Does the morbidity management and disability prevention (MMDP) clinic serve the filarial lymphedema (FLE) patients’ preeminent expectation?

@#Advocacy and training on “Home care” for filarial lymphoedma (FLE) patients are provided through morbidity management and disability prevention (MMDP) clinic commonly known as filariasis clinic and clinical improvement is assessed by follow-up visits. While the physicians aim at reducing the recurrent ADL (coined as ADLA in 1997) episodes, the patients expect reduction in LE volume. The objective of the present study was to know whether the MMDP clinic serves the primary expectation of the FLE patients. LE patients who attended the clinic for at least four follow-up consultations and had LE volume measurements at three points of time during the one year period of observation were considered for analysis. Clinical assessment was done for LE grading and LE volume was measured by water displacement volumetry. Sixty-three patients who fulfilled the follow up criteria were included. It was observed that the median LE volume was 914ml (IQR 269 – 1935) at first visit of the observation period which reduced to 645ml (IQR 2151666) and 752ml (IQR 215 – 1720) at first and second follow-up visits respectively. Over all, in short span of one year, 21 of the 63 patients (33.3%) who visited MMDP clinic at least four times in a year were benefitted through the MMDP advocacy and the National filariasis control programme need to emphasise on the importance of follow up visits to FLE patients.

Does the morbidity management and disability prevention (MMDP) clinic serve the filarial lymphedema (FLE) patients' preeminent expectation?

Advocacy and training on "Home care" for filarial lymphoedma (FLE) patients are provided through morbidity management and disability prevention (MMDP) clinic commonly known as filariasis clinic and clinical improvement is assessed by follow-up visits. While the physicians aim at reducing the recurrent ADL (coined as ADLA in 1997) episodes, the patients expect reduction in LE volume. The objective of the present study was to know whether the MMDP clinic serves the primary expectation of the FLE patients. LE patients who attended the clinic for at least four follow-up consultations and had LE volume measurements at three points of time during the one year period of observation were considered for analysis. Clinical assessment was done for LE grading and LE volume was measured by water displacement volumetry. Sixty-three patients who fulfilled the follow up criteria were included. It was observed that the median LE volume was 914ml (IQR 269 - 1935) at first visit of the observation period which reduced to 645ml (IQR 215- 1666) and 752ml (IQR 215 - 1720) at first and second follow-up visits respectively. Over all, in short span of one year, 21 of the 63 patients (33.3%) who visited MMDP clinic at least four times in a year were benefitted through the MMDP advocacy and the National filariasis control programme need to emphasise on the importance of follow up visits to FLE patients.

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653).

An investigation on the diversity of mosquitocidal bacteria and its relationship with incidence of vector borne diseases

Control of mosquitoes is the most important aspect of public health, as mosquitoes transmit many human diseases, including the fatal infection, Japanese encephalitis. This paper addresses the isolation of new mosquitocidal bacteria from soil samples in the Union Territory of Pondicherry, India, where, no clinical cases of vector borne infections have been reported. Bacterial isolates from soil samples were screened for potential mosquitocidal strains and bioassays against mosquito vectors (Culex quinquefasciatus, Anopheles stephensi and Aedes aegypti) were carried out. Genomic DNA of potential mosquitocidal isolates was amplified and species identification was carried out using BLASTn program (NCBI). Phylogenetic analysis of 16S rRNA sequences of mosquitocidal bacteria revealed seven potential isolates. SDS-PAGE results have shown that there was considerable difference in the protein profiles. Numerical analysis revealed 4 distinct groups at similarity level 25%. The relationship between VBDs and prevalence of soil mosquitocidal bacteria in the study sites has elicited considerable interest in the diversity of mosquitocidal bacteria and their application for mosquito borne diseases control.

Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT

Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier – NCT02005653)

Studies on rapid assessment methods in leprosy.

