- Email: [email protected]
Optimisation of mass chemotherapy to control soil-transmitted helminth infection
Comment
Optimisation of mass chemotherapy to control soil-transmitted helminth infection Leaders from international agencies, including WHO and the World Bank, charities, and pharmaceutical companies, together with politicians from donor and recipient countries, will meet in London on Jan 30, 2012,1 to pledge increased support and collaboration for the control of neglected tropical diseases (NTDs).2 A London Declaration from this meeting will mark an expanded vision from WHO for the elimination of some NTDs and improved implementation of control efforts for other NTDs by 2020. Advocacy has been important for raising awareness of NTDs,3 highlighting the low costs of treatments and attracting donors. Governments in the USA and UK have given generously, as have charities such as the Bill & Melinda Gates Foundation and the Carter Centre. Drug donations from pharmaceutical companies have had a catalytic role, especially for the treatment and control of helminth infections. Mobilisation of the education sector has also provided a clear policy framework for deworming delivered through schools.4,5 NTDs are found predominately among poor rural populations in Africa, Asia, and Latin America and more than a third of the world’s population is infected with worms (helminths). Rapid progress to control helminth infections is possible, however, given the availability of cheap and effective drugs that can be administered to entire at-risk populations. For soil-transmitted helminth infections, the use of albendazole or mebendazole, and to a lesser extent levamisole or pyrantel pamoate, provides effective treatment for roundworms (Ascaris lumbricoides), whipworms (Trichuris trichuria), and hookworms (Necator americanus or Ancylostoma duodenale), which are the most widespread infections.6 The increased availability of funds to control soiltransmitted helminth infections raises the question of how best to use these resources, since reinfection means that treatment must be administered repeatedly to individuals in endemic areas. A crucial step for programmes is to ensure that treatment is targeted to areas of greatest need. The development of online resources, such as the Global Atlas of Helminth Infection, provides countries with vital information for planning and implementing treatment. WHO guidelines for the interval between rounds of treatment for common soil-transmitted helminths, and www.thelancet.com Vol 379 January 28, 2012
for who should be treated and for how long, are based on the consensus opinion of experts in helminth control5 and do not take account of analytical methods based on current understanding of the transmission dynamics of helminths. The key questions for control by chemotherapy alone focus on how to achieve the greatest impact with the minimum use of anthelmintic drugs (panel). Disease transmission during drug treatment is a dynamic process, with loss and acquisition of worms determined by many factors, including coverage and efficacy. Models of these processes provide predictive information about the effect of intervention at the community level, whether by mass or targeted chemotherapy.7 This knowledge, however, is rarely applied in practice. Helminths have much more predictable dynamics than most viruses, bacteria, and protozoa. After treatment, worm populations return to precontrol levels in a monotonic way, because of density-dependent processes that influence parasite reproduction, infection, and mortality and are partly related to the build-up of a small degree of acquired immunity; the long life expectancy of established worms in the human host (years rather than days) is also a factor.5 This understanding should be used more widely to refine community-based guidelines and to inform policy makers of what to expect from a given intervention programme.
This online publication has been corrected. The corrected version first appeared at thelancet.com on March 23, 2012
For Global Atlas of Helminth Infection see http://www. thiswormyworld.org
Panel: Key questions for control of soil-transmitted infections by chemotherapy 1 For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? 2 In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? 3 As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? 4 How is the interval between treatments affected by the species mix in the community? 5 How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? 6 What level of infection across a community should trigger mass chemotherapy to minimise morbidity? 7 Is elimination in a defined area possible by chemotherapy alone? 8 How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? 9 What should be the target of control programmes? 10 What are the best indicators for assessing the impact of control?
