Assessment of the performance of community-directed treatment with ivermectin strategy for the control and elimination of onchocerciasis in Edo State, Nigeria.

BACKGROUND: Community-directed treatment with ivermectin (CDTI) was developed in the mid 1990's as a solution for the control and elimination of onchocerciasis. It requires that ivermectin be administered continuously over a period of at least 14 years with community involvement before elimination can be achieved. OBJECTIVES: The objective of this study is to assess the performance of CDTI strategy for control and elimination of onchocerciasis in endemic Local Government areas of Edo State. METHODS: A descriptive evaluation in a cross-sectional, descriptive study design was conducted among 720 community members selected from six communities using multistage sampling technique, 11 Community directed distributors (CDDs), and 17 health workers involved in the implementation of the CDTI strategy in Edo State. Primary data were collected using an interviewer's administered questionnaire while secondary data were obtained from the State Ministry of Health. IBM SPSS version 21 software was used for data analysis. RESULTS: The highest therapeutic coverage (95.5%) was observed in Aden II community while the least therapeutic coverage (56.6%) was observed in Imeke community. Regarding the performance indicators, ivermectin supply, work of CDDs, training, monitoring and supervision, finances by communities had scores ≥2.5 and were therefore considered as having satisfactory performance. However, community participation and ownership and health education and mobilization had scores <2.5 and as such considered as having unsatisfactory performance. CONCLUSION: Sustainability of the CDTI program in the study area is likely but not guaranteed as there is need for improvement in areas regarding community mobilization, participation, and ownership.

Onchocerciasis control in the Democratic Republic of Congo (DRC): challenges in a post-war environment.

OBJECTIVE: To evaluate onchocerciasis control activities in the Democratic Republic of Congo (DRC) in the first 12 years of community-directed treatment with ivermectin (CDTI). METHODS: Data from the National Programme for Onchocerciasis (NPO) provided by the National Onchocerciasis Task Force (NOTF) through the annual reports of the 21 CDTI projects for the years 2001-2012 were reviewed retrospectively. A hypothetical-inputs-process-outputs-outcomes table was constructed. RESULTS: Community-directed treatment with ivermectin expanded from 1968 communities in 2001 to 39 100 communities by 2012 while the number of community-directed distributors (CDD) and health workers (HW) multiplied. By 2012, there were ratios of 1 CDD per 262 persons and 1 HW per 2318 persons at risk. More than 80% of the funding came from the fiduciary funds of the African Programme for Onchocerciasis Control. The cost of treatment per person treated fell from US$ 1.1 in 2001 to US$ 0.1 in 2012. The therapeutic coverage increased from 2.7% (2001) to 74.2% (2012); the geographical coverage, from 4.7% (2001) to 93.9% (2012). Geographical coverage fell in 2005 due to deaths in loiasis co-endemic areas, and the therapeutic coverage fell in 2008 due to insecurity. CONCLUSIONS: Challenges to CDTI in DRC have been serious adverse reactions to ivermectin in loiasis co-endemic areas and political conflict. Targets for personnel or therapeutic and geographical coverages were not met. Longer term funding and renewed efforts are required to achieve control and elimination of onchocerciasis in DRC.

Estimating The Effects Of COVID-19 On Globalized Markets For Active Pharmaceutical Ingredients.

Global supply chains for active pharmaceutical ingredients (APIs) are highly centralized in certain countries and are susceptible to supply-chain shocks. However, there is no systematic monitoring or global coordination to manage risk and ensure equitable supply continuity during public health emergencies. In this study, we applied quasi-experimental methods on shipment-level customs data to determine how prices and export volume for APIs exported from India were affected by the COVID-19 pandemic. We found that API prices for key essential medicines not used for COVID-19 did not change significantly in the year after the World Health Organization pandemic declaration, but volume decreased by 80 percent. Prices for medicines speculatively repurposed for COVID-19, such as hydroxychloroquine and ivermectin, increased by as much as 250 percent compared with prices for nonrepurposed medicines, but only ivermectin saw a decrease in volume. Systematic monitoring of API markets, investments to promote supply diversification, and legal and political reforms to disincentivize price speculation could support supply-chain resilience and safeguard access to medicines.

Ivermectin to reduce malaria transmission: a research agenda for a promising new tool for elimination.

