Coding and non-coding polymorphisms in VDR gene and susceptibility to pulmonary tuberculosis in tribes, castes and Muslims of Central India.

Vitamin D receptor (VDR) plays an important role in activating immune response against various infectious agents. This study was aimed to investigate the association between VDR gene polymorphisms and different clinical forms of pulmonary tuberculosis (TB) in different population groups. Four common polymorphisms (TaqI, ApaI, BsmI and FokI) of VDR gene were studied in clinically diagnosed TB patients and healthy controls from Sahariya tribe (n=377), Bhil tribe (n=95), Chhattisgarh tribe (n=33), general population from North-Central (NC) (n=1021) and South-Eastern (SE) region (n=646) and Muslims (n=217). Genotyping was carried out using PCR-RFLP method and re-confirmed by direct sequencing. The haplotype analysis was performed on Haploview 4.1 and statistical analysis was done using SPSS 13.0 software. We found that bb genotype of BsmI polymorphism conferred significant risk to smear positive and multiple drug resistant (MDR) TB in tribes [OR (CI)=3.7 (1.5-9.2), p=0.002], SE population [OR (CI)=2.1 (1.4-3.3), p=0.0004] and Muslims [OR (CI)=6.7 (1.1-39), p=0.01]. The subjects with FF genotype of FokI polymorphism appeared less likely (p=0.004) to develop MDR TB in NC population, whereas, those with Ff [OR (CI)=2.5 (1.3-5.0), p=0.004] and ff [OR (CI)=3.4 (1.2-9.3), p=0.01] genotypes were at high risk of MDR and smear positive disease, respectively. Similarly, tt genotype of TaqI polymorphism was found associated with high risk of smear positive TB in NC [OR (CI)=3.6 (0.9-14.2), p=0.05] as well as in SE [OR (CI)=4.7 (1.8-12.3), p=0.00003] population. Interestingly, tt genotype appeared strongly associated [OR (CI)=8.9 (2.7-29), p=0.00001] with high bacillary load outcome. In conclusion, genetic polymorphisms in VDR gene, alone or in combination (haplotypes) are associated with different clinical outcomes in pulmonary TB.

Operational feasibility of lot quality assurance sampling (LQAS) as a tool in routine process monitoring of filariasis control programmes.

Lot quality assurance sampling (LQAS) with two-stage sampling plan was applied for rapid monitoring of coverage after every round of mass drug administration (MDA). A Primary Health Centre (PHC) consisting of 29 villages in Thiruvannamalai district, Tamil Nadu was selected as the study area. Two threshold levels of coverage were used: threshold A (maximum: 60%; minimum: 40%) and threshold B (maximum: 80%; minimum: 60%). Based on these thresholds, one sampling plan each for A and B was derived with the necessary sample size and the number of allowable defectives (i.e. defectives mean those who have not received the drug). Using data generated through simple random sampling (SRSI) of 1,750 individuals in the study area, LQAS was validated with the above two sampling plans for its diagnostic and field applicability. Simultaneously, a household survey (SRSH) was conducted for validation and cost-effectiveness analysis. Based on SRSH survey, the estimated coverage was 93.5% (CI: 91.7-95.3%). LQAS with threshold A revealed that by sampling a maximum of 14 individuals and by allowing four defectives, the coverage was >or=60% in >90% of villages at the first stage. Similarly, with threshold B by sampling a maximum of nine individuals and by allowing four defectives, the coverage was >or=80% in >90% of villages at the first stage. These analyses suggest that the sampling plan (14,4,52,25) of threshold A may be adopted in MDA to assess if a minimum coverage of 60% has been achieved. However, to achieve the goal of elimination, the sampling plan (9, 4, 42, 29) of threshold B can identify villages in which the coverage is <80% so that remedial measures can be taken. Cost-effectiveness analysis showed that both options of LQAS are more cost-effective than SRSH to detect a village with a given level of coverage. The cost per village was US dollars 76.18 under SRSH. The cost of LQAS was US dollars 65.81 and 55.63 per village for thresholds A and B respectively. The total financial cost of classifying a village correctly with the given threshold level of LQAS could be reduced by 14% and 26% of the cost of conventional SRSH method.

A campaign of "communication for behavioural impact" to improve mass drug administrations against lymphatic filariasis: structure, implementation and impact on people's knowledge and treatment coverage.

