Dr.R.K.Shenoy, Former Professor & HOD Medicine, Member, WHO Global Lymphatic Filariasis Elimination Programme-
Progress Review Group for Southeast Asia Region, Chief, Filariasis Research Unit, T.D.Medical College Hospital, Alappuzha
Tele-fax: (0477) 2251353, E-mail :firstname.lastname@example.org email@example.com
GLOBAL PROGRAMME FOR ELIMINATION OF LYMPHATIC FILARIASIS:
The WHO International Task Force for Disease Eradication had identified lymphatic filariasis (LF) as one of only six potentially eradicable diseases in the year 1993 (CDC, 1993). Based on this the World Health Assembly resolved in the year 1997, to eliminate lymphatic filariasis as a public health problem globally (Ottesen, 1998). In accordance to this and consequent on several recent advances in the diagnosis and treatment of LF, the World Health Organization launched the Global Programme for Elimination of LF (GPELF) with an aim to eliminate this disease globally by 2020. India, a signatory to the World Health Assembly resolution, has set the target for elimination of filariasis by the year 2015. This programme is based on a dual approach consisting of (i) interruption of transmission to prevent the disease by mass drug administration (MDA) and (ii) alleviation of the disability in those who already have the disease (Seim et al., 1999).
To support GPELF by raising funds and helping in various other ways, a global coalition was forged among 43 different donors constituting the Global Alliance to Eliminate Lymphatic Filariasis (GAELF). One of the partners GlaxoSmithKline has volunteered to supply the total quantity of albendazole tablets required to eliminate LF globally, free of cost (WHO, 2002). They have thus supplied more than 200 million tablets by now. The Diethylcarbamazine (DEC) tablets needed for the programme in India is being supplied by the Central Government.
Lymphatic filariasis (LF) is a parasitic disease caused by thin, thread-like filarial worms transmitted to humans by the bite of mosquitoes. The adult worms lie deep in the lymph vessels of the scrotum, groin, armpit and around the breasts where they may live for 4-6 years. These worms grow and mature in the lymph vessels and produce millions of baby worms called microfilaria (mf), which appear in the peripheral blood at night and can be identified to certain extent by night blood examination. When the mosquito bites a person having microfilaria in his blood, it takes in microfilaria also along with the blood. In the mosquito microfilaria develop into infective larvae in 7 - 21 days. When this mosquito bites another person, he gets infected.
The two parasite species prevalent in India causing LF are the nocturnally periodic forms of Wuchereria bancrofti transmitted by Culex quinquefasciatus and Brugia malayi transmitted by Mansonia mosquitoes. The former is responsible for nearly 95% of the national disease burden and the latter accounts for the remaining.
The adult filarial worms living in the lymphatics are responsible for the initial changes in these vessels, which predispose to the later development of clinical manifestations. Filariasis is the commonest cause of lymphoedema and hydrocele in India. Attacks of acute adenolymphangitis (ADL) associated with fever and painful swelling of the affected limbs commonly occur in these patients.
Incidence of LF:
An estimated total of 120 million people are infected globally with LF, which is ranked as the second most common cause of physical disability. Among the debilitating vector-borne tropical diseases LF is next only to malaria (WHO, 1995). India alone contributes to about 40% of the global filariasis disease burden and harbors 50% of the global population at risk of infection (Michael et al., 1996). While W. bancrofti infection is endemic in 17 States and 6 Union territories, B. malayi is limited to some areas in Kerala and in 7 other States (WHO, 1992; NFCP, 1995). A recent mapping of the district level endemicity of LF has shown that out of the 289 districts surveyed, 257 are endemic for this disease (Sabesan et al., 2000). India has a total of 31.26 million microfilaraemics; 7.44 million having lymphoedema and 12.88 million suffering from hydrocele and it is estimated that in this population, a total of 40.65 million episodes of acute adenolymphangitis (ADL) occur in a year. The total disability adjusted life years (DALYs) lost in India due to this disease are around 2.06 million, resulting in an annual wage loss of US $ 811 million (Ramaiah et al., 2000).
LF - A childhood disease:
Contrary to earlier belief, several recent studies have indicated that LF is first acquired during childhood, even though the clinical disease manifests only later in adult life. In endemic areas the blood microfilaria (mf) prevalence rates in children were found to be ~30% of adult prevalence for <10 year olds and ~ 69% for 10-19 years olds (Witt & Ottesen, 2001). The ICT card test showed filarial antigenaemia in 6% of the two-year old children, which increased to 30% in four-year olds (Lamie et al., 1998). In a study from Madurai it is reported that 92.3% of children in the age group of 2-5 years were circulating filaria antigen (CFA) positive, when their blood smear was negative for mf. The antigenaemia was highest among the 5 years old children (Sunish et al., 2001).
