Progress Toward Onchocerciasis Elimination in Brazil.

The single onchocerciasis-endemic focus in the remote Amazon rainforest is shared by Brazil and Venezuela and affects primarily the indigenous Yanomami people. Regional elimination of onchocerciasis is challenged by the magnitude and inaccessibility of this area. In Brazil, 272 onchocerciasis-endemic communities are operationally organized through 21 health centers ("polos bases"). Mass drug administration of ivermectin began in 1995, with 36 effective biannual rounds (≥85% coverage of the eligible population) through 2022. The national on chocerciasis program maintains community-level monitoring to prioritize treatment activities and epidemiological surveys. The Onchocerciasis Elimination Program for the Americas and the WHO onchocerciasis elimination guidelines have helped Brazil move toward its goal of stopping ivermectin treatment by 2025 and verifying transmission elimination by 2030. Additional challenges to the Brazilian onchocerciasis program include cross-border movements and insecurity due to illegal mining and inter-community conflicts. The new government in Brazil offers hope given its commitment to the equity of indigenous people and preservation of the Amazon environment.

Evaluation of the International Task Force for Disease Eradication: A Review of Past Deliberations.

The International Task Force for Disease Eradication (ITFDE) was formed at The Carter Center in 1988. Its primary purpose is to review activities and provide recommendations related to programs focused on eradication. The ITFDE also considers opportunities for disease elimination and improved control. Over the last two decades, the ITFDE has held 33 meetings, discussed 22 diseases, and made 244 recommendations. This report aims to analyze the patterns in recommendations made by the ITFDE between 2001 and 2022 and assess the ITFDE's role, impacts, and successes in advancing elimination and eradication efforts for selected diseases. Using a thematic analysis, recommendation categories were crafted, followed by a scoping review to determine evidence of implementation for each recommendation. Categories of recommendations included research (24%), leadership (20%), medical (17%), advocacy (11%), collaboration (13%), development (8%), and financial (8%). We determined that 123 (50.4%) ITFDE recommendations were implemented in some form. Notably, the ITFDE has helped raise the profile of neglected tropical diseases. Four salient outcomes include 1) the identification of the potential eradicability of lymphatic filariasis (1993), 2) the recognition of the critical need for improved treatments of human African trypanosomiasis (2002), 3) a recommendation for the elimination of lymphatic filariasis and malaria from Hispaniola (2006), and 4) recommendations for effective and safe ways to avoid disruption of elimination and eradication programs during the COVID-19 pandemic (2020). This review of the ITFDE will help to devise new approaches to monitor its impact in the future.

Scorecard Approach to Eliminate Onchocerciasis in Venezuela.

In the Americas, onchocerciasis has been eliminated in 11 of 13 endemic foci by mass administration of ivermectin. The remaining at-risk population resides in a contiguous cross-border transmission zone located in the Amazon jungle in northwest Brazil and southern Venezuela, known as the Yanomami Focus Area. Here, we describe the development and implementation of a data-driven tool, called the Scorecard Approach (SCA), for the 393 communities that comprise the Venezuela South Focus. The SCA was first applied in 2018 and is reassessed on an annual basis. This operational strategy seeks to prioritize communities with low ivermectin coverage while taking into account the nature and variation of other epidemiological and logistical variables. Numeric scores are assigned for each factor and added together to yield a composite score for each community that is categorized as high, medium, or low priority. In this way, the SCA serves as a valuable and comprehensive strategy for planning, monitoring, and maximizing programmatic efficiency. In addition, it has allowed the country to face the main challenges of this endemic area: its remoteness, its large areas of territory to cover, the semi-nomadic nature of the Yanomami people, and their continuous cross-border movements. For 2022, the SCA categorized 54 (13.7%), 108 (27.5%), and 231 (58.8%) communities as high, medium, and low priority, respectively. The results presented here show that prioritizing communities at risk and with greatest needs increases the feasibility of interrupting the transmission of onchocerciasis by 2025 in the last endemic focus in the Americas.

Do Residents Believe that Onchocerciasis Transmission Was Eliminated? Results of A Post-Treatment Surveillance Knowledge, Attitude, and Practices Survey in Three Foci of Uganda.

