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.

Diurnally subperiodic filariasis among the Nicobarese of Nicobar district - epidemiology, vector dynamics & prospects of elimination.

In India diurnally subperiodic filariasis (DspWB) is prevalent only in the Nicobar district of Andaman and Nicobar Islands. Studies undertaken at different points of time indicate that this form of filariasis is restricted to a small region in Nancowry group of islands where it is transmitted by mosquito Downsiomyia nivea, a day biting mosquito. Studies on prevalence, distribution, and assessment of endemicity status, vector incrimination, bioecology, host seeking behaviour, population dynamics of the vector, transmission dynamics and clinical epidemiology indicate the prevalence and persistence of this infection in the Nancowry group of islands with perennial transmission. There was no control programme in these islands, until the National programme to eliminate filariasis was launched in 2004. Eight rounds of annual mass drug administration (MDA) with diethyl carbamazine (DEC) + albendazole have been completed. Despite this, microfilaria prevalence remains at above one per cent, the level identified for initiating transmission assessment survey to decide on continuation of MDA further. This necessitates adjunct measures to the ongoing MDA programme in these islands. The vector control options could be an adjunct measure, but the vector is a forest dweller with a unique bio-ecology, therefore, not a technically feasible option. Use of DEC fortified salt for six months to one year could hasten the process of elimination. Although administration of DEC-fortified salt is simple, rapid, safe, and cost-effective, challenges are to be tackled for evolving operationally realistic strategy. Such a strategy requires commitment of all sections of the society, a distribution mechanism that ensures the use of DEC-fortified salt in the Nancowry islands. Here we discuss the plan of action to serve the indigenous communities and operationalizing DEC fortified salt strategy through an inter-sectoral approach involving multiple stakeholders.

Survival of diurnally sub periodic Wuchereria bancrofti in Downsiomyia nivea (Diptera: Culicidae): a density dependent factor from Andaman & Nicobar Islands.

Background & objectives: In India, diurnally sub periodic Wuchereria bancrofti transmitted by Downsiomyia nivea is prevalent only in the Nicobar district of Andaman and Nicobar Islands. The ongoing LF elimination programme aims at transmission interruption by bringing down the microfilarie (mf) load in the community, which has implication on the parasite load in mosquito vector. Therefore, understanding density dependent constraints on transmission assumes significance from control perspective. The present study was undertaken in Teressa Island to understand the density dependent parasite mortality and survival probability of the parasite Do. nivea. Methods: The entomological data collected from Teressa Island, endemic for the diurnally sub periodic form of W. bancrofti were used to examine the parasite loss and its survival up to infectivity. Patterns of parasite distribution in Do. nivea were examined. Results: Distribution patterns of microfilariae were found to be over dispersed in Do. nivea. The later stages of the parasite in the vector were randomly distributed. Distribution pattern of various filarial larval stages suggested that the loss of parasites occurred as development progressed and was maximal between the first and second stages. Further, both the prevalence of infection and the degree of parasite aggregation in the vector population have fallen significantly with development of parasite stage. Interpretation & conclusions: Results indicate the operation of parasite density dependent mortality of vectors or parasite loss or combination of both. The present study with Aedes transmitted filariasis conducted before launching LF elimination programme in the study area indicates a comparable level of parasite regulation in the vector which has similar implications on the transmission threshold. Thus, the consideration of Aedes with Culex in deriving the critical level of antigen positive for making decisions on cessation of mass drug administration (MDA) can be justified. However, with MDA aiming at reducing parasite load in the community, the operation of density dependent factor in the transmission becomes less pronounced in the subsequent rounds of MDA.

Rural-urban Population Movement, Community Context and Impact on DEC Fortified Salt Program to Eliminate Lymphatic Filariasis.

Diethylcarbamazinecitrate (DEC) salt in conjunction with annual singledose mass drug administration (MDA) with DEC tablets can be considered as potential option to hasten the process of Lymphatic Filariasis (LF) elimination. Consumption of DEC tablet/salt by at least 80% of the endemic population is crucial in achieving elimination in five years. This study examines the determinants of rural-urban population movement and its implication on DEC fortified salt program to control LF. Data was collected through questionnaire from 150 each movers and non-movers from 10 randomly selected villages and also using Key informant (KI) interviews in Villupuram district in Tamil Nadu. Households with at least one family member engaged in movement at any point of time in the previous year, range from 24 - 43% in different villages. Knowledge on cause, control, ongoing LF elimination programs and compliance with DEC tablets (28.7%) and salt (30%) were significantly higher (p<0.05) among non-movers than movers (4.7% and 3.3%respectively). In order to achieve the goal of elimination of LF by 2020, measures need to be undertaken to ensure that the social mobilization activities and LF intervention programs need to cover the 24 - 43% of mobile population.