289
Comment
See Online for webappendix
290
A series of important principles emerge from analytical studies. First, prediction is possible given the relatively simple dynamics of these infections. Analytical methods can answer specific questions, such as who should be treated, how frequently, and whether the frequency can be decreased as repeated treatment lowers average worm burdens.7 Second, prevalence is an inadequate way to monitor the impact of control measures (see webappendix).8 Third, the optimum interval between rounds of treatment to keep worm loads to very low levels depends on the species mix of parasites and the prevailing reproductive success in a defined location. For example, if roundworm is the major infection in areas of high-to-medium reproductive success, treatment needs to be administered every year, whereas if hookworm is the major problem, treatment rounds can shift to every 2 years. For schistosomes, with much longer estimated life expectancy in the human host, the equivalent interval is 3–5 years, depending on reproductive success. In areas of low transmission, intervals can be much longer for all soil-transmitted helminth infections. In mixed-species infections, which are typical in many regions, the species with the shortest life expectancy will determine the frequency of treatment to sustain low burdens. Eradication in a given community is possible if treatment coverage is high and frequent, and the basic reproductive number R0 not too high (see webappendix for typical dynamics of hookworm).7,8 In some communities where hookworm is endemic, such as rural communities in Kenya and India,9 children younger than 15 years often constitute almost 40% of the population and host perhaps up to 75% of the total worm population, which is why treatment targeted at school children alone can result in effective control. Again, based on demographic and epidemiological measures, predictions of impact can be made to guide the design of who should be treated and how often. Human movement and migration patterns will lead to reintroduction from surrounding areas if treatment is not uniform and intense across a large area. Simulations show that the interval between rounds of treatment can be lengthened after a few rounds of frequent and intense application (see webappendix for simulations about effect of increasing frequency of treatment for school children). The use of predictive tools in the design of control programmes for soil-transmitted helminth infections is not widespread, but they should be used if the goals of the London Declaration are to be met and value for money achieved from new drug donations and increased
donor support for implementation. Such predictive models should become part of WHO’s guidelines for control of soil-transmitted helminths. Developing analytical approaches for the design of community-based chemotherapy will provide scientific precision and predictability. But, as always in public health, other factors have a confounding role. Integrating control of soil-transmitted helminth infections with schoolfeeding programmes has been proven to be effective,4,9 as has integration with other disease control activities (ie, horizontal as opposed to vertical approaches). Optimum treatment rounds will be tempered by opportunity, logistics, and delivery costs. Mass and widespread chemotherapy alone will not eliminate soil-transmitted helminth infections in the longer term. Concomitant improvements in sanitation and hygiene are essential.2 Perhaps the biggest challenge to effective control will be to sustain the interest of governments and international donors once worm burdens are reduced to very low levels and obvious morbidity is averted. *Roy Anderson, T Deirdre Hollingsworth, James Truscott, Simon Brooker Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK (RA, TDH, JT); London School of Hygiene and Tropical Medicine, London, UK (SB); and Kenya Medical Research Institute-Wellcome Trust Research Programme, Nairobi, Kenya (SB) [email protected] This work is supported by grants from the Bill & Melinda Gates Foundation and the Partnership for Child Development, who fund RA, JT, DH, and RP. SB is supported by a Research Career Development Fellowship (#081673) from the Wellcome Trust. DH is supported by an Imperial College Junior Research Fellowship. RA is a non-executive director of and shareholder in GlaxoSmithKline. TDH, JT, and SB declare that they have no conflicts of interest. 1
2 3 4 5
6 7 8 9
Department for International Development. UK to protect 140 million from neglected tropical diseases. Jan 21, 2012. http://www.dfid.gov.uk/ News/Latest-news/2012/Britain-to-protect-more-than-140-million-inglobal-effort-to-rid-the-world-of-neglected-tropical-diseases (accessed Jan 23, 2011). WHO. Working to overcome the global impact of neglected tropical diseases. Geneva: World Health Organization, 2010. Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 2009; 373: 1570–75. Miguel E, Kremer M. Worms: identifying impacts on education and health in the presence of treatment externalities. Econometrica 2004; 72: 159–217. Montresor A, Gyorkos TW, Crompton DW, Bundy DA, Savioli L. Monitoring helminth control programmes: guidelines for monitoring the impact of control programmes aimed at reducing morbidity caused by soil-transmitted helminths and schistosomes, with particular reference to school-age children. Geneva: World Health Organization, 1999. Bethony J, Brooker S, Albonico M, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 2006; 367: 1521–32. Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press, 1991. Anderson RM, Medley GF. Community control of helminth infections of man by mass and selective chemotherapy. Parasitology 1985; 90: 629–60. Pullan RL, Gething PW, Smith JL, et al. Spatial modelling of soil-transmitted helminth infections in Kenya: a disease control planning tool. PLoS Negl Trop Dis 2011; 5: e958. www.thelancet.com Vol 379 January 28, 2012
