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An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis
- J. HORTON, C. WITT, E.A. OTTESEN, J.K. LAZDINS, D.G. ADDISS, K. AWADZI, M.J. BEACH, V.Y. BELIZARIO, S.K. DUNYO, M. ESPINEL, J.O. GYAPONG, M. HOSSAIN, M.M. ISMAIL, R.L. JAYAKODY, P.J. LAMMIE, W. MAKUNDE, D. RICHARD-LENOBLE, B. SELVE, R.K. SHENOY, P.E. SIMONSEN, C.N. WAMAE, M.V. WEERASOORIYA
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- Journal:
- Parasitology / Volume 121 / Issue S1 / October 2000
- Published online by Cambridge University Press:
- 16 July 2001, pp. S147-S160
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This review of the safety of the co-administration regimens to be used in programmes to eliminate lymphatic filariasis (albendazole+ivermectin or albendazole+diethylcarbamazine [DEC]) is based on 17 studies conducted in Sri Lanka, India, Haiti, Ghana, Tanzania, Kenya, Ecuador, the Philippines, Gabon, Papua New Guinea, and Bangladesh. The total data set comprises 90635 subject exposures and includes individuals of all ages and both genders. Results are presented for hospital-based studies, laboratory studies, active surveillance of microfilaria-positive and microfilaria-negative individuals, and passive monitoring in both community-based studies and mass treatment programmes of individuals treated with albendazole (n=1538), ivermectin (9822), DEC (576), albendazole+ivermectin (7470), albendazole+DEC (69020), or placebo (1144). The most rigorous monitoring, which includes haematological and biochemical laboratory parameters pre- and post-treatment, provides no evidence that consistent changes are induced by any treatment; the majority of abnormalities appear to be sporadic, and the addition of albendazole to either ivermectin or DEC does not increase the frequency of abnormalities. Both DEC and ivermectin show, as expected, an adverse event profile compatible with the destruction of microfilariae. The addition of albendazole to either single-drug treatment regimen does not appear to increase the frequency or intensity of events seen with these microfilaricidal drugs when used alone. Direct observations indicated that the level of adverse events, both frequency and intensity, was correlated with the level of microfilaraemia. In non microfilaraemic individuals, who form 80–90% of the ‘at risk’ populations to be treated in most national public health programmes to eliminate lymphatic filariasis (LF), the event profile with the compounds alone or in combination does not differ significantly from that of placebo. Data on the use of ivermectin+albendazole in areas either of double infection (onchocerciasis and LF), or of loiais (with or without concurrent LF) are still inadequate and further studies are needed. Additional data are also recommended for populations infected with Brugia malayi, since most data thus far derive from populations infected with Wuchereria bancrofti.
Ivermectin: effectiveness in lymphatic filariasis
- K.R. BROWN, F.M. RICCI, E.A. OTTESEN
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- Parasitology / Volume 121 / Issue S1 / October 2000
- Published online by Cambridge University Press:
- 15 June 2001, pp. S133-S146
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This detailed review of the published studies underlying ivermectin's recent registration for use in lymphatic filariasis (LF) demonstrates the drug's single-dose efficacy (over the range of 20–400μg/kg) in clearing microfilaraemia associated with both Wuchereria bancrofti and Brugia malayi infections of humans. While doses as low as 20μg/kg could effect transient microfilarial (mf) clearance, higher dosages induced greater and more sustained mf reduction. The single dose of 400μg/kg yielded maximal responses, but a number of practical considerations suggest that either 400μg/kg or 200μg/kg doses would be acceptable for use in LF control programmes. Associated safety assessments indicate that adverse events, which occur commonly following treatment of microfilaraemic individuals, develop not because of drug toxicity but because of host inflammatory responses to dying microfilariae killed by the ivermectin treatment. Ivermectin is, therefore, a highly effective and generally well tolerated microfilaricide that may soon become an essential component of many public health initiatives to interrupt transmission of lymphatic filarial infection in an effort to eliminate LF globally.
