonable time frames. METHODS: Using 2 individual-based stochastic LF transmission models, we assess the maximum permissible level of NT for which the 1% microfilaremia (mf) prevalence threshold can be achieved (with 90% probability) within 10 years under different scenarios of annual MDA coverage, drug combination and transmission setting. RESULTS: For Anopheles-transmission settings, we find that treating 80% of the eligible population annually with ivermectin + albendazole (IA) can achieve the 1% mf prevalence threshold within 10 years of annual treatment when baseline mf prevalence is 10%, as long as NT <10%. Higher proportions of NT are acceptable when more efficacious treatment regimens are used. For Culex-transmission settings with a low (5%) baseline mf prevalence and diethylcarbamazine + albendazole (DA) or ivermectin + diethylcarbamazine + albendazole (IDA) treatment, elimination can be reached if treatment coverage among eligibles is 80% or higher. For 10% baseline mf prevalence, the target can be achieved when the annual coverage is 80% and NT ≤15%. Higher infection prevalence or levels of NT would make achieving the target more difficult. CONCLUSIONS: The proportion of people never treated in MDA programmes for LF can strongly influence the achievement of elimination and the impact of NT is greater in high transmission areas. This study provides a starting point for further development of criteria for the evaluation of NT.

Application of eprinomectin-containing parasiticides at label doses causes neurological toxicosis in cats homozygous for ABCB11930_1931del TC.

The feline MDR1 mutation (ABCB11930_1931delTC) has been associated with neurological toxicosis after topical application of eprinomectin products labeled for feline use. Information was collected from veterinarians who submitted samples for ABCB11930_1931delTC genotyping. In most cases, the submission form indicated an adverse event involving eprinomectin, in other cases submitting veterinarians were contacted to determine whether the patient had experienced an adverse drug event involving eprinomectin. If so, additional information was obtained to determine whether the case met inclusion criteria. 14 cases were highly consistent with eprinomectin toxicosis. Eight cats were homozygous for ABCB11930_1931del TC (3 died; 5 recovered). Six cats were homozygous wildtype (2 died; 4 recovered). The observed ABCB11930_1931delTC frequency (57%) was higher than the expected frequency (≤1%) in the feline population (Fisher Exact test, p < 0.01). Among wildtype cats, four were concurrently treated with potential competitive inhibitors of P-glycoprotein. Results indicate that topical eprinomectin products, should be avoided in cats homozygous for ABCB11930_1931delTC. This is a serious, preventable adverse event occurring in an identifiable subpopulation treated with FDA-approved products in accordance with label directions. Acquired P-glycoprotein deficiency resulting from drug interactions may enhance susceptibility to eprinomectin-induced neurological toxicosis in any cat, regardless of ABCB1 genotype.

Epidemia de escabiosis: los nuevos retos de una enfermedad ancestral / Epidemic Scabies: New Treatment Challenges in an Ancient Disease

La escabiosis es una de las enfermedades transmisibles más prevalentes en el mundo, actualmente en auge en nuestro entorno. Existen diferentes causas que explican la problemática de esta epidemia: una incorrecta aplicación o pauta del tratamiento; la disminución de la sensibilidad o la resistencia al tratamiento tópico y las carencias en el conocimiento del parásito y su transmisibilidad. Por este motivo es necesario un nuevo enfoque en el tratamiento de esta enfermedad que contemple los problemas y la evidencia actual. Si hay una persistencia de la clínica tras un correcto tratamiento es importante corroborar el fracaso terapéutico y estandarizar la actitud. Por último, ante un caso recalcitrante cabría plantear la posibilidad de priorizar el tratamiento oral, aumentar su dosis, realizar tratamientos combinados o plantear su uso fuera de ficha técnica en poblaciones especiales. La aparición de nuevos tratamientos, como el spinosad o, sobre todo, la moxidectina, aportan esperanza en el control de esta enfermedad (AU)