Optimisation of mass chemotherapy to control soil-transmitted helminth infection Leaders from international agencies, including WHO and the World Bank, charities, and pharmaceutical companies, together with politicians from donor and recipient countries, will meet in London on Jan 30, 2012,1 to pledge increased support and collaboration for the control of neglected tropical diseases (NTDs).2 A London Declaration from this meeting will mark an expanded vision from WHO for the elimination of some NTDs and improved implementation of control efforts for other NTDs by 2020. Advocacy has been important for raising awareness of NTDs,3 highlighting the low costs of treatments and attracting donors. Governments in the USA and UK have given generously, as have charities such as the Bill & Melinda Gates Foundation and the Carter Centre. Drug donations from pharmaceutical companies have had a catalytic role, especially for the treatment and control of helminth infections. Mobilisation of the education sector has also provided a clear policy framework for deworming delivered through schools.4,5 NTDs are found predominately among poor rural populations in Africa, Asia, and Latin America and more than a third of the world’s population is infected with worms (helminths). Rapid progress to control helminth infections is possible, however, given the availability of cheap and effective drugs that can be administered to entire at-risk populations. For soil-transmitted helminth infections, the use of albendazole or mebendazole, and to a lesser extent levamisole or pyrantel pamoate, provides effective treatment for roundworms (Ascaris lumbricoides), whipworms (Trichuris trichuria), and hookworms (Necator americanus or Ancylostoma duodenale), which are the most widespread infections.6 The increased availability of funds to control soiltransmitted helminth infections raises the question of how best to use these resources, since reinfection means that treatment must be administered repeatedly to individuals in endemic areas. A crucial step for programmes is to ensure that treatment is targeted to areas of greatest need. The development of online resources, such as the Global Atlas of Helminth Infection, provides countries with vital information for planning and implementing treatment. WHO guidelines for the interval between rounds of treatment for common soil-transmitted helminths, and www.thelancet.com Vol 379 January 28, 2012
for who should be treated and for how long, are based on the consensus opinion of experts in helminth control5 and do not take account of analytical methods based on current understanding of the transmission dynamics of helminths. The key questions for control by chemotherapy alone focus on how to achieve the greatest impact with the minimum use of anthelmintic drugs (panel). Disease transmission during drug treatment is a dynamic process, with loss and acquisition of worms determined by many factors, including coverage and efficacy. Models of these processes provide predictive information about the effect of intervention at the community level, whether by mass or targeted chemotherapy.7 This knowledge, however, is rarely applied in practice. Helminths have much more predictable dynamics than most viruses, bacteria, and protozoa. After treatment, worm populations return to precontrol levels in a monotonic way, because of density-dependent processes that influence parasite reproduction, infection, and mortality and are partly related to the build-up of a small degree of acquired immunity; the long life expectancy of established worms in the human host (years rather than days) is also a factor.5 This understanding should be used more widely to refine community-based guidelines and to inform policy makers of what to expect from a given intervention programme.
This online publication has been corrected. The corrected version first appeared at thelancet.com on March 23, 2012
For Global Atlas of Helminth Infection see http://www. thiswormyworld.org
Panel: Key questions for control of soil-transmitted infections by chemotherapy 1 For a given transmission level, how often should mass or targeted chemotherapy be administered to sustain infection prevalence and intensity below defined levels? 2 In terms of cost-effectiveness, is it best to target school children, those predisposed to heavy infection, or the entire community? 3 As the prevalence and intensity fall after repeated rounds of treatment, can the interval between treatments increase, and by how much? 4 How is the interval between treatments affected by the species mix in the community? 5 How do the demography of the population and the starting geographical distribution of infection affect the structure of optimum treatment programmes when resources are finite? 6 What level of infection across a community should trigger mass chemotherapy to minimise morbidity? 7 Is elimination in a defined area possible by chemotherapy alone? 8 How might repeated mass treatment affect the evolution of drug resistance and how can this risk be minimised? 9 What should be the target of control programmes? 10 What are the best indicators for assessing the impact of control?
