LESSONS FROM THE FIELD
Intégration des programmes de traitement de masse au Nigéria : le cas difficile de la schistosomiase
Integración de los programas de administración masiva de medicamentos en Nigeria: el reto de la esquistosomiasis
Frank O Richards JrI,1; Abel EigegeII; Emmanuel S MiriII; MY JinaduIII; Donald R HopkinsI
IThe Carter Center, 1 Copenhill, Atlanta, GA 30307, USA
IIThe Carter Center, Jos, Plateau State, Nigeria
IIIFederal Ministry of Health, Lagos, Nigeria
PROBLEM: Annual mass drug administration (MDA) with safe oral anthelminthic drugs (praziquantel, ivermectin and albendazole) is the strategy for control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis. District health officers seek to integrate treatment activities in areas of overlapping disease endemicity, but they are faced with having to merge different programmatic guidelines.
APPROACH: We proceeded through the three stages of integrated MDA implementation: mapping the distribution of the three diseases at district level; tailoring district training and logistics based on the results of the mapping exercises; and implementing community-based annual health education and mass treatment where appropriate. During the process we identified the "knowdo" gaps in the MDA guidelines for each disease that prevented successful integration of these programmes.
LOCAL SETTING: An integrated programme launched in 1999 in Plateau and Nasarawa States in central Nigeria, where all three diseases were known to occur.
RELEVANT CHANGES: Current guidelines allowed onchocerciasis and LF activities to be integrated, resulting in rapid mapping throughout
the two states, and states-wide provision of over 9.3 million combined ivermectinalbendazole treatments for the two diseases between 2000 and 2004. In contrast, schistosomiasis activities could not be effectively integrated because of the more restrictive guidelines, resulting in less than half of the two states being mapped, and delivery of only 701 419 praziquantel treatments for schistosomiasis since 1999.
LESSONS LEARNED: Integration of schistosomiasis into other MDA programmes would be helped by amended guidelines leading to simpler mapping, more liberal use of praziquantel and the ability to administer praziquantel simultaneously with ivermectin and albendazole.
PROBLÉMATIQUE: Le traitement annuel de masse au moyen d'anthelminthiques oraux sûrs (praziquantel, ivermectine et albendazole) est la stratégie de choix pour lutter contre l'onchocercose, la filariose lymphatique et la schistosomiase. Les responsables sanitaires de district s'efforcent d'intégrer les activités de traitement dans les zones d'endémie de plusieurs maladies, mais sont confrontés au problème d'avoir à concilier des recommandations programmatiques différentes.
APPROCHE: Nous avons suivi les trois étapes de l'intégration des programmes de traitement de masse : cartographie de la distribution des trois maladies au niveau des districts ; adaptation de la formation et de la logistique au niveau des districts en fonction des résultats des exercices de cartographie ; et mise en uvre d'activités communautaires annuelles d'éducation pour la santé et de traitement de masse selon les besoins. Ce faisant, nous avons constaté, dans les recommandations de traitement concernant chaque maladie, des décalages entre la théorie et son application qui empêchent la bonne intégration de ces programmes.
CONTEXTE LOCAL: Un programme intégré lancé en 1999 dans les Etats du Plateau et de Nasarawa dans le centre du Nigéria, où l'on sait que les trois maladies sévissent.
CHANGEMENTS PERTINENTS: Les recommandations actuelles ont permis d'intégrer les activités de lutte contre l'onchocercose et la filariose lymphatique, d'où des résultats cartographiques rapides pour ces deux Etats et par la distribution à l'échelle de ceux-ci de plus de 9,3 millions de traitements associés ivermectine-albendazole contre les deux maladies entre 2000 et 2004. En revanche, les activités de lutte contre la schistosomiase n'ont pu être efficacement intégrées en raison de recommandations plus restrictives, ce qui fait que moins de la moitié des deux Etats ont pu être cartographiés et que l'on n'a distribué que 701 419 traitements par le praziquantel depuis 1999.
