Elimination of onchocerciasis in Africa by 2025: the need for a broad perspective.

BACKGROUND: In response to the recent publication "Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes" by Dadzie et al., it is important to clarify and highlight the positive and unequivocal research and operational contributions from the American experience towards the worldwide elimination of human onchocerciasis (river blindness). MAIN TEXT: The strategies of twice or more rounds of mass drug administration (MDA) of ivermectin per year, as well as the use of OV-16 serology have allowed four American countries to be verified by World Health Organization to have eliminated transmission of Onchocerca volvulus, the etiological agent. These advances were also implemented in Sudan and Uganda; currently, both are the only African countries where ivermectin MDA was safely stopped in several transmission zones. CONCLUSIONS: Programmatic treatment and evaluation approaches, pioneered in the Americas, are the most efficient among the existing tools for elimination, and their broader use could catalyze the successful elimination of this disease in Africa.

Operational Performance of the Onchocerca volvulus "OEPA" Ov16 ELISA Serological Assay in Mapping, Guiding Decisions to Stop Mass Drug Administration, and Posttreatment Surveillance Surveys.

Onchocerciasis is a neglected tropical disease targeted for elimination. The World Health Organization (WHO) has developed guidelines for the verification of onchocerciasis elimination that include entomological and epidemiological criteria. The latter require demonstrating with statistical confidence that the infection prevalence in children is less than 0.1%, necessitating an assay with a high degree of specificity. We present an analysis of the performance of the Onchocerciasis Elimination Program for the Americas (OEPA) version of the Ov16 enzyme-linked immunosorbant assay (ELISA) when used under operational conditions. In Africa and Latin America, the assay demonstrated 99.98% specificity in 69,888 children in 20 foci where transmission was believed to be interrupted. The assay produced a prevalence estimate equal to that of skin snip microscopy when applied in putatively hypo-endemic zones of Ethiopia. The OEPA Ov16 ELISA demonstrated the specificity required to be effectively deployed to verify transmission elimination under the WHO guidelines, while exhibiting a sensitivity equivalent to skin snip microscopy to identify hypo-endemic areas.

Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980-2017.

A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators-distributed throughout the country by strata and informed via the national surveillance system-enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador's experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.

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.

A Knowledge, Attitudes and Practices Survey Conducted Three Years after Halting Ivermectin Mass Treatment for Onchocerciasis in Guatemala.

BACKGROUND: Mass drug administration (MDA) with ivermectin for onchocerciasis was provided in Guatemala's Central Endemic Zone (CEZ) over a 24 year period (1988-2011). Elimination of Onchocerca volvulus transmission was declared in 2015 after a three year post MDA surveillance period (2012-2014) showed no evidence of recrudescence. The purpose of the present study was to evaluate the knowledge, attitudes and practices (KAP) towards onchocerciasis and ivermectin among residents in the post endemic CEZ. A major interest in this study was to determine what community residents thought about the end of the ivermectin MDA program. METHODOLOGY/PRINCIPAL FINDINGS: A total of 148 interviews were conducted in November 2014 in four formerly hyperendemic communities using a standard questionnaire on smart phones. The majority (69%) of respondents knew that the MDA program had ended because the disease was no longer present in their communities, but a slight majority (53%) was personally unsure that onchocerciasis had really been eliminated. Sixty-three percent wanted to continue to receive ivermectin because of this uncertainty, or because ivermectin is effective against intestinal worms. Eighty-nine percent of respondents said that they would seek medical attention immediately if a family member had symptoms of onchocerciasis (especially the presence of a nodule), which is a finding very important for ongoing surveillance. CONCLUSIONS/SIGNIFICANCE: Many respondents wanted to continue receive ivermectin and more than half did not believe onchocerciasis had been eliminated. The ministry of health outreach services should be prepared to address ongoing concerns about onchocerciasis in the post endemic CEZ.

