DHR-ICMR Guidelines for diagnosis & management of Rickettsial diseases in India.

Rickettsial diseases, caused by a variety of obligate intracellular, gram-negative bacteria from the genera Rickettsia, Orientia, Ehrlichia, Neorickettsia, Neoehrlichia, and Anaplasma, belonging to the Alphaproteobacteria, are considered some of the most covert emerging and re-emerging diseases and are being increasingly recognized. Among the major groups of rickettsioses, commonly reported diseases in India are scrub typhus, murine flea-borne typhus, Indian tick typhus and Q fever. Rickettsial infections are generally incapacitating and difficult to diagnose; untreated cases have case fatality rates as high as 30-45 per cent with multiple organ dysfunction, if not promptly diagnosed and appropriately treated. The vast variability and non-specific presentation of this infection have often made it difficult to diagnose clinically. Prompt antibiotic therapy shortens the course of the disease, lowers the risk of complications and in turn reduces morbidity and mortality due to rickettsial diseases. There is a distinct need for physicians and health care workers at all levels of care in India to be aware of the clinical features, available diagnostic tests and their interpretation, and the therapy of these infections. Therefore, a Task Force was constituted by the Indian Council of Medical Research (ICMR) to formulate guidelines for diagnosis and management of rickettsial diseases. These