CSU 68/2011: ONCHOCERCIASIS CONTROL AND ELIMINATION

Tuesday, 1st of March 2011

AFRICA

Since the late ‘80s, onchocerciasis control, originally based on vector control, has had as its mainstay the periodic distribution of ivermectin during annual campaigns. Here is a description of the programme by one involved in it:

The launch of the Mectizan Donation Program (MDP) in 1987, by Merck & Co., Inc., created a number of new opportunities for onchocerciasis control. The microfilaricide Mectizan was rapidly put to use by the Onchocerciasis Control Programme in West Africa (OCP), for mass treatment by field teams in selected areas. Other milestones in Mectizan treatment included the establishment, in 1992, of the Onchocerciasis Elimination Program for the Americas, and the creation of the African Programme for Onchocerciasis Control (APOC) in 1995, the latter programme covering all African countries in need outside of the OCP area. In 1998, the donation of Mectizan was expanded to include the treatment of lymphatic filariasis in those African countries where that disease is co-endemic with onchocerciasis. In the past, the development of a broad partnership around the MDP played a very important role, including non-governmental development organizations collaborating with the ministries of health in endemic countries. A new community-directed treatment strategy, which made it easier to reach out to all those in need, including those in remote areas, was developed by the APOC in collaboration with the World Health Organization's Special Programme for Research and Training in Tropical Diseases (TDR). Several drug-management issues, including dosing, shelf-life, safety, and the reporting of severe adverse experiences, were addressed by the MDP, through its Mectizan Expert Committee, and by Merck & Co., Inc. A major research effort for the safe treatment of onchocerciasis in loiasis-endemic areas has also been supported by the MDP. Presently there are national programmes for Mectizan mass treatment in all 33 endemic countries in need of such treatment; >69 million Mectizan treatments for onchocerciasis were provided during 2006, and this number is expected to grow to at least 100 million treatments/year by 2010. This achievement has resulted in great public-health and socio-economic benefits for the populations concerned. Future challenges will include additional support to 'fragile states' resulting from conflicts or natural disasters, and the need for a strengthened primary healthcare (PHC) infrastructure. The community-directed-treatment approach has been a great success but there is still a need to link the treatments to PHC, for the long-term sustainability of the treatments. The presence of loiasis in vast areas of Central Africa imposes a need for the mapping of that disease, and the application of safety precautions when distributing Mectizan in those areas. The recent decision to extend the APOC up to 2015 should facilitate the building of sustainable Mectizan treatment programmes that are integrated with the control of other neglected tropical diseases, such as lymphatic filariasis, intestinal helminths and trachoma. It will be important to define the safe end-point for Mectizan treatment in various settings, and an ongoing study by TDR will address this issue. There is also a need to consider the application of more frequent Mectizan treatments, possibly with adjunct measures, such as ground-based vector control in selected areas, or new chemotherapeutic approaches (as and when they become available). (Thylefors B., 'The Mectizan Donation Program (MDP),' Ann Trop Med Parasitol. 2008 Sep; 102 Suppl 1:39-44, )

Concerns have been raised whether ivermectin resistance might blunt the effect of mass drug administration. Lustigman and McCarter discuss these and related issues at http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17989789

They point out, notably, that

‘. . . IVM treatment of at least 65% of the population for 25 or more years will be necessary to eliminate infection [9,12]. There are significant logistical obstacles to achieving such broad-ranging and prolonged treatment, and there is also concern that O. volvulus resistance to IVM will emerge.’

In Africa, would it be useful to accelerate the pace by twice yearly administration of ivermectin during Child Health Days? This modality, not possible a decade ago, would permit sharing of overhead costs in countries already giving vitamin A twice yearly in mass campaigns.

The African literature concentrates on western and central Africa, but this recent item from The Lancet gives a view about the needs of Tanzania.

The Lancet, Volume 372, Issue 9651, Pages 1721 - 1722, 15 November 2008

doi:10.1016/S0140-6736(08)61716-X

Tanzania's fight against onchocerciasis

Original Text

Samuel Loewenberg

Despite the success of WHO's African Programme for Onchocerciasis Control, many challenges remain for Tanzania as it tries to tackle the disease. Funding shortages for drug distribution and poor treatment compliance are hampering the country's progress. Samuel Loewenberg reports.

Leo Khalfam Msakile is blind, and he does not know why. The middle-aged Tanzanian maize farmer sits on the ground in front of his hut with his five children around him, as his wife tends a pot over a wooden fire. He gestures to his clouded up eyes, which he says began to itch 3 years ago, before his sight failed completely. In his village, Mngazi, 50 people have epilepsy, including his son, and another 20 are becoming blind. Msakile's community has endemic onchocerciasis.