Burden of chikungunya in India: estimates of disability adjusted life years (DALY) lost in 2006 epidemic.

BACKGROUND & OBJECTIVES: During 2006, chikungunya emerged as a major ever known epidemic in India. Disability adjusted life years (DALY) is an appropriate summary measure of population health to express epidemiological burden of diseases. We estimated the burden due to suspected chikungunya using DALYs for the first time and compared between the states and also with the burden due to other vector-borne diseases in India. The economic burden was also assessed in terms of productivity loss. METHODS: Data on the reported cases of fever/suspected cases of chikungunya from different states during 2006 in India were used. Years lived with disability (YLD) were calculated for non-fatal cases to estimate DALY. Since the disability weight for chikungunya is not available, the weights available for rheumatic arthritis, comparable to the disease outcome of chikungunya were used for the estimation. The burden was estimated for both acute and chronic cases. It is considered that about 11.5% of cases were reported to have extended morbidity with persisting arthralgia. For acute disease, the average duration of illness was considered to be nine days and for chronic cases it was six months on an average. The productivity loss due to income foregone by the working class was calculated using minimum official wage. RESULTS: National burden of chikungunya was estimated to be 25,588 DALYs lost during 2006 epidemic, with an overall burden of 45.26 DALYs per million. It varied from 0.01 to 265.62 per million in different states. Karnataka alone contributed as high as 55% of the national burden. Persistent arthralgia was found to impose heavy burden, accounting for 69% of the total DALYs. The productivity loss in terms of income foregone was estimated to be a minimum of Rs. 391 million. INTERPRETATION & CONCLUSION: The chikungunya epidemic in the year 2006 imposed heavy epidemiological burden and productivity loss to the community. The burden of chikungunya in terms of DALY was estimated for the first time. In view of re-emergence and spread of this infection in recent times it is warranted for derivation of disability weight for different health states of chikungunya to facilitate realistic estimates of DALYs. Quality epidemiological data from surveillance system to monitor vector-borne and zoonotic diseases would pave way for more realistic estimates of burden. The productivity loss in-terms of income foregone could be minimal as the estimation was made by using the minimum wage fixed by the government although the actual loss is expected to be higher.

Transmission dynamics of diurnally subperiodic lymphatic filariasis transmitted by Ochlerotatus (Finlaya) niveus in the Andaman & Nicobar Islands.

BACKGROUND & OBJECTIVE: In India diurnally subperiodic filariasis is prevalent only in the Nicobar district of Andaman and Nicobar Islands, with significant health problem. Sample surveys indicated that this form of filariasis is restricted to a small region of Nancowry group of islands with Ochlerotatus niveus as the vector. We therefore carried out a comprehensive study to assess the transmission dynamics of LF in Teressa island in Nicobar district in view of its control and evaluation of interventions. METHODS: Entomological studies were carried out for a period of twelve months covering all the seasons in the year, by means of man landing catches in Teressa Island, an endemic island for this form of filariasis. Parameters viz., the annual biting rate (ABR), annual infective biting rate (AIBR), annual transmission index (ATI), risk of infection index (RII) and annual transmission potential (ATP), which reflect the dynamics and intensity of transmission of filariasis, were estimated. Host efficiency of Oc. niveus was also assessed. RESULTS: The number of vectors biting a person in a year was estimated to be 21851, of which 107 were harbouring infective parasite. Risk of infection intensity was 0.02332. Every person in this study area was at the risk of receiving an estimated number of 22 infective stage larvae per year. The host efficiency index of Oc. niveus indicated that over 40 per cent of the microfilariae ingested were able to develop into infective stages. The ATP was 169 with evidence of year round transmission. The pattern of monthly transmission potential suggested that the intensity of transmission was high during summer months. INTERPRETATION & CONCLUSION: Perennial transmission of subperiodic Wuchereria bancrofti in the typical forest ecosystem was evident in Teressa Island with transmission parameters suggesting that summer is a high risk season for transmission. Personal protection measure is the method of choice to protect from the risk of infection, because of day biting, exophilic and exophagic behaviour of the vector and larvae are not amenable to larvicidal measures. An alternative method to control the transmission would be to use selective or periodic mass chemotherapy to reduce the parasite load in this community.

Long-term outcome of patients operated for large ventricular septal defects with increased pulmonary vascular resistance.