289
Comment
See Online for webappendix
290
A series of important principles emerge from analytical studies. First, prediction is possible given the relatively simple dynamics of these infections. Analytical methods can answer specific questions, such as who should be treated, how frequently, and whether the frequency can be decreased as repeated treatment lowers average worm burdens.7 Second, prevalence is an inadequate way to monitor the impact of control measures (see webappendix).8 Third, the optimum interval between rounds of treatment to keep worm loads to very low levels depends on the species mix of parasites and the prevailing reproductive success in a defined location. For example, if roundworm is the major infection in areas of high-to-medium reproductive success, treatment needs to be administered every year, whereas if hookworm is the major problem, treatment rounds can shift to every 2 years. For schistosomes, with much longer estimated life expectancy in the human host, the equivalent interval is 3–5 years, depending on reproductive success. In areas of low transmission, intervals can be much longer for all soil-transmitted helminth infections. In mixed-species infections, which are typical in many regions, the species with the shortest life expectancy will determine the frequency of treatment to sustain low burdens. Eradication in a given community is possible if treatment coverage is high and frequent, and the basic reproductive number R0 not too high (see webappendix for typical dynamics of hookworm).7,8 In some communities where hookworm is endemic, such as rural communities in Kenya and India,9 children younger than 15 years often constitute almost 40% of the population and host perhaps up to 75% of the total worm population, which is why treatment targeted at school children alone can result in effective control. Again, based on demographic and epidemiological measures, predictions of impact can be made to guide the design of who should be treated and how often. Human movement and migration patterns will lead to reintroduction from surrounding areas if treatment is not uniform and intense across a large area. Simulations show that the interval between rounds of treatment can be lengthened after a few rounds of frequent and intense application (see webappendix for simulations about effect of increasing frequency of treatment for school children). The use of predictive tools in the design of control programmes for soil-transmitted helminth infections is not widespread, but they should be used if the goals of the London Declaration are to be met and value for money achieved from new drug donations and increased
donor support for implementation. Such predictive models should become part of WHO’s guidelines for control of soil-transmitted helminths. Developing analytical approaches for the design of community-based chemotherapy will provide scientific precision and predictability. But, as always in public health, other factors have a confounding role. Integrating control of soil-transmitted helminth infections with schoolfeeding programmes has been proven to be effective,4,9 as has integration with other disease control activities (ie, horizontal as opposed to vertical approaches). Optimum treatment rounds will be tempered by opportunity, logistics, and delivery costs. Mass and widespread chemotherapy alone will not eliminate soil-transmitted helminth infections in the longer term. Concomitant improvements in sanitation and hygiene are essential.2 Perhaps the biggest challenge to effective control will be to sustain the interest of governments and international donors once worm burdens are reduced to very low levels and obvious morbidity is averted. *Roy Anderson, T Deirdre Hollingsworth, James Truscott, Simon Brooker Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK (RA, TDH, JT); London School of Hygiene and Tropical Medicine, London, UK (SB); and Kenya Medical Research Institute-Wellcome Trust Research Programme, Nairobi, Kenya (SB) [email protected] This work is supported by grants from the Bill & Melinda Gates Foundation and the Partnership for Child Development, who fund RA, JT, DH, and RP. SB is supported by a Research Career Development Fellowship (#081673) from the Wellcome Trust. DH is supported by an Imperial College Junior Research Fellowship. RA is a non-executive director of and shareholder in GlaxoSmithKline. TDH, JT, and SB declare that they have no conflicts of interest. 1
2 3 4 5
6 7 8 9
Department for International Development. UK to protect 140 million from neglected tropical diseases. Jan 21, 2012. http://www.dfid.gov.uk/ News/Latest-news/2012/Britain-to-protect-more-than-140-million-inglobal-effort-to-rid-the-world-of-neglected-tropical-diseases (accessed Jan 23, 2011). WHO. Working to overcome the global impact of neglected tropical diseases. Geneva: World Health Organization, 2010. Hotez PJ, Fenwick A, Savioli L, Molyneux DH. Rescuing the bottom billion through control of neglected tropical diseases. Lancet 2009; 373: 1570–75. Miguel E, Kremer M. Worms: identifying impacts on education and health in the presence of treatment externalities. Econometrica 2004; 72: 159–217. Montresor A, Gyorkos TW, Crompton DW, Bundy DA, Savioli L. Monitoring helminth control programmes: guidelines for monitoring the impact of control programmes aimed at reducing morbidity caused by soil-transmitted helminths and schistosomes, with particular reference to school-age children. Geneva: World Health Organization, 1999. Bethony J, Brooker S, Albonico M, et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm. Lancet 2006; 367: 1521–32. Anderson RM, May RM. Infectious diseases of humans: dynamics and control. Oxford: Oxford University Press, 1991. Anderson RM, Medley GF. Community control of helminth infections of man by mass and selective chemotherapy. Parasitology 1985; 90: 629–60. Pullan RL, Gething PW, Smith JL, et al. Spatial modelling of soil-transmitted helminth infections in Kenya: a disease control planning tool. PLoS Negl Trop Dis 2011; 5: e958. www.thelancet.com Vol 379 January 28, 2012