In the mass drug administrations (MDA) that form the principal strategy of the Global Programme to Eliminate Lymphatic Filariasis, treatment coverages of at least 65%-80% will be needed if the programme is to be successful. In the Indian state of Tamil Nadu, where treatment coverages were typically <65%, a comprehensive strategy of advocacy and communication, called the "communication for behavioural impact" (COMBI) campaign, has been developed and implemented, in an attempt to improve treatment coverage. This strategy combined advocacy, aimed at state-, district- and village-level administrations, with communication activities targeted at individual communities. The main aim was to alter the behaviour of many of those included in the rounds of MDA, so that they would be more likely to accept and consume the diethylcarbamazine tablets offered to them. The COMBI campaign had two variants, COMBI(+) and the more intensive COMBI(+ +), each of which has been implemented in six districts. Both the variants included the "personal selling" of treatment, via door-to-door visiting by a total of 113,500 filaria-prevention assistants. These assistants were able to visit 34%-49% of the households in each target community. In the COMBI(+ +) districts, up to 44% and 38% of households received information on lymphatic filariasis and its elimination via television commercials and posters, respectively. Overall, 78% of the villages in the COMBI(+ +) districts and 33% of those in the COMBI(+) districts were considered to have had good exposure to the communication campaign. At the end of this campaign about 30% more people (than pre-campaign) believed that lymphatic filariasis could be eliminated and many of those targeted considered lymphatic filariasis to be a dreadful disease, knew that a particular day had been designated "Filaria Day", and thought that the tablets offered in MDA should be consumed to prevent or eliminate the disease. Apparently as the result of the COMBI campaign, drug consumption increased, from 33% of those living in endemic communities, to 37% in the COMBI(+) districts and to 49% in the COMBI(+ +). Coverages as high as 65%-73% were recorded among those who had had the maximum exposure to the communication campaign. These results indicate that the COMBI campaign favourably changed the perception and behaviour of the people towards the elimination of lymphatic filariasis. The costs of the COMBI(+) and COMBI(+ +) strategies were only U.S.$0.002 and U.S.$0.009 per capita, respectively.

Diversity and divergence among the tribal populations of India.

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within-population heterozygosity (range: 0.54 - 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 - 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between-tribe differentiation is high and exceeds that for eight sub-Saharan African populations (4.8% vs. 3.7%). Telugu-speaking populations are less differentiated than non-Telugu speakers (F(ST): 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.

Genetic studies among seven endogamous populations of the Koshi Zone, Bihar (India).

The distribution of AB0 and Rhesus blood groups, PTC taste sensitivity and colour blindness was studied among seven endogamous populations (Tharu, Mushar, Santal, Dhobi, Julaha, Kulhaiya and Karan Kayastha) in the Koshi Zone of Bihar (India). The phenotype and allele frequencies of the four gene loci (AB0, RH, PTC and colour blindness) show considerable differences between these populations. The measurement of genetic distances revealed, that the lowest genetic distance is seen between Dhobi and Julaha, the highest between Mushar and Tharu. From the genetic distance analysis there is some evidence for a close genetic relationship among the population groups belonging to the same region, irrespective of their caste, religion, linguistic or any other affinities. It may be concluded that all these populations have arisen through a common ancestor and changed gene frequencies among them is due to evolutionary forces like mutation, selection, migration, temporal variation and genetic drift. However, these populations retain their separate entities by practising endogamy. Gene diversity analysis reveals that these populations are at an early stage of genetic differentiation.

The mosquito problem and type and costs of personal protection measures used in rural and urban communities in Pondicherry region, South India.

Personal protection measures have become an important tool against mosquito nuisance. The severity of mosquito nuisance and the type and costs of personal protection measures in the Pondicherry region in South India have been investigated, using a structured questionnaire. The number of respondents sampled was 300 in the urban area and 100 in rural areas. 87 and 63% of the urban and rural respondents, respectively, felt that mosquito nuisance was severe in their locality. 83% of the urban and 27% of the rural respondents are aware that mosquitoes transmit diseases and were able to name at least one mosquito-borne disease. All the neighbourhood shops in urban and a majority in rural areas stocked personal protection products. As many as 99.3 and 73% of the urban and rural respondents, respectively, were found to use personal-protection measures during some or all seasons of the year. Mosquito coils were the most widely used measure in both urban and rural areas, followed by vaporising mats in the former and electric fans in the latter areas. 48 and 40% in urban and rural areas, respectively, used personal-protection measures daily. In urban areas 46% used the measures in more than one room. Only a small proportion (3-14%) used bed nets. The average monthly expenditure on the measures was Rupees (Rs.) 62.17 (US$ 1.30) (range: Rs. 0.00-500.00) in urban areas and Rs. 8.03 (US$ 0.17) (range Rs. 0.00-45.00) in rural areas. Annual expenditure on personal protection measures in urban areas amounted to 0.63% of the per capita income. 73.7% of the respondents in urban areas expressed satisfaction with the protective effect of the measures used by them. However, 46.3% of the urban and 15% of the rural respondents felt that the personal-protection measures are harmful to health. Some of the perceived harmful effects are allergy, breathing problems, cough and head ache.