BACKGROUND: There is a paucity of data regarding the long-term outcome of patients operated for ventricular septal defect with severe pulmonary arterial hypertension and elevated pulmonary vascular resistance. METHODS AND RESULTS: We evaluated the long-term follow-up results of a selected cohort of patients with nonrestrictive ventricular septal defect and elevated pulmonary vascular resistance (>6 Wood units). Thirty-eight patients, median age 7.5 years (range 6 months-27 years), with nonrestrictive ventricular septal defect with severe pulmonary hypertension were operated between 1985 and 1996 at our institute. Preoperative pulmonary vascular resistance, ratio of pulmonary blood flow to systemic blood flow, and ratio of pulmonary vascular resistance to systemic vascular resistance were 7.63+/-1.8 Wood units, 1.9+/-0.48, and 0.41+/-0.12, respectively. The majority (68.4%) had perimembranous ventricular septal defect. Thirty patients (79%) had a good outcome and were asymptomatic at a mean follow-up of 8.7 years, with significant reduction in pulmonary artery pressures. Eight patients (21%) had a poor outcome, which included 5 immediate postoperative deaths, 1 late death and 2 surviving patients with persistent severe pulmonary arterial hypertension. There was no significant difference regarding hemodynamic parameters at baseline between those who had a good outcome and those who did not. Eleven patients with a preoperative pulmonary blood flow to systemic blood flow ratio of <2:1. who had a good outcome following surgery, underwent repeat catheterization at follow-up. There was a significant reduction in their mean pulmonary vascular resistance (8.03+/-1.4 v. 4.16+/-1.6 Wood units, p=0.001) and pulmonary vascular resistance to systemic vascular resistance ratio (0.41+/-0.12 v. 0.19+/-0.06, p=0.05). CONCLUSIONS: The late results of surgery on this selected group of patients with nonrestrictive ventricular septal defect with high pulmonary vascular resistance are encouraging. Operative correction of the ventricular septal defect should be actively considered in all children presenting with nonrestrictive ventricular septal defect with a significant left-to-right shunt, despite moderately elevated pulmonary vascular resistance. Even among older patients with ventricular septal defect and moderately elevated pulmonary vascular resistance, there is a specific group that does well after operation.

Left atrial and pulmonary artery wedge pressure monitoring during balloon mitral valvuloplasty.

OBJECTIVE: We tested the accuracy of pulmonary artery wedge (PAW) pressure as a guide to the degree of pulmonary venous hypertension. METHODS: Left atrial (LA) pressure and PAW pressure were analysed before and after balloon mitral valvuloplasty (BMV) in patients with rheumatic mitral stenosis. RESULTS: Correlations between LA and PAW pressures for a wave, v wave and mean pressure were excellent before BMV (r=0.96, r=0.97 and r=0.99 respectively) and after BMV (r=0.98, r=0.98 and r=1.00 respectively). The fall in mean LA pressure (11.3 +/- 7.9 mm Hg) and in mean PAW pressure (11.1 +/- 7.9 mm Hg) also correlated well. Correlation was good both before and after BMV when subgrouping was done based on average pulmonary vascular resistance and average LA mean pressure in each group. CONCLUSIONS: There is good correlation of PAW pressure with LA pressure even in the presence of pulmonary arterial or venous hypertension. It can replace LA pressure monitoring in any clinical setting.

Atrial fibrillation in patients with pure isolated severe rheumatic mitral regurgitation.

OBJECTIVE: This study examines the significance of the parameters that identify patients with mitral regurgitation (MR) and atrial fibrillation (AF) and discusses the indications for surgery in such patients. METHODS: Patients with MR and chronic AF (group I, n=64) and those without AF (group II, n=138) were studied by clinical and echocardiographic methods. Stepwise regression analysis identified factors associated with the presence of atrial fibrillation. RESULTS: Group I patients were older and more symptomatic. They had larger left ventricular (LV) end systolic dimension (4.6+/-1.1 cm vs 3.8+/-0.8 cm, p=0.03), left atrial (LA) dimension (5.4+/-2.0 cm vs 4.1+/-1.3 cm, p=0.02), LA area (55.9+/-27.1 cm2 vs 35.9+/-17.5 cm, p=0.003) and lower LV ejection fraction (58.8+/-8.0% vs 72.4+/-7.4%, p=0.0003). Right ventricular systolic pressure was higher (57.6+/-18.1 mm Hg vs 33.6+/-12.1 mm Hg, p=0.02). By stepwise regression analysis, factors that predicted the presence of AF were age (p < 0.03) and LA dimension (p < 0.01). A higher LV end systolic dimension and lower LV ejection fraction than the recommended value for good operative outcome were present in them. Emerging indications for surgery and predictors of poor outcome were seen. CONCLUSIONS: Atrial fibrillation in MR indicates a more chronic and severe disease process with worsening of left as well as right sided haemodynamics in spite of digoxin. Drifting towards decompensation, these patients are likely candidates for early surgery.

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.

Simultaneous echocardiographic and catheterisation gradients and mitral valve area during balloon mitral valvuloplasty.