In Uganda, 15 of 17 foci have interrupted transmission of onchocerciasis (river blindness) and stopped mass drug administration (MDA) of ivermectin. This 2016 study describes the results of a knowledge, attitude, and practices survey regarding river blindness among participants (N = 1,577) 3-5 years after ivermectin MDA was halted in three foci: Imaramagambo halted in 2012, Kashoya-Kitomi in 2013, and Mt. Elgon in 2011. The study showed high levels of composite knowledge (focus-specific range: 66.8-81.2%) related to river blindness transmission, signs, symptoms, and treatment. However, 38.1% of respondents did not know that blackflies transmitted river blindness. Notably, 72.2% claimed they had not been informed why MDA was stopped, 56.3% did not believe river blindness had been eliminated, and 83.1% wanted ivermectin MDA to resume. During the 3-5 year post-treatment surveillance period, only 27.7% (438 of 1,577) reported being informed of what to do once treatments stopped, with the most knowledgeable hailing from the Mt. Elgon focus (47.9%). This study reinforces the need for programs to intensify health education and information dissemination when MDA is stopped. Programs must remind residents that although biting insects may persist, they no longer transmit river blindness. Incorporating messages about the elimination of river blindness into community health education campaigns can help improve the community's perceptions related to the disease's absence and the ending of a long-standing MDA intervention.

Integrated Prevalence Assessment of Wuchereria bancrofti and Onchocerca volvulus in Three Co-Endemic Districts of Gambella Region, Ethiopia.

Lymphatic filariasis (LF) and onchocerciasis (OV) are among the neglected tropical diseases (NTD) targeted for elimination in Ethiopia. We used a transmission assessment survey (TAS-1) to evaluate the serological status of OV in three co-endemic districts in Gambella simultaneously. During May and June 2019, blood samples were collected from 6- to 7-year-old children who were randomly selected through standard community-based TAS methodology. Children were tested for both circulating filarial antigen (CFA) for LF via filariasis test strip and for Onchocerca volvulus 16 (Ov16) antibody for OV via laboratory-based ELISA. A total of 3,377 children from 150 villages in the three districts were tested; 1,823 (54.0%) were male. All three districts had CFA results below the critical threshold for stopping LF mass drug administration (MDA). In contrast, 40 children (1.2%) were positive for Ov16 antibody, well above the WHO's OV stop MDA threshold of 0.1%. The integrated assessment indicated two programmatic decisions: stop MDA for LF and continue MDA for OV. Accordingly, albendazole MDA was discontinued in the districts but ivermectin MDA continued. This integrated assessment showed that a random sample for TAS can give important information about OV transmission status in co-endemic areas.

Two Nigerian States (Plateau and Nasarawa) Have Eliminated Transmission of Human Onchocerciasis-A Report of Post-Ivermectin Mass Drug Administration Surveillance.

Transmission of Onchocerca volvulus (causing "river blindness") was interrupted in two states of Nigeria (Plateau and Nasarawa) in 2017 in accordance with 2016 WHO guidelines. Ivermectin mass drug administration was halted in January 2018, and posttreatment surveillance activities were conducted over a 3-year period. Vector Simulium damnosum s.l. flies were collected during the 2019 (39 sites) and 2020 (42 sites) transmission seasons. Head pools were tested by polymerase chain reaction for the presence of third-stage O. volvulus larvae; 15,585 flies were all negative, demonstrating an infective rate of < 1/2,000 with 95% confidence. In 2021, the Nigerian Federal Ministry of Health declared the two-state area as having eliminated transmission. Plateau and Nasarawa states are the first of 30 endemic states in Nigeria to have met the WHO criteria for onchocerciasis elimination. Post-elimination surveillance will need to continue given the risk of reintroduction of transmission from neighboring states.

Impact of Three to Five Rounds of Mass Drug Administration on Schistosomiasis and Soil-Transmitted Helminths in School-Aged Children in North-Central Nigeria.