Integrated programme for control of geohelminths: a perspective.

Infestation by geohelminths is an important public health problem in developing countries like India. It is a major cause of morbidity in school-age children who have the highest burden of worm infestation. Some of the morbid conditions attributed to intestinal helminthiasis are malnutrition, growth retardation, anaemia, vitamin A deficiency and impaired intellectual performance. Chemotherapy targeted at school-age children has been recommended as a cost-effective and feasible control programme for the control of geohelminths. To optimize resources a geohelminth control programme can be integrated with other existing national health programmes. The availability of drugs such as diethyl carbamazine (DEC) and albendazole, which have anthelminthic and antifilarial properties, opens the possibility of integrating a geohelminth control programme with a filaria control programme. However, co-administration of DEC and albendazole raises several issues of frequency of administration, efficacy, compliance and cost-effectiveness. Thus, integrating a geohelminth control programme with the existing mid-day meal or anaemia prophylaxis programme would be a more appropriate and cost-effective strategy to control geohelminths, alleviate the morbidity caused by them and improve the overall health of the community.

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.

The economic burden of lymphatic filariasis in India.

Lymphatic filariasis affects 119 million people living in 73 countries, with India accounting for 40% of the global prevalence of infection. Despite its debilitating effects, lymphatic filariasis is given very low control priority. One of the reasons for this is paucity of information on the economic burden of the disease. Recent studies in rural areas of south India have shown that the treatment costs and loss of work time due to the disease are considerable. Based on the results of these studies, Kapa Ramaiah et al. here estimate the annual economic loss because of lymphatic filariasis for India and discuss the implications of their findings.

Development of rapid assessment procedures for the delimitation of lymphatic filariasis-endemic areas.

Lymphatic filariasis caused by Wuchereria bancrofti is a major public health problem in 73 tropical and subtropical countries including India. Delimitation of endemic areas is essential to plan control operations. The current method of night blood survey (NBS) for delimitation is cumbersome, time-consuming and expensive. Therefore, there is a need to develop assessment procedures which can rapidly delimit endemic areas. For this purpose we evaluated three procedures: direct interviewing of key informants using structured questionnaires, an indirect method of a self-administered questionnaires to key informants and physical examination by health workers for the presence of chronic filarial disease. Thirty rural communities in a filariasis-endemic region in Cuddalore district in Tamil Nadu State in southern India constituted the study population. The determination of filariasis endemicity in the village communities assessed by the above procedures was compared in terms of rapidity, specificity, sensitivity and cost with the microfilaria rate and disease rate obtained by night blood sample survey and clinical examination by physicians. Prevalence score, control preference score and weighted mean number of cases with filarial disease per village were calculated using the key informant questionnaire techniques. While the prevalence and control preference score showed low sensitivity and moderate specificity, weighted mean number of cases showed high sensitivity and moderate specificity in identifying endemic villages. The prevalence of disease as determined by the physical examination of a sample population by health workers was highly sensitive in identifying communities endemic for filariasis. The degree of association between the disease rates estimated by physician and trained health workers was significant (r = 0.56; P < 0.05). These observations suggest that the weighted mean number of cases per village obtained through key informant techniques may be considered at a primary level to crudely identify endemic areas, followed by physical examination by health workers for filariasis, since it is relatively cheap and rapid.

Treatment costs and loss of work time to individuals with chronic lymphatic filariasis in rural communities in south India.