The parasitic disease is endemic throughout much of sub-Saharan Africa. It is almost impossible to avoid, as it is transmitted via black flies, which breed in clean, fast-moving water that villagers depend on for drinking, bathing, and washing their clothes. The flies are the vector for a parasitic worm that is transmitted to people through fly bites. The worms enter the body, nestling near bone protuberances, where they breed millions of offspring.

It is these microfilariae that cause the debilitating symptoms of onchocerciasis. The early stages produce incessant itching that makes it difficult to work and can cause people to lose sleep for years at a time. The latter stages can result in epilepsy, and ultimately in blindness.

The disease affects some 4 million people in Tanzania alone. The number of people with the disease worldwide, most of them in Africa, was long thought to be 18 million, but has recently been established as twice that amount.

As pervasive as the disease is, it is even more difficult to treat. The only effective medication is ivermectin, which was originally produced as a veterinary drug. The drug does not kill the adult worms but stops them from breeding and kills off the belligerent offspring. The drug must be taken annually for the life of the worm, which is about 15 years. Further, the drug must be taken by everyone in the village—with the exception of small children, the very ill, and pregnant and nursing women—or else the worms will continue to breed and can reinfect the population.

Although it has been possible to spray to kill off the parasites in west Africa, in much of east Africa the mountainous geography and numerous rivers make it unfeasible.

In 1995, WHO's African Programme for Onchocerciasis Control (APOC) developed a method to distribute the medicine by recruiting a network of thousands of local volunteers to handle the distribution of ivermectin. The drug is donated free by its manufacturer, Merck & Co.

The programme treats nearly 54 million people annually in 19 countries. It has achieved a 30% reduction in the prevalence of infection, and a 55% reduction in itching. The rate of blindness has dropped by 65%.

Still, many challenges remain. Tanzania's Minister of Health and Social Welfare, David Mwakyusa, told The Lancet that the lack of education about basic public-health issues remains a problem, especially for a slow-moving disease like onchocerciasis that takes such a long time to treat. A frequent problem is that people stop taking the drug once the symptoms of the worm subside, often after 3 years of treatment. The challenge is “to convince people to continue to take the drug when they are symptom free”, Mwakyusa said.

Another major problem is keeping up the funding for the volunteer distribution programme. As planned, WHO has gradually withdrawn funding in order to turn over responsibility to domestic governments. But keeping funding for the disease a priority remains difficult since it competes for attention with high-profile diseases that have attracted massive amounts of international attention and have drawn funding from large donors.

“Onchocerciasis is not high up on the budget list compared with HIV/AIDS and tuberculosis”, said Wade Asyukile Kabuka, an ophthalmologist who coordinates the project in the Ruvuma region of Tanzania. This situation is especially difficult when new local officials come into power, who are not familiar with the disease. Constant advocacy is necessary, he said.

Still the programme seems to be working, although there has not yet been any follow-up assessment in Tanzania. “After 15 years we do not know what will happen”, said Kabuka.

The Bill & Melinda Gates Foundation recently concluded a study of the programme's effectiveness in Senegal and Mali, and it seems to have been a success, although the results have not yet been published, said APOC director Uche V Amazigo.

Still, she acknowledged that keeping the villagers focused on taking the medicine for such a long time remains difficult. In communities that have been receiving treatment for a long time, the younger generation is sometimes unaware of the disease, said Amazigo. “They do not even remember what onchocerciasis is, and that is part of the problem we have”, she said.

In the village of Litowa, population about 1500, located amid the lush and hilly southern highlands, the prevalence rate of onchocerciasis is 98%. The village has been under treatment since the mid-1990s, so the disease should not be manifesting, but it is. Kabuka points to a woman by the river itching and young children who appear to have signs of itching on their legs. “After 15 years of treatment you do not expect to see a fresh case of onchocerciasis. There is something wrong”, said Kabuka.

Village leaders in Litowa say that many people do not want to take the medicine in November because they are concerned it will interfere with their ability to work in the harvest season. The drug also produces side-effects for the first 72 h after it is first ingested, which can include severe itching and swelling.

The fact that the medicine is distributed freely also raises suspicions among the villagers; health officials must combat a widespread belief that it is a part of a conspiracy to sterilise them. Their strategy is to convince the villagers, plagued by itching, that the medicine will actually increase their sex drive. After taking the medicine, “people found they had increased libido, so they thought different”, said Meshack Massi, the Regional Medical Officer in Ulanga. “The itching stops and you remember you have a partner in your bed.”

One of the biggest challenges is retaining a sufficient number of volunteers to distribute the medicine—it is the key component of the onchocerciasis programme, and one which WHO officials hope to use in other public-health efforts.

In the district of Namtumbo, where 70—80% of the population of 200 000 have river blindness and is in its 8th year of treatment, keeping the volunteers year-to-year remains a problem, said Timothy Ndunguru, the local medical officer.

