Trends in Parasitology
Volume 19, Issue 11, November 2003, Pages 516-522
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Mass drug treatment for lymphatic filariasis and onchocerciasis

https://doi.org/10.1016/j.pt.2003.09.004Get rights and content

Abstract

This review summarizes the progress towards control of lymphatic filariasis (LF) and onchocerciasis, focussing on the impact of mass drug administration (MDA) programmes, in particular those that have developed following the donation of ivermectin and albendazole. The contrasting strategies and objectives of the different programmes are compared, and the impact on transmission, clinical disease and public health assessed. The constraints on programme success are: (i) the absence of a macrofilaricide, which can be used in a public health context; (ii) the sustainability of high coverage of ivermectin over many years in onchocerciasis control; and (iii) the problem of treatment in areas where Loa loa (tropical eye worm) is co-endemic with onchocerciasis because of the rare severe adverse events. LF programmes are expanding rapidly in over 30 countries, where circa 60 million people received treatments in 2002. No serious adverse events have been associated with MDAs for LF elimination. Research on new approaches to treatment using antibiotics are showing promising results in pilot settings because doxycyline has been shown to have long-term embryostatic effects and sustained reductions of microfilaria loads in onchocerciasis and bancroftian filariasis.

Section snippets

Control programmes and drug strategy

The OCP in West Africa ended in 2002 after 28 years of operations apart from the special intervention zones (SIZ), where the unsatisfactory epidemiological situation requires ongoing control due to difficulties of vector control and ivermectin coverage in Togo and civil unrest in Sierra Leone 1, 2 (http://www.who.int/ocp/apoc). The remaining programmes – the African Programme for Onchocerciasis Control (APOC; http://www.who.int/ocp/apoc); the Onchocerciasis Elimination Programme in the Americas

Ivermectin in co-endemic settings: opportunities for integration

The case of the Dano district in the Bougouriba Basin, Burkina Faso is intriguing. LF has been found there with prevalences of circulating filarial antigen (CFA) between 40% and 75% in >15-year-olds in communities adjacent to those under control for onchocerciasis [12]. The biannual regimen of ivermectin has been undertaken since 1996 using CDT, and its impact on LF was assessed in two groups of communities in close proximity and with similar characteristics: (i) one group treated with

Alternative chemotherapeutic strategies

Studies to evaluate the value of the milbemycin compound moxidectin (Cydectin, Fort Dodge; http://www.wyeth.com/) (a drug used in veterinary medicine and animal health, but not yet registered for human use) as an alternative to ivermectin in controlling filariae [18] have found moxidectin more efficacious than ivermectin in most Onchocerca models [O. volvulus and Onchocerca lienalis in mice, and on microfilariae (Mf) in vitro] and in Onchocerca ochengi in cattle [19], in addition to rodent

Prophylactic effect of ivermectin

Community distribution of ivermectin on an annual basis is the strategy of APOC 3, 10, which treats people under conditions of continuing exposure to infection; hence, it is prudent to ascertain the effect of ivermectin on third-stage (L3) and fourth-stage (L4) larvae. A prospective controlled study conducted against natural infection of calves with O. ochengi in Cameroon showed that monthly treatment of growing calves with ivermectin at 200 μg kg−1 or at 500 μg kg−1 of body weight completely

Antibiotics and Wolbachia

There is broad recognition of the need for a macrofilaricide to enable programme closure; recently, the focus on the potential of antibiotics as adult worm sterilants has become the subject of intense research [21]. Over recent years, alternative approaches to classical chemotherapy have emerged as the Wolbachia endosymbionts of filariae have been recognized as potential drug targets 22, 23, 24, 25. Wolbachia have also been identified as potential contributors to disease pathology [26] and

Programme constraints: the problem of Loa loa

Loa loa is a filarial worm transmitted by a tabanid fly of the genus Chrysops. It is found in west and central Africa and manifests itself as tropical eye worm or Calabar swelling (transient subcutaneous oedema) when adult worms migrate through the eye and cutaneous tissues. Microfilariae are found in the peripheral blood during the day.