This year-round case-control study investigated treatment costs and work time loss to people affected by chronic lymphatic filariasis in two rural communities in south India. About three-quarters of the patients sought treatment for filariasis at least once and 52% of them paid for treatment, incurring a mean annual expenditure of Rs. 72 (US $2.1; range Rs. 0-1360 (US $39.0)). Doctor's fees and medicines constituted 57% and 23% of treatment costs. The proportion of people seeking treatment was smaller and treatment costs constituted a higher proportion of household income in lower income groups. Most patients did not leave work, but spent only 4.36+/-3.41 h per day on economic activity compared to 5.25+/-3.52 h worked by controls; the mean difference of 0.89+/-4.20 h per day was highly significant (P<0.01). This loss of work time is perpetual, as chronic disease manifestations are mostly irreversible. An estimated 8% of potential male labour input is lost due to the disease. Regression analyses revealed that lymphatic filariasis has a significant effect on work time allotted to economic activity (P<0.05) but not on absenteeism from work (P>0.05). Female patients spent 0.31+/-1.42 h less on domestic activity compared to their matched controls (P<0.05). The results clearly show that the chronic form of lymphatic filariasis inflicts a considerable economic burden on affected individuals.

Functional impairment caused by lymphatic filariasis in rural areas of south India.

The functional impairment caused by lymphatic filariasis was assessed through qualitative and quantitative methods in rural areas of Tamil Nadu, South India. About 66% of the patients said that their occupational activities were hampered by the disease. They either work fewer hours or alter their activity. Some had completely given up their job. Domestic chores of most of the female patients were also impeded. Most of those affected try to avoid travel. The disability was worse in patients with acute disease. In view of the results of our and other similar studies, the disability-adjusted life years lost due to lymphatic filariasis must be revised and the public health importance of the disease reassessed. Considerable functional impairment coupled with recent information on economic burden and productivity loss caused by lymphatic filariasis necessitates paying more attention to the control of the disease.

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.

An occupational health programme for adults and children in the carpet weaving industry, Mirzapur, India: a case study in the informal sector.

The Indo-Dutch Environmental and Sanitary Engineering Project under Ganga action Plan in Kanpur and Mirzapur is being executed within the framework of Indo-Dutch bilateral development cooperation. The project aims to integrate technological, social and health related improvements. It is expected that the development approach and methodology can be replicated in other urban settlements in India. The project is being supplemented by a training and institutional strengthening programme, which will facilitate the transfer of new technologies and improvements in operation and maintenance of these new technologies. One of the project's goals is to improve living conditions in the targeted areas by installing drinking water and drainage systems. A socio-economic unit (SEU) in the project supports these technical interventions by encouraging the community to participate in project activities. The Occupational Health Programme in Mirzapur was conceived by the SEU to improve the health and living conditions of child and adult weavers. At the start of the programme, 200 weavers and 60 non-weaver workers from Mirzapur city, matched for age and socio-economic status, were interviewed and underwent a physical examination. The mean age of the weavers is 27 years, reflecting the relatively large percentage of child labour (13.5%). Illiteracy among them is 73%, whereas 14% have had only a primary education. 64.5% of the carpet weavers are Muslims and 35.6% are Hindus. 61% own a loom or work in a family owned loom shed. 95% of the weavers have a monthly income of less than 600 Rs. Complaints of a persistent cough and cough with expectoration, backache, the common cold and joint pains occurred more often in the weaver population than in the comparison group and have been identified as 'occupational hazards'. An intervention programme has been implemented based on the results of the occupational health survey. These interventions include awareness camps, installment of plexiglass tiles for light improvement in the loom sheds, training of community health volunteers and house-to-house health education. Another essential part of the programme is the provision of functional literacy classes for child and adult labourers in the carpet weaving industry. Occupational health as an entry point proved to be a successful approach in this segment of the informal sector, where child labour plays an important role.

Microlevel epidemiological variations in malaria & its implications on control strategy.

Microlevel epidemiological variations in designing malaria control strategies were studied. Quantitative and qualitative variations were observed between two physiographic zones and between four different ecotypes within the zones of the Koraput district. While the peak transmission occurred in rainy season in the 600 m plateau (Jeypore zone), the same was observed in cold season in 150 m plateau (Malkangiri zone). The age specific parasite prevalence indicated a high degree of transmission and high level of acquired immunity in top- and foot-hill villages of both zones as compared to plain and riverine villages. Transmission was perennial in top-hill and foot-hill villages while it was of short period (indicated by infant parasite rate) in others. Since the period and intensity of transmission vary, an uniform residual insecticidal spray schedule as followed at present is not necessary. Majority of fever patients in top-hill villages were positive for Plasmodium falciparum and therefore may be treated for malaria without slide collection and examination. Evaluations may be done by sample surveys. These steps can optimize the malaria control operation in the district.