BACKGROUND: The heterogeneity of malaria transmission makes widespread elimination a difficult goal to achieve. Most of the current vector control measures insufficiently target outdoor transmission. Also, insecticide resistance threatens to diminish the efficacy of the most prevalent measures, indoor residual spray and insecticide treated nets. Innovative approaches are needed. The use of endectocides, such as ivermectin, could be an important new addition to the toolbox of anti-malarial measures. Ivermectin effectively targets outdoor transmission, has a novel mechanism of action that could circumvent resistance and might be distributed over the channels already in place for the control of onchocerciasis and lymphatic filariasis. METHODS: The previous works involving ivermectin and Anopheles vectors are reviewed and summarized. A review of ivermectin's safety profile is also provided. Finally three definitive clinical trials are described in detail and proposed as the evidence needed for implementation. Several smaller and specific supportive studies are also proposed. CONCLUSIONS: The use of ivermectin solves many challenges identified for future vector control strategies. It is an effective and safe endectocide that was approved for human use more than 25 years ago. Recent studies suggest it might become an effective and complementary strategy in malaria elimination and eradication efforts; however, intensive research will be needed to make this a reality.

Towards elimination of lymphatic filariasis: social mobilization issues and challenges in mass drug administration with anti-filarial drugs in Tamil Nadu, South India.

India is a signatory to World Health Assembly resolution for elimination of lymphatic filariasis (LF) and National Health Policy has set the goal of LF elimination by 2015. Annual mass drug administration (MDA) is ongoing in endemic districts since 1996-97. Compliance rate is a crucial factor in achieving elimination and was assessed in three districts of Tamil Nadu for 10th and 11th treatment rounds (TRs). An in-depth study assessed the impact of social mobilization by drug distributors (DDs) in two areas from each of the three districts. Overall coverage and compliance for assessed TRs were 76.3 and 67.7% which is below the optimum level to achieve LF elimination. Modifiable determinants continue to be the reason for non-consumption even in the 11th TR and 20.8% were systematic non-compliers. In 76.4% of the cases, DDs failed to adhere to three mandatory visits as per the guidelines. Number of visits by DDs in relation to low and high MDA coverage areas showed a significant relationship (P ≤ 0.000). MDA is limited to drug distribution alone and efforts by DDs in preparing the community were inadequate. Probable means to meet the challenges in preparation of the community is discussed.

Community-directed interventions for priority health problems in Africa: results of a multicountry study.

OBJECTIVE: To determine the extent to which the community-directed approach used in onchocerciasis control in Africa could effectively and efficiently provide integrated delivery of other health interventions. METHODS: A three-year experimental study was undertaken in 35 health districts from 2005 to 2007 in seven research sites in Cameroon, Nigeria and Uganda. Four trial districts and one comparison district were randomly selected in each site. All districts had established ivermectin treatment programmes, and in the trial districts four other established interventions - vitamin A supplementation, use of insecticide-treated nets, home management of malaria and short-course, directly-observed treatment for tuberculosis patients - were progressively incorporated into a community-directed intervention (CDI) process. At the end of each of the three study years, we performed quantitative evaluations of intervention coverage and provider costs, as well as qualitative assessments of the CDI process. FINDINGS: With the CDI strategy, significantly higher coverage was achieved than with other delivery approaches for all interventions except for short-course, directly-observed treatment. The coverage of malaria interventions more than doubled. The district-level costs of delivering all five interventions were lower in the CDI districts, but no cost difference was found at the first-line health facility level. Process evaluation showed that: (i) participatory processes were important; (ii) recurrent problems with the supply of intervention materials were a major constraint to implementation; (iii) the communities and community implementers were deeply committed to the CDI process; (iv) community implementers were more motivated by intangible incentives than by external financial incentives. CONCLUSION: The CDI strategy, which builds upon the core principles of primary health care, is an effective and efficient model for integrated delivery of appropriate health interventions at the community level in Africa.

COVID-19 and Fake News in the Dominican Republic.

The first case of novel coronavirus disease (COVID-19) in the Dominican Republic coincided with a period of political crisis. Distrust in governmental institutions shaped the critical phase of early response. Having a weak public health infrastructure and a lack of public trust, the Ministry of Health (MoH) began the fight against COVID-19 with a losing streak. Within 45 days of the first reported case, the political crisis and turmoil caused by "fake news" are limiting the capacity and success of the MoH response to the pandemic.

GlaxoSmithKline and Merck: private-sector collaboration for the elimination of lymphatic filariasis.

