LYMPHATIC FILARIASIS

Lymphatic filariasis (LF) is an important public health problem in India where about a third of the global population lives at risk of this disease. In India, description of a disease that resembles filariasis was found in “Susruta Samhita” as early as 600 B.C. Madhavakara in his treatise “Madhava Nidhana” (700 A.D.) has described the signs and symptoms of this disease  and has referred to the elephantoid legs in Cochin as ‘Malabar Legs’. Lymphatic filariasis has thus been the scourge of civilization since time immemorial. The infection is acquired in childhood, progresses with age and often leads to irreversible clinical manifestations that mainly include lympheodema/elephantiasis of lower limbs and hydrocele. The disease is a significant cause of stigma, akin to leprosy, psychological distress, shame, inferiority and marital discord and impairs occupational, educational, recreational activities. LF is a disease of the poor and is a cause and effect of poverty. Majority of the people at risk of this disease live in rural areas.

 

The most widespread LF infection is due to Wuchereria bancrofti (98%) and the remaining infection by Brugia malayi (2%), and they are commonly called Bancroftian and Brugian filariasis respectively. Nocturnally periodic W. bancrofti (microfilaria (mF) appear in peripheral blood circulation only during night) is the most widespread form, transmitted by Culex quinquefasciatus, a ubiquitous mosquito that breeds in almost all organically polluted water bodies. The diurnally sub-periodic W. bancrofti (mF appear in peripheral blood circulation at any time, but in high count during daytime) is limited to a small focus  in Nicobar Islands, transmitted by Ochlerotatus  (Finlaya) niveus, an outdoor day-biting mosquito that breeds in tree holes. The nocturnally periodic B. malayi is restricted to a single largest focus in the central coastal part of Kerala and only a few villages in six other States. Mansonia mosquitoes (Ma. annulifera, Ma. uniformis and Ma. Indiana) are the vectors of this infection that breed in association with floating hydrophytes in freshwater bodies.

 

Being a mosquito borne disease, the feasibility of control of filariasis apparently is by attacking the parasites in the microfilaria carriers, and the vector. With this objective, a pilot project by  Govt. of India was launched in Orissa in 1949 to control Bancroftian filariasis by the conventional methods namely (i) mass drug therapy with diethylcarbamazine (DEC), (ii) recurrent anti larval measure and (iii) recurrent anti adult mosquito measure. The pilot project was terminated in 1954, with the conclusion that each one of the above methods had its own drawback; but a multiple approach using all the three methods was considered appropriate for the control of the disease. Thus, the National Filaria Control Programme (NFCP) was started during 1955-56 under National Institute of Communicable Diseases (NICD) after an agreement between Government of India and United States Technical Cooperation Mission for the purpose of controlling bancroftian filariasis. The main objectives of the programme were (a) to carry out filariasis surveys in different States of the country where the problem was known to exist, in order to determine the extent of prevalence, types of infection and their vectors, (b) to undertake large scale pilot studies to evaluate the known methods of filariasis control in selected areas in different States and (c) to train professional and ancillary personnel required for the programme. The main control measures were mass DEC administration, antilarval measures in urban areas and indoor residual spray in rural areas. The NFCP and the Urban Malaria Scheme (UMS) were akin in having similar strategies of anti vectors measures and their operation being restricted to urban agglomerations. Keeping these basic aspects in view, the programme part of NFCP was transferred from NICD to National Malaria Eradication Programme (NMEP) in 1978 leaving only research and training activities under the jurisdiction of NICD.

 

The NFCP was independently assessed four times under the aegis of ICMR between 1960 and 1995 and each committee made recommendations. The First ICMR Assessment Committee (1960) reported failure of mass DEC administration due to community non-cooperation and ineffectiveness of insecticidal indoor spray due to high level of resistance in the vector. The programme was withdrawn from rural areas while in urban areas, antilarval measures continued to be the main control method. Second ICMR Assessment Committee (1970) recommended selective treatment of mf carriers at a dose of 6 mg/kg per day for 12 days as a compliment to antilarval measures, delimitation of the problem in unsurveyed districts and regionalisation of control me asures  in contiguous areas . Third ICMR Assessment Committee (1982) recommended extension of NFCP to rural areas through primary health care system with 100% central assistance for material & equipment, undertaking DEC medicated salt regimen in high endemic districts and control of B malayi infection. Fourth ICMR Assessment Committee (1995) recommended a project on eradication of B. malayi infection, 100% Central assistance for material and equipment including vehicles, Integrated vector control measures for all vector borne diseases, adaptation of Model bye-laws for effective control of vectors in domestic situation, antigen and DNA based detection of microfilaria initiation of fresh delimitation surveys in rural areas, community health education through intensified mass media and training of different categories of workers and trainers training including operational research.

