The Challenge of Schistosomiasis Frank O Richards Jr,A Abel Eigege,B Emmanuel S Miri,B MY Jinadu,C & Donald R Hopkins A

Integration of mass drug administration programmes in Nigeria: the challenge of schistosomiasis Frank O Richards Jr,a Abel Eigege,b Emmanuel S Miri,b MY Jinadu,c & Donald R Hopkins a

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 “know–do” 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 ivermectin–albendazole 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.

Bulletin of the World Health Organization 2006;84:673-676.

ميكن االطالع عىل امللخص بالعربية يف صفحة Voir page 675 le résumé en français. En la página 675 figura un resumen en español. .676

Background Community-based annual mass albendazole, praziquantel is not donated drug administration (MDA) with safe and costs approximately US$ 0.20 per Pablos-Mendez et al., in their October and effective oral drugs is the principal treatment. 2005 editorial in the Bulletin entitled: strategy for the control of onchocerc- Knowledge translation in global health 1 ciasis, lymphatic filariasis (LF) and argued that research must be part of a Context of the translation schistosomiasis.3 Annual treatment with strategic process that moves evidence- microfilaricide ivermectin (Mectizan, of knowledge: is there based, cost-effective interventions to true donated by Merck & Co., Inc.) prevents a know–do gap in the practice. Barriers to the implementation the severe eye and skin manifestations integration of mass drug of effective interventions lead to what of onchocerciasis. Transmission of LF by the authors called the “know–do” gap. mosquitoes can be interrupted in Africa by administration? Research should help us to understand annual single-dose combination therapy When the Global Alliance to Eliminate those barriers that prevent bringing with ivermectin (also donated by Merck LF (GAELF) was launched in 1998, we what we know to the logical conclusion & Co.) and albendazole (donated by noted the potential synergy and cost of action in the field and resultant bet-t GlaxoSmithKline).4 Schistosomiasis in savings to be made in Nigeria from ter health or better health services. The Africa is usually caused by Schistosoma linking the LF activities to those being Carter Center-assisted mass treatment mansoni or S. haematobium. School-aged supported by the African Programme for programmes in Nigeria 2 provided an children are the most heavily infected, Onchocerciasis Control (APOC).6,7 Both opportunity to demonstrate how dif-f and the most frequent symptom of WHO initiatives were based on World ferences in mass treatment guidelines urinary schistosomiasis (infection with Health Assembly-approved strategies and resources create a know–do gap S. haematobium) is blood in the urine. of annual MDA and health education; presenting a barrier to the integration of Mass distribution of praziquantel can both were working in many of the same programmes that should logically work significantly reduce schistosomiasis morb- countries; both had access to donated together synergistically. bidity.5,6 However, unlike ivermectin and drugs; and both used ivermectin. This

a The Carter Center, 1 Copenhill, Atlanta, GA 30307, USA. Correspondence to this author (email: [email protected]). b The Carter Center, Jos, Plateau State, Nigeria. c Federal Ministry of Health, Lagos, Nigeria. Ref. No. 06-029652 (Submitted: 3 January 2006 – Final revised version received: 9 March 2006 – Accepted: 11 May 2006)