Scabies, which is among the most prevalent diseases worldwide, is becoming more frequent in Spain. The problems of this epidemic can be explained by several factors: improper application or prescription of treatments, resistance or reduced sensitivity to topical treatments, and poor understanding of the parasite and contagion. We require a new evidence-based approach to therapy that takes these problems into consideration. If symptoms persist after proper treatment, it is important to identify the reason for failure and standardize our approach. In refractory cases, the prescriber should prioritize oral medication, indicate a higher dose, combine treatments, or evaluate the use of off-label treatments in certain populations. The availability of new medications —such as spinosad or, especially, moxidectin— offer hope for bringing this disease under control (AU)

[Translated article] Epidemic Scabies: New Treatment Challenges in an Ancient Disease / Epidemia de escabiosis: los nuevos retos de una enfermedad ancestral

Scabies, which is among the most prevalent diseases worldwide, is becoming more frequent in Spain. The problems of this epidemic can be explained by several factors: improper application or prescription of treatments, resistance or reduced sensitivity to topical treatments, and poor understanding of the parasite and contagion. We require a new evidence-based approach to therapy that takes these problems into consideration. If symptoms persist after proper treatment, it is important to identify the reason for failure and standardize our approach. In refractory cases, the prescriber should prioritize oral medication, indicate a higher dose, combine treatments, or evaluate the use of off-label treatments in certain populations. The availability of new medications —such as spinosad or, especially, moxidectin— offer hope for bringing this disease under control (AU)

La escabiosis es una de las enfermedades transmisibles más prevalentes en el mundo, actualmente en auge en nuestro entorno. Existen diferentes causas que explican la problemática de esta epidemia: una incorrecta aplicación o pauta del tratamiento; la disminución de la sensibilidad o la resistencia al tratamiento tópico y las carencias en el conocimiento del parásito y su transmisibilidad. Por este motivo es necesario un nuevo enfoque en el tratamiento de esta enfermedad que contemple los problemas y la evidencia actual. Si hay una persistencia de la clínica tras un correcto tratamiento es importante corroborar el fracaso terapéutico y estandarizar la actitud. Por último, ante un caso recalcitrante cabría plantear la posibilidad de priorizar el tratamiento oral, aumentar su dosis, realizar tratamientos combinados o plantear su uso fuera de ficha técnica en poblaciones especiales. La aparición de nuevos tratamientos, como el spinosad o, sobre todo, la moxidectina, aportan esperanza en el control de esta enfermedad (AU)

Entomological impact of mass administration of ivermectin and dihydroartemisinin-piperaquine in The Gambia: a cluster-randomized controlled trial.

BACKGROUND: Vector control interventions in sub-Saharan Africa rely on insecticide-treated nets and indoor residual spraying. Insecticide resistance, poor coverage of interventions, poor quality nets and changes in vector behavior threaten the effectiveness of these interventions and, consequently, alternative tools are needed. Mosquitoes die after feeding on humans or animals treated with ivermectin (IVM). Mass drug administration (MDA) with IVM could reduce vector survival and decrease malaria transmission. The entomological impact of MDA of combined IVM and dihydroartemisinin-piperaquine was assessed in a community-based, cluster-randomized trial. METHODS: A cluster-randomized trial was implemented in 2018 and 2019 in 32 villages in the Upper River Region, The Gambia. The with the inhabitants of 16 intervention villages eligible to receive three monthly rounds of MDA at the beginning of the malaria transmission season. Entomological surveillance with light traps and human landing catches (HLC) was carried out during a 7- to 14-day period after each round of MDA, and then monthly until the end of the year. The mosquitocidal effect of IVM was determined by direct membrane feeding assays. RESULTS: Of the 15,017 mosquitoes collected during the study period, 99.65% (n = 14,965) were Anopheles gambiae sensu lato (An. gambiae s.l.), comprising Anopheles arabiensis (56.2%), Anopheles coluzzii (24.5%), Anopheles gambiae sensu stricto (An. gembiae s.s.; 16.0%) and Anopheles funestus sensu lato (An. funestus s.l.; 0.35%). No effect of the intervention on vector parity was observed. Vector density determined on light trap collections was significantly lower in the intervention villages in 2019 (adjusted incidence rate ratio: 0.39; 95% confidence interval [CI]: 0.20, 0.74; P = 0.005) but not in 2018. However, vector density determined in HLC collections was similar in both the intervention and control villages. The entomological inoculation rate was significantly lower in the intervention villages than in the control villages (odds ratio: 0.36, 95% CI: 0.19, 0.70; P = 0·003). Mosquito mortality was significantly higher when blood fed on IVM-treated individuals up to 21 days post-treatment, particularly in adults and individuals with a higher body mass index. CONCLUSION: Mass drug administration with IVM decreased vector density and the entomological inoculation rate while the effect on vector parity was less clear. Survival of mosquitoes fed on blood collected from IVM-treated individuals was significantly lower than that in mosquitoes which fed on controls. The influence of host characteristics on mosquito survivorship indicated that dose optimization could improve IVM efficacy. Future detailed entomological evaluation trials in which IVM is administered as stand-alone intervention may elucidate the contribution of this drug to the observed reduction in transmission.

