Diethylcarbamazine citrate-fortified salt for lymphatic filariasis elimination in India

Lymphatic filariasis (LF) is a vector-borne neglected tropical disease, causing permanent disability. The disease is debilitating and widespread, leading to tremendous productivity and economic loss. The Government of India (GOI) prioritized the elimination of LF through the annual mass drug administration (MDA) programme in 2004 and continued with a single dose of diethylcarbamazine citrate (DEC), 6 mg/kg of body weight, plus albendazole annually over a period of 5-6 years. The GOI had set the target to achieve LF elimination by 2015 and now by 2030. The progress so far has been suboptimal. Much remains to be done as about 84 per cent of the total 328 endemic districts are still under MDA. The major challenge in implementing MDA is poor compliance. It is necessary to have a feasible alternative strategy addressing the above challenge to achieve the desired goal of LF elimination. At this juncture, a well-researched approach, i.e. the use of DEC-fortified salt, also advocated by the World Health Organization, as a unique form of MDA, is proposed. As per this strategy, a low dose of DEC (0.2% w/w) is added to the cooking salt at the manufacturing facility of iodized salt and consumed by the LF-endemic communities for about two years. Many examples of successful use of this strategy for LF elimination in small- and large-scale trials have been documented in India and several other endemic countries in the world. Implementing DEC–iodine-fortified salt is a safe, less expensive, more efficient and prompt approach for achieving the elimination of LF in India. Adverse effects are none or minor and self-limiting. The DEC-fortified salt strategy can easily piggyback on the existing countrywide deployment of iodized salt under the National Iodine Deficiency Disorders Control Programme (NIDDCP), which has achieved a great success in reducing iodine-deficiency disorders such as hypothyroidism. This existing robust programme can be leveraged to launch DEC-fortified salt for the community. If implemented appropriately, this strategy will ensure the complete cessation of LF transmission within two years from its introduction. If the said strategy is implemented in 2022, it is expected that India will be able to achieve the LF elimination by 2024, much before the global target of 2030.

Cost of mass annual single dose diethylcarbamazine distribution for the large scale control of lymphatic filariasis.

Economic analysis of the revised strategy to control lymphatic filariasis with mass annual single dose diethylcarbamazine (DEC) at 6 mg/kg body weight launched in one of the districts of Tamil Nadu in 1996 was carried out. This exploratory study, proposed for five years in 13 districts under 7 states on a pilot scale through the Department of Public Health is an additional input of the existing National Filaria Control Programme in India. A retrospective costing exercise was undertaken systematically from the provider's perspective following the completion of the first round of drug distribution. The major activities and cost components were identified and itemized cost menu was prepared to estimate the direct (financial) and indirect (opportunity) cost related to the implementation of the Programme. The total financial cost of this Programme to cover 22.7 lakh population in the district was Rs. 22.05 lakhs. The opportunity cost of labour and capital investment was calculated to be Rs. 7.98 lakhs. The total per capita cost was Rs. 1.32, with Rs. 0.97 and Rs. 0.35 as financial and opportunity cost respectively. Based on these estimates, the implementation cost of the Programme at Primary Health Centre (PHC) level was calculated and projected for five years. The additional financial cost for the existing health care system is estimated to be Rs. 27,800 per PHC every year. DEC tablets (50 mg) was the major cost component and sensitivity analysis showed that the cost of the Programme could be minimized by 20 per cent by switching over to 100 mg tablets. The analysis indicates that this Programme is a low-cost option and the results are discussed in view of its operational feasibility and epidemiological impact.

Rapid assessment procedures (RAP) for lymphatic filariasis.

BACKGROUND: New strategies are emerging for control of filariasis in terms of chemotherapy and vector control. Field application of these tools requires mapping and prioritization of filaria-endemic areas and quantification of the infection/ disease burden. Available procedures are time-consuming, costly and have poor sensitivity. Therefore, rapid assessment procedures need to be developed to assess the disease burden as well as monitor and evaluate control programmes. METHODS: Data collected on different variables from 25 areas in India and elsewhere were used. The relationship between prevalence of human infection and vector infection rate was analysed quantitatively. Due to lack of independent samples, only qualitative analysis was carried out between other epidemiological variables such as infection and disease prevalence in relation to age, gender and manifestation. RESULTS: There was a significant positive correlation between vector infection rate and infection prevalence in humans, suggesting that vector infection can be used as an indicator in the rapid assessment of infection prevalence. Scatter plots showed that community screening may be limited to the age group of 11-30 years for infection prevalence and 20-50 years for disease prevalence. Further, clinical surveys may be limited to only hydrocele prevalence which may be sufficient to predict the total disease. This can also be used as an alternative method by the community itself for delimiting endemic areas. CONCLUSIONS: Vector infection rate may be used as an indicator for rapid assessment of human infection. Alternatively, blood smear examination could be limited to the age group of 11-30 years. For a rapid survey of the diseases, males in the age group of 20-50 years could be examined only for hydrocele.