More than 1000 million people in 82 countries are at risk of contracting the tropical disease lymphatic filariasis (LF). Although the disease is wide-spread, transmission of the causative parasites can be stopped through mass drug administrations based on a combination of anti-parasitic medicines. For more than 10 years, the pharmaceutical companies GlaxoSmithKline (GSK) and Merck & Co., Inc., have participated in a unique private-sector collaboration to support the global efforts to eliminate LF, through donations of drugs to prevent the disease. GSK's albendazole and Merck's ivermectin (Mectizan) now reach hundreds of millions of people each year, through national LF-elimination programmes carried out in collaboration with Ministries of Health, the World Health Organization, non-governmental organizations and local communities. Working in support of the Global Programme to Eliminate Lymphatic Filariasis, GSK and Merck not only provide donated medicines but also offer financial, programmatic and management expertise to support LF-elimination efforts worldwide.

The Global Programme to Eliminate Lymphatic Filariasis: health impact during its first 8 years (2000-2007).

During its first 8 years, the Global Programme to Eliminate Lymphatic Filariasis provided more than 1900 million treatments with antifilarial drugs (albendazole, ivermectin and diethylcarbamazine) to at least 570 million people in 48 countries with endemic lymphatic filariasis (LF). As a result of this impressive global effort and an unprecedented public-private partnership, 8 years of mass drug administration (MDA) have prevented the spread of filarial infection to an estimated 6.6 million newborns, stopped the progression to clinical morbidity in 9.5 million individuals already infected with the parasites that cause LF, and drastically reduced the burden of several co-infections. The resulting health benefits of the MDA, in terms of reduced morbidity and disability-adjusted life-years, are thus enormous. The next step should be an analysis of the Global Programme's economic impact from its first 8 years of MDA.

Operational lessons from 20 years of the Mectizan Donation Program for the control of onchocerciasis.

The donation of ivermectin (Mectizan, Merck & Co., Inc.) to control onchocerciasis (river blindness) was established in 1987 and has since gradually expanded to provide for >570 million treatments cumulatively over the past 20 years. The Mectizan Donation Program (MDP) operates within a broad partnership in 33 endemic countries in need of mass treatment. Particular operational methods and tools are applied to facilitate ivermectin mass treatment. Drug management has been streamlined, including dosing, tablet size and packaging, and monitoring for adverse events. Much of the experience gained in the development of ivermectin mass treatment can be usefully applied in the recent broader perspective of control of neglected tropical diseases. The most important operational lessons of the MDP include: (i) the need to easily define the target population for treatment using rapid, non-invasive techniques; (ii) the value of a broad partnership; (iii) the great potential of working through community-directed treatment; (iv) the need to streamline all drug management aspects and (v) the importance of operations research to tackle new challenges.

Progress toward elimination of onchocerciasis in the Americas.

The Onchocerciasis Elimination Program for the Americas (OEPA) is a regional initiative and international partnership that has made considerable progress toward its goal since it was launched in 1993. Its strategy is based on mass drug administration of ivermectin (Mectizan, donated by MSD, also known as Merck & Co., Inc., Kenilworth, NJ, USA), twice or four times per year, with at least 85% coverage of eligible populations. From 1989 to 2016, 11 741 276 ivermectin treatments have been given in the Americas, eliminating transmission in 11 of 13 foci. The OEPA's success has had a great influence on programs in Africa, especially Sudan and Uganda, which moved from a control to an elimination strategy in 2006 and 2007, respectively. The successes in the Americas have also greatly influenced WHO guidelines for onchocerciasis transmission elimination. With four of the six originally endemic American countries now WHO verified as having eliminated onchocerciasis transmission, and 95% of ivermectin treatments in the region halted, the regional focus is now on the remaining active transmission zone, called the Yanomami Area, on the border between Venezuela and Brazil. Both countries have difficult political climates that hinder the elimination task in this remote and relatively neglected region. As with other elimination efforts, 'the final inch' is often the most difficult task of all.

Diagnostics for onchocerciasis in the era of elimination.

In the past few years, efforts to eliminate onchocerciasis from Africa have intensified. These efforts are primarily based on the mass distribution of the anti-helminthic drug Mectizan™ (ivermectin). This program has led to the development of new guidelines by the World Health Organization for the verification that transmission has been suppressed and eventually eliminated. The requirements of diagnostic tools for this purpose differ in many ways from tests used to diagnose infection in individuals. In this review, we summarize the progress that has been made to identify diagnostics that meet the specialized requirements needed to verify onchocerciasis elimination, discuss why these tests were selected and summarize the needs that still exist to complete the arsenal of diagnostic tools that will be useful as the goal of elimination is achieved.

For as Long as Necessary: Examining 30 years of MSD's Focus on Achieving Elimination of Onchocerciasis and Lymphatic Filariasis.