Nasarawa and Plateau states of north-central Nigeria have implemented programs to control schistosomiasis (SCH) and soil-transmitted helminths (STH) in children since the 1990s. Statewide mapping surveys were conducted in 2013, when 11,332 school-aged children were sampled from 226 schools. The local government areas (LGAs) then received varying combinations of mass drug administration (MDA) for the next 5 years. We revisited 196 (87%) schools in 2018 plus an additional six (202 schools in total), sampling 9,660 children. We calculated overall prevalence and intensity of infection and evaluated associations with gender; age; behaviors; water, sanitation, and hygiene (WASH); and treatment regimen. Urine heme detection dipsticks were used for Schistosoma hematobium in both surveys, with egg counts added in 2018. Stool samples were examined by Kato-Katz for Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni, and hookworm. Schistosomiasis prevalence among sampled students dropped from 12.9% (95% confidence interval [CI]: 11.1-14.9%) to 9.0% (95% CI: 7.5-10.9%), a statistically significant change (P < 0.05). In 2018, eight LGAs still had > 1% of children with heavy-intensity schistosome infections. Prevalence of STH infection did not significantly change, with 10.8% (95% CI: 9.36-12.5%) of children positive in 2013 and 9.4% (95% CI: 8.0-10.9%) in 2018 (P = 0.182). Heavy-intensity STH infections were found in < 1% of children with hookworm, and none in children with A. lumbricoides or T. trichiura in either study. The WASH data were collected in 2018, indicating 43.6% of schools had a latrine and 14.4% had handwashing facilities. Although progress is evident, SCH remains a public health problem in Nasarawa and Plateau states.

Simulating a Transmission Assessment Survey: An evaluation of current methods used in determining the elimination of the neglected tropical disease, Lymphatic Filariasis.

INTRODUCTION: The World Health Organization (WHO) recommends Transmission Assessment Surveys (TAS) to determine when an evaluation unit (EU) (a designated population survey area) has achieved elimination of transmission of the vector-borne macroparasitic disease Lymphatic Filariasis (LF). These determinations are based on combining data from multiple survey units within an EU; it is unclear how underlying cluster-level variation influences the outcome of the TAS at EU level. We simulate LF infection distribution in an EU and compare three methods for assessing whether LF elimination has occurred based on currently recommended decision thresholds and sampling methods. METHODS: We simulate an EU divided into clusters of varying size and disease prevalence. We produce 1000 samples according to LF TAS examples and WHO guidelines and compare three decision-making approaches: lot quality assurance sampling (LQAS) (recommended by WHO), one-sided interval estimate (CI), and nth order statistic (MAX). Summary statistics demonstrating the "pass" rate for the EU under different disease transmission conditions are generated using a versatile SAS® macro. RESULTS: As the prevalence of LF decreases, the LQAS and CI approaches produce increased likelihood of a pass outcome for an EU while some cluster units may still have a high likelihood of transmission. The MAX provides an alternative that increases the likelihood of determining a pass only once the whole area has a low likelihood of transmission. LQAS and CI approaches designed to estimate the LF prevalence in the EU miss hotspots that will continue to transmit infection while the MAX approach focuses on identifying clusters with high risk of transmission. CONCLUSIONS: The current TAS methodology has a flaw that may result in false predictions of LF transmission interruption throughout an EU. Modifying the TAS methodology to address results from extreme clusters rather than being based on mean prevalence over an EU will result in greater success for global elimination of LF.

The role of non-governmental development organizations in the implementation of lymphatic filariasis programmes.

The Lymphatic Filariasis (LF) Non-governmental Development Organization (NGDO) Network was established to engage in supporting both international and national LF elimination agendas covering areas such as assisting ministries of health as an on-the-ground link between communities and programmes, which additionally gives the Network members an important voice from the field at international meetings; playing key roles in programme evolution (especially helping to both scale up and scale down mass drug administration [MDA] as elimination thresholds are met); having a role in operational research and developing new programme delivery models that can be taken to scale (such as linkages with other disease programmes and approaches to morbidity management and disability prevention); developing advocacy and policy approaches with other partners; convening other important stakeholders (academic, technical, programmatic and funding); mobilizing financial and technical resources to support programmes; supporting national human resource capacity building to catalyse national ownership of LF programmes; providing leadership in LF governance structures and working in areas of conflict to ensure that everybody in LF-endemic areas enjoys treatment services. Three case studies will illustrate the roles identified for NGDOs in LF programmes covering development of operational research, policy and advocacy linkage between LF and malaria programmes; launching LF morbidity management projects and NGDO's ability to work and deliver LF services in areas of conflict. In addition, the case studies will show the role of NGDOs in mobilising financial and technical resources that support national human resources, leading to national ownership of programmes. Conclusions will be drawn on the role of NGDOs in the Global Alliance for LF elimination and the need for continued partnerships to reach programme goals.

Assessing Hypoendemic Onchocerciasis in Loa loa Endemic Areas of Southeast Nigeria.

