Monitoring of Drug Efficacy in Large Scale Treatment Programmes for Human Helminthiasis
Helminth infections impose a great burden on poor populations in the developing world. Yet there are robust, low-cost and effective public health interventions to relieve that burden. The huge benefits of large scale deworming have been widely demonstrated. Such interventions are based on regular, large scale treatment of populations or sub-populations at high risk of morbidity with effective, safe, single dose drugs (preventive chemotherapy). Preventive chemotherapy aims at using available anthelminthic drugs1 either alone or in combination as a public health tool for preventing morbidity due to multiple helminth infections. With the expansion of regular, large scale use of anthelminthic drugs, regular monitoring of drug efficacy becomes a crucial issue, in order to safeguard the effectiveness of interventions.
With integrated preventive chemotherapy as currently promoted by WHO, a massive scale up is expected in the coming years. However, the strategy is relying on a few (good) drugs with a limited number of new ones in pipeline. The area of human helminthology has also been neglected in many respects with respect to tools and surveillance systems to monitor drug efficacy, pharmacology, and even basic biology. An adequate response to this new challenge was urgently needed.
A meeting on "Monitoring of drug efficacy in large scale treatment programmes in human helminthiasis", jointly organized by WHO and the World Bank, took place in Washington, DC at the World Bank Headquarters from 31 October to 2 November 2007, with the aim of addressing the issue of monitoring of anthelminthic drug efficacy in a comprehensive way, in line with the WHO recommended strategy of preventive chemotherapy (see list of participants in Annex).
The objectives of the meeting were: 1) to review the current status of drug efficacy for the different drug-parasite combinations (in veterinary medicine and in human public health); 2) to learn from drug efficacy surveillance in other fields (HIV, TB, malaria, and veterinary parasitology); 3) to review the adequacy of currently available tools and strategies for monitoring anthelminthic drug efficacy; 4) to plan for the development of an operational plan for more effective monitoring using current tools; 5) to discuss what cut-off levels could be set for action and what actions could be taken if efficacy was reduced; and 6) identify research priorities for the development of improved tools and strategies
During the first day of the meeting, a situation analysis was carried out for each of the different drug/parasite combinations. This was complemented by a presentation on the dynamics of drug resistance in the treatment of helminth infections. The main conclusions of the first day were that: 1) anthelminthic drug resistance is a severe problem in veterinary medicine, and the lessons learned need to be applied to the human side; 2) although there have been reports of reduced efficacy in human helminthiasis (of benzimidazole on hookworm, of praziquantel on schistosomiasis and, more recently, of ivermectin on onchocerciasis), these reports have not been able to fully exclude the influence of (operational, methodological, statistical, and other) confounding factors on the observed results and therefore indisputably conclude that the reduced efficacy could be attributed to emerging drug resistance; 3) there is general agreement that we need to put a monitoring system in place, as in other fields; but 4) current detection tools are not ideal to deliver accurate monitoring. It was recommended to standardize and validate existing methods and procedures, to clearly define early signs of (potential) resistance, and to boost development of sensitive new (molecular) tools.
On day 2, drug efficacy monitoring systems currently in place for TB, malaria, HIV and veterinary parasitology were presented. It was concluded that: 1) surveillance of drug efficacy is well established in other fields (TB, Malaria, HIV); 2) surveillance methods for identifying anthelminthic drug resistance are standardized and routinely used in veterinary parasitology, but there is no organized global surveillance system; 3) there are important lessons to be learned from the veterinary field in terms of the potential threat of resistance, management practices to delay or prevent it, and standardization of methodologies & procedures; 4) early detection of drug resistance is key to long term success of control programmes and 5) more basic research on the genetics and mechanism of anthelmintic resistance is required to enable the development of molecular detection tools.
During the third day, the discussions focused on how to operationalize this agenda in the short and medium term. Working groups were established to create standard operating procedures for surveillance tools for the different drugs/parasites, as well as to set clear definitions for the early detection of drug resistance. These should lead to the establishment of draft guidelines for anthelminthic drug efficacy monitoring. WHO would then organize a meeting to get consensus for such a manual. After having field-tested this manual, a monitoring network would progressively be set up. It was estimated that such a process could be completed within a time-frame of 12-18 months.
- To establish standard operating procedures for surveillance tools
- To establish guidelines for monitoring systems
- To set up a network of laboratories with transfer of knowledge between North and South
- To set up a repository for clinical samples
- To resolve research versus control issues – and convince donors that monitoring of anthelminthic drug efficacy involves both
- To carry out research on molecular tools as a most pressing need