A study was undertaken in Pudukottai district, Tamilnadu, India to test rapid assessment methods: viz (i) sample surveys with lower coverages for clinical examination in estimating the disease problem in the community, (ii) utility of registered case prevalence for estimating the actual prevalence in a given area, (iii) leprosy in school-going children and its utility in estimating leprosy prevalence in the community, and (iv) information on disability and smear positivity in estimating leprosy prevalence; and develop correction factors for estimating leprosy situation. A sample of 23 clusters from 582 clusters of contiguous villages and hamlets was further divided into two random sub-samples for two surveys with differing coverages. One team covered nine clusters comprising 34 villages with a population of 17,562 and examined 15,596 with a population of 26,927 and examined 16,622 (62%) persons for leprosy. The results showed that: (i) leprosy sample surveys with lowered coverages would tend to miss valuable information, in terms of quality and quantity; (ii) from 'known case' registers, to estimate the true burden of leprosy disease and to monitor its trend over time is inadequate; (iii) school surveys are of limited value for estimating the disease burden in the community or to monitor its trend over time; (iv) the number of smear-positive cases is to small to serve as an indicator for the total case load in the community; and (v) the prevalence of active disease and that of grade 2 disability in the community are poorly correlated. Reliable methods other than those used here need to be developed for evaluation and monitoring of the disease burden particularly in the post-MDT era.

Comparative leprosy vaccine trial in south India.

This report provides results from a controlled, double blind, randomized, prophylactic leprosy vaccine trial conducted in South India. Four vaccines, viz BCG, BCG+ killed M. leprae, M.w and ICRC were studied in this trial in comparison with normal saline placebo. From about 3,00,000 people, 2,16,000 were found eligible for vaccination and among them, 1,71,400 volunteered to participate in the study. Intake for the study was completed in two and a half years from January 1991. There was no instance of serious toxicity or side effects subsequent to vaccination for which premature decoding was required. All the vaccine candidates were safe for human use. Decoding was done after the completion of the second resurvey in December 1998. Results for vaccine efficacy are based on examination of more than 70% of the original "vaccinated" cohort population, in both the first and the second resurveys. It was possible to assess the overall protective efficacy of the candidate vaccines against leprosy as such. Observed incidence rates were not sufficiently high to ascertain the protective efficacy of the candidate vaccines against progressive and serious forms of leprosy. BCG+ killed M. leprae provided 64% protection (CI 50.4-73.9), ICRC provided 65.5% protection (CI 48.0-77.0), M.w gave 25.7% protection (CI 1.9-43.8) and BCG gave 34.1% protection (CI 13.5-49.8). Protection observed with the ICRC vaccine and the combination vaccine (BCG+ killed M. leprae) meets the requirement of public health utility and these vaccines deserve further consideration for their ultimate applicability in leprosy prevention.

Regional lymphadenitis following antileprosy vaccine BCG with killed Mycobacterium leprae.

Phase-II and extended Phase-II studies were conducted in three different sets of the population in Thiruthani Taluk, Chengalpattu District, South India, involving BCG and killed Mycobacterium leprae (KML) combination vaccines to ascertain the acceptability of the vaccines. In the Phase-II study, 997 healthy volunteers were vaccinated on individual randomization with one of the vaccines arms: BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, BCG 0.1 mg + 5 x 10(6) KML, BCG, 0.1 mg or normal saline. Blood samples were taken and the serum was tested for antibody levels against phenolic glycolipid-I (PGL-I) and the 35-kDa protein of M. leprae. In this study, we observed regional suppurative adenitis in 6% (6 out of 100), 3% (3 out of 100), and 3% (3 out of 100) of the vaccinees in the BCG 0.1 mg + 6 x 10(8) KML, BCG 0.1 mg + 5 x 10(7) KML, and BCG 0.1 mg + 5 x 10(6) KML vaccine arms, respectively, in the 13-70 year age group. Earlier BCG scar status, skin-test reactions to lepromin-A, Rees' MLSA, and serum antibody levels against PGL-I and the 35-kDa protein did not help to identify the group at risk of developing suppurative adenitis. Suppurative adenitis appears to have a different relationship between the age of the subject and the dose of the vaccine. In order to overcome the problem of regional suppurative adenitis and to know the mechanism involved, an extended Phase-II study was conducted in similar groups of the population by reducing the BCG and KML doses, i.e., with BCG 0.05 mg + 6 x 10(8) KML, BCG 0.05 mg + 5 x 10(7) KML, and BCG 0.01 mg + 5 x 10(7) KML. Biopsy specimens were collected from lymph nodes of the suppurative adenitis cases and were subjected for culture and histopathological examination. The observations showed that regional suppurative adenitis could be reduced to 1% in the BCG 0.05 + 6 x 10(8) KML group, 0.5% in the BCG 0.05 + 5 x 10(7) KML group, and 0.5% in the BCG 0.01 + 5 x 10(7) KML group. This phenomenon of suppurative adenitis appears to be related to the total dose of mycobacterial antigens. Suppurative adenitis was seen by weeks 18 and 20 post-vaccination in the latter two lower doses; whereas it was seen by week 8 in the higher dose of the combination vaccines. No case of suppurative adenitis was observed in the BCG 0.1 mg group. Culture and histopathology ruled out the possibilities of progressive BCG infection and superadded infection. Considering the above results, BCG 0.05 mg + 6 x 10(8) KML was acceptable for a large-scale vaccine trial in South India.

