Frank O. Richards

Control of Onchocerciasis

Onchocerciasis is a filarial infection which causes blindness and debilitating skin lesions. The disease occurs in 37 countries, of which 30 are found in Africa (the most affected in terms of the distribution and the severity of the clinical manifestations of the disease), six in the Americas and one in the Arabian Peninsula. The latest WHO Expert Committee on Onchocerciasis estimated that in 1995 around 17.7 million persons were infected, about 270,000 of whom were blind and another 500,000 severely visually impaired. The disease is responsible for 1 million DALYs. Eye disease from onchocerciasis accounts for 40% of DALYs annually although severe skin disease is also recognized as of public health significance. Great progress has been made in the last thirty years in the control of onchocerciasis, both in Africa and the Americas, and this progress has been due largely to international public-private partnerships, sustained funding regional programmes, and new tools and technology. Landmarks in the global control of river blindness include the significant success of the Onchocerciasis Control Programme of West Africa (1975-2002), and the donation of ivermectin (Mectizan) by Merck & Co. Inc., in 1988, a medicine that is distributed to millions free of charge each year. Future major technical challenges of onchocerciasis control include ivermectin mass administration in areas co-endemic for the parasite Loa loa in the light of possible severe adverse reactions, ivermectin treatment in hypoendemic areas hitherto excluded from African control programmes, sustainability of ivermectin distribution, post-control surveillance for recrudescence detection, surveillance for emergence of resistance, and decisions of when to stop mass ivermectin treatments. There is the need to develop the appropriate information systems and diagnostic tools to help in accomplishing many of these tasks. A search for a second-line treatment or as an additional drug to ivermectin as well as a search for a macrofilaricide are issues that need to be addressed in the future.

Control of onchocerciasis today: status and challenges

The filarid parasite Onchocerca volvulus is the causative agent of human onchocerciasis (river blindness), an infection characterized by chronic skin and eye lesions. There are three regional programs currently dedicated to controlling onchocerciasis in the endemic areas of Africa and the Americas: the Onchocerciasis Control Programme of West Africa, the African Programme for Onchocerciasis Control and the Onchocerciasis Elimination Program for the Americas. All three programs use periodic mass treatment with the microfilaricidal drug ivermectin with differing strategic purposes and, as a result, face different challenges to reach their goals. This paper will review the strategies, status and challenges of these three programs.

Individual, household and environmental risk factors for malaria infection in Amhara, Oromia and SNNP regions of Ethiopia

We assessed malaria infection in relation to age, altitude, rainfall, socio-economic factors and coverage of control measures in a representative sample of 11437 people in Amhara, Oromia and SNNP regions of Ethiopia in December 2006-January 2007. Surveys were conducted in 224 randomly selected clusters of 25 households (overall sample of 27884 people in 5708 households). In 11538 blood slides examined from alternate households (83% of those eligible), malaria prevalence in people of all ages was 4.1% (95% CI 3.4-4.9), with 56.5% of infections being Plasmodium falciparum. At least one mosquito net or one long-lasting insecticidal net (LLIN) was present in 37.0% (95% CI 31.1-43.3) and 19.6% (95% CI 15.5-24.5) of households, respectively. In multivariate analysis (n=11437; 82% of those eligible), significant protective factors were: number of LLINs per household (odds ratio [OR] (per additional net)=0.60; 95% CI 0.40-0.89), living at higher altitude (OR (per 100 m)=0.95; 95% CI 0.90-1.00) and household wealth (OR (per unit increase in asset index)=0.79; 95% CI 0.66-0.94). Malaria prevalence was positively associated with peak monthly rainfall in the year before the survey (OR (per additional 10 mm rain)=1.10; 95% CI 1.03-1.18). People living above 2000 m and people of all ages are still at significant risk of malaria infection.