Nigeria changed its goal for onchocerciasis from control to transmission elimination. Under the control program, ivermectin mass drug administration (MDA) focused only on hyper/meso-endemic local government areas (LGAs) identified by Rapid Epidemiological Mapping of Onchocerciasis as having ≥ 20% nodule rates. Because transmission is likely in some LGAs where nodule rates are < 20%, the new elimination paradigm requires MDA expansion. Determining which hypoendemic areas require MDA, termed onchocerciasis elimination mapping, is a major challenge. In 2016, we studied 19 ivermectin-naive hypoendemic LGAs in southern Nigeria that bordered LGAs under MDA. Fifty adults and 50 children (aged 5-10 years) were tested in 110 villages for onchocerciasis IgG4 antibody using an Ov16 rapid diagnostic test (RDT). A 10% subset of subjects provided a blood spot for confirmatory Ov16 ELISA. The mean prevalence of RDT positives was 0.5% in the 5,276 children tested (village range, 0.0-4.0%) versus 3.3% in 5,302 adults (village range, 0.0-58.0%). There was 99.3% agreement between the Ov16 RDT and ELISA. Six different MDA launch thresholds were applied to the RDT results based on different recommendations by the Nigeria Onchocerciasis Elimination Committee and the Onchocerciasis Technical Advisory Subgroup of the WHO. Mass drug administration targets for the same area varied tenfold by threshold chosen, from one LGA (population to be treated 221,935) to 13 LGAs (population 2,426,987). Because the Ov16 threshold selected will have considerable cost and resource implications, the decision to initiate MDA should incorporate entomological data demonstrating onchocerciasis transmission.

Predicting lymphatic filariasis elimination in data-limited settings: A reconstructive computational framework for combining data generation and model discovery.

Although there is increasing importance placed on the use of mathematical models for the effective design and management of long-term parasite elimination, it is becoming clear that transmission models are most useful when they reflect the processes pertaining to local infection dynamics as opposed to generalized dynamics. Such localized models must also be developed even when the data required for characterizing local transmission processes are limited or incomplete, as is often the case for neglected tropical diseases, including the disease system studied in this work, viz. lymphatic filariasis (LF). Here, we draw on progress made in the field of computational knowledge discovery to present a reconstructive simulation framework that addresses these challenges by facilitating the discovery of both data and models concurrently in areas where we have insufficient observational data. Using available data from eight sites from Nigeria and elsewhere, we demonstrate that our data-model discovery system is able to estimate local transmission models and missing pre-control infection information using generalized knowledge of filarial transmission dynamics, monitoring survey data, and details of historical interventions. Forecasts of the impacts of interventions carried out in each site made by the models estimated using the reconstructed baseline data matched temporal infection observations and provided useful information regarding when transmission interruption is likely to have occurred. Assessments of elimination and resurgence probabilities based on the models also suggest a protective effect of vector control against the reemergence of LF transmission after stopping drug treatments. The reconstructive computational framework for model and data discovery developed here highlights how coupling models with available data can generate new knowledge about complex, data-limited systems, and support the effective management of disease programs in the face of critical data gaps.

Elimination of Simulium neavei-Transmitted Onchocerciasis in Wambabya-Rwamarongo Focus of Western Uganda.

Wambabya-Rwamarongo onchocerciasis focus is one of the eight foci Uganda verified using the WHO verification guidelines. The approach for elimination was twice yearly treatment with ivermectin for every round, treating at least 90% of all the eligible population. This was in combination with vector elimination using Abate® (BASF SE, Limburgerhof, Germany) since elimination nationwide policy was launched. From 2008 to 2013, the program distributed ivermectin with a mean treatment coverage of the ultimate treatment goal (UTG) or eligible population of 91.2%, with a range of 85-96%. In 2009, vector elimination based on ground larviciding had a dramatic impact on the Simulium vectors, as the last fly was observed in October 2009. No more Simulium vectors were observed during a period of at least 7 years, including the 3-year posttreatment surveillance (PTS) until the focus was reclassified as eliminated in August 2017. During the PTS period, none of the 10,578 trapped crabs were found infested with the aquatic stages of the vector. The last infested crab was observed in March 2010, and for at least 7 years, no infested crabs were observed. Serological surveys showed that of 2,978 young children examined in 2013, only one was OV16 positive (0.0%; 95% CI: 0-0.21). In 2017, after the PTS period, all 3,079 young children examined were negative for OV16 (95% CI: 0-0.16). Therefore, entomological and serological results provided evidence that resulted in the reclassification of Wambabya-Rwamarongo focus from "transmission interrupted" to "transmission eliminated" with no possibility of recrudescence.

