Policy and practice Unfulfilled potential: using diethylcarbamazine-fortified salt to eliminate lymphatic filariasis Patrick Lammie,a Trevor Milner b & Robin Houston c

Abstract Fortifying salt with diethylcarbamazine (DEC) is a safe, low-cost and effective strategy to eliminate transmission of lymphatic filariasis. DEC-fortified salt has been used successfully in pilot projects in several countries and has been used operationally by China to eliminate lymphatic filariasis. The successful use of iodized salt to eliminate iodine-deficiency disorders is encouraging; similarly, fortified salt could be used as a vehicle to eliminate lymphatic filariasis. Despite the potential programmatic advantages of fortifying salt with DEC instead of undertaking mass administration of tablets, DEC-fortified salt remains an underutilized intervention. We discuss the reasons for this and suggest settings in which the use of DEC-fortified salt should be considered.

Bulletin of the World Health Organization 2007;85:545–549.

الرتجمة العربية لهذه الخالصة يف نهاية النص الكامل لهذه املقالة. .Une traduction en français de ce résumé figure à la fin de l’article. Al final del artículo se facilita una traducción al español

Introduction regimen.5 With the advent of these new maintain high coverage levels for 5 years diagnostic and therapeutic approaches or more, and diminishing compliance Unbeknownst to many, a global effort is being undertaken to eliminate the as well as strategies to control morbid- over subsequent cycles of mass drug parasitic disease colloquially known as ity, widespread interest has developed administration because of adverse reac- in eliminating these infections. As a tions associated with the parasite’s death elephantiasis. This little-known public 10,11 health effort against lymphatic filariasis result, the World Health Assembly following treatment. As discussed in has achieved considerable momentum called for the elimination of lymphatic greater detail below, salt fortified with filariasis to become a global public DEC offers an alternative to mass drug and successes, but is competing for 5 scarce global funding. Approximately health goal. Most endemic countries administration and has the potential to 80 million people in more than 75 coun- have now initiated or completed map- overcome these obstacles; it could, in tries harbour the transmission stages of ping, and more than 30 have established principle, eliminate filariasis faster and Wuchereria bancrofti and Brugia malayi, programmes that use albendazole and more cost-effectively than tablet-based 12–16 the disease’s causative agents. An ad- either ivermectin or diethylcarbamazine programmes. ditional 40 million people are affected (DEC) for mass drug administration Despite its theoretical advantages, 6 by disfiguring damage to their limbs programmes. DEC-fortified salt has not been em- and genitalia, making the disease a The single greatest barrier to ex- braced by the lymphatic filariasis com- leading cause of disability worldwide.1,2 panding elimination programmes to all munity as a public health intervention. Interrupting transmission of the disease at-risk people is financing. Although Ironically, two major public health suc- requires careful identification of endemic mass drug administration programmes cesses have also not received the public areas and the use of drugs designed to have been successful in reducing micro- attention they deserve and they have reduce microfilaraemia and break the filaraemia and providing important col- direct relevance to the use of DEC-forti- transmission cycle. The mapping of lateral de-worming benefits, elimination fied salt. First, China, the country with areas endemic for W. bancrofti has been programmes are competing for scarce the largest number of cases and largest made easier with the use of a rapid public health dollars.7–9 Additional bar- population at risk, has eliminated trans- antigen detection test.3,4 The standard riers to implementing filariasis elimina- mission of the disease owing to, at least drug intervention has been simplified tion programmes based on mass drug partly, the use of DEC-fortified salt.17,18 from a 12-day regimen, often directed at administration include the difficulty of Second, the salt industry has been mo- people with clinical disease, to mass drug developing an infrastructure capable of bilized on a country-by-country basis to administration for at-risk populations distributing drugs to the entire at-risk increase the household use of iodized salt of a single annual dose of a two-drug population, the need to achieve and from low levels worldwide to more than

a Division of Parasitic Diseases, Centers for Disease Control and Prevention, 4770 Buford Highway, Atlanta, GA 30341, USA. Correspondence to Patrick Lammie (e-mail: [email protected]). b Pan American Health Organization, Washington, DC, USA. c Emory University Lymphatic Filariasis Support Center, Atlanta, GA, USA. doi: 10.2471/BLT.06.034108 (Submitted: 23 June 2006 – Final revised version received: 1 November 2006 – Accepted: 16 November 2006)

Bulletin of the World Health Organization | July 2007, 85 (7) 545 Policy and practice DEC-fortified salt to eliminate lymphatic filariasis Patrick Lammie et al.