Bulletin of the World Health Organization | August 2006, 84 (8) 673 Special Theme – Knowledge Translation in Global Health Mass administration of schistosomiasis drugs in Nigeria Frank O Richards Jr et al. was an excellent opportunity to link the launch point for the urinary schistoso-m questionnaires to be used to ask children two multicountry WHO programmes miasis programme in 1999 and the LF if they have blood in their urine — as in Nigeria. The approach taken was to programme in 2000. Working through a less expensive alternative for mapping launch the LF programme from within the ministries of health of the state and — but in our pilot study of this quest- the mature APOC-supported prog- the LGAs, the partners added each new tionnaire we found its sensitivity to be gramme. Albendazole tablets would be MDA programme in three phases: only 50% that of urine reagent dipsticks given concurrently with the ivermectin • mapping distribution of the diseases; (Eigege, unpublished data).) Guidelines tablets already being delivered, together • tailoring training and treatment logist- also require stratification of villages into with additional health education. tics based on results of the mapping; three groups: But we hoped for more than the and • those who do not qualify for praziqua- obvious linkage of onchocerciasis and • implementing community-based antel mass treatment (under 20% LF. Efforts to control schistosomiasis annual health education and MDA urine blood prevalence); were (and are) lagging behind the LF where appropriate according to the • mass treatment of school-aged child- and onchocerciasis initiatives in Nigeria. WHO guidelines.6 dren (20–49%); and The Schistosomiasis Control Initiative,4 • community-wide treatment (50%). another large regional initiative similar The results of the LF and schist- to APOC and GAELF, had not chosen tosomiasis mapping were the key to This complex operational treatment Nigeria as a one of its programme count- the decision-making and action plans recommendation differed considerably tries. We wondered if linking the LF and of the LGAs. Because ivermectin and from that of “treat or not treat”; used in onchocerciasis programmes with urinary albendazole are donated, guidelines for the onchocerciasis and LF programmes. schistosomiasis control could invigorate the distribution of these medicines are Lastly, praziquantel is not approved for this MDA programme as well. A suc-c “liberalized”, calling for blanket treatm- combined treatment with ivermectin cessful know–do programme with three ment within the LGAs; this made LF and albendazole. Thus, schistosomiasis drugs for three diseases in “triendemic mapping relatively easy. Only one village treatment had to be temporally separated areas” might show national and global per LGA (on average there are 100 per from MDA activities for the control of decision-makers how they could expand LGA) needed to be visited, and in total LF and onchocerciasis by at least one integrated helminthic disease control to only 30 villages needed to be visited to week. include schistosomiasis and therefore completely map the two states for LF. Thirteen LGAs need MDA and stimulate new thinking, new policy, new A sample of 100 adult residents in each health education for LF only; eight investments and partnerships, and perh- of the villages visited submitted to a need integrated LF and onchocerciasis haps even a donation of praziquantel. finger-prick blood test that detected LF activities; five need integrated LF and circulating antigen;8 guidelines called schistosomiasis activities; and four need Information collected for MDA of the whole LGA when one all three. All nine LGAs mapped so far for schistosomiasis have villages that The large-scale integration project is a of these 100 tests was positive (i.e. an were in all three mass praziquantel treatm- combined effort by the Federal Ministry LF antigen prevalence of 1%). All 30 ment schemes (not treat, treat school- of Health and The Carter Center and is villages sampled were found to be above aged or treat community-wide), and situated in Plateau and Nasarawa States, this threshold, and LF mapping was 21 LGAs have yet to be mapped for an area which has an estimated populat- completed by the end of 1999. schistosomiasis. tion of 4 million inhabitants and comp- In contrast, as praziquantel is not Not surprisingly, a know–do gap prises 30 administrative districts (local donated, mapping guidelines for schist- has been identified as to how to link government areas (LGAs)), all of which tosomiasis are designed to be “restrict- the programmes cost-effectively, and were mapped for onchocerciasis in the tive” and “medicine sparing”. Decisions the schistosomiasis programme lags early 1990s. Twelve districts were found on schistosomiasis treatment are based accordingly. Since 1999, distribution act- to have meso-hyperendemic onchocerc- on assessments at the individual vill- tivities by community-based volunteers, ciasis (defined as a nodule prevalence of lage level. This required visiting over working with support from ministry of >20%) requiring ivermectin MDA. Full 3000 villages in the two states (100 health and Carter Center national staff, geographical coverage with ivermectin times the number required by the LF have reported only 701 419 praziquantel (about 800 000 treatments per year) was programme). In these village-by-village treatments for schistosomiasis (at a drug reached in 1993 and has since continued assessments, the mobile teams use heme cost of over US$ 100 000, including with financial support from APOC and reagent dipsticks to test urine for blood 150 000 donated tablets). In contrast, the Lions Club’s SightFirst Program. The in random samples of 30 children (aged the same volunteers have successfully logistical system for the onchocerciasis 10–14 years) drawn from one randomly met the challenge of integrating the MDA in those 12 LGAs served as the selected school. (Guidelines also allow treatment of onchocerciasis and LF. Since 2000, they have reported a total of 3 731 465 ivermectin/albendazole Box 1. Benefits of integrated MDA programmes combination treatments for LF alone, Community based, annual mass drug administration (MDA) provides an opportunity to improve and 5 621 221 ivermectin/albendazole the health of millions of potential beneficiaries who have the parasitic diseases onchocerciasis, combination treatments for LF and onc- lymphatic filariasis and schistosomiasis. Integrating the MDA programmes for these diseases chocerciasis together (at no drug costs). would be feasible if schistosomiasis guidelines were simplified to be on a par with those for lymphatic filariasis and onchocerciasis. All LGAs requiring MDA for LF and onchocerciasis are receiving treatment.