 

The major constraint of the NFCP was that it did not cover the vast majority of the population at risk residing in rural areas and that the strategy demanded detection of parasite carriers by night blood survey, which is less sensitive, expensive, time-consuming and poorly accepted by the community. The transformation from pilot scale studies and interventions to in-depth studies and development of strategies for filariasis control came with the ICMR establishing the Vector Control Research Centre at Pondicherry in the year 1975. The VCRC began its work with the quantification of vector abundance and the microfilaria rate in Pondicherry and in due course of time Filariasis became the focus of research for the Centre.

 

Filariasis Control Demonstration Project (FCDP)

 

A project on “Demonstration of control of bancroftian filariasis in Pondicherry urban agglomeration (2.7 lakh population) by controlling the vector Culex quinquefasciatus” was launched by the VCRC. This 5 year project (1981 – 1985) came to be commonly known as the Filariasis Control Demonstration Project (FCDP). One of the major aims of the project was to reduce the transmission of filariasis by lowering the vector density to the minimum level possible by IVM strategy. No special efforts were made to augment the chemotherapeutic treatment of microfilaria carriers carried out routinely by the State Government. The project achieved drastic reduction of the vector population and was maintained at a very low level throughout the project period. Man biting density was reduced from 25,561 to 1,662 per person per year (93.7% reduction).  The annual transmission index and the risk of infection index were also reduced drastically. Children born during the project period were free from filarial infection. The prevalence of microfiaria was reduced from 10.3% to 6.3% after 5 years of IVM programme. The cost of IVM to protect an individual was Rs 6.40 per year and was more cost effective than the conventional methods. The most important outcome of the project was the clear demonstration that only Integrated Vector Management techniques, with main emphasis on environmental sanitation and making vector control a multi-departmental affair, can bring about a drastic reduction in man vector contact. The technology was handed over to the State Health Department since then it is implemented in Pondicherry for the control of vector of W. bancrofti and the local population is benefited from the programme. This was considered as a role model for such situation elsewhere, not only for the control of vectors but also protecting the people from mosquito nuisance. It was also shown that to reduce the infectivity of the population to mosquito, administration of drug to every mf carrier is necessary in a high endemic area like Pondicherry. Otherwise the potential reservoirs will continue to be in the population for vector infection. The most important by-product of this project was the creation of a trained scientific cadre of young scientists.

 

The Cherthala Project

 

The experience gained from the Pondicherry IVM project showed that besides reducing vector density, liquation of parasite load in the population is of at most importance to eliminate the source of infection. With  mass drug administration for parasite control as an integral part, a community based project for control of brugian filariasis was initiated in Cherthala taluk in Alappuzha district, Kerala, the  ‘hot-bed’ of this disease for several decades. The scourge of filariasis in Cherthala is well documented since 1855, when Waring, the Durbar physician of erstwhile Travancore State, made an epidemiological survey and recorded that one out of 23 of the population was afflicted by chronic filarial disease. This project, carried out as Technology Mission Project (TMP) from 1986 to 1998 aimed at the elimination of the transmission of filariasis in this region, through application of known technologies and newer strategies, with active community involvement and inter-sectoral collaboration. In 1991, it was delinked from the Mission and was brought under extramural plan of ICMR. Following the successful demonstration of transfer of technology to the community, the achievements accomplished were consolidated and the inputs were gradually withdrawn to ensure sustenance of the programme and extension of activities. The impact assessment showed that the vector density recorded in 1997 was only 22.6% of that obtained during the pre control period. None of the mosquitoes was found to be infected with filarial parasite. This zero infection rate brought down from 2.05% during the pre control period was maintained since 1995. The mf rates were reduced to 0.2% and 0.05% in 1997 from the respective pre control values of 4.02% and 3.36% in 1986. No new case of infection in the age class 1 -9 years was recorded since 1991. The success of the project was evidenced by the total interruption of transmission of filariasis. The children born after launching the project were free from filarial infection. The integrated control strategy adopted for brugian filariasis, such as deweeding of ponds which was simple and promotion of composite fish culture including phytophagous fishes that was income generating to the community was helpful in implementing the project with active participation of the community. The Department of Health, Government of Kerala took over the project to ensure the sustenance of the programme and is currently working for the elimination of brugian filariasis through mass drug administration following the national strategy.