One Hundred Years After Its Discovery in Guatemala by Rodolfo Robles, Onchocerca volvulus Transmission Has Been Eliminated from the Central Endemic Zone.

We report the elimination of Onchocerca volvulus transmission from the Central Endemic Zone (CEZ) of onchocerciasis in Guatemala, the largest focus of this disease in the Americas and the first to be discovered in this hemisphere by Rodolfo Robles Valverde in 1915. Mass drug administration (MDA) with ivermectin was launched in 1988, with semiannual MDA coverage reaching at least 85% of the eligible population in > 95% of treatment rounds during the 12-year period, 2000-2011. Serial parasitological testing to monitor MDA impact in sentinel villages showed a decrease in microfilaria skin prevalence from 70% to 0%, and polymerase chain reaction (PCR)-based entomological assessments of the principal vector Simulium ochraceum s.l. showed transmission interruption by 2007. These assessments, together with a 2010 serological survey in children 9-69 months of age that showed Ov16 IgG4 antibody prevalence to be < 0.1%, meeting World Health Organization (WHO) guidelines for stopping MDA, and treatment was halted after 2011. After 3 years an entomological assessment showed no evidence of vector infection or recrudescence of transmission. In 2015, 100 years after the discovery of its presence, the Ministry of Health of Guatemala declared onchocerciasis transmission as having been eliminated from the CEZ.

Elimination of Onchocerca volvulus Transmission in the Huehuetenango Focus of Guatemala.

In Latin America, onchocerciasis is targeted for elimination by 2012 through twice-yearly mass treatment of the eligible population with ivermectin. In Guatemala, two of the four historical endemic foci have demonstrated elimination of transmission, following World Health Organization guidelines. Using established guidelines ophthalmological, serological, and entomological evaluations were conducted in 2007-8 to determine the transmission status of onchocerciasis in the Huehuetenango focus. The prevalence of Onchocerca volvulus microfilariae in the anterior segment of the eye in 365 residents was 0% (95% confidence interval [CI] 0-0.8%), the prevalence of infection of O. volvulus in Simulium ochraceum among 8252 flies collected between November 2007 and April 2008 was 0% (95% CI 0-0.02%), and the prevalence of antibodies to a recombinant O. volvulus antigen in 3118 school age children was 0% (95% CI 0-0.1%). These results showed transmission interruption; thus, in 2009 mass treatment was halted and posttreatment surveillance began. To verify for potential recrudescence an entomological evaluation (from December 2010 to April 2011) was conducted during the 2nd and 3rd year of posttreatment surveillance. A total of 4587 S. ochraceum were collected, and the prevalence of infection of O. volvulus was 0% (95% CI 0-0.04%). Transmission of onchocerciasis in the Huehuetenango focus has been eliminated.

Onchocerciasis in the Americas: from arrival to (near) elimination.

Onchocerciasis (river blindness) is a blinding parasitic disease that threatens the health of approximately 120 million people worldwide. While 99% of the population at-risk for infection from onchocerciasis live in Africa, some 500,000 people in the Americas are also threatened by infection. A relatively recent arrival to the western hemisphere, onchocerciasis was brought to the New World through the slave trade and spread through migration. The centuries since its arrival have seen advances in diagnosing, mapping and treating the disease. Once endemic to six countries in the Americas (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela), onchocerciasis is on track for interruption of transmission in the Americas by 2012, in line with Pan American Health Organization resolution CD48.R12. The success of this public health program is due to a robust public-private partnership involving national governments, local communities, donor organizations, intergovernmental bodies, academic institutions, non-profit organizations and the pharmaceutical industry. The lessons learned through the efforts in the Americas are in turn informing the program to control and eliminate onchocerciasis in Africa. However, continued support and investment are needed for program implementation and post-treatment surveillance to protect the gains to-date and ensure complete elimination is achieved and treatment can be safely stopped within all 13 regional foci.

Exposure of seasonal migrant workers to Onchocerca volvulus on coffee plantations in Guatemala.