Villagers want to be paid to do their work, which can take up to a month, but this is a request WHO has specifically resisted. The programme's administrators are concerned that payment would disrupt delicate village dynamics, and instead want the volunteers to be compensated in a traditional manner, by being exempted from certain village-wide duties.

Still, volunteers frequently complain, said Kabuka, who said that they say: “You are the ones who bring the medicine, so you are the ones who are supposed to pay us.”

According to APOC's initial guidelines there should be one volunteer for every 200—400 villagers, but that ratio is too big, so now they are trying to bring it down to one per 100, says Oscar Kaitaba, the deputy director of the Tanzanian Onchocerciasis Control Programme. At a minimum, that means doubling the number of volunteers they now have, which now number about 11 000 people. As of now, the funds are lacking for such a broad expansion, even though the cost of training the individual volunteers over 2—4 days is only a few pounds.

Another problem with getting people to take the drug over such a long period is that frequent migration of workers, especially men, who are drawn to other regions of the country for jobs in the mining industry and tea plantations. In trying to recruit new volunteers they are seeking women, because they are less transient then men, said Kaitaba.

In many ways, Tanzania is better off than most African countries, with a lush climate and a widespread, if rudimentary, health infrastructure. But as one local officials puts it, “in every village there's a school but not enough teachers”, and the same can be said for health clinics, which lack sufficient staff. On the other hand, even the most remote villages in forests on the sides of mountains seem to have mobile phone antennae towers incongruously placed among the banana trees, proving that where there is a will there is a way.

“Onchocerciasis is a forgotten disease. We do not see it as a serious disease compared with other diseases that are costing lots of lives”, said Sungwa Ndagabewene, a district medical officer. “It needs more attention. It is a disease which we can eliminate if we put more effort into it.”

LATIN AMERICA

Even as oncho control meets new challenges in Africa, the Latin American programmes seem to be moving towards area elimination.

1: Ann Trop Med Parasitol. 2008 Sep;102 Suppl 1:25-9.

The Onchocerciasis Elimination Program for the Americas (OEPA).

Sauerbrey M.

Onchocerciasis Elimination Program for the Americas (OEPA), 14 Calle 3-51 Zona 10, Edificio Murano Center, Oficina 1401, Guatemala City, Guatemala. oepa@oepa.net

Human onchocerciasis (river blindness) occurs in 13 foci distributed among six countries in Latin America (Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela), where about 500,000 people are considered at risk. An effort to eliminate the disease from the region was launched in response to a specific resolution adopted by the PanAmerican Health Organization (PAHO) in 1991: to eliminate onchocerciasis from the region, as a public-health problem, by 2007. The effort took advantage of the donation of the drug Mectizan (ivermectin) by Merck & Co., Inc. In 1992, the Onchocerciasis Elimination Program for the Americas (OEPA) was launched, with its headquarters in Guatemala, to act as a technical and co-ordinating body of a multinational, multi-agency coalition that includes the endemic countries, PAHO, The Carter Center, Lions Clubs, the United States Centers for Disease Control and Prevention, The Bill and Melinda Gates Foundation, Merck & Co., Inc., and other partners. This public-private partnership facilitated the establishment of programmes for the semi-annual mass administration of Mectizan in the six countries with onchocerciasis. The aims were to (1) provide sustained treatments, with coverage reaching at least 85% of those eligible to receive the drug (in the 1845 endemic communities that are distributed within the 13 regional foci); (2) eliminate new morbidity caused by Onchocerca volvulus infection by 2007; and (3) eliminate transmission of the parasite wherever feasible. Significant progress has already been made in all six countries, each of which has active programmes with treatment coverages exceeding the target of 85%. The progress is being documented in accordance with certification guidelines for onchocerciasis elimination established by the World Health Organization. No new cases of onchocercal blindness are being reported in the region, and ocular disease attributable to O. volvulus has been eliminated from nine of the 13 foci. Treatment is no longer needed in Santa Rosa, Guatemala, where transmission has been eliminated, and will be halted in at least three other foci in 2008, as they confirm the interruption of transmission. Treatment efforts should now be concentrated on the five foci where significant transmission remains: Central (Guatemala), Amazonas/Roraima (Brazil), North-central (Venezuela), North-east (Venezuela) and South (Venezuela). Based upon the experience gained, the well-established operations and the success achieved so far, it seems reasonable to estimate that onchocerciasis could be eliminated from most of the remaining foci in the Americas by 2012. The protocol, criteria and deadline for stopping all onchocerciasis treatment in the region should soon be addressed by OEPA's Program Co-ordinating Committee (PCC), in co-ordination with the PAHO.

If the Region of the Americas made it over the finish line first, this would not be surprising. The same phenomenon has already been observed with smallpox, polio, and measles, all of them cleared from the Western Hemisphere before elimination from Asia and Africa. This simply underlines the fact that, quite aside from technical factors, more health infrastructure and more health spending tend to move elimination programmes along with greater speed.

Good reading.