Onchocerciasis in the Cameroon-Chad border area after more than 20 years of annual mass ivermectin distribution.

BACKGROUND: The main vectors of onchocerciasis in Africa are Simulium damnosum sensu lato, which transmit the causative agent Onchocerca volvulus. The force of transmission is driven by the vector density, hence influencing the disease prevalence and intensity. Onchocerciasis is currently targeted for elimination using mass drug administration (MDA) of ivermectin, a potent microfilaricide. MDA in Cameroon began in 1987 in the Vina Valley, an endemic cross-border area with Chad, known for high vector densities and precontrol endemicity. Evaluations in 2008-2010 in this area showed ongoing transmission, while border areas in Chad were close to interrupting transmission. This study aimed to evaluate transmission in this area after several rounds of MDA since the last evaluation surveys. METHODS: Black flies were collected by human landing catches at seven border sites in Cameroon, twice a week, from August 2021 to March 2022. A fraction of the flies was dissected for parity assessment and identification of Onchocerca larval stages. The transmission indices were estimated. Black fly larvae were also collected from the breeding sites at the fly catching sites and identified to species level by cytotaxonomy. RESULTS: A total of 14,303 female flies were collected, and 6918 were dissected. Of these, 4421 (64.0%) were parous. The total biting rates were high, reaching up to 16,407 bites/person/study period, and transmission potential (third-stage larvae (L3) from head/all L3) were 367/702, 146/506, 51/55, 20/32, 0/3, 0/0, and 0/0 infective larvae/person, respectively, for Mbere-Tchad, Babidan, Hajam/V5, Gor, Djeing, Touboro, and Koinderi. Infectivity rates (L3 from head) were 16.00, 12.75, 5.15, and 4.07 infective females (L3H)/1000 parous flies for Haijam, Mbere-Tchad, Babidan, and Gor, respectively. These values exceed the World Health Organization (WHO) thresholds of ≤ 20 annual transmission potential (ATP) or < 1 infective female/1000 parous females. The major vectors identified were Simulium damnosum sensu stricto, S. squamosum, and for the first time in the area, S. yahense. CONCLUSIONS: More than 20 years of MDA has not eliminated onchocerciasis in the study area; hence, this area is a potential source of reintroduction of onchocerciasis in Chad and would require alternative treatment strategies. Many factors such as MDA efficiency, effectiveness of ivermectin, and cytospecies composition may be contributing to transmission persistence.

A single subcutaneous dose of eprinomectin (Eprecis®) is effective against common gastrointestinal nematodes and lungworms in experimentally infected lactating goats.

BACKGROUND: The health and productivity of dairy goats continue to be impacted by gastrointestinal nematodes (GIN) and lungworms (LW). Eprinomectin (EPN) is frequently selected for treatment because it is generally effective and does not require a milk withdrawal period. However, some factors, such as lactation, can have an impact on EPN pharmacokinetics and potentially its efficacy. To evaluate whether this can alter the efficacy of Eprecis® 2%, an eprinomectin injectable solution, a study was performed in lactating goats using the dose currently registered in cattle, sheep and goats (0.2 mg/kg). METHODS: This study was a blinded, randomized, controlled trial performed according to the VICH guidelines. Eighteen (18) worm-free lactating goats were included and experimentally challenged on day 28 with a mixed culture of infective gastrointestinal and lung nematode larvae (Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta, Dictyocaulus filaria). At D-1, fecal samples were collected to confirm patent infection in all animals. On D0, the goats were randomly allocated into two groups of nine goats; group 1 was treated with Eprecis® 2% at 0.2 mg/kg BW by subcutaneous injection, while group 2 remained untreated. Fecal samples for egg counts were collected from all animals on days 3, 5, 7, 9, 11 and 14. On D14, all goats were killed, and the abomasum, small intestine and lungs were removed, processed and subsampled to record the number and species of worms. RESULTS: The treatment was well tolerated. After treatment, the arithmetic mean FEC decreased in the treated group and remained < 5 EPG until the end of the study, while the arithmetic mean FEC in the control group remained > 849.0 EPG. At D14, goats in the treated group had very limited or zero total worm counts, whereas all animals from the control group had a high worm burden. The measured efficacy was 100.0% against H. contortus and T. colubriformis, 99.9% against T. circumcincta and 98.0% against D. filaria. CONCLUSIONS: Eprinomectin (Eprecis®, 20 mg/ml), administered at the label dose (0.2 mg/kg), is highly effective against gastrointestinal nematodes and lungworms in lactating goats.

Codelivery of ivermectin and methyl dihydrojasmonate in nanostructured lipid carrier for synergistic antileukemia therapy.