 

Towards elimination of Lymphatic Filariasis in India

 

The World Health Assembly passed a resolution in 1997 which called upon the member states to make all efforts to eliminate LF as a public health problem by 2020 and the WHO launched the Global Programme to Eliminate LF (GPELF) in 2000 with Mass drug administration (MDA) with DEC and  albendazole as the strategy for transmission control. Much earlier during 1990-95,  VCRC had carried out trials with annual and semiannual rounds of MDA against both bancroftian and brugian filariasis. The results of these studies and that of the NVBDCP in 1996 that introduced a revised strategy on a pilot scale with DEC in 13 endemic districts for the control of filariasis with active participation of VCRC served as the basis for adopting MDA strategy for the GPELF and also provided evidence for operatonal and technical feasibility of MDA. 

 

In India the lymphatic filariasis elimination programme was launched in 2004. The  NICD  and  the  NVBDCP  were  the  nodal  agencies  for implementation, supported by the  WHO and ICMR   [1] on technical components. The Institutes of ICMR, notably the VCRC,  RMRC,  Bhubaneshwar, RMRC Port Blair and TRC are collaborating in this programme. Operationalization of GPELF, had been a huge challenge in India, particularly establishment and implementation of mass drug administration (MDA) programme to cover the entire population living in rural and urban areas of significant socio-cultural-economic differences. This required active operational research support for the programme for which the ICMR established an "ICMR Cell towards Elimination of Filariasis" at the VCRC  [2]. The cell is working in close co-operation with the National/State Programme managers/Officers, other Government departments, NGOs, researchers and the Members of endemic community at large. The overall objectives included,  providing technical information on filariasis and its control through website, facilitating formulation of policy on co-administration of DEC plus albendazole, foster effective linkages with all partners, assisting programme personnel in the development and implementation of site-specific strategy (guidelines for programme managers and drug distributors), developing tools and designs for monitoring and evaluation, carrying out independent assessment (Indepth review of LF programme on the request of NVBDCP), imparting required training and human resource development and facilitating the documentation of the process at all levels.

 

The contributions of CRME on the scope of vector control in the elimination of LF, RMRC Port Blair on the epidemiology and control of sub-periodic bancroftian filariasis and RMRC, Bhubaneswar on evolving chemotherapeutic regimens have formed important steps in formulating suitable strategies towards LF elimination. The VCRC carried out extensive field, community and health system oriented operational research to support the national and global programme to eliminate LF and significant contributions have been made in the following aspects.

 

Economic burden

 

In a series of field studies carried out at VCRC  it was shown that (a) in addition to chronic disease, acute disease is a significant health problem, (ii) people’s knowledge of disease is poor, highlighting the necessity of community mobilization for LF elimination progeramme, (iii) LF causes significant functional, occupational, and educational impairment, (v) the treatment costs are considerable, (vi) the disease reduces productivity by 27% and (vii) LF inflicts an annual economic loss of close to Rs.4,500 crores, equivalent to 0.67% GNP. These data provided basis for advocacy, enhancing the support for LF elimination programme and raise awareness among donors.

 

Rapid assessment

 

Identification of endemic areas and delimitation of areas for MDA is the first step in planning elimination programme. Robust information on the distribution of LF is therefore necessary to rule out the possibility of missing some endemic areas for intervention for which a  rapid assessment technique is of primary importance.  A grid sampling technique (with grid size of 25X25 Km) using Rapid Assessment Procedure following a sequential application of the RAP (Questionnaire Method  followed by Physical Examination by Health Workers followed by ICT) was developed for identification of endemic areas. Further,  preparation of a stratified ‘Filariasis Map’ combining the existing information on prevalence and Geographic Information System (GIS), use of geo-environmental variables and ICT card test as diagnostic tool for defining ‘at risk’ areas to rule out the prevalence of LF in designated non-endemic areas,  were other inputs that facilitated delineation of endemic areas and resources required to implement PELF.

 

Diagnostic tools

 

Monitoring and evaluation of the elimination progamme is based on assessing various epidemiological parameters and parasite infection in vectors. Consequent to the low prevalence of infection during post intervention period, a large number of samples needs to be tested for detection parasite infection in the vectors. This would require a diagnostic tool that could process large number of samples in a shorter period of time. Towards meeting this requirement a PCR based xenomonitoring process has been developed. Further, with the objective of reducing the costs of the PCR, rapid DNA extraction technique has been perfected. However, these methods, though widely applicable to the programme, cannot differentiate the mosquitoes with infective stage larvae, an indicator of transmission, from mosquitoes with any-stage infection. Recently, a RT-PCR based assay to differentiate infective mosquitoes (those with L3) from infected mosquitoes has been developed.