Historical Elimination of Onchocerciasis from Victoria Nile Focus in Central Uganda Verified Using WHO Criteria.

Uganda has verified elimination of seven onchocerciasis foci since 2007 when the nationwide onchocerciasis elimination policy was launched. However, the Victoria Nile focus (which was eliminated in the early 1970s) had not been verified. The objective of this study was to verify this focus to the WHO verification guidelines and bring it in line with recently eliminated foci. Vector control with dichlorodiphenyltrichloroethane was the main intervention used at the Victoria Nile from the 1950s to the 1970s. Historical fly collection sites along River Nile were identified for recent fly collection. Relevant health workers near the sites were trained to supervise fly collection activity. With support from communities, fly collectors were identified, trained, and equipped to collect Simulium flies for at least a year. A total of 854 Simulium flies were collected and analyzed by polymerase chain reaction to detect Onchocerca volvulus DNA. The communities and their leaders provided consent for the collection of dry blood spots (DBS) from children younger than 10 years for investigation of recent exposure to the disease. A total of 2,953 DBS were collected and analyzed by OV16 ELISA to detect the presence of IgG4 antibodies recognizing the OV16 antigen. The results showed that none of the flies carried O. volvulus DNA. Similarly, all the children were OV16 negative, showing no exposure to onchocerciasis. All the flies collected were identified as Simulium adersi, which is not a known vector for O. volvulus. The results confirmed that onchocerciasis and its vector Simulium damnosum had been eliminated in the Victoria Nile focus.

Post-Treatment Surveillance for Lymphatic Filariasis in Plateau and Nasarawa States, Nigeria: Results of Transmission Assessment Surveys.

Following the halt of mass drug administration (MDA) for lymphatic filariasis (LF), the WHO recommends at least 4 years of post-treatment surveillance (PTS) to confirm that transmission recrudescence or importation does not occur. The primary means of evaluation during PTS is repeated transmission assessment surveys (TASs) conducted at 2- to 3-year intervals after TAS-1 stop-MDA surveys. This study reports the results of TAS-2 and TAS-3 surveys in Plateau and Nasarawa states (pop. 6.9 million) of Nigeria divided into a minimum of seven evaluation units (EUs) per TAS. A total of 26,536 first- and second-year primary school children (approximately 6-7 years old) were tested for circulating filarial antigen (CFA) between 2014 and 2017. Of 12,313 children tested in TAS-2 surveys, only five (0.04%) were CFA positive, with no more than two positive samples from any one EU, which was below the critical value of 20 per EU. Of 14,240 children tested in TAS-3 surveys, none (0%) were CFA positive. These results indicate that LF transmission remains below sustainable transmission levels and suggest that elimination of transmission has been achieved in Plateau and Nasarawa, Nigeria.

Data-driven modelling and spatial complexity supports heterogeneity-based integrative management for eliminating Simulium neavei-transmitted river blindness.

Concern is emerging regarding the challenges posed by spatial complexity for modelling and managing the area-wide elimination of parasitic infections. While this has led to calls for applying heterogeneity-based approaches for addressing this complexity, questions related to spatial scale, the discovery of locally-relevant models, and its interaction with options for interrupting parasite transmission remain to be resolved. We used a data-driven modelling framework applied to infection data gathered from different monitoring sites to investigate these questions in the context of understanding the transmission dynamics and efforts to eliminate Simulium neavei- transmitted onchocerciasis, a macroparasitic disease that causes river blindness in Western Uganda and other regions of Africa. We demonstrate that our Bayesian-based data-model assimilation technique is able to discover onchocerciasis models that reflect local transmission conditions reliably. Key management variables such as infection breakpoints and required durations of drug interventions for achieving elimination varied spatially due to site-specific parameter constraining; however, this spatial effect was found to operate at the larger focus level, although intriguingly including vector control overcame this variability. These results show that data-driven modelling based on spatial datasets and model-data fusing methodologies will be critical to identifying both the scale-dependent models and heterogeneity-based options required for supporting the successful elimination of S. neavei-borne onchocerciasis.

