Evidence of Nonsusceptibihty to Diethylcarbamazine in Wucheria bancrofti

Eberhard, Mark L.; Lammie, Patrick J.; Dickinson, Charlotte M.; Roberts, Jacquelin M.

doi:10.1093/infdis/163.5.1157

Cited by 44 publications

(27 citation statements)

References 11 publications

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“…drug resistance ͉ helminth parasites ͉ Onchocerca volvulus ͉ overdispersion T he recent dramatic increase in the use of mass drug administration for the control of helminth infections in humans has raised the possibility that anthelmintic drug resistance may impede the success of such control programs. Anthelmintic resistance is already a major problem in veterinary parasitic nematodes (1), and suboptimal responses to treatment have been reported in a number of human helminthiases (2)(3)(4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

Churcher

Pion

Osei-Atweneboana

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12-17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance. drug resistance ͉ helminth parasites ͉ Onchocerca volvulus ͉ overdispersion

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mentioning

confidence: 99%

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

Churcher

Pion

Osei-Atweneboana

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…36 If true, it is possible that in children, W. bancrofti are more accessible to the adulticidal mechanisms triggered by DEC. Alternatively, children and adults may have different proportions of susceptible and non-susceptible adult worm populations. 37,38 DEC-fortified salt appeared to affect intestinal parasite infection prevalence and intensity. It should be noted that in this setting, we have observed that helminth infection prevalence and intensity may vary seasonally.…”

Section: Discussionmentioning

confidence: 95%

A community-based trial for the control of lymphatic filariasis and iodine deficiency using salt fortified with diethylcarbamazine and iodine.

Freeman

Lammie²,

Houston³

et al. 2001

Am J Trop Med Hyg

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Abstract. To evaluate the effectiveness of salt fortified with diethylcarbamazine (DEC) and iodine for elimination of Bancroftian filariasis and iodine deficiency, all consenting residents of Miton, Haiti (n ϭ 1,932) were given salt fortified with 0.25% diethylcarbamazine and 25 ppm of iodine for one year. Wuchereria bancrofti microfilaria prevalence and intensity, antigenemia, and urinary iodine were measured before and one year after salt distribution began. To measure the effect of DEC-fortified salt on adult worm motility, 15 microfilaria-positive men were examined by ultrasound of the scrotal area. Entomologic surveys were conducted to determine the proportion of W. bancroftiinfected Culex quinquefasciatus. After one year of treatment, the prevalence and intensity of microfilaremia were both reduced by more than 95%, while antigenemia levels were reduced by 60%. The motility of adult worms, as detected by ultrasound, was decreased, but not significantly, by DEC-fortified salt. The proportion of vector mosquitoes carrying infective stage larvae decreased significantly from 2.3% in the nine months before the intervention to 0.2% in the last three-month follow-up period. Iodine deficiency, which had been moderate to severe, was eliminated after one year of iodized salt consumption. The DEC-fortified salt was well accepted by the community and reduced microfilaremia and transmission to low levels in the absence of reported side effects. Based on these results, salt cofortified with DEC and iodine should be considered as a concurrent intervention for lymphatic filariasis and iodine deficiency elimination programs.

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“…Persistence of LF microfilaraemia has been reported in Haiti after DEC treatment [124], [125]. More recently, a sharp decline in all therapeutic indices with the mf count returning to pre-treatment levels by the fourth year of single annual DEC therapy was reported [126].…”

Section: Monitoring and Evaluationmentioning

confidence: 99%

A Research Agenda for Helminth Diseases of Humans: Intervention for Control and Elimination

et al. 2012

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Recognising the burden helminth infections impose on human populations, and particularly the poor, major intervention programmes have been launched to control onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, and cysticercosis. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. A summary of current helminth control initiatives is presented and available tools are described. Most of these programmes are highly dependent on mass drug administration (MDA) of anthelmintic drugs (donated or available at low cost) and require annual or biannual treatment of large numbers of at-risk populations, over prolonged periods of time. The continuation of prolonged MDA with a limited number of anthelmintics greatly increases the probability that drug resistance will develop, which would raise serious problems for continuation of control and the achievement of elimination. Most initiatives have focussed on a single type of helminth infection, but recognition of co-endemicity and polyparasitism is leading to more integration of control. An understanding of the implications of control integration for implementation, treatment coverage, combination of pharmaceuticals, and monitoring is needed. To achieve the goals of morbidity reduction or elimination of infection, novel tools need to be developed, including more efficacious drugs, vaccines, and/or antivectorial agents, new diagnostics for infection and assessment of drug efficacy, and markers for possible anthelmintic resistance. In addition, there is a need for the development of new formulations of some existing anthelmintics (e.g., paediatric formulations). To achieve ultimate elimination of helminth parasites, treatments for the above mentioned helminthiases, and for taeniasis and food-borne trematodiases, will need to be integrated with monitoring, education, sanitation, access to health services, and where appropriate, vector control or reduction of the parasite reservoir in alternative hosts. Based on an analysis of current knowledge gaps and identification of priorities, a research and development agenda for intervention tools considered necessary for control and elimination of human helminthiases is presented, and the challenges to be confronted are discussed.

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Evidence of Nonsusceptibihty to Diethylcarbamazine in Wucheria bancrofti

Cited by 44 publications

References 11 publications

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

Identifying sub-optimal responses to ivermectin in the treatment of River Blindness

A community-based trial for the control of lymphatic filariasis and iodine deficiency using salt fortified with diethylcarbamazine and iodine.

A Research Agenda for Helminth Diseases of Humans: Intervention for Control and Elimination

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