ENSEIGNEMENTS TIRÉS: L'intégration de la schistosomiase dans d'autres programmes de chimiothérapie de masse serait facilitée par un aménagement des recommandations qui permettrait de simplifier la cartographie, de généraliser l'utilisation du praziquantel et de pouvoir administrer celui-ci en même temps que l'ivermectine et l'albendazole.
PROBLEMA: La administración masiva anual de antihelmínticos orales seguros (prazicuantel, ivermectina y albendazol) constituye la estrategia de control de la oncocercosis, la filariasis linfática y la esquistosomiasis. Los funcionarios de salud de distrito procuran integrar las actividades de tratamiento en zonas de superposición de la endemicidad de esas enfermedades, pero se encuentran con que tienen que conciliar distintas directrices programáticas.
MÉTODOS: Seguimos las tres etapas de aplicación integrada de la administración masiva de medicamentos (AMM): mapeo de la distribución de las tres enfermedades a nivel de distrito; planificación de la formación y la logística de distrito a partir de los resultados de los trabajos de mapeo; y aplicación de educación sanitaria y tratamiento masivo anuales basados en la comunidad en caso necesario. Durante el proceso identificamos las brechas «teórico-prácticas» de las directrices de AMM para cada enfermedad que impedían una integración eficaz de esos programas.
CONTEXTO LOCAL: Un programa integrado lanzado en 1999 en los Estados de Plateau y Nasarawa en el centro de Nigeria, donde se sabía que se daban las tres enfermedades.
CAMBIOS DESTACABLES: Las directrices existentes permitieron integrar las actividades contra la oncocercosis y la filariasis linfática, lo que se tradujo en un rápido mapeo en los dos Estados, y en el suministro en el conjunto de esos territorios de más de 9,3 millones de tratamientos combinados de ivermectina-albendazol contra las dos enfermedades entre 2000 y 2004. Sin embargo, las actividades contra la esquistosomiasis no pudieron integrarse eficazmente debido al carácter más restrictivo de las directrices, lo que se tradujo en un mapeo de menos de la mitad de los dos Estados, y el suministro de sólo 701 419 tratamientos de prazicuantel contra la esquistosomiasis desde 1999.
ENSEÑANZAS RESULTANTES: La integración de la esquistosomiasis en otros programas de AMM se vería facilitada si se modificaran las directrices para poder simplificar el mapeo, usar de forma más flexible el prazicuantel, y administrar simultáneamente este producto junto con la ivermectina y el albendazol.
Pablos-Mendez et al., in their October 2005 editorial in the Bulletin entitled: Knowledge translation in global health1 argued that research must be part of a strategic process that moves evidence-based, cost-effective interventions to true practice. Barriers to the implementation of effective interventions lead to what the authors called the "knowdo" gap. Research should help us to understand those barriers that prevent bringing what we know to the logical conclusion of action in the field and resultant better health or better health services. The Carter Center-assisted mass treatment programmes in Nigeria 2 provided an opportunity to demonstrate how differences in mass treatment guidelines and resources create a knowdo gap presenting a barrier to the integration of programmes that should logically work together synergistically.
Community-based annual mass drug administration (MDA) with safe and effective oral drugs is the principal strategy for the control of onchocerciasis, lymphatic filariasis (LF) and schistosomiasis.3 Annual treatment with microfilaricide ivermectin (Mectizan, donated by Merck & Co., Inc.) prevents the severe eye and skin manifestations of onchocerciasis. Transmission of LF by mosquitoes can be interrupted in Africa by annual single-dose combination therapy with ivermectin (also donated by Merck& Co.) and albendazole (donated by GlaxoSmithKline).4 Schistosomiasis in Africa is usually caused by Schistosoma mansoni or S. haematobium. School-aged children are the most heavily infected, and the most frequent symptom of urinary schistosomiasis (infection with S. haematobium) is blood in the urine. Mass distribution of praziquantel can significantly reduce schistosomiasis morbidity.5,6 However, unlike ivermectin and albendazole, praziquantel is not donated and costs approximately US$ 0.20 per treatment.
Context of the translation of knowledge: is there a knowdo gap in the integration of mass drug administration?