 

Approach for drug distribution in MDA

 

It has been stated while recommending MDA for filariasis elimination, >65% treatment coverage, often called ‘effective treatment coverage’, is required to achieve LF elimination. It is essential to develop appropriate drug delivery strategy to ensure adequate coverage and consumption. Studies on drug delivery through PHC system and community volunteers showed that the former was more acceptable but the latter ensured better coverage, but drug delivery through a combination of both the PHC and community volunteers was found to be more appropriate. This finding has led to its adaptation in the national programme. 

 

Treatment coverage

 

Treatment coverage, which reflects the efficiency of the programme implementation, is the most important determinant of the outcome of MDA programmes. Independent assessment of treatment coverage showed that the overall drug distribution and consumption rates were 70% and 54% respectively. These findings suggested the necessity to improve the system to ensure >65-75% drug consumption rates. The reasons for low coverage were identified and suitable remedial measures were recommended for improvement. It was also demonstrated that ‘Communication for Behavioral Impact’ (COMBI) has a good potential to improve the treatment coverage. In villages with COMBI, 30% more people believed that LF can be eliminated and 12% more people consumed the drug.

 

Trials with Co administration of DEC with albendazole

 

While GPELF recommended DEC-Albendazole mass administration, India initially preferred to distribute only DEC. However, an operational feasibility study of administration of DEC+albendazole was undertaken, which demonstrated that people accept the combination therapy and its impact is better than the single drug therapy Compared to DEC alone, DEC+albendazole reduced the mf prevalence in 19% more people and antigenaemia prevalence significantly after 3 rounds of MDA. A policy change in the national programme to replace the single drug therapy with combination therapy in the year 2006 was made based on these findings.

 

Mathematical Models

 

The data generated  from the VCRC project on the control of filariasis in Pondicherry (FCDP) was used to develop  stochastic and simulation models to predict the outcome of the LF control/elimination programmes. A simulation model that predicts the outcome of the MDA, based on relationship between impact of drug, treatment coverage and duration of MDA, is in advanced stage of development for programme use. With the given actual treatment coverage of 65 % under operational settings, the model predicts that  10 rounds of DEC are necessary to achieve LF elimination.

 

Supplementary measures to hasten the process of elimination

 

In some situations, particularly where the baseline LF prevalence is high, some supplementary measures may be necessary, in addition to MDA, to achieve LF elimination in a reasonable time frame. Studies were undertaken to demonstrate the role of DEC-medicated salt in elimination of post-MDA  microfilaraemia.  Administration of medicated salt for one year period, in addition to MDA, reduced community mf prevalence from 3.62% to 0.34%, compared to stable level of prevalence at 1.60% in the community administered with only MDA (no DEC medicated salt). More strikingly, the antigenaemia in children was reduced from 17.70% to 0.32% in the community with supplementary measures. These results clearly suggest that DEC-medicated salt has excellent potential to play supplementary role to MDA. Implementation of vector control, in addition to MDA over a period of four years yielded 4% higher reduction in Mf prevalence and antigenaemia prevalence and reduced the risk of resurgence of infection.

 

Management of lymphoedema cases

 

Morbidity management is the second pillar of GPELF. Simple leg hygiene measures reduce the intensity and frequency of acute adenolymphangitis episodes, often precipitated by bacterial infections. A study carried out on the cause and control of secondary infection showed that prevention of secondary infection by simple foot care is superior than treating the infection with antibioticts in reducing the frequency of acute adenolymphangitis episodes. . Dynamics of disease progression was studied through histopathological and immunopathological in­vestigations of lym­phoedema patients and appropriate management therapy has been developed.

 

Costs and benefits

 

In order to provide inputs to planners, administrators and programme managers and stakeholders, the costs and benefits of the programme are being assessed from time to time. The costs of the programme are relatively cheap as the cost of the principal drug, DEC, and its distribution is only Rs. 1.32 per capita and the costs of 6-8 treatments will be in the range of Rs. 20.00 to 25.00. In contrast, the returns from the treatment are much higher and the cost-benefit ratio of the programme was shown to be as low as 0.019, highlighting that PELF is one of the cheapest intervention programmes in the annals of public health history.

 

The progress of PELF in India is a shining example of  a public health programme being carried out with  fruitful collaboration between programme and research organizations of ICMR.   The research outcome of VCRC formed valuable inputs for LF elimination programme at National as well as at global level.



[1] Policy Note 2002-2003, Health and Family Welfare Department, Government of Tamil Nadu, www.tn.gov.in

[2]  Vcrc.res.in (ICMR CELLTowards Elimination of Lymphatic Filariasis)

 

 

Last Updated on : 16/04/2014