Sensitization and reactogenicity of two doses of candidate antileprosy vaccine Mycobacterium w.

M.w vaccine is one of the antileprosy vaccines under test in an ongoing comparative vaccine trial in South India. The objective of the present study was to examine the sensitizing ability, as measured by skin test reactions to Rees' MLSA and lepromin, and reactogenicity of M.w vaccine in the local population. Two doses of M.w, 1 x 10(9) bacilli and 5 x 10(9) bacilli, were used, in two separate studies of 395 and 400 "healthy" individuals aged 1-65 years. In each study, the study subjects received either M.w vaccine or normal saline (control), by random allocation. The results showed that healing of vaccination lesions was uneventful although the healing process was somewhat prolonged with the higher dose. The mean size of lesions was 7.0 mm and 9.5 mm with the low and high doses of the vaccine, respectively. The results also showed that M.w vaccine in a dose of 1 x 10(9) bacilli, failed to induce post-vaccination sensitization as measured by reactions to Rees' MLSA and by Fernandez and Mitsuda reactions to lepromin-A. However, when the dose of the vaccine was increased to 5 x 10(9) bacilli the mean sizes of post-vaccination reactions to Rees' MLSA and lepromin-A (both early and late) were significantly larger in the vaccine group compared to that in the control group. The sensitizing effect attributable to the vaccine was of the order of 1.5 mm to 1.8 mm.

Sensitization potential and reactogenicity of BCG with and without various doses of killed Mycobacterium leprae.

A study was conducted in 997 individuals in two villages in south India to find the acceptability and sensitizing effect of the antileprosy combination vaccine of BCG plus killed Mycobacterium leprae (KML). Three preparations of the combination, BCG 0.1 mg + 6 x 10(8) KML (I), BCG 0.1 mg + 5 x 10(7) KML (II), and BCG 0.1 mg + 5 x 10(6) KML (III), along with BCG 0.1 mg (IV), and normal saline (V), were used in the study. Each individual received one of the above five preparations by random allocation. They were also tested with Rees' M. leprae soluble skin-test antigen (MLSA) and lepromin-A, both at intake and 12 weeks after vaccination. Reactions to Rees' MLSA were measured after 48 hr; those to lepromin-A after 48 hr and 3 weeks. The character and size of the local response at the vaccination site were recorded at 3, 8, 12, 15, and 27 weeks after vaccination. The mean sizes of postvaccination sensitization to both Rees' MLSA and lepromin-A in the vaccine groups were significantly larger than those in the normal saline group, clearly demonstrating the ability of the vaccines to induce sensitization as measured by responses to the two skin tests. The sensitizing effect was the highest following vaccination with vaccine I. It was not significantly different for vaccines II, III, and IV, although, generally, a dose-response effect was observed. The sensitizing effect attributable to the vaccine was more clearly seen in children than in adults. The above conclusions were the same irrespective of which results were considered, reactions to Rees' MLSA or Fernandez or Mitsuda reactions to lepromin-A. A significant finding of the study was that at intake the Mitsuda reactions provided a measure of sensitizing effect due to vaccine. The healing of vaccination lesions was uneventful. In more than 90% of vaccinated individuals, the lesions had healed by the 12th week in vaccine groups II, III, and IV, and by the 15th week in vaccine group I. The results showed that vaccination with BCG or combination vaccines was equally safe in individuals with or without previous BCG scars. Thirteen persons, aged 10 years or older, developed suppurative lymphadenitis around the 8th week (7 in vaccine group I, 3 each in vaccine groups II and III). However, healing was prompt after drainage in these individuals.