Established by MSD, also known as Merck & Co., Inc., Kenilworth, NJ USA in 1987, the Mectizan Donation Program (MDP) is the longest running disease-specific program of its kind. Initially aimed at control of onchocerciasis (river blindness), the company expanded its commitment through the MDP in 1998 to include lymphatic filariasis (LF). Both diseases are now candidates for elimination and the company is engaged in several global partnerships to help advance towards that goal. To support the steadily growing demand from country-led disease elimination programs, the company has put in place several administrative and operational improvements. In addition, the company is involved 'beyond the pill', including making financial and management contributions to partners such as the END Fund and the Expanded Special Project to Eliminate NTDs (ESPEN) to support the technical needs of elimination programs. While the time-bound elimination targets are challenging, clear progress is being made for both onchocerciasis and LF, with several national and subnational areas in Latin America and Africa having stopped transmission of one or both diseases. The company's donation of Mectizan and contributions of financial, management and technical resources reflect the company's long-standing commitment to pursue inventive ways to expand and enhance access to medicine. Continued support from MSD and other partners will enable countries to advance towards their elimination targets for LF and onchocerciasis.

After 70 years of fighting an age-old scourge, onchocerciasis in Uganda, the end is in sight.

Onchocerciasis causes severe itching, serious skin disease and ocular damage leading to visual impairment or permanent blindness. It is associated with hanging groin, epilepsy, Nakalanga dwarfism and, most recently, nodding disease. This disease affected communities in 17 transmission foci in 37 districts of Uganda, where about 6.7 million people are once at risk. The efforts against onchocerciasis in Uganda commenced in the late 1940s, when vector control was launched using dichlorodiphenyltrichloroethane; by 1973, Simulium damnosum had been eliminated in the Victoria focus. Success outside of the Victoria focus was short-lived due to changes in government priorities and the political upheavals of the 1970s and 1980s. With the return of political stability, annual treatment with ivermectin through mass drug administration was launched in the early 1990s. Control of the disease has been successful, but there has been failure in interrupting transmission after more than 15 years. In 2007 Uganda launched a nationwide transmission elimination policy based on twice-per-year treatment and vector control/elimination, with a goal of eliminating river blindness nationwide by 2020. By 2017, 1 157 303 people from six foci had been freed from river blindness. This is the largest population ever declared free under World Health Organization elimination guidelines, providing evidence that elimination of river blindness in Africa is possible.

Onchocerciasis in Yemen: moving forward towards an elimination program.

The onchocerciasis focus in Yemen has been known for many years as an endemic area with unique characteristics, notably the atypical and most severe form of onchodermatitis, known as sowda or reactive onchodermatitis (ROD). The national effort to control the disease began in 1992 as an individual case treatment program by administering ivermectin to those presenting with ROD. The challenging geography of the endemic area and the current political and military unrest both underscore a need for special approaches when attempting to eliminate onchocerciasis from this country. An assessment of the national situation regarding this disease was carried out in 2011-2013 aimed at defining the best approach for moving from individual clinical case treatment to elimination of transmission. The history of the control efforts and the current status of the disease are reviewed and the essential changes needed to a mass drug administration (MDA) approach are identified as the national program addresses elimination. Yemen, despite the current troubles, has shown that it can successfully implement MDA programs despite many difficulties and therefore should be supported in its efforts towards countrywide elimination of this infection; however, success will need renewed national and international efforts.

Programmatic factors associated with the limited impact of Community-Directed Treatment with Ivermectin to control Onchocerciasis in three drainage basins of South West Cameroon.