Costs of mass drug administration for scabies in Fiji.

In 2019, the Murdoch Children's Research Institute in partnership with the Fiji Ministry of Health and Medical Services carried out an integrated mass drug administration (MDA) for the treatment of scabies and lymphatic filariasis in the Northern Division of Fiji (population estimate 131,914). We conducted a retrospective micro-costing exercise focused on the cost of scabies control in order to inform budgeting and policy decision making in an endemic setting. We collected detailed information on financial and economic costs incurred by both parties during the course of the MDA campaign (April 2018 to July 2019). We also conducted interviews with personnel involved in the financial administration of the MDA campaign. The economic cost of delivering two doses of ivermectin was US$4.88 per person. The cost of donated drugs accounted for 36.3% of total MDA costs. In this first large-scale MDA for the public health control of scabies, the estimated cost of delivering MDA per person for scabies was considerably more expensive than the costs reported for other neglected tropical diseases. The important cost drivers included the remuneration of health care workers who were extensively involved in the campaign, coverage of hard-to-reach, mainly rural populations and the two-dose regimen of ivermectin. These results highlight the importance of these cost determinants and can be used to plan current and future MDA programs.

Repurposing the drug, ivermectin, in COVID-19: toxicological points of view.

The global COVID-19 pandemic has affected the world's population by causing changes in behavior, such as social distancing, masking, restricting people's movement, and evaluating existing medication as potential therapies. Many pre-existing medications such as tocilizumab, ivermectin, colchicine, interferon, and steroids have been evaluated for being repurposed to use for the treatment of COVID-19. None of these agents have been effective except for steroids and, to a lesser degree, tocilizumab. Ivermectin has been one of the suggested repurposed medications which exhibit an in vitro inhibitory activity on SARS-CoV-2 replication. The most recommended dose of ivermectin for the treatment of COVID-19 is 150-200 µg/kg twice daily. As ivermectin adoption for COVID-19 increased, the Food and Drug Administration (FDA) issued a warning on its use during the pandemic. However, the drug remains of interest to clinicians and has shown some promise in observational studies. This narrative reviews the toxicological profile and some potential therapeutic effects of ivermectin. Based on the current dose recommendation, ivermectin appears to be safe with minimum side effects. However, serious questions remain about the effectiveness of this drug in the treatment of patients with COVID-19.

Safety and efficacy of mass drug administration with a single-dose triple-drug regimen of albendazole + diethylcarbamazine + ivermectin for lymphatic filariasis in Papua New Guinea: An open-label, cluster-randomised trial.

BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG. METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, Madang Province, PNG were enrolled, screened for W. bancrofti antigenemia and microfilaria (Mf) and randomised to receive IDA (N = 2382) or DA (N = 2181) according to their village of residence. Adverse events (AE) were assessed by active follow-up for 2 days and passive follow-up for an additional 5 days. Antigen-positive participants were re-tested one year after MDA to assess treatment efficacy. PRINCIPAL FINDINGS: Of the 4,563 participants enrolled, 96% were assessed for AEs within 2 days after treatment. The overall frequency of AEs were similar after either DA (18%) or IDA (20%) treatment. For those individuals with AEs, 87% were mild (Grade 1), 13% were moderate (Grade 2) and there were no Grade 3, Grade 4, or serious AEs (SAEs). The frequency of AEs was greater in Mf-positive than Mf-negative individuals receiving IDA (39% vs 20% p<0.001) and in Mf-positive participants treated with IDA (39%), compared to those treated with DA (24%, p = 0.023). One year after treatment, 64% (645/1013) of participants who were antigen-positive at baseline were re-screened and 74% of these participants (475/645) remained antigen positive. Clearance of Mf was achieved in 96% (52/54) of infected individuals in the IDA arm versus 84% (56/67) of infected individuals in the DA arm (relative risk (RR) 1.15; 95% CI, 1.02 to 1.30; p = 0.019). Participants receiving DA treatment had a 4-fold higher likelihood of failing to clear Mf (RR 4.67 (95% CI: 1.05 to 20.67; p = 0.043). In the DA arm, a significant predictor of failure to clear was baseline Mf density (RR 1.54; 95% CI, 1.09 to 2.88; p = 0.007). CONCLUSION: IDA was well tolerated and more effective than DA for clearing Mf. Widespread use of this regimen could accelerate LF elimination in PNG. TRIAL REGISTRATION: Registration number NCT02899936; https://clinicaltrials.gov/ct2/show/NCT02899936.

Impact of ivermectin mass drug administration on burden of soil-transmitted helminths in onchocerciasis control and elimination programs, Yeki district, southwest Ethiopia.

Community-directed treatment with ivermectin (CDTi) is the primary strategy employed to control and eliminate human onchocerciasis in Ethiopia. After long-term mass distribution for onchocerciasis, ivermectin is expected to have additional benefits beyond the envisioned targets by reducing the burden of other co-endemic parasitic infections as to STHs. To date, studies focused on the collateral impact of CDTi on STH in Ethiopia are scanty. Two community-based cross-sectional surveys (baseline in 1997 and post-CDTi in 2017) were conducted to evaluate the impact of long-term CDTi employed to control and eliminate onchocerciasis on the burden of STH infections in Yeki district of southwest Ethiopia. Stool samples were collected and examined using Ritchie`s concentration and Kato-Katz techniques in the baseline and current study, respectively. Overall, 188(38.3%, 95% Confidence interval (CI) 34.1-42.7%) individuals were positive at least for any of the STH species from 491 study participants in the post-CDTi. The prevalence of A. lumbricoides, hookworms, and T. trichiura was 11.2% (95% CI 8.7-14.3%), 16.3% (95% CI 13.3-19.8%), and 29.9% (95% CI 26.1-34.1%), respectively. Individuals aged 5-9 years had a significantly higher prevalence of A. lumbricoides (Adjusted odds ratio (AOR) 6.5, 95% CI 1.7-25.4), T. trichuria (AOR 8, 95% CI 2.6-25.1), and any STH infection (AOR 5, 95% CI 1.7-14.7) than those of ≥ 51 years. Also, significantly higher prevalences of T. trichuria infection were observed in individuals aged 10-14 years (AOR 4.1, 95% CI 1.7-9.9), 15-20 years (AOR 3.1, 95% CI 1.2-8.1), 21-30 years (AOR 2.4, 95% CI 1.1-5.5), and 31-40 years (AOR 3.2, 95% CI 1.3-7.5) compared with those of ≥ 51 years. The prevalence of A. lumbricoides was significantly higher in males (AOR 0.5, 95% CI 0.3-0.9). Of the 491 study participants, only data from 400 individuals who had not been involved in a mass drug administration (MDA) with other STH anthelmintics were considered in the comparative analysis. Before CDTi, the prevalence of A. lumbricoides, T. trichiura, hookworm, and any STH infection was 47.1% (95% CI 41.6-52.7%), 3.3% (95% CI 1.8-5.9%), 37.9% (95% CI 32.7-43.5%), and 58.8% (95% CI 53.2-64.1%), respectively. Long-term CDTi considerably reduced the prevalences of A. lumbricoides and hookworm by 76.2% and 56.9%, respectively (p < 0.001). Nonetheless, CDTi did not affect the prevalence of T. trichiura infection and, in contrast, it was significantly higher in the current study (P < 0.001). Overall post-CDTi prevalence of any STH infection was considerably lower than reported in the baseline (p < 0.001). It is evidenced that long-term CDTi for onchocerciasis control and elimination had additional benefits by reducing the prevalence of STH infections specifically of A. lumbricoides and hookworm, but had no impact on infections with T. trichuria. Our finding of additional health benefits of large-scale ivermectin administration taking it will aid to increase positive engagement and sustain participation of communities during MDA campaigns, and strengthen governmental and non-governmental organizations (NGOs) support for the undergoing national onchocerciasis elimination program.