Onchocerciasis (river blindness), which is close to being eliminated from Guatemala through semiannual administration of ivermectin, is still transmitted in one area of the country that coincidentally receives an annual influx of migrant workers to harvest coffee. Migrant workers generally are not included in semiannual ivermectin treatments, but if infected could serve as a reservoir. We report on two studies undertaken to measure the exposure to onchocerciasis (presence of IgG4 antibodies to a recombinant Onchocerca volvulus antigen, OV-16) among migrant workers. During two coffee harvest seasons, 170 migrant workers with a history of working in the disease-endemic area were tested and 1 (0.6%, 95% confidence interval = 0-3.2%) was seropositive. This low rate of exposure in migrant workers indicates that they are unlikely to play a significant role in transmission of onchocerciasis and may indicate that transmission in the last remaining disease-endemic area of Guatemala is decreasing significantly.

Successful interruption of transmission of Onchocerca volvulus in the Escuintla-Guatemala focus, Guatemala.

BACKGROUND: Elimination of onchocerciasis (river blindness) through mass administration of ivermectin in the six countries in Latin America where it is endemic is considered feasible due to the relatively small size and geographic isolation of endemic foci. We evaluated whether transmission of onchocerciasis has been interrupted in the endemic focus of Escuintla-Guatemala in Guatemala, based on World Health Organization criteria for the certification of elimination of onchocerciasis. METHODOLOGY/PRINCIPAL FINDINGS: We conducted evaluations of ocular morbidity and past exposure to Onchocerca volvulus in the human population, while potential vectors (Simulium ochraceum) were captured and tested for O. volvulus DNA; all of the evaluations were carried out in potentially endemic communities (PEC; those with a history of actual or suspected transmission or those currently under semiannual mass treatment with ivermectin) within the focus. The prevalence of microfilariae in the anterior segment of the eye in 329 individuals (> or =7 years old, resident in the PEC for at least 5 years) was 0% (one-sided 95% confidence interval [CI] 0-0.9%). The prevalence of antibodies to a recombinant O. volvulus antigen (Ov-16) in 6,432 school children (aged 6 to 12 years old) was 0% (one-sided 95% IC 0-0.05%). Out of a total of 14,099 S. ochraceum tested for O. volvulus DNA, none was positive (95% CI 0-0.01%). The seasonal transmission potential was, therefore, 0 infective stage larvae per person per season. CONCLUSIONS/SIGNIFICANCE: Based on these evaluations, transmission of onchocerciasis in the Escuintla-Guatemala focus has been successfully interrupted. Although this is the second onchocerciasis focus in Latin America to have demonstrated interruption of transmission, it is the first focus with a well-documented history of intense transmission to have eliminated O. volvulus.

Rapid suppression of Onchocerca volvulus transmission in two communities of the Southern Chiapas focus, Mexico, achieved by quarterly treatments with Mectizan.

The impact of quarterly Mectizan (ivermectin) treatments on transmission, microfiladermia, and ocular lesions was evaluated in two formerly hyperendemic communities (Las Golondrinas and Las Nubes II) located in the main endemic focus for onchocerciasis in Southern Chiapas, Mexico. The data suggest that Onchocerca volvulus transmission has been suppressed after elimination of microfiladermia in these two communities. Increasing the frequency of Mectizan treatment to four times per year appears to have resulted in the rapid suppression of transmission in communities with residual transmission.

Evidence for suppression of Onchocerca volvulus transmission in the Oaxaca focus in Mexico.

Entomologic and serologic surveys were performed in four sentinel communities in the Oaxaca focus in southern Mexico to assess the level of transmission and exposure incidence to Onchocerca volvulus. All communities have been receiving ivermectin mass treatment twice per year since 1997. In one community, parasite DNA was detected by polymerase chain reaction-enzyme-linked immunosorbent assay in 2004 in one pool of 50 vector heads of 170 such pools (8,500 flies) examined, which indicated an estimated transmission potential of 6.7 third-stage larvae/person/year. No evidence for transmission was found in the three other communities in 13,650 flies examined. All persons in a cohort consisting of 117 children in the four communities remained serologically negative for antibodies recognizing a cocktail of recombinant antigens over a four-year period from 2001 to 2004, which indicated an exposure incidence of 0%. Taken together, these data suggest that transmission has been suppressed in the four communities.