INTRODUCTION: The CDTI model is known to have enhanced community participation in planning and resource mobilization toward the control of onchocerciasis. These effects were expected to translate into better individual acceptance of the intervention and hence high Treatment Coverage, leading to a sustainable community-led strategy and reduction in the disease burden. A survey revealed that after 10-12 rounds of treatment, prevalence of onchocerciasis was still high in three drainage basins of South West Cameroon and transmission was going on. METHODS: We designed a three (3)-year retrospective (2012, 2013 and 2014), descriptive cross-sectional study to explore the roles of operational challenges in the failure of CDTI to control the disease as expected. We administered 83 semi-structured questionnaires and conducted 12 in-depth interviews with Chiefs of Bureau Health, Chiefs of Centers, CDDs and Community Heads. Descriptive statistics was used to explore indicators of performance which were supported with views from in-depth interviews. RESULTS: We found that community participation was weak; communities were not deciding time and mode of distributions. Only 6 (15.0%) of 40 Community Drug Distributors reported they were selected at general community meetings as required. The health service was not able to meet and discuss Community-Directed Treatment with Ivermectin activities with individual communities partly due to transportation challenges; this was mostly done through letters. Funding was reported to be inadequate and not timely. Funds were not available to conduct Community-Self Monitoring after the 2014 Mass Drug Administration. There was inadequate health staff at the frontline health facility levels, and some Chiefs of Center reported that Community-Directed Treatment with Ivermectin work was too much for them. The mean operational Community Drug Distributor-population ratio was 1 Community Drug Distributor per 317 populations (range: 194-464, expected is 1:250). Community Drug Distributor attrition rate was 14% (2012), 11% (2013) and 12% (2014) of total Community Drug Distributors trained in the region. Lack of incentive for Community Drug Distributor was primary reason for Community Drug Distributor attrition. Number of Community Drug Distributors trained together by health area ranged from 14 to 127 (mean ± SD = 51 ±32) with duration of training ranging from 4-7 hours (mean ± SD = 5.05 ± 1.09). The trainings were conducted at the health centers. Community Drug Distributors always conducted census during the past three distributions (Mean ± SD = 2.85 ± 0.58). Community-Self Monitoring was facing challenge. Several of the community heads, Chiefs of Bureau Health and Chiefs of Center agreed that Community-Self Monitoring was not being carried out effectively due to lack of incentives for monitors in the communities. CONCLUSION: Inadequate human resource, funding issues and transportation challenges during distribution periods reduced the ability of the health service to thoroughly sensitize communities and supervise CDTI activities. This resulted in weak community understanding, acceptance and participation in the process. CDTI in our study area did not achieve sustainable community-led campaign and this may have led to the reduced impact on Onchocerciasis.

Community-perceived benefits of ivermectin treatment in northeastern Nigeria.

A 3-step approach involving focus group discussion, structured interviews and informal conversations with key individuals was used to investigate community usage and perceived benefits of ivermectin in nine Nigerian villages participating in a WHO-sponsored investigation of community-directed treatment with ivermectin (CDTI). Only 27% of 284 persons interviewed had received treatment. An under-estimation of the district's ivermectin needs led to inadequate supply of ivermectin to the communities, which was cited as the main reason (65%) for non-treatment. All those treated (N=76) were further interviewed using questionnaires. Worm expulsion (80%) and blindness prevention (68%) were the most frequently stated benefits. Other perceived benefits were an increase in vitality (68%), sexual drive and performance (29%). The sudden relief from a heavy burden of worms, which had built up over a long period, may have indirect effect on all aspects of an individual's health and account for the diverse experiences. The feeling of vitality, good appetite and general health following ivermectin treatment is an animating experience to many communities. Health planners face the challenge of preparing communities for fewer 'sensational' experiences and preventing a possible feeling of disappointment that may result from frequent usage.

Can community leaders' preferences be used to proxy those of the community as a whole?

BACKGROUND: Community-based distribution of ivermectin and other drugs requires people in the endemic communities who are capable of distributing the drug. It is essential also to collect information on local people's views concerning different financing mechanisms and approaches to distributing ivermectin. However, studies at household level are resource-intensive. Eliciting the preferences of the community by interviewing a smaller number of community leaders offers an alternative strategy. METHODS: A comparison of information from community leaders and household heads on the financing and distribution of ivermectin through communities was conducted in three communities in Nigeria to determine whether rapidly collected information from key community leaders could represent broad community preferences. RESULTS: The preferences of community leaders and household heads were comparable in relation to the method of collecting payments, managing payments and making payments, who should set the level of payments and the drug distribution mechanisms. However, there were differences between community leaders' views and those of heads of households concerning how the scheme should be supervised. CONCLUSIONS: This study has shown that community leaders' views can only be used as a partial substitute for more laborious methods of data collection insofar as they have the attraction of being quicker and less costly to use. However, they should not be assumed to be identical with the views of the community as a whole.

Disseminated strongyloidiasis successfully treated with extended duration ivermectin combined with albendazole: a case report of intractable strongyloidiasis.

We describe a patient with an overlapping syndrome disseminated strongyloidiasis and gram-negative sepsis. She was previously treated with albendazole 400 mg/day 14 days before admission without success. This admission, she was treated with a combination of oral ivermectin (injectable solution form), with a dosage of 200-400 microg/kg/day, and albendazole for 14 days. Strongyloides larvae disappeared from the stool by day 4 and from the sputum by day 10. No side effects were encountered during hospitalization or at the 1-month follow-up visit.