Quantitative Analysis of Abamectin, Albendazole, Levamisole HCl and Closantel in Q-DRENCH Oral Suspension Using a Stability-Indicating HPLC-DAD Method.

Combination therapy of many anthelmintic drugs has been used to achieve fast animal curing. Q-DRENCH is an oral suspension, containing four different active drugs against GIT worms in sheep, commonly used in Australia and New Zeeland. The anti-parasitic drugs are Albendazole (ALB), Levamisole HCl (LEV), Abamectin (ABA), and Closantel (CLO). The main purpose of this study is to present a new simultaneous stability-indicting HPLC-DAD method for the analysis of the four drugs. The recommended liquid system was 1 mL of Triethylamine/L water, adjusting the pH to 3.5 by glacial acetic acid: acetonitrile solvent (20:80, v/v). Isocratic elusion achieved the desired results of separation at a 2 mL/min flow rate using Zorbax C-18 as a stationary phase. Detection was performed at 210 nm. The linearity ranges were 15.15 to 93.75 µg/mL for ALB, 25 to 150 µg/mL for LEV, 30 to 150 µg/mL for ABA, and 11.7 to 140.63 µg/mL for CLO. Moreover, the final greenness score was 0.62 using the AGREE tool, which reflects the eco-friendly nature. Moreover, the four drugs were determined successfully in the presence of their stressful degradation products. This work presents the first chromatographic method for simultaneous analysis for Q-DRENCH oral suspension drugs in the presence of their stressful degradation products.

Ivermectin as an endectocide may boost control of malaria vectors in India and contribute to elimination.

Malaria constitutes one of the largest public health burdens faced by humanity. Malaria control has to be an efficient balance between diagnosis, treatment and vector control strategies. The World Health Organization currently recommends indoor residual spraying and impregnated bed nets as two malaria vector control methods that have shown robust and persistent results against endophilic and anthropophilic mosquito species. The Indian government launched the National Framework for Malaria Elimination in 2016 with the aim to achieve the elimination of malaria in a phased and strategic manner and to sustain a nation-wide malaria-free status by 2030. India is currently in a crucial phase of malaria elimination and novel vector control strategies maybe helpful in dealing with various challenges, such as vector behavioural adaptations and increasing insecticide resistance among the Anopheles populations of India. Ivermectin can be one such new tool as it is the first endectocide to be approved in both animals and humans. Trials of ivermectin have been conducted in endemic areas of Africa with promising results. In this review, we assess available data on ivermectin as an endectocide and propose that this endectocide should be explored as a vector control tool for malaria in India.

Mass drug administration of ivermectin and dihydroartemisinin-piperaquine against malaria in settings with high coverage of standard control interventions: a cluster-randomised controlled trial in The Gambia.