674 Bulletin of the World Health Organization | August 2006, 84 (8) Special Theme – Knowledge Translation in Global Health Frank O Richards Jr et al. Mass administration of schistosomiasis drugs in Nigeria Lessons learned and the necessary drugs are donated (Box 1). LF and schistosomiasis throughout large solutions proposed The cost of praziquantel will continue to parts of Africa. O limit the extent to which schistosomiasis We have learned the obvious lessons: activities can be integrated into the larger Funding: The LF and urinary schistos- similar things are easily combined and MDA programme until there is a cheaper somiasis activities in this project were dissimilar things are not. It was easy to or donated source. This problem will not carried out with support from GlaxoS- integrate MDA for LF with that for be easily solved. However, the require-m SmithKline, and the LF activities with onchocerciasis, largely because one of ment to temporally separate by at least the support of the Bill & Melinda Gates the medicines used was the same for one week praziquantel schistosomiasis Foundation. The Carter Center works both diseases; both medicines are being treatments from LF and onchocerciasis in close partnership with Lions Club’s donated; both can be given simultaneo- MDA (due to concerns about drug int- SightFirst Program in its onchocerciasis ously; and LF spatial targeting is easily teractions) has been resolved by a recent activities; additional support for the accomplished. The know–do gap resulted clinical trial in Thailand, which found onchocerciasis activities was provided from the complexity of the guidelines for no clinically relevant pharmacokinetic by the African Program for Onchocerc- schistosomiasis control, and we found changes or adverse reactions when iverm- ciasis Control. Mectizan was donated that as a result, working in areas where mectin, praziquantel and albendazole by Merck & Co, and albendazole by there is overlap of all three parasitic were given concurrently compared to GlaxoSmithKline. The 150 000 tablets infections did not greatly enhance the when these drugs were given individu-a of praziquantel used in the projected opportunities for success of all three ally.9 This study paves the way to “triple were donated to The Carter Center by programmes. It is understandable that therapy” by village volunteers, thereby Bayer (Germany), Medochemie (Cyprus) schistosomiasis MDA guidelines are potentially overcoming a constraint on and Shin Poong (the Republic of Korea) “restricted” by the burden of the cost of multiple village treatment rounds that (50 000 tablets each). praziquantel, while guidelines for onchoc- currently hinders the field practice of cerciasis and LF are “liberated” because integrated treatment of onchocerciasis, Competing interests: none declared.

Résumé Intégration des programmes de traitement de masse au Nigéria : le cas difficile de la schistosomiase Problématique Le traitement annuel de masse au moyen Etats du Plateau et de Nasarawa dans le centre du Nigéria, où d’anthelminthiques oraux sûrs (praziquantel, ivermectine l’on sait que les trois maladies sévissent. et albendazole) est la stratégie de choix pour lutter contre Changements pertinents Les recommandations actuelles l’onchocercose, la filariose lymphatique et la schistosomiase. ont permis d’intégrer les activités de lutte contre l’onchocercose Les responsables sanitaires de district s’efforcent d’intégrer les et la filariose lymphatique, d’où des résultats cartographiques activités de traitement dans les zones d’endémie de plusieurs rapides pour ces deux Etats et par la distribution à l’échelle de maladies, mais sont confrontés au problème d’avoir à concilier ceux-ci de plus de 9,3 millions de traitements associés ivermectine- des recommandations programmatiques différentes. albendazole contre les deux maladies entre 2000 et 2004. En Approche Nous avons suivi les trois étapes de l’intégration revanche, les activités de lutte contre la schistosomiase n’ont pu des programmes de traitement de masse : cartographie de la être efficacement intégrées en raison de recommandations plus distribution des trois maladies au niveau des districts ; adaptation restrictives, ce qui fait que moins de la moitié des deux Etats de la formation et de la logistique au niveau des districts en fonction ont pu être cartographiés et que l’on n’a distribué que 701 419 des résultats des exercices de cartographie ; et mise en œuvre traitements par le praziquantel depuis 1999. d’activités communautaires annuelles d’éducation pour la santé et Enseignements tirés L’intégration de la schistosomiase dans de traitement de masse selon les besoins. Ce faisant, nous avons d’autres programmes de chimiothérapie de masse serait facilitée constaté, dans les recommandations de traitement concernant par un aménagement des recommandations qui permettrait chaque maladie, des décalages entre la théorie et son application de simplifier la cartographie, de généraliser l’utilisation du qui empêchent la bonne intégration de ces programmes. praziquantel et de pouvoir administrer celui-ci en même temps Contexte local Un programme intégré lancé en 1999 dans les que l’ivermectine et l’albendazole.