Elimination of Onchocercia volvulus transmission in the Santa Rosa focus of Guatemala.

To eliminate transmission of Onchocerca volvulus, semiannual mass treatment with ivermectin (Mectizan; donated by Merck & Co) has been underway in Guatemala since 2000. We applied the 2001 World Health Organization (WHO) elimination criteria in the Santa Rosa focus of onchocerciasis transmission in Guatemala (10,923 persons at risk). No evidence of parasite DNA was found in 2,221 Simulium ochraceum vectors (one-sided 95% confidence interval [CI], 0-0.086%), and no IgG4 antibody positives to recombinant antigen OV16 were found in a sample of 3,232 school children (95% CI, 0-0.009%). We also found no evidence of microfilariae in the anterior segment of the eye in 363 area residents (95% CI, 0-0.08%). Our interpretation of these data, together with historical information, suggest that transmission of O. volvulus is permanently interrupted in Santa Rosa and that ivermectin treatments there can be halted.

The reliability of anterior segment lesions as indicators of onchocercal eye disease in Guatemala.

World Health Organization certification criteria for onchocerciasis elimination use anterior segment eye lesion prevalence as an indicator of mass ivermectin treatment program success. Lesions either contain visible microfilaria (noninflammatory punctate keratitis [PK] or microfilariae in anterior chamber [MFAC]), or microfilaria obscured by inflammation (inflammatory PK). To assess the utility of these disease indicators, two experienced ophthalmologists independently examined persons from endemic (N = 325) and nonendemic (N = 348) Guatemalan communities. Thirty-six (11.1%) and nine (2.6%) persons from endemic and nonendemic areas respectively had lesions found by either ophthalmologist (prevalence ratio = 4.3, 95% CI 2.1-8.8, P < 0.001). All lesions in nonendemic areas were inflammatory PK in whom no persons were seropositive for onchocerciasis. Overall, observer agreement was moderate (Kappa = 0.49), and most (61%) discordance occurred with inflammatory PK lesions. Our findings suggest that inflammatory punctate keratitis is neither a specific nor a reliable indicator of onchocercal eye disease. Future prevalence surveys should rely upon noninflammatory lesions as disease indicators.

The effects of long-term community level treatment with ivermectin (Mectizan) on adult Onchocerca volvulus in Latin America.

The objective of this study was to examine nodules from Mexico, Guatemala, and Ecuador collected over a one-year period (2001) to determine the effects of semi-annual ivermectin treatments on Onchocerca volvulus macrofilarial populations. Nodules were sectioned, stained with hematoxylin and eosin, and histologic findings were compared between countries and with historical data prior to the introduction of ivermectin into the region. Nodules from Ecuador had 10 times more dead or moribund worms than the historical control (66.6% versus 6.5%); nodules from patients from Mexico and Guatemala did not differ from the control. More than 80% of the female worms in each country were uninseminated and producing unfertilized oocytes. Nodules containing males differed in each country from the historical control (P < 0.0001), with presence of males ranging from 19.7% in Mexico to 13.6% in Ecuador versus 73% in the control. Nodules with females producing active microfilariae ranged from 7.8% (Mexico) to 2.7% (Ecuador) versus 60% in the historical control (P < 0.0001). Nodules from Ecuador and Mexico were significantly smaller in size than those from Guatemala or historical controls (P < 0.0005). These results depict a deteriorating condition of adult O. volvulus populations in Mexico, Guatemala and Ecuador, indicating that semi-annual ivermectin treatment of >/=6 years has had a profound effect on survival and reproduction of this species.