Ultrasonography and lymphoscintigraphy have helped to understand the early changes in the lymphatics brought about by the adult worms. Abnormalities of the lymph vessels like dilation of lymph vessels and renal involvement in the form of microscopic haematuria have been demonstrated even in early stages of the infection, when the affected person had only microfilaria in the blood without any overt clinical disease (Dreyer et al., 1992; 1999). The important fact is that once established, this early lymphatic pathology appears to be irreversible even with treatment, causing progression of the disease (Freedman et al., 1995).
One interesting aspect of LF is that in the early stages of the disease when the person harbors the adult worms in the lymph vessels and has microfilaria in the blood there is no outward evidence of any disease. By the time the person develops swelling of the limbs, usually there are no microfilaria in the blood and CFA tends to be negative, especially in established cases of lymphoedema. But hydrocele may be associated with antigenaemia and microfilaraemia.
Sufferings caused by the disease:
Many recent studies have illustrated the devastating social, psychological, sexual and economic issues due to the deformities caused by this disease. The massive swellings of the limbs in elephantiasis interfere with the day to day activities of these patients. Genito-urinary disease, especially hydrocele, results in strong feelings of shame, fear and embarrassment associated with sexual disability and dysfunction. It is the repeated attacks of ADL more than the swelling of the limbs that incapacitate the patients with LF, calling for urgent medical intervention.
Inability to care for self, isolation from the community, loss of social support and family stress are the other problems faced by these patients. This disease hampers the marriage prospects of the young, mainly females. Other social problems among young patients include feeling of shame, embarrassment and frequent absence from or even discontinuation of studies.
In the light of this knowledge, it is important that steps are initiated to prevent this disease in the population at risk, so that the next generation is free of this horrid malady.
MASS DRUG ADMINISTRATION:
Recent studies have shown that annual administration of single dose of antifilarial drugs keep down the microfilaria levels in the blood to very low levels even at the end of the year. It is shown that the drug has to be given once every year for 4-6 years, which is the duration of the reproductive phase in the life cycle of the filarial worms (Ottesen et al., 1997).
The spread of the disease depends on the load of microfilaria in the blood of individuals in a community and the presence of appropriate mosquito species. Bringing down the levels of microfilaria in blood will prevent spread of this disease since mosquitoes will then fail to pick them up and transmit the disease. To effectively prevent the transmission of filariasis by the mosquito, the drugs have to be consumed every year by at least by 80% of the eligible population in the endemic States.
Why all persons should take the drugs:
So far the diagnosis of LF infection depended on the demonstration of the microfilaria in the peripheral blood obtained by finger prick at night. There are several fallacies in the blood examination. The mf appear in peripheral blood between 10pm and 2am. Most often the blood examination is done before this time. The preparation, staining of the blood smear, effort put in identifying the parasite etc. are important factors in detecting infection. These are often not carried out satisfactorily and many LF infections are missed. In early stages of infection, especially in children mf may be absent from blood since the adult worms have not started producing mf or when only adult parasites of single sex are present.
Results of recent filaria antigen detection methods using ICT card and Og4C3 ELISA have shown that night blood examination is not sensitive enough to detect all parsons who are infected (Weil et al., 1996). Several studies have shown that the percentage of prevalence of LF as indicated by antigen detection methods is always much higher than the mf detection through night blood examination (Lammie et al., 1994). In a report from Tamil Nadu, India the prevalence of antigenaemia was found to be 11.3 - 12.7% more than microfilaria prevalence rates in all age groups (Sunish et al., 2002).
The above findings stress the importance of treating all persons 'at risk' of infection in a community by MDA, because all infected people cannot be identified presently by night blood examination. The antigen detection methods are costly and are not available to screen whole populations.
Vector control: In the past various methods were used for mosquito control, including integrated approach together with identification of LF infection in individuals and treatment. Over the years, in most of the endemic countries these methods have failed to control LF and they were not cost effective. Vector control will be a useful adjunct to MDA if it is practiced at the community level through participation of people and at a lesser cost.
DRUGS USED IN MDA:
Diethylcarbamazine (DEC): This drug, which is being used in the control and treatment of LF during the last 57 years, has stood the test of time. This is the drug of choice for both W.bancrofti and B.malayi infections. DEC is very effective in destroying microfilaria in the blood and hence is a very effective tool in prevention of transmission of infection. Its action against the adult worms is variable as has been made out by ultrasound examination, which has shown that the adult parasites are killed in only ~50% of persons harboring them. Ultrasonography has also shown that single dose of DEC kills the adult worms when they are sensitive to this drug. If they are insensitive, even repeated doses do not have any effect (Noroes et al., 1997). For the past several years the recommended dose of DEC in LF was 6 mg/kg daily for 12 days (WHO, 1992). However recent drug trials have shown that a single dose of 6 mg/kg is as effective as the 12 days course (Ottesen et al., 1997). Single annual administration of 6 mg/kg DEC results in sustained lowering of blood microfilaria levels even at the end of one year (Shenoy et al., 1993; Andrade et al., 1995; Ottesen, 2000).