Resumen Integración de los programas de administración masiva de medicamentos en Nigeria: el reto de la esquistosomiasis Problema La administración masiva anual de antihelmínticos Métodos Seguimos las tres etapas de aplicación integrada orales seguros (prazicuantel, ivermectina y albendazol) de la administración masiva de medicamentos (AMM): mapeo constituye la estrategia de control de la oncocercosis, la de la distribución de las tres enfermedades a nivel de distrito; filariasis linfática y la esquistosomiasis. Los funcionarios planificación de la formación y la logística de distrito a partir de salud de distrito procuran integrar las actividades de de los resultados de los trabajos de mapeo; y aplicación de tratamiento en zonas de superposición de la endemicidad de educación sanitaria y tratamiento masivo anuales basados en la esas enfermedades, pero se encuentran con que tienen que comunidad en caso necesario. Durante el proceso identificamos conciliar distintas directrices programáticas. las brechas «teórico-prácticas» de las directrices de AMM para

Bulletin of the World Health Organization | August 2006, 84 (8) 675 Special Theme – Knowledge Translation in Global Health Mass administration of schistosomiasis drugs in Nigeria Frank O Richards Jr et al. cada enfermedad que impedían una integración eficaz de esos las actividades contra la esquistosomiasis no pudieron integrarse programas. eficazmente debido al carácter más restrictivo de las directrices, Contexto local Un programa integrado lanzado en 1999 en los lo que se tradujo en un mapeo de menos de la mitad de los Estados de Plateau y Nasarawa en el centro de Nigeria, donde se dos Estados, y el suministro de sólo 701 419 tratamientos de sabía que se daban las tres enfermedades. prazicuantel contra la esquistosomiasis desde 1999. Cambios destacables Las directrices existentes permitieron Enseñanzas resultantes La integración de la esquistosomiasis integrar las actividades contra la oncocercosis y la filariasis linfática, en otros programas de AMM se vería facilitada si se modificaran lo que se tradujo en un rápido mapeo en los dos Estados, y en las directrices para poder simplificar el mapeo, usar de forma el suministro en el conjunto de esos territorios de más de 9,3 más flexible el prazicuantel, y administrar simultáneamente este millones de tratamientos combinados de ivermectina-albendazol producto junto con la ivermectina y el albendazol. contra las dos enfermedades entre 2000 y 2004. Sin embargo,

