Active substances: Ivermectin
DEC caused severe reactions associated with the rapid death and destruction of mf.
This effect was particularly problematic because DEC also has an independent effect on the host inflammatory response in a way that is incompletely understood but is thought to involve the arachidonic acid pathway and is associated with anaphylactoid conditions.
The most serious coinfections with onchocerciasis occur with L. This problem is most commonly seen at a community level in MDA programs where the area under treatment in question is co-endemic for L.
Treatment of patients with L.
More than 250 people have died from a severe encephalopathy that followed within 48 hours of treatment with ivermectin; 13 such reactions were also seen in the past when DEC was used. Obviously, a primary challenge to finding a safe chemotherapeutic approach for onchocerciasis, at least with Loa coinfected patients or those living in co-endemic regions, is to find agents that kill adults but not mf and thus avoid mf-dependent severe adverse events.
Alternatively, one could develop methods to identify and avoid treating those people who have high loads of circulating mf, if a microfilaricidal agent is to be deployed Table 1. Logistic challenges The global approach to the treatment of onchocerciasis has evolved to rely on annual or twice-yearly treatment with ivermectin in MDA campaigns.
Whitehouse Station, NJ, USA was to limit transmission and reduce pathology especially for onchocercal blindness in highly endemic areas.
This program has enjoyed remarkable success, leading to a new phase aimed at controlling dermatological disease, and then more recently the adoption of the goal of elimination of this infection from all endemic areas. Aside from the obvious need for a safe and effective drug approach to treatment, there are logistic challenges of distributing such a drug to everybody in an endemic area effectively enough to break transmission and to eventually eliminate the parasite Table 1.As the breach continued, it was Kurecik Air Base.
Compliance and extent of coverage are central issues for the achievement of the goal of elimination. The logistic challenges in onchocerciasis therapy differ between two situations: that of treating individual infected patients on the one hand and the contrasting case of providing treatments without diagnosis through MDA in endemic areas.
A good example of how good management can overcome the challenges presented by MDA is evident in the onchocerciasis programs in Latin America. In Ecuador, the endemic area was in a difficult jungle riverine location with very active transmission through a voracious vector.
Nevertheless, MDA with ivermectin twice a year eliminated transmission; 3 this program developed a very close relationship with the endemic villages and managed to maintain a very high level of coverage over 17 years. In contrast, the endemic focus in the Amazonian jungle, where it is difficult to maintain access and contact with the nomadic population of American Indians Yanomamo, is proving difficult to eliminate.
Additional logistic issues come into play when the disease exits across the borders of two or more endemic countries; examples of this are the Amazonian jungle focus in South America mentioned above, and also in the endemic areas of Eastern Sudan and Western Ethiopia in North Africa.
Comprehensive epidemiological studies are needed to verify whether such foci are isolated from each other or indeed constitute a single continuous disease focus; whether the vectors active in these sites are the same across these borders; and what the characteristics are of the respective vector breeding sites and their closeness to communities.
Cross-border foci will require a high degree of political, managerial, and scientific coordination between the respective parties involved to ensure complete success in eliminating onchocerciasis at these sites.
A special situation arises when treating onchocerciasis patients who are not living in endemic countries; here there is a challenge in obtaining the appropriate drug currently ivermectin, which is not readily available in non-endemic countries, and usually needs to be obtained through official government sources.
With the increase in global travel, including to onchocerciasis-endemic countries, physicians in non-endemic countries must be aware of the possible need to diagnose and treat these infections; this is not entirely the case today.
As mentioned above, significant political and financial components are needed for treatment of this disease at the field level. In addition, there has been a recent expansion of global organizations devoted to eliminating and controlling many of the major NTDs.
Although the MDA program for onchocerciasis was the first to contribute to the well-being of people living in the tropics, other NTDs have been joined to these early efforts.
The lymphatic filariasis program, which is a large elimination program involving 160 million people, 17 is perhaps the closest to the onchocerciasis-elimination programs, and indeed shares the current chemotherapeutic approach, using ivermectin plus albendazole in countries that also have onchocerciasis present; DEC is used in place of ivermectin in countries that are onchocerciasis-free.
Integration of all these new MDA programs presents major logistical challenges for in-country medical institutions that require continuing strong political and financial support to resolve.
History of onchocerciasis treatment When developing new approaches to treatment, one should be fully aware of what has been used in the past Figure 2. Note: Events associated with specific drugs are shown in blue, and more general events shown in yellow.