Clinical manifestations of bancroftian filariasis with special reference to lymphoedema grading.

We report on some aspects of progression of chronic disease and its association with acute manifestations with special reference to grades of lymphoedema in bancroftian filariasis. These analyses were based on the clinical history and clinical findings of 1300 individuals at the time of their first visit to the filariasis clinic at a centre in south India. The mean number of adenolymphangitis (ADL) attacks in one year was 4.9 +/- 1.7, 5.5 +/- 0.9 and 10.4 +/- 3.2 in patients with grade I, grade II and grade III lymphoedema respectively. The mean duration of oedema was 47.4 +/- 5.9 days, 6.2 +/- 0.5 and 8.6 +/- 0.9 yr in patients with grade I, grade II and grade III lymphoedema respectively. These findings suggest that the progression of lymphoedema from one grade to the next in bancroftian filariasis is associated with increased frequency of ADL attacks.

Micro-spatial variation in filarial disease and risk of developing disease associated with microfilaremia in urban situation.

Clinical and parasitological surveys were carried out concurrently during 1986 in Pondicherry. The analyses showed that there was no significant micro-spatial variation in prevalence of total diseases (acute and chronic) and the manifestations such as hydrocele and lymphedema in the different zones and stations of Pondicherry urban area, a stable endemic area. Analyses on different filariometric indices in different stations showed a significant correlation between disease and mf prevalence (r = 0.4106; p = 0.037). The prevalence of disease and hydrocele in microfilaremic individuals (9.4% and 20.0% respectively) was higher compared to that observed in amicrofilaremic persons (6.4% and 11.2% respectively). The relative risk (RR) of parasite carriers developing disease (any manifestations) was marginally higher compared to amicrofilaremic persons (1.18). However, the RR of developing hydrocele manifestation due to microfilaremia was much greater (1.5) compared to amicrofilaremic persons. The attributable risk (AR) due to microfilaremia for developing hydrocele was 0.05. This suggests that although the risk is high in mf carriers, there might be alternate ways of developing disease without the infected person becoming microfilaremic. The limitations of point prevalence data on understanding complex dynamics of infection and disease are discussed.

Cumulative exposure and its relationship with chronic filarial disease in bancroftian filariasis.

Several hypotheses have been put forth about the factors influencing the dynamics of infection and disease in lymphatic filariasis. However, appropriate validation of these hypotheses by real situation analyses of epidemiological data is lacking. The present analyses examine the relationship between cumulative exposure to infection and prevalence of disease by utilizing the existing entomological and clinical data collected between 1981 and 1986 in Pondicherry, South India, endemic for bancroftian filariasis. While there was a significant negative association when the cumulative exposure was correlated with total prevalence of disease (r = 0.70, p = 0.024) as well as hydrocele alone (r = 0.74, p = 0.014), a significant positive association was found with prevalence of lymphedema (r = 0.72, p = 0.018). These results suggest that hydrocele development follows early after exposure, but prolonged exposure could result either in development of lymphedema or immune tolerance resulting in microfilaremia. These could also suggest that the pathomechanisms in development of hydrocele and lymphedema could follow different pathways. Implications of the present findings are discussed in light of the various hypotheses put forward by earlier studies.

Utility of the force of infection model for assessing changes in the dynamics of bancroftian filarial infections.

Force of infection is measured in terms of the number of effective contacts that have been introduced into the population by infective vectors. The utility of such a measure in describing the dynamics of bancroftian filarial infection was tested. Force of infection (beta) incorporating the durations of patent period and pre-patent period was estimated for different age classes (assuming that it is constant in that particular age class) and it was found that the predicted post-control prevalences were close to the observed figures. Utility of Remme's model in areas with different transmission levels is discussed. It was examined whether the empirical function generally used in helminth infections to describe the functional relationship between beta and age could be used for lymphatic filariasis. The relationship between the two was not adequately described by the function. Force of infection, when compared with rate of acquisition calculated using longitudinal data, showed that this measure could be used as a crude estimate of rate of acquisition in places which do not have longitudinal data sets.

Filariasis and blood groups.

BACKGROUND. Using modern statistical techniques, we investigated the controversial relationship between lymphatic filariasis and blood groups in a very large number of patients. METHODS. The ABO blood group, microfilaraemia and symptomatic disease status of 1444 persons was determined. The association between the filarial status and ABO blood group was studied by the Chi-square test and the method of logistic regression by fitting a model. This method simultaneously tested for association of factors such as blood groups and age with the occurrence of parasitaemia or filarial disease. RESULTS. The ABO blood groups were not risk factors in the occurrence of patent parasitaemia or filarial disease though age was associated with the occurrence of microfilaraemia and symptomatic disease. CONCLUSION. ABO blood groups are not associated with the occurrence of bancroftian filariasis.