This study was aimed at estimating mean transmitral gradients by simultaneous Doppler echocardiography and cardiac catheterisation and determining mitral valve area by pressure half time, Gorlin's formula and two-dimensional echocardiography so as to assess the relative accuracy of these methods before and after balloon mitral valvuloplasty in patients with rheumatic mitral stenosis. Left atrium-left ventricular, pulmonary artery wedge-left ventricular and echo gradients were simultaneously recorded in 18 patients undergoing balloon mitral valvuloplasty. Mitral valve area was estimated by pressure half time, Gorlin's equation and two-dimensional echocardiography. The correlation between left atrium-left ventricular and echo mean gradient before balloon mitral valvuloplasty was 0.96 (p < 0.03). Between pulmonary artery wedge-left ventricular and echo mean gradient, it was 0.95 (p < 0.04). The correlations between left atrium-left ventricular and pulmonary artery wedge-left ventricular mean gradient were also good. After balloon mitral valvuloplasty, similar good correlations were seen. On subgrouping the patients into those with high and low pulmonary artery pressure, good correlation persisted both before and after balloon mitral valvuloplasty. Mitral valve area by all the methods were similar before balloon mitral valvuloplasty. After balloon mitral valvuloplasty, mitral valve area by pressure half time was the least and by two-dimensional echocardiography, the maximum. All the three methods are equally accurate in estimating transmitral gradients and mitral valve area in mitral stenosis before balloon mitral valvuloplasty. Two-dimensional echocardiography is the best to estimate mitral valve area after balloon mitral valvuloplasty. Echocardiography can replace haemodynamic measurement of gradients and mitral valve area before and after balloon mitral valvuloplasty. But pressure half time is not recommended for measuring mitral valve area immediately after balloon mitral valvuloplasty where two-dimensional echocardiography mitral valve area is to be employed.

Estimated costs of acute adenolymphangitis to patients with chronic manifestations of bancroftian filariasis in India.

In India, lymphatic filariasis persists as a major cause of clinical morbidity and as an impediment to socio-economic development. The direct costs incurred for the treatment of adeno-lymphangitis (ADL) episodes and the consequent indirect costs due to loss of income were determined from selected agricultural labour-intensive rural endemic pockets in Tamil Nadu. Information on the occurrence of ADL, its frequency and duration were collected using semi-structured questionnaire from randomly selected patients afflicted with chronic manifestations of bancroftian filariasis. Direct (treatment) cost per year per patient was found to range from Rs. 30 to 101 among patients with different manifestations. Income foregone (indirect cost) annually by each patient, which is a function of frequency and duration of ADL ranged from Rs. 182 to 702. ADL episodes among filarial patients alone cost a minimum of Rs. 4515 million for the nation every year. Cost benefit analysis of filariasis control programme in India showed that the benefits in terms of savings on treatment and work lost due ADL alone exceeded the cost by 24%. The per capita cost of the National Filaria Control Programme was calculated to be Rs. 2.6 per annuam.

Factors influencing response to lymphonodovenous shunt in filarial lymphoedema.

BACKGROUND: Although several studies have been published on lymphonodovenous shunt, there are no objective data either on the outcome of lymphoedema or on various parameters likely to influence the results. METHODS: A trial of lymphonodovenous shunt was carried out in 75 patients with unilateral filarial lymphoedema. The primary aim of the trial was to identify a cohort of responders as against non-responders and to correlate the outcome with various factors such as age, gender, duration and preoperative grade of lymphoedema, number of preoperative attacks of adenolymphangitis, operative impression of the lymph node, effect of venous reflex and type of nodovenous anastomoses. Change in oedema volume was measured objectively by water displacement method using the normal limb as a control. RESULTS: There was no operative mortality. Predominant postoperative complications included wound haematoma (8.5%), wound infection (13.6%) and transient lymphorrhoea (13.6%). In the immediate postoperative period, a reduction of 25%-50% in the oedema volume was recorded in 46.7% of cases and of more than 50% in 17.3% cases. The difference in response with respect to the type of lymphonodovenous shunt was not statistically significant, although the end-to-side type of shunt showed marginally better results. The response was significantly higher in patients with preoperative oedema volume more than 2 L. There was a significant reduction in postoperative attacks of adenolymphangitis, irrespective of the reduction in oedema volume. Of the 75 patients, 22 showed regression of oedema volume to preoperative or higher levels in the postoperative phase. A majority (21/22) could be identified as non-responders within 3 months of surgery. CONCLUSION: The best results of lymphonodovenous shunt were seen in patients with large-volume lymphoedema. The results are better when combined with early excisional surgery. Other factors did not significantly affect the outcome. Non-responders could be identified within 3 months after surgery. Even in patients who did not respond well, a significant decrease in the frequency of adenolymphangitis attacks was observed. Higher initial oedema volume and history of higher frequency (25-50 per year) of adenolymphangitis attacks can be considered as indicators for good response to lymphonodovenous shunt.