A particular constraint on programme expansion is the serious adverse effects associated with ivermectin use in co-endemic settings in areas with hyperendemic

Monitoring and evaluation

In GPELF, there has been a rapid upscaling in the number of countries covered by the programme (>34 countries) [5], the first mass drug administration (MDA) commencing in late 1999 in Samoa and early 2000 in Egypt, Tanzania and Vanuatu. Small-scale studies have evaluated the parasitological parameters of the impact of MDA on prevalence and intensity [39], but five years of MDA are required to ascertain what the full impact of MDA (with whatever combination of drugs) with high coverage will

LF: pharmacovigilance in mass drug distribution

The expansion of the LF programme in all countries has been accompanied by a period of intense safety monitoring of two-drug combinations: (i) ivermectin and albendazole (in Africa and Yemen); and (ii) DEC and albendazole (where onchocerciasis is not co-endemic in Africa, and throughout all other endemic regions). The need for such studies was required because albendazole is not registered as treatment for LF, despite its extensive use and excellent safety record in intestinal helminth control

Drug resistance

There is currently no formal evidence for the development of resistance to any drug used against filariasis. Although this is obviously encouraging, it is hardly surprising considering the lack of any comprehensive monitoring strategy. The co-administration of two drugs for LF MDA has the advantage of avoiding potential development of resistance to single drug treatment, assuming that the drugs have different molecular targets. Nevertheless, resistance to one of the drugs could still compromise

Conclusion

The programmes to control human filarial infections (with the exception of guinea worm, dracunculiasis) have been based on chemotherapeutic interventions regarded primarily as methods of transmission control and in onchocerciasis symptom alleviation. Different strategies of chemotherapy have been applied from selective treatment of microfilaraemics with DEC for filariasis, to DEC-fortified salt in China for whole populations. The global LF programme now relies on annual, time-limited treatment

References (54)

  • H.F Cross

    Severe reactions to filarial chemotherapy and release of Wolbachia endosymbionts into blood

    Lancet

    (2001)
  • J Gardon

    Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection

    Lancet

    (1997)
  • M.C Thomson

    Satellite mapping of Loa loa prevalence in relation to ivermectin use in western central Africa

    Lancet

    (2000)
  • S.K Dunyo et al.

    Ivermectin and albendazole alone and in combination for the treatment of lymphatic filariasis in Ghana: follow-up after re-treatment with the combination

    Trans. R. Soc. Trop. Med. Hyg.

    (2002)
  • Z Shaoqing

    A successful control programme for lymphatic filariasis in Hubei, China

    Trans. R. Soc. Trop. Med. Hyg.

    (1994)
  • M Bradley et al.

    Assessing the risk of benzimidazole therapy during pregnancy

    Trans. R. Soc. Trop. Med. Hyg.

    (2001)
  • M.M Ali

    Immunocompetence may be important in the effectiveness of Mectizan (ivermectin) in the treatment of human onchocerciasis

    Acta Trop.

    (2002)
  • Y.J Huang et al.

    Identification and stage-specific expression of two putative P-glycoprotein coding genes in Onchocerca volvulus

    Mol. Biochem. Parasitol.

    (1999)
  • B Benton

    Partnership and promise: evolution of the African river-blindness campaigns

    Ann. Trop. Med. Parasitol.

    (2002)
  • E.A Ottesen

    Strategies and tools for the control/elimination of lymphatic filariasis

    Bull. WHO

    (1997)
  • D.H Molyneux et al.

    Lymphatic filariasis elimination: progress in global programme development

    Ann. Trop. Med. Parasitol.

    (2002)
  • D.H Molyneux et al.

    Current status and future prospects of the Global Lymphatic Filariasis Programme

    Curr. Opin. Infect. Dis.

    (2001)
  • A Abiose

    Onchocerciasis control strategies

    Lancet

    (2000)
  • J Gardon

    Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial

    Lancet

    (2002)
  • G.J.J.M Boorsboom

    Impact of ivermectin on onchocerciasis transmission. Assessing the empirical evidence that repeated mass treatments may lead to elimination/eradication in West Africa

    Filaria J.

    (2003)
  • J.O Gyapong

    The use of spatial analysis in mapping the distribution of bancroftian filariasis in four West African countries

    Ann. Trop. Med. Parasitol.

    (2002)
  • H Schulz-Key

    Unterschiedliche Wirkung von Mectizan® auf Mikrofilarien von Onchocerca volvulus and Mansonella perstans in Patienten

    Mitteilungen-Österreichischen Gesellschaft für Tropenmedizin und Parastiologie

    (1990)
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