When the Global Alliance to Eliminate LF (GAELF) was launched in 1998, we noted the potential synergy and cost savings to be made in Nigeria from linking the LF activities to those being supported by the African Programme for Onchocerciasis Control (APOC).6,7 Both WHO initiatives were based on World Health Assembly-approved strategies of annual MDA and health education; both were working in many of the same countries; both had access to donated drugs; and both used ivermectin. This was an excellent opportunity to link the two multicountry WHO programmes in Nigeria. The approach taken was to launch the LF programme from within the mature APOC-supported proggramme. Albendazole tablets would be given concurrently with the ivermectin tablets already being delivered, together with additional health education.
But we hoped for more than the obvious linkage of onchocerciasis and LF. Efforts to control schistosomiasis were (and are) lagging behind the LF and onchocerciasis initiatives in Nigeria. The Schistosomiasis Control Initiative,4 another large regional initiative similar to APOC and GAELF, had not chosen Nigeria as a one of its programme countries. We wondered if linking the LF and onchocerciasis programmes with urinary schistosomiasis control could invigorate this MDA programme as well. A successful knowdo programme with three drugs for three diseases in "triendemic areas" might show national and global decision-makers how they could expand integrated helminthic disease control to include schistosomiasis and therefore stimulate new thinking, new policy, new investments and partnerships, and perhaps even a donation of praziquantel.
The large-scale integration project is a combined effort by the Federal Ministry of Health and The Carter Center and is situated in Plateau and Nasarawa States, an area which has an estimated population of 4 million inhabitants and comprises 30 administrative districts (local government areas (LGAs)), all of which were mapped for onchocerciasis in the early 1990s. Twelve districts were found to have meso-hyperendemic onchocercciasis (defined as a nodule prevalence of >20%) requiring ivermectin MDA. Full geographical coverage with ivermectin (about 800 000 treatments per year) was reached in 1993 and has since continued with financial support from APOC and the Lions Club's SightFirst Program. The logistical system for the onchocerciasis MDA in those 12 LGAs served as the launch point for the urinary schistosomiasis programme in 1999 and the LF programme in 2000. Working through the ministries of health of the state and the LGAs, the partners added each new MDA programme in three phases:
· mapping distribution of the diseases;
· tailoring training and treatment logistics based on results of the mapping; and
· implementing community-based annual health education and MDA where appropriate according to the WHO guidelines.6
The results of the LF and schistosomiasis mapping were the key to the decision-making and action plans of the LGAs. Because ivermectin and albendazole are donated, guidelines for the distribution of these medicines are "liberalized", calling for blanket treatment within the LGAs; this made LF mapping relatively easy. Only one village per LGA (on average there are 100 per LGA) needed to be visited, and in total only 30 villages needed to be visited to completely map the two states for LF. A sample of 100 adult residents in each of the villages visited submitted to a finger-prick blood test that detected LF circulating antigen;8 guidelines called for MDA of the whole LGA when one of these 100 tests was positive (i.e. an LF antigen prevalence of >1%). All 30 villages sampled were found to be above this threshold, and LF mapping was completed by the end of 1999.
In contrast, as praziquantel is not donated, mapping guidelines for schistosomiasis are designed to be "restrictive" and "medicine sparing". Decisions on schistosomiasis treatment are based on assessments at the individual villlage level. This required visiting over 3000 villages in the two states (100 times the number required by the LF programme). In these village-by-village assessments, the mobile teams use heme reagent dipsticks to test urine for blood in random samples of 30 children (aged 1014 years) drawn from one randomly selected school. (Guidelines also allow questionnaires to be used to ask children if they have blood in their urine as a less expensive alternative for mapping but in our pilot study of this questionnaire we found its sensitivity to be only 50% that of urine reagent dipsticks (Eigege, unpublished data).) Guidelines also require stratification of villages into three groups:
· those who do not qualify for praziquantel mass treatment (under 20% urine blood prevalence);
· mass treatment of school-aged children (2049%); and
· community-wide treatment (>50%).