ملخص إدماج برامج املعالجة الجموعية باألدوية يف نيجرييا: التحدِّي يف داء البلهارسيات املشكلة:إن اسرتاتيجية مكافحة داء كُالَّبيات الذَنَب وداء الفيالريات اللمفية التغ رُّ اتري املتعلِّقة إن بالبحث:الدالئل اإلرشادية املتاحة يف الوقت الحارض وداء البلهارسيات تتمثَّل باملعالجة الجموعية باألدوية الفموية اآلمنة املضادة تسمح بدمج األنشطة الخاصة بكلٍّ من داء كُالَّبيات الذَنَب وداء الفيالريات للديدان )الربازيكوانتيل واإليفريمكتني واأللبندازول(. ويحاول املوظفون اللمفية، مام يؤدِّي إىل رسم رسيع للخرائط يف جميع أنحاء الواليتَينْ ، مع الصحيون يف مستوى املنطقة إدماج أنشطة املعالجة يف املناطق املوطونة تقديم ما يزيد عىل 9.3مليون عبوة مزدوجة من اإليفرمكتني واأللبندازول بأدواء متعدِّدة،إال أنهم يواجهون بوجوب دمج دالئل إرشادية متعدِّدة لعدَّة ملعالجة املرضَ ينْ معاً وذلك يف جميع أنحاء الواليتَينْ يف الفرتة بني عامَيْ 2000 برامج معاً. و2004. وباملقابل مل يكن إدماج أنشطة معالجة داء البلهارسيات ممكناً األسلوب: اتَّبعنا ثالث مراحل لتنفيذ إدماج املعالجة الجموعية باألدوية، بشكل فعَّال بسبب الدالئل اإلرشادية األكرث تقيـيداً والتي أدَّت إىل رسم وهي: رسم خرائط لتوزُّع هذه األمراض الثالث عىل مستوى املناطق، وتصميم الخرائط ملا يقل عن نصف الواليتَينْ فقط، مع تقديم ما يقل عن 701 419 مواد تدريبية ولوجستية )إمدادية( بناءً عىل النتائج التي توصَّ لنا إليها أثناء من عبوات الربازكوانتيل ملكافحة داء البلهارسيات منذ عام 1999. رسم الخرائط، وتنفيذ أنشطة التثقيف الصحي واملعالجة الجموعية الـمُرْتَكِزة الدروس املستفادة: ميكن املساعدة يف إدماج البلهارسيا ضمن برامج املعالجة عىل املجتمع يف األماكن املالمئة. وقد كشفنا أثناء التنفيذ العميل الفجوة بني الجموعية باألدوية املضادة للديدان بتعديل الدالئل اإلرشادية لتؤدِّي إىل املعارف والعمل ضمن الدالئل اإلرشادية للمعالجة الجموعية باألدوية لكل رسم أبسط للخرائط، وحرية أكرث الستخدام الربازيكوانتيل، وقدرة أكرث عىل مرض عىل حدة وهي الفجوة التي متنع اإلدماج الناجح لهذه الربامج. إعطاء الربازيكوانتيل مع اإليفرمكتني واأللبنداوزول معاً. املوقع املحيل:بدئ بالربنامج يف عام يف 1999واليات بالتو وناساراوا يف وسط نيجرييا، حيث تنترش هذه األمراض الثالثة معاً.

References 1. Pablos-Mendez A, Chunharas S, Lansang MA, Shademani R, Tugwell P. Knowledge 6. Hopkins DR, Eigege A, Miri ES, Gontor I, Ogah G, Umaru J, et. al. Lymphatic translation in global health [editorial]. Bull World Health Organ 2005;83:723. filariasis elimination and schistosomiasis control in combination with 2. Richards F, Miri E, Katabarwa M, Eyamba A, Sauerbrey M, Zea-Flores G, onchocerciasis control in Nigeria. Am J Trop Med Hyg 2002;67:266-72. et al. The Carter Center’s assistance to river blindness control programs: 7. Richards FO, Hopkins DR, Cupp E. Commentary: varying programmatic establishing treatment objectives and goals for monitoring ivermectin goals and approaches to river blindness. Lancet 2000;255:1663-4. delivery systems on two continents. Am J Trop Med Hygiene 2001;65:108-14. 8. Weil GJ, Lammie PJ, Weiss, N. The ICT filariasis test: a rapid-format antigen 3. Richards F, Boatin B, Sauerbrey M, Sékétéli A. Control of onchocerciasis. test for diagnosis of bancroftian filariasis.Parasitology Today 1997;13:401-4. Onchocerciasis today: status and challenges. Trends Parasitol 2001; 9. Na-Bangchang K, Kietinun S, Pawa KK, Hanpitakpong W, Na-Bangchang C, 17:558-63. Lazdins J. Assessments of pharmacokinetic drug interactions and tolerability 4. Ottesen EA. Major progress toward eliminating lymphatic filariasis. N Engl J of albendazole, praziquantel and ivermectin combination. Trans Royal Soc Med 2002;347:1885-6. Trop Med Hyg 2006;100:335-45. 5. Savioli L, Engels D, Roungou JB, Fenwick A, Endo H. Schistosomiasis control. Lancet 2004;363:658-66.

676 Bulletin of the World Health Organization | August 2006, 84 (8)