Elimination of human onchocerciasis: History of progress and current feasibility using ivermectin (Mectizan®) monotherapy

We review and analyze approaches over a 65 year period that have proven successful for onchocerciasis control in several different epidemiological settings. These include vector control with the goal of transmission interruption versus the use of mass drug administration using ivermectin (Mectizan(®)) monotherapy. Ivermectin has proven exceedingly effective because it is highly efficacious against Onchocerca volvulus microfilariae, the etiological agent of onchocercal skin and ocular disease and the infective stage for the vector. For these reasons, the drug was donated by the Merck Company for regional control programs in Africa and the Americas. Recurrent treatment with ivermectin at semi-annual intervals also impacts adult worms and result in loss of fecundity and increased mortality. Using a strategy of 6-monthly treatments with high coverage rates, the Onchocerciasis Elimination Program for the Americas has interrupted transmission in seven of the thirteen foci in the Americas and is on track to eliminate onchocerciasis in the region by 2015. Treatments given annually or semi-annually for 15-17 years in three hyperendemic onchocerciasis foci in Mali and Senegal also have resulted in a few infections in the human population with transmission levels below thresholds postulated for elimination. Follow-up evaluations did not detect any recrudescence of infection or transmission, suggesting that onchocerciasis elimination could be feasible with Mectizan(®) treatment in some endemic foci in Africa.

Integrating an NTD with one of "The big three": combined malaria and trachoma survey in Amhara Region of Ethiopia.

Background Amhara Regional State of Ethiopia has a population of approximately 19.6 million, is prone to unstable and epidemic malaria, and is severely affected by trachoma. An integrated malaria and trachoma control program is being implemented by the Regional Health Bureau. To provide baseline data, a survey was conducted during December 2006 to estimate malaria parasite prevalence, malaria indicators, prevalence of trachoma, and trachoma risk factors in households and people of all ages in each of the ten zones of the state, excluding three urban centers (0.4% of the population). Methodology/Principal Findings The study was designed to provide prevalence estimates at zone and state levels. Using multi-stage cluster random sampling, 16 clusters of 25 households were randomly selected in each of the ten zones. Household heads were interviewed for malaria indicators and trachoma risk factors (N = 4,101). All people were examined for trachoma signs (N = 17,242), and those in even-numbered households provided blood films for malaria parasite detection (N = 7,745); both thick and thin blood films were read. Zonal malaria parasite prevalence ranged from 2.4% to 6.1%, with the overall state-wide prevalence being 4.6% (95% confidence interval (CI): 3.8%–5.6%). The Plasmodium falciparum: Plasmodium vivax ratio ranged from 0.9–2.1 with an overall regional ratio of 1.2. A total of 14.8% of households reported indoor residual spraying in the past year, 34.7% had at least one mosquito net, and 16.1% had one or more long-lasting insecticidal net. Zonal trachoma prevalence (trachomatous inflammation follicular [WHO grade TF] in children aged 1–9 years) ranged from 12.6% to 60.1%, with the overall state-wide prevalence being 32.7% (95% CI: 29.2%–36.5%). State-wide prevalence of trachomatous trichiasis (TT) in persons aged over fifteen was 6.2% (95% CI: 5.3–7.4), and 0.3% (95% CI: 0.2–0.5) in children aged 0–14 years. Overall, an estimated 643,904 persons (lower bound 419,274, upper bound 975,635) have TT and require immediate corrective surgery. Conclusions/Significance The results provide extensive baseline data to guide planning, implementation, and evaluation of the integrated malaria and trachoma control program in Amhara. The success of the integrated survey is the first step towards demonstration that control of priority neglected tropical diseases can be integrated with one of the “big three” killer diseases.

Programmatic goals and approaches to onchocerciasis

Onchocerciasis is an endemic disease in 37 countries (in Africa, in the Americas, and in Yemen). It infects at least 17.7 million people and causes visual impairment in 500,000 and blindness in another 270,000. It is transmitted by black flies that breed in rapidly flowing rivers and streams. As response to an endemic disease, programs have focused on the control of onchocerciasis transmission. In Africa, the African Programme for Onchocerciasis Control is based on an ivermectin-distribution strategy designed to control the skin and eye disorders that result from heavy infections. By contrast, the strategy of the African Onchocerciasis Control Program is a vector control to completely interrupt the transmission cycle of the parasite by applying larvicide to riverine breeding sites. In the Americas, another strategy being implemented is to use ivermectin more than once a year, not only to stop progression of disease, but also to interrupt transmission. Moreover, the global lymphatic-filariasis initiative aims to halt transmission of lymphatic filariasis in endemic African communities by annual mass administration of single-dose combination therapy with albendazole and Mectizan.