Malnutrition and parasitic helminth infections
- L.S. STEPHENSON, M.C. LATHAM, E.A. OTTESEN
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- Journal:
- Parasitology / Volume 121 / Issue S1 / October 2000
- Published online by Cambridge University Press:
- 15 June 2001, pp. S23-S38
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The Global Burden of Disease caused by the 3 major intestinal nematodes is an estimated 22·1million disability-adjusted life-years (DALYs) lost for hookworm, 10·5million for Ascaris lumbricoides, 6·4million for Trichuris trichiura, and 39·0million for the three infections combined (as compared with malaria at 35·7million) (World Bank, 1993; Chan et al. 1994); these figures illustrate why some scarce health care resources must be used for their control. Strongyloides stercoralis is the fourth most important intestinal worm infection; its nutritional implications are discussed, and the fact that its geographic distribution needs further study is emphasized. Mechanisms underlying the malnutrition induced by intestinal helminths are described. Anorexia, which can decrease intake of all nutrients in tropical populations on marginal diets, is likely to be the most important in terms of magnitude and the probable major mechanism by which intestinal nematodes inhibit growth and development. We present a revised and expanded conceptual framework for how parasites cause/aggravate malnutrition and retard development in endemic areas. Specific negative effects that a wide variety of parasites may have on gastrointestinal physiology are presented. The synergism between Trichuris and Campylobacter, intestinal inflammation and growth failure, and new studies showing that hookworm inhibits growth and promotes anaemia in preschool (as well as school-age) children are presented. We conclude by presenting rationales and evidence to justify ensuring the widest possible coverage for preschool-age children and girls and women of childbearing age in intestinal parasite control programmes, in order to prevent morbidity and mortality in general and specifically to help decrease the vicious intergenerational cycle of growth failure (of low-birth-weight/intrauterine growth retardation and stunting) that entraps infants, children and girls and women of reproductive age in developing areas.
Global malnutrition
- L.S. STEPHENSON, M.C. LATHAM, E.A. OTTESEN
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- Parasitology / Volume 121 / Issue S1 / October 2000
- Published online by Cambridge University Press:
- 15 June 2001, pp. S5-S22
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The four most important forms of malnutrition worldwide (protein-energy malnutrition, iron deficiency and anaemias (IDA), vitamin A deficiency (VAD), and iodine deficiency disorders (IDD)) are examined below in terms of their global and regional prevalences, the age and gender groups most affected, their clinical and public health consequences, and, especially, the recent progress in country and regional quantitation and control. Zinc deficiency, with its accompanying diminished host resistance and increased susceptibility to infections, is also reviewed. WHO estimates that malnutrition (underweight) was associated with over half of all child deaths in developing countries in 1995. The prevalence of stunting in developing countries is expected to decline from 36% in 1995 to 32·5% in 2000; the numbers of children affected (excluding China) are expected to decrease from 196·59millions to 181·92millions. Stunting affects 48% of children in South Central Asia, 48% in Eastern Africa, 38% in South Eastern Asia, and 13–24% in Latin America. IDA affects about 43% of women and 34% of men in developing countries and usually is most serious in pregnant women and children, though non-pregnant women, the elderly, and men in hookworm-endemic areas also comprise groups at risk. Clinical VAD affects at least 2·80million preschool children in over 60 countries, and subclinical VAD is considered a problem for at least 251millions; school-age children and pregnant women are also affected. Globally about 740million people are affected by goitre, and over two billions are considered at risk of IDD. However, mandatory salt iodisation in the last decade in many regions has decreased dramatically the percentage of the population at risk. Two recent major advances in understanding the global importance of malnutrition are (1) the data of 53 countries that links protein-energy malnutrition (assessed by underweight) directly to increased child mortality rates, and (2) the outcome in 6 of 8 large vitamin A supplementation trials showing decreases of 20–50% in child mortality.
Controlling intestinal helminths while eliminating lymphatic filariasis
- L.S. STEPHENSON, C.V. HOLLAND, E.A. OTTESEN
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- Parasitology / Volume 121 / Issue S1 / October 2000
- Published online by Cambridge University Press:
- 15 June 2001, p. S1
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The Programme to Eliminate Lymphatic Filariasis (LF), launched in 1997, is a public-sector/private- sector partnership organized as a Global Alliance, with the World Health Organization serving as secretariat. Its principal purpose is to carry out the mandate of the 50th World Health Assembly (1997) to eliminate lymphatic filariasis as a public health problem worldwide, but its tools and strategies for achieving this end also have important additional public health benefits. Foremost among these are the effects the Programme can have on the control of intestinal helminth infections in treated populations, largely because of certain similarities, or overlaps, of the drugs and strategies used in the public health approaches to these parasitic infections. The principal health benefits from treating these intestinal helminth infections are reviewed in detail below, but in addition there might even be an entirely new justification for aggressive treatment and control of these infections if the recently described effects they have on potentiating HIV infections in affected populations can also be further substantiated and extended.