Chronic myeloid leukemia is a life-threatening blood-cancer prevalent among children and adolescents. Research for innovative therapeutics combine drug-repurposing, phytotherapeutics and nanodrug-delivery. Ivermectin (Ivn) is a potent anthelmintic, repurposed for antileukemic-activity. However, Ivn exerts off-target toxicity. Methyl-dihydrojasmonate (MJ) is a phytochemical of known antileukemic potential. Herein, we developed for the first-time Ivn/MJ-coloaded nanostructured-lipid-carrier (Ivn@MJ-NLC) for leveraging the antileukemic-activity of the novel Ivn/MJ-combination while ameliorating possible adverse-effects. The developed Ivn@MJ-NLC possessed optimum-nanosize (97 ± 12.70 nm), PDI (0.33 ± 0.02), entrapment for Ivn (97.48 ± 1.48 %) and MJ (99.48 ± 0.57 %) and controlled-release of Ivn (83 % after 140 h) and MJ (80.98 ± 2.45 % after 48 h). In-vitro K562 studies verified Ivn@MJ-NLC prominent cytotoxicity (IC50 = 35.01 ± 2.23 µg/mL) with pronounced Ivn/MJ-synergism (combination-index = 0.59) at low-concentrations (5-10 µg/mL Ivn). Superior Ivn@MJ-NLC cytocompatibility was established on oral-epithelial-cells (OEC) with high OEC/K562 viability-ratio (1.49-1.85). The innovative Ivn@MJ-NLC enhanced K562-nuclear-fragmentation and afforded upregulation of caspase-3 and BAX (1.71 ± 0.07 and 1.45 ± 0.07-fold-increase, respectively) compared to control. Ex-vivo hemocompatibility and in-vivo-biocompatibility of parenteral-Ivn@MJ-NLC, compared to Ivn-solution, was verified via biochemical-blood analysis, histological and histomorphometric studies of liver and kidney tissues. Our findings highlight Ivn@MJ-NLC as an Ivn/MJ synergistic antileukemic platform, ameliorating possible adverse-effects.

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.

Changes in Anti-OV-16 IgG4 Responses to Onchocerciasis after Elimination of Transmission in the Central Endemic Zone of Guatemala.

Current WHO guidelines for onchocerciasis elimination provide requirements for stopping mass drug administration of ivermectin and the verification of elimination of transmission. These guidelines also recommend post-elimination surveillance (PES) based on entomological surveys. Serological markers in humans could complement entomological PES once the longevity of anti-OV-16 antibody responses is better understood. In 2014-2015 we evaluated ELISA anti-OV-16 IgG4 antibody persistence among previously seropositive people from the central endemic zone of Guatemala. The country stopped all onchocerciasis program interventions in 2012 and was verified by WHO as having eliminated transmission of onchocerciasis in 2016. A total of 246 participants with prior OV-16 ELISA results from 2003, 2006, 2007, or 2009 were enrolled in a follow-up study. Of these, 77 people were previously OV-16 seropositive and 169 were previously seronegative. By 2014 and 2015, 56 (72.7%) previously seropositive individuals had sero-reverted, whereas all previous negatives remained seronegative. The progression of antibody responses over time was estimated using a mixed-effects linear regression model, using data from seropositive participants who had sero-reverted. The temporal variation showed a mean activity unit decay of 0.20 per year (95% credible interval [CrI]: 0.17, 0.23), corresponding to an estimated antibody response half-life of 3.3 years (95% CrI: 2.7, 4.1). These findings indicate that the majority of seropositive people will sero-revert over time.

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.

Comparative growth performance of backgrounded beef heifers treated with an injectable fixed-dose combination (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) or single-active (0.2 mg/kg ivermectin) endectocide.

Gastrointestinal nematodes (GINs) can negatively impact all production classes of cattle, particularly growing cattle. A global decline in efficacy of broad-spectrum single-active anthelmintics requires alternative GIN control methods without the aid of novel drug classes. Here, we present a new fixed-dose combination injectable (FDCI) endectocide for cattle that combines doramectin (5 mg/ml) and levamisole hydrochloride (150 mg/ml). A 56-day comparative performance confinement backgrounding trial was conducted in stocker beef heifers (n = 1548) with confirmed GIN infections to (1) compare the Day 14 post-treatment effectiveness of the new FDCI endectocide to pen mates treated with the injectable single-active endectocide ivermectin, as evidenced by fecal egg counts (FECs) conducted for a randomly selected subset (10%) of both treatment groups, and (2) determine if the greater GIN control by the FDCI evidenced in the subsample improved growth performance in all FDCI-treated heifers. Heifers were procured in four cohorts, with a 10-week timeframe between enrollment of the first and last cohort. Treatment groups were comingled within dirt-floor pens (n = 31; 7-8 per cohort) and offered a standard backgrounding diet ad libitum for the study duration. Heifers with enrollment FEC ≥ 30 eggs per gram (EPG) were randomly allocated to receive the FDCI (n = 773) or ivermectin (n = 775) on Day 0. Day 0 FECs conducted on 10% of enrolled heifers (FDCI, n = 78; ivermectin, n = 79) were not different between treatment groups (p = 0.491). Day 14 FECs for the same heifers were reduced compared to Day 0 within each treatment group. Heifers given the FDCI had lower Day 14 AM FECs and higher FEC reduction test (FECRT) result (0.07 EPG; 0.999) than ivermectin-treated heifers (21.58 EPG; FECRT = 0.850). Mean body weight (BW) was not different between treatment groups on Day 0 (p = 0.2762) and Day 14 (p = 0.2010) but was significantly greater (p = 0.0007) for FDCI-treated heifers compared to ivermectin-treated heifers on Day 56. Compared to ivermectin-treated heifers, overall average daily gain from all evaluation periods (Day 0-14, Day 14-56, and Day 0-56) was greater (p ≤ 0.0052) in FDCI-treated heifers, and FDCI-treated heifers had 4.223 kg greater total weight gain over the 56-day study. The FDCI (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) was highly effective in reducing GIN infections and thus promoted improved growth performance in beef heifers over a 56-day backgrounding period.

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.

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.

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.

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.