The Interruption of Transmission of Human Onchocerciasis by an Annual Mass Drug Administration Program in Plateau and Nasarawa States, Nigeria.

Plateau and Nasarawa states in central Nigeria were endemic for onchocerciasis. The rural populations of these two states received annual ivermectin mass drug administration (MDA) for a period of 8-26 years (1992-2017). Ivermectin combined with albendazole was given for 8-13 of these years for lymphatic filariasis (LF); the LF MDA program successfully concluded in 2012, but ivermectin MDA continued in areas known to have a baseline meso-/hyperendemic onchocerciasis. In 2017, serological and entomological assessments were undertaken to determine if MDA for onchocerciasis could be stopped in accordance with the current WHO guidelines. Surveys were conducted in 39 sites that included testing 5- to < 10-year-old resident children by using ELISA for OV16 IgG4 antibodies, and Onchocerca volvulus O150 pooled polymerase chain reaction (PCR) testing of Simulium damnosum s.l. vector heads. Only two of 6,262 children were OV16 positive, and none of 19,056 vector heads were positive for parasite DNA. Therefore, both states were able to meet WHO stop-MDA thresholds of an infection rate in children of < 0.1% and a rate of infective blackflies of <1/2,000, with 95% statistical confidence. Transmission of onchocerciasis was declared interrupted in Plateau and Nasarawa states by the Federal Ministry of Health, and 2.2 million ivermectin treatments/year were stopped in 2018. Post-treatment Surveillance was launched focusing on entomological monitoring on borders with neighboring onchocerciasis-endemic states. An apparent positive impact of the LF MDA program on eliminating hypo-endemic onchocerciasis was observed. This is the first stop-MDA decision for onchocerciasis in Nigeria and the largest single stop-MDA decision for onchocerciasis yet reported. This achievement, along with the process used in adapting and implementing the 2016 WHO stop-MDA guidelines, will be important as a potential model for decision makers and national onchocerciasis elimination committees in other African countries that are charged with advancing their programs.

The Galabat-Metema cross-border onchocerciasis focus: The first coordinated interruption of onchocerciasis transmission in Africa.

BACKGROUND: Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. METHODS/PRINCIPLE FINDINGS: The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia's Metema subfocus in 2016 and in the Sudan's Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was <0.1% for the overall focus and 0.14 positive fly heads per 2000 (UCL = 0.39/2000). However, an entomological 'hotspot' was detected on the Wudi Gemzu river in Metema district. The hotspot was confirmed when 4 more positive fly pools were found on repeat testing in 2017 (1.04 L3/2000 flies (UCL = 2.26/2000). Information exchange between the two countries led to stopping MDA in a coordinated fashion in 2018, with the exception of the hotspot at Wudi Gemzu, where MDA with ivermectin was increased to every three months to hasten interruption of transmission. CONCLUSION: Coordinated stop MDA decisions were made by Sudan and Ethiopia based on data satisfying the World Health Organization's criteria for interruption of onchocerciasis transmission. Definitions of entomological 'hotspots' and buffer zones around the focus are proposed.

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool.

In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

Accelerating river blindness elimination by supplementing MDA with a vegetation "slash and clear" vector control strategy: a data-driven modeling analysis.

Attention is increasingly focusing on how best to accelerate progress toward meeting the WHO's 2030 goals for neglected tropical diseases (NTDs). For river blindness, a major NTD targeted for elimination, there is a long history of using vector control to suppress transmission, but traditional larvicide-based approaches are limited in their utility. One innovative and sustainable approach, "slash and clear", involves clearing vegetation from breeding areas, and recent field trials indicate that this technique very effectively reduces the biting density of Simulium damnosum s.s. In this study, we use a Bayesian data-driven mathematical modeling approach to investigate the potential impact of this intervention on human onchocerciasis infection. We developed a novel "slash and clear" model describing the effect of the intervention on seasonal black fly biting rates and coupled this with our population dynamics model of Onchocerca volvulus transmission. Our results indicate that supplementing annual drug treatments with "slash and clear" can significantly accelerate the achievement of onchocerciasis elimination. The efficacy of the intervention is not very sensitive to the timing of implementation, and the impact is meaningful even if vegetation is cleared only once per year. As such, this community-driven technique will represent an important option for achieving and sustaining O. volvulus elimination.