Due to its sustained microfilaricidal action even in single annual doses, DEC is a good tool to prevent the transmission of LF (Ottesen et al., 1997; Ottesen, 2000a). The adverse effects noticed with DEC are mostly in subjects who have microfilaraemia due to their rapid destruction. Characterized by fever, headache, myalgia, sore throat or cough that last from 24 to 48 hours, these symptoms are usually mild, self-limiting and require only symptomatic treatment (Andrade et al., 1995; Addiss et al., 2000). Direct adverse effects related to the drug are very rare. Studies have shown that the side effects are well correlated with the level of microfilariae.
Even though DEC is conventionally not recommended for administration during pregnancy, in several earlier community studies where this drug was used for mass distribution, no adverse effect has been reported in pregnant women (Ottesen et al., 1997). This drug is reported to be safe for use in pregnancy (Hardman et al., 1996; Moore, 2001)
Albendazole: This well-known anthelmintic drug when given in annual single dose of 400 mg in combination with DEC or ivermectin there is sustained lowering of blood microfilaria levels (Shenoy et al., 2000). Consequent on this effect and its action against many intestinal parasites, albendazole combined either with DEC or ivermectin is recommended for the filariasis elimination programme (Ottesen et al., 1997).
PRESENT SCENARIO OF GELF:
The Global Programme for Elimination of Filariasis is presently being carried out in 38 out of the 83 endemic countries in the world using DEC and Albendazole. In countries like Solomon Islands, Costa Rica, Surinam, Trinidad, Tobago and Egypt, the prevention of transmission of the disease has become a reality.
In the year 2000, 2.9 million people in 12 countries were covered by MDA and in 2001, this was increased to 28.89 million. In 2002, 60 million people in 34 countries were covered and in 2003 it was 100 million people in 38 countries. In the year 2004 - 2005, in India 202 endemic districts having a population of 408 million were brought under MDA (NVBDCP, 2005). So far no serious adverse reactions to DEC or DEC + albendazole are reported in the MDA, other than the mild to moderate symptoms due to the large scale killing of mf in the blood. This strategy recommended by the World Health Organization has proved to be safe for the treated communities (Molyneux, 2003).
It is seen that in India, the actual number of people who consumed the drug during MDA is far less than the 80% coverage required to prevent transmission of filariasis. Studies have shown that if higher coverage is not achieved, the drug administration will have to be continued for many more years.
At present the only available and effective method to eliminate LF is the properly conducted MDA. Now that the whole world is pursuing the goal of elimination of lymphatic filariasis, this is the right time to put all our effort for the success of this national programme because of the high prevalence of this disease in India.
Addiss DG, Dreyer G. Treatment of lymphatic filariasis. In: TB Nutman (ed.). Lymphatic Filariasis, Imperial College Press, London, 2000; 151-199.
Andrade LA, Medeiros Z, Pires ML et al. Comparative efficacy of three different diethylcarbamazine regimens in lymphatic filariasis. Trans R Soc Trop Med Hyg 1995; 89: 319-321.
Centers for Disease Control and Prevention (CDC), Atlanta, USA. Recommendations of the International Task Force for Disease Eradication. MMWR 1993; 42: 1-38.
Dreyer G, Ottesen EA, Galdiono. Renal abnormalities in microfilaraemic patients with bancroftian filariasis. Am J Trop Med Hyg 1992; 46: 745-749.
Dreyer G, Noroes J, Addiss D, Santos A, Medeiros Z, Figueredo-Silva J. Bancroftian filariasis in a paediatric population: a ultrasonographic study. Trans R Soc Trop Med Hyg 1999; 93: 633-636.
Freedman DO, Bui T, de Almeida Filho PJ et al. Lymphoscintigraphic assessment of the effect of diethylcarbamazine treatment on lymphatic damage in human bancroftian filariasis. Am J Trop Med Hyg 1995; 52: 258-261.
Hardman JG, GoodmanGilman A, Limbird LE (Eds) Goodman & Gilman's The Pharmacological basis of Therapeutics, 9th Ed, McGraw Hill Publishers. New York. 1996; P 1016
Lammie PJ, Hightower AW, Ebhard ML. The age-specific prevalence of antigenaemia in a Wuchereria bancrofti exposed population. Am J Trop Med Hyg 1994; 51: 348-355.