The onchocerciasis elimination program for the Americas: a history of partnership

The decision in 1987 by the pharmaceutical firm Merck & Co. to provide Mectizan (ivermectin) free of charge to river blindness control programs has challenged the international public health community to find effective ways to distribute the drug to rural populations most affected by onchocerciasis. In the Americas, PAHO responded to that challenge by calling for the elimination of all morbidity from onchocerciasis from the Region by the year 2007 through mass distribution of ivermectin. Since 1991, a multinational, multiagency partnership (consisting of PAHO, the endemic countries, nongovernmental development organizations, the Centers for Disease Control and Prevention in Atlanta, Georgia, as well as academic institutions and funding agencies) has developed the political, financial, and technical support needed to move toward the realization of that goal. This partnership is embodied in the Onchocerciasis Elimination Program for the Americas (OEPA), which is supported by the River Blindness Foundation (RBF) and now by the Carter Center. OEPA was conceived as a means of maintaining a regional initiative to eliminate what is otherwise a low priority disease. Since its inception in 1993, the OEPA has provided more than US

Factors associated with mosquito net use by individuals in households owning nets in Ethiopia

2 million in financial, managerial, and technical assistance to stimulate and/or support programs in Brazil, Colombia, Ecuador, Guatemala, Mexico, and Venezuela, so as to take full advantage of the Merck donation. Now halfway into a five-year, US

Transmission of Onchocerciasis in Wadelai Focus of Northwestern Uganda Has Been Interrupted and the Disease Eliminated

4 million grant provided through the Inter-American Development Bank, the OEPAs capacity to support the regional initiative is assured through 1999.

Controlling onchocerciasis by community-directed, ivermectin-treatment programmes in Uganda: why do some communities succeed and others fail?

BackgroundOwnership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use.MethodsGeneralized linear latent and mixed models (GLLAMM) were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS) in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy); net factors (condition, age, net density); household factors (number of rooms [2006] or sleeping spaces [2007], IRS, womens knowledge and school attendance [2007 only], wealth, altitude); and cluster level factors (rural or urban) were investigated in univariate and multi-variable models for each survey.ResultsIn 2006, increased net use was associated with: age 25-49 years (adjusted (a) OR = 1.4, 95% confidence interval (CI) 1.2-1.7) compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5); fewer nets with holes (Ptrend = 0.002); and increasing net density (Ptrend < 0.001). Reduced net use was associated with: age 5-24 years (aOR = 0.2; 95% CI 0.2-0.3). In 2007, increased net use was associated with: female gender (aOR = 1.3; 95% CI 1.1-1.6); fewer nets with holes (aOR [all nets in HH good] = 1.6; 95% CI 1.2-2.1); increasing net density (Ptrend < 0.001); increased womens malaria knowledge (Ptrend < 0.001); and urban clusters (aOR = 2.5; 95% CI 1.5-4.1). Reduced net use was associated with: age 5-24 years (aOR = 0.3; 95% CI 0.2-0.4); number of sleeping spaces (aOR [per additional space] = 0.6, 95% CI 0.5-0.7); more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7); and increasing household altitude (Ptrend < 0.001).ConclusionIn both surveys, net use was more likely by women, if nets had fewer holes and were at higher net per person density within households. School-age children and young adults were much less likely to use a net. Increasing availability of nets within households (i.e. increasing net density), and improving net condition while focusing on education and promotion of net use, especially in school-age children and young adults in rural areas, are crucial areas for intervention to ensure maximum net use and consequent reduction of malaria transmission.