70% globally within the past 15 years; mass drug administration the propor- or onchocerciasis is endemic because of this has resulted in the likely elimination tion of people who experience mild the potential for adverse events. Other of cretinism, the most severe form of adverse reactions may approximate the barriers play a part: lack of experience iodine deficiency, as well as a dramatic prevalence of microfilaraemia in the in managing a commodity like salt reduction in less severe iodine-deficiency community. Although these reactions may be a disincentive for initiating a disorders, and it has likely improved the typically are not serious, adverse events programme to fortify salt with DEC. IQ of millions of people.19–21 These two do contribute to noncompliance.10,11 Many public health managers have no successes highlight the importance of Although the impact of noncompliance experience working with manufactur- considering the contribution that salt on efforts to interrupt transmission is not ers and distributors largely from the containing DEC and iodine could make known, there is concern that mass drug private sector, and this partnership calls to the global effort to prevent lymphatic administration will not be successful if for expanding public health skills. The filariasis. coverage declines because of noncompli- long history of tablet-based treatment ance. Adverse reactions following the use for microfilaria carriers, the familiarity DEC salt: the other of DEC-fortified salt are mild or absent, of annual mass treatment campaigns and thus they should not exacerbate and the added benefit of donated al- intervention issues of noncompliance.13,15,17,31 It is bendazole for de-worming may lead In 1967, at a time when lymphatic fila- important to point out that the use of programme managers to overlook the riasis was being addressed primarily as a DEC is contraindicated in people with DEC-fortified-salt option. clinical problem by case identification onchocerciasis because of fears of ocular and its standard treatment was a 12-day damage associated with death of mi- Linking to salt iodization regimen, initial studies were done on us- crofilariae in the eye.32,33 Although one In 1990, the World Summit for Chil- ing DEC-fortified salt to reduce micro- pilot study of the use of DEC-fortified dren included the elimination of iodine- filaraemia.22 These studies showed that salt by patients with onchocerciasis has deficiency disorders as a critical goal for DEC did not alter the colour or taste been done, additional clinical research the decade. Iodine deficiency, having of salt, that it was stable in cooking and is needed to determine whether lower been for the most part eliminated from that it retained its efficacy in reducing doses of DEC can be delivered in salt the developed world, remained highly microfilaraemia even when used in this without provoking inflammatory pa- 34 prevalent in poorer countries and thus fashion. The scientific efficacy of DEC- thology. remained the leading cause of prevent- fortified salt is well established; pilot The length of time required to inter- able mental impairment worldwide. studies in Brazil,22 Haiti,13 India 23,24 and rupt transmission of lymphatic filariasis, Over the subsequent decade, national the United Republic of Tanzania12,25,26 whether through mass drug adminis- salt iodization programmes were estab- have all shown that DEC-fortified salt tration or using DEC-fortified salt, is lished in virtually all endemic countries, reduces microfilaraemia. The studies not known, so it can be estimated only 35,36 resulting in more than 70% of house- in the United Republic of Tanzania from mathematical models. Both interventions depend on effective social holds using iodized salt and a dramatic that compared different DEC interven- reduction in iodine deficiency.19–21 This tions suggested that DEC-fortified salt mobilization to maximize coverage. Assuming equal coverage, the duration public health success was the result of provided a longer-lasting reduction in of a DEC-fortified salt programme working in partnership with the salt in- microfilaraemia than DEC tablets.14,25 should not need to be as long as the dustry. The partnership used advocacy, Regional programmes in Chi- duration of a mass drug administration provided assistance with capital costs for na17,18,27,28 and India29,30 have demon- programme, both because of its greater the purchase of iodization equipment, strated success with DEC salt inter- effectiveness and because of its likely established laboratories at production ventions at the programmatic level. prophylactic benefit against infective facilities, subsidized the purchase of DEC-fortified salt was used extensively larvae. This antilarval effect is the basis potassium iodate, and supported edu- in China, both alone and in combina- for periodically administering DEC cational and promotional efforts at the tion with mass drug administration. tablets for prophylaxis against infec- national level. China previously had the largest num- tions with Loa loa as well as preventing The dramatic success of salt iodiza- ber of people with lymphatic filariasis, infections with Dirofilaria in veterinary tion globally has increased the potential and hundreds of millions were living in medicine.37,38 DEC-fortified salt also for adding DEC to salt, thereby en- endemic areas. Each province in China may achieve higher effective coverage abling a link to be made between pro- used different combinations of inter- through the consumption of foods pre- grammes for eliminating filariasis and ventions, but more than 194 000 000 pared with DEC-fortified salt outside those for eliminating iodine deficiency. people used DEC-fortified salt; in the home by people not using fortified From a technical perspective, adding some provinces it was the principal salt in their own households. DEC to an existing salt fortification intervention.17 In 1994, all provinces in Despite its real and theoretical process is as straightforward as adding China had reached the criteria for basic advantages and the success in China, iodine to salt. DEC can be added in elimination of filariasis, and according DEC-fortified salt remains an under- the same fashion as iodine regardless of to national experts DEC-fortified salt utilized intervention. This likely reflects whether iodine is added to salt as part played a critical part.17 a combination of technical and behav- of a dry mix or sprayed on as a liquid. One programmatic advantage of ioural barriers. A significant technical Increased attention to quality control is using DEC-fortified salt is that it obstacle to the use of DEC-fortified salt needed in both instances to verify that causes few or no adverse reactions when is related to the recommendation that the iodine and DEC levels are in the ap- compared with DEC tablets. During DEC not be used in areas where loiasis propriate therapeutic range (0.1–0.6%