Lammie PJ, Reiss MD, Dimock KA, Streit TG, Roberts JM, Eberhard ML. Longitudinal analysis of the development of filarial infection and antifilarial immunity in a cohort of Haitian children. Am J Trop Med Hyg 1998; 59, 217-221.
Michael E, Bundy DAP, Grenfell BT. Re-assessing the global prevalence and distribution of lymphatic filariasis. Parasitology 1996; 112: 409-428.
Molyneux D. Lymphatic Filriasis (Elephantiasis) Elimination: A public health success and development opportunity. Filaria Journal 2003; 2:13.
Moore TA. Therapy for parasitic infections In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL (Eds) Harrison's Principles of Internal Medicine, 15th Ed, McGraw Hill Publishers. New York. 2001; P 1196.
National Filariasis Control Programme Operational Manual. Directorate, National Malaria Eradication Programme, Delhi 1995.
National Vector Borne Disease Control Programme. Operational guidelines on elimination of lymphatic filariasis. Gov. of India, Directorate of NVBDCP, Delhi 2005.
Noroes J, Dreyer G, Santos A, Mendes VG, Medeiros Z & Addiss D. Assessment of efficacy of diethylcarbamazine on adult Wuchereria bancrofti in vivo. Transactions of Royal Society of Tropical Medicine and Hygiene. 1997; 91,78-81.
Ottesen EA, Duke BOL, Karam M, Bebehani K. Strategies and tools for the control/elimination of lymphatic filariasis. Bull World Health Organ 1997; 75: 491-503.
Ottesen EA. Towards elimination of lymphatic filariasis. In Infectious Diseases and Public Health Angelico M and Rocchi G (eds.). Balaban Publishers, Tel Aviv, 1998; 58-64.
Ottesen EA. Towards eliminating lymphatic filariasis. In: TB Nutman (ed.). Lymphatic Filariasis, Imperial College Press, London, 2000; 201-215.
Ottesen EA The global programme to eliminate lymphatic filariasis. Ann Trop Med Int Hlth 2000; 5: 591 - 594.
Ramaiah KD, Das PK, Michael E, Guyatt H. The economic burden of lymphatic filariasis in India. Parasitol Today 2000; 16: 251-253.
Sabesan S, Palaniyandi M, Das PK. Mapping of lymphatic filariasis in India. Ann Trop Med Parasitol 2000; 94: 591-606.
Seim AR, Dreyer G, Addiss DG. Controlling morbidity and interrupting transmission: twin pillars of lymphatic filariasis elimination. Revista da Sociedade Brasileria de Medicina Tropical 1999; 32: 325-328.
Shenoy RK, Kumaraswami V, Rajan K, Thankom S, Jalajakumari. A comparative study of the efficacy and tolerability of single and split doses of ivermectin and diethylcarbamazine in periodic Brugian filariasis. Ann Trop Med Parasitol 1993; 87: 459-467.
Shenoy RK, John A, Babu BS, Suma TK, Kumaraswami V. Two-year follow-up of the microfilaraemia of asymptomatic brugian filariasis, after treatment with two, annual, single doses of ivermectin, diethylcarbamazine or albendazole in various combinations. Ann Trop Med Parasitol 2000; 94: 607-614.
Sunish IP, Rajendran R, Satyanarayana K, Muniratnam A, Gajanana A. Immunochromatographic test (ICT) for estimation of true prevalence of bancroftian filariasis in an endemic area in southern India. Trans R Soc Trop Med Hyg 2001; 95: 607-609.
Sunish IP, Rajendran R, Mani TR, Muniratnam A, Tewari SC, Gajanana A, Satyanarayana K. Resurgence in filarial transmission after withdrawal of mass drug administrationand the relationship between antigenaemia and microfilaraemia. Trop Med Int Hlth 2002; 7: 59-69.
Weil GJ, Ramzy RMR, Chandrashekhar R, Gad AM, Lowrie JR. RC, Faris R. Parasite antigenaemia without microfilaraemia in bancroftian filariasis. Am J Trop Med Hyg 1996; 55: 333-337.
Witt C, Ottesen EA. Lymphatic filariasis: an infection of childhood. Trop Med Int Hlth 2001; 6: 582-606.
World Health Organization. Lymphatic filariasis: The disease and its control. World Health Organ; 1992. Tech Rep Ser 821.
World Health Organization. Bridging the Gaps World Health Report. WHO; Geneva.1995.
World Health Organization. Global Programme to eliminate Lymphatic Filariasis - Annual Report on Lymphatic Filariasis. 2002; WHO/CDS/CPE/CEE/2002.28.