BACKGROUND: Although the malaria burden has substantially decreased in sub-Saharan Africa, progress has stalled. We assessed whether mass administration of ivermectin (a mosquitocidal drug) and dihydroartemisinin-piperaquine (an antimalarial treatment) reduces malaria in The Gambia, an area with high coverage of standard control interventions. METHODS: This open-label, cluster-randomised controlled trial was done in the Upper River region of eastern Gambia. Villages with a baseline Plasmodium falciparum prevalence of 7-46% (all ages) and separated from each other by at least 3 km to reduce vector spillover were selected. Inclusion criteria were age and anthropometry (for ivermectin, weight of ≥15 kg; for dihydroartemisinin-piperaquine, participants older than 6 months); willingness to comply with trial procedures; and written informed consent. Villages were randomised (1:1) to either the intervention (ivermectin [orally at 300-400 µg/kg per day for 3 consecutive days] and dihydroartemisinin-piperaquine [orally depending on bodyweight] plus standard control interventions) or the control group (standard control interventions) using computer-based randomisation. Laboratory staff were masked to the origin of samples. In the intervention group, three rounds of mass drug administration once per month with ivermectin and dihydroartemisinin-piperaquine were given during two malaria transmission seasons from Aug 27 to Oct 31, 2018, and from July 15 to Sept 30, 2019. Primary outcomes were malaria prevalence by qPCR at the end of the second intervention year in November 2019, and Anopheles gambiae (s l) parous rate, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03576313. FINDINGS: Between Nov 20 and Dec 7, 2017, 47 villages were screened for eligibility in the study. 15 were excluded because the baseline malaria prevalence was less than 7% (figure 1). 32 villages were enrolled and randomised to either the intervention or control group (n=16 in each group). The study population was 10 638, of which 4939 (46%) participants were in intervention villages. Coverage for dihydroartemisinin-piperaquine was between 49·0% and 58·4% in 2018, and between 76·1% and 86·0% in 2019; for ivermectin, coverage was between 46·9% and 52·2% in 2018, and between 71·7% and 82·9% in 2019. In November 2019, malaria prevalence was 12·8% (324 of 2529) in the control group and 5·1% (140 of 2722) in the intervention group (odds ratio [OR] 0·30, 95% CI 0·16-0·59; p<0·001). A gambiae (s l) parous rate was 83·1% (552 of 664) in the control group and 81·7% (441 of 540) in the intervention group (0·90, 0·66-1·25; p=0·537). In 2019, adverse events were recorded in 386 (9·7%) of 3991 participants in round one, 201 (5·4%) of 3750 in round two, and 168 (4·5%) of 3752 in round three. None of the 11 serious adverse events were related to the intervention. INTERPRETATION: The intervention was safe and well tolerated. In an area with high coverage of standard control interventions, mass drug administration of ivermectin and dihydroartemisinin-piperaquine significantly reduced malaria prevalence; however, no effect of ivermectin on vector parous rate was observed. FUNDING: Joint Global Health Trials Scheme. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Concurrent subcutaneous and ocular infections with Dirofilaria repens in a Polish patient: a case report in the light of epidemiological data.

Dirofilariasis is an emerging zoonosis caused by nematodes of the genus Dirofilaria, most often D. repens and D. immitis. The main final hosts and reservoirs of pathogens are dogs. The intermediate hosts and vectors of infection are female mosquitoes (Culicidae). Human is an accidental host in which the parasite does not usually mature. Over the past 20 years, the range of Dirofilaria spp. in Europe has expanded. We present an unusual case of multifocal dirofilariasis of mixed subcutaneous-ocular course caused by D. repens in a 52-year-old Polish patient who was probably infected in Spain or Croatia, where she stayed one year before the onset of symptoms. Surgical removal of the nematodes followed by treatment with Ivermectin in a single dose of 1200 µg and Doxycycline 200 mg daily for 7 days resulted in complete recovery. We believe that all cases of human dirofilariasis, especially in countries where the disease is not frequent at present, should be registered for epidemiological purposes. Moreover, due to the widening of the range of D. repens and D. immitis occurrence and the possibility of atypical courses of infection with both nematodes, diagnostics should include the species identification of the parasite.