546 Bulletin of the World Health Organization | July 2007, 85 (7) Policy and practice Patrick Lammie et al. DEC-fortified salt to eliminate lymphatic filariasis by weight for DEC), but the experience manufacturing the fortified salt, it is dif- grammatic option where traditional ap- with quality control gained by iodiza- ficult for distribution networks created proaches to tablet distribution are likely tion programmes has shown that this by a single importer to reach all retail to be problematic because of cost or can be done. From the programmatic outlets. In addition, DEC-fortified salt persistently low coverage, or in rapidly perspective, a pilot study conducted competes with unfortified salt brought expanding urban areas where health in- in a community with both lymphatic in by other importers. This is an impor- frastructure and social services have not filariasis and iodine deficiency showed tant lesson for other countries consider- kept pace with population growth. In that 12 months of use of salt fortified ing the use of DEC-fortified salt. Unfor- sub-Saharan Africa, where Onchocerca with DEC and iodine led to dramatic tified salt is often unpackaged and may volvulus is found, it will also be necessary declines in both microfilaraemia and threaten the lymphatic filariasis elimina- to determine whether DEC-fortified iodine deficiency.13 tion programme because it costs less. To salt alone or following treatment with support both iodization and lymphatic ivermectin can be used safely in people The Guyana experience filariasis elimination programmes, either with low levels of microfilariae in their skin. If so, this also would open the Lymphatic filariasis is endemic in more restrictive regulatory controls are door to the use of DEC-fortified salt, Guyana’s coastal belt, where 80% of the needed, including enforced consumer especially in urban areas or where oncho- population lives. Limited availability of packaging, or governments need to de- cerciasis control programmes have been health staff led the Ministry of Health velop active partnerships with importers implemented and have led to low levels to select DEC-fortified salt rather than and salt producers to increase supplies of O. volvulus infection.42 In the latter tablet-based mass drug administration of and consumer demand for DEC- context, DEC-fortified salt could play as the basis of their elimination strategy. fortified salt. a significant role in maintaining gains The programme in Guyana is the first achieved by mass drug administration of its kind: a national programme to Other opportunities and could alleviate concerns that have eliminate lymphatic filariasis based on The initial consumer demand created in arisen about the potential for develop- the introduction of DEC-fortified salt Guyana for DEC-fortified salt makes ment of resistance to ivermectin.43 into a competitive market. Social mobi- the case that the strategy for salt for- lization activities and the launch of the tification should be considered more Conclusions product in July 2003 were extremely widely than it has been. Lessons learned successful, based on assessments of the from Guyana can be applied to other The iodization of salt stands out as a tre- knowledge of DEC-fortified salt and the countries to increase programme suc- mendous public health success, a model rapid initial sales of the product. Three cess. Settings where salt iodization pro- of a safe and effective programme. Add- key factors that had a role in the early grammes have achieved high coverage ing DEC to salt that is being iodized is success of the programme stand out as straightforward: there is no incompat- and where iodization is mandated offer important lessons to be shared with ibility between the two additives and the the best opportunities, and in such set- other countries considering the use of fortification process is identical. Salt is tings, integrating fortification with DEC DEC-fortified salt. used in relatively consistent amounts in into existing salt iodization programmes • A permissive regulatory environment all countries, and all countries have an may offer a simple, rapid approach to is necessary so that DEC-fortified established salt production or importa- eliminating lymphatic filariasis. In the salt can be made available as a food tion and distribution system. Thus, with context of a functioning iodization product and not as a pharmaceutical. government commitment, establishing • Strong partnerships with salt pro- programme, existing salt distribution a programme to fortify salt with DEC ducers and importers are required so networks can be exploited and the costs and distribute it to eliminate lymphatic that normal marketing channels can for the intervention are largely driven filariasis does not need to be compli- be used to introduce and sell DEC- by the cost of the DEC, approximately cated. What is needed at the country fortified salt. US$ 0.05–0.10 per person per year. level is review of how salt is manufac- • Social marketing is critical to build Such costs compare favourably with an- tured or imported and distributed (a salt consumer demand for DEC-fortified nual costs for mass drug administration situation analysis) and the salt iodization 39,40 salt. in many countries and fortification programme as well as development of a with DEC has been noted to be a cost- strategy to prepare the salt industry to After early successes with the marketing effective intervention by the Disease produce DEC-fortified salt.44 Establish- of DEC-fortified salt, consumer con- Control Priorities Project (a joint project ing a DEC-fortified salt programme is fidence was impacted by problems as- of the Fogarty International Center of likely to greatly enhance the possibility sociated with discoloured salt, followed the US National Institutes of Health, of sustaining reductions in microfilarae- by disruptions in the overall salt supply. WHO and the World Bank).41 mia below the point where transmission Although technical problems appear to In countries with efficient vector is possible, and salt fortification should have been resolved by increasing quality transmission, such as areas of the Pacific not be overlooked as an important ap- control, consumer demand for DEC- where Aedes polynesiensis is the vector, proach for eliminating transmission of fortified salt has not reached previous DEC-fortified salt could have a criti- lymphatic filariasis. The success in China levels. Several factors may be responsible cal role in eliminating transmission by with DEC-fortified salt highlights its for lower coverage, including the limited maintaining a low level of drug pressure contribution, and the success with salt availability of DEC-fortified salt. With to provide a prophylactic benefit as well iodization provides the opportunity. O periodic interruption of household salt as a therapeutic benefit. DEC-fortified supplies and only a single producer salt also represents an attractive pro- Competing interests: None declared.

Bulletin of the World Health Organization | July 2007, 85 (7) 547 Policy and practice DEC-fortified salt to eliminate lymphatic filariasis Patrick Lammie et al.

Résumé L’utilisation de sel de cuisine enrichi en diéthylcarbamazine pour éliminer la filariose lymphatique: un potentiel partiellement inutilisé L’enrichissement du sel de cuisine avec de la diéthylcarbamazine avantages que pourrait avoir, dans le cadre des programmes de (DEC) constitue une stratégie sans risque, économique et efficace lutte contre la filariose, l’utilisation de sel enrichi en DEC au lieu pour éliminer la transmission de la filariose lymphatique. Le d’une administration massive de comprimés de ce produit, cette sel enrichi en DEC a été employé avec succès dans des projets possibilité reste sous-exploitée. Nous avons examiné les raisons pilotes menés par plusieurs pays et de manière opérationnelle de cette situation et proposé des lieux où l’on pourrait envisager en Chine pour éliminer la filariose lymphatique. Malgré les d’utiliser du sel ainsi enrichi.

Resumen Una posibilidad desaprovechada: el uso de sal enriquecida con dietilcarbamazina para eliminar la filariasis linfática El enriquecimiento de la sal con dietilcarbamazina (DEC) es vehículo para eliminar la filariasis linfática. Pese a las ventajas una estrategia segura, de bajo costo y eficaz para eliminar la programáticas potenciales del enriquecimiento de la sal con transmisión de la filariasis linfática. La sal enriquecida con DEC DEC, por oposición a la administración masiva de comprimidos, se ha empleado con éxito en proyectos piloto emprendidos en esa alternativa sigue siendo una intervención infrautilizada. varios países y ha sido utilizada operacionalmente por China para Analizamos las razones de ello, y señalamos en qué circunstancias eliminar esa enfermedad. El éxito conseguido con la sal yodada se debería considerar la posibilidad de emplear sal enriquecida para eliminar los trastornos por carencia de yodo es alentador; con DEC. de forma parecida, la sal enriquecida podría utilizarse como

ملخص إمكانية مل تتحقق: استخدام امللح املقوَّى بدي إيثيل كاربامازين للتخلُّص من داء الفيالريات اللمفي تعد تقوية امللح بدي إيثيل كاربامازين استـراتيجية مأمونة ورخيصة وفعّالة امللح املقوَّىكأداة ناقلة لدي إيثيل كاربامازين للتخلُّص من داء الفيالريات للتخلُّص منرساية داء الفيالريات اللمفي. وقد استُخْدِم امللح املقوَّى بدي اللمفي بدالً من تنفيذ حمالت جموعية إلعطاء األقراص، إال أن امللح املقوَّى إيثيل كاربامازين يف مشاريع ارتيادية يف العديد من البلدان، كام استُخْدِم بدي إيثيل كاربامازين اليزال من التدخالت القليلة االستخدام. وقد ناقشنا بنجاح ميداين يف الصني للتخلص من داء الفيالريات اللمفي؛ وقد كان النجاح هذه األسباب واقرتحنا املواقع التي ميكن تطبيق هذه االسرتاتيجية فيها. يف استخدام امللح الـمُيَوْدَنللتخلُّص من عوز اليود مشجعاً؛ إذ ميكن استخدام

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