This complex operational treatment recommendation differed considerably from that of "treat or not treat"; used in the onchocerciasis and LF programmes. Lastly, praziquantel is not approved for combined treatment with ivermectin and albendazole. Thus, schistosomiasis treatment had to be temporally separated from MDA activities for the control of LF and onchocerciasis by at least one week.
Thirteen LGAs need MDA and health education for LF only; eight need integrated LF and onchocerciasis activities; five need integrated LF and schistosomiasis activities; and four need all three. All nine LGAs mapped so far for schistosomiasis have villages that were in all three mass praziquantel treatment schemes (not treat, treat school-aged or treat community-wide), and 21 LGAs have yet to be mapped for schistosomiasis.
Not surprisingly, a knowdo gap has been identified as to how to link the programmes cost-effectively, and the schistosomiasis programme lags accordingly. Since 1999, distribution activities by community-based volunteers, working with support from ministry of health and Carter Center national staff, have reported only 701 419 praziquantel treatments for schistosomiasis (at a drug cost of over US$ 100 000, including 150 000 donated tablets). In contrast, the same volunteers have successfully met the challenge of integrating the treatment of onchocerciasis and LF. Since 2000, they have reported a total of 3 731 465 ivermectin/albendazole combination treatments for LF alone, and 5 621 221 ivermectin/albendazole combination treatments for LF and onchocerciasis together (at no drug costs). All LGAs requiring MDA for LF and onchocerciasis are receiving treatment.
Lessons learned and solutions proposed
We have learned the obvious lessons: similar things are easily combined and dissimilar things are not. It was easy to integrate MDA for LF with that for onchocerciasis, largely because one of the medicines used was the same for both diseases; both medicines are being donated; both can be given simultaneously; and LF spatial targeting is easily accomplished. The knowdo gap resulted from the complexity of the guidelines for schistosomiasis control, and we found that as a result, working in areas where there is overlap of all three parasitic infections did not greatly enhance the opportunities for success of all three programmes. It is understandable that schistosomiasis MDA guidelines are "restricted" by the burden of the cost of praziquantel, while guidelines for onchocerciasis and LF are "liberated" because the necessary drugs are donated (Box 1). The cost of praziquantel will continue to limit the extent to which schistosomiasis activities can be integrated into the larger MDA programme until there is a cheaper or donated source. This problem will not be easily solved. However, the requirement to temporally separate by at least one week praziquantel schistosomiasis treatments from LF and onchocerciasis MDA (due to concerns about drug interactions) has been resolved by a recent clinical trial in Thailand, which found no clinically relevant pharmacokinetic changes or adverse reactions when ivermectin, praziquantel and albendazole were given concurrently compared to when these drugs were given individually.9 This study paves the way to "triple therapy" by village volunteers, thereby potentially overcoming a constraint on multiple village treatment rounds that currently hinders the field practice of integrated treatment of onchocerciasis, LF and schistosomiasis throughout large parts of Africa.
Funding: The LF and urinary schistosomiasis activities in this project were carried out with support from GlaxoSmithKline, and the LF activities with the support of the Bill & Melinda Gates Foundation. The Carter Center works in close partnership with Lions Club's SightFirst Program in its onchocerciasis activities; additional support for the onchocerciasis activities was provided by the African Program for Onchocerciasis Control. Mectizan was donated by Merck & Co, and albendazole by GlaxoSmithKline. The 150 000 tablets of praziquantel used in the projected were donated to The Carter Center by Bayer (Germany), Medochemie (Cyprus) and Shin Poong (the Republic of Korea) (50 000 tablets each).
Competing interests: none declared.
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9. Na-Bangchang K, Kietinun S, Pawa KK, Hanpitakpong W, Na-Bangchang C, Lazdins J. Assessments of pharmacokinetic drug interactions and tolerability of albendazole, praziquantel and ivermectin combination. Trans Royal Soc Trop Med Hyg 2006;100:335-45.
(Submitted: 3 January 2006 Final revised version received: 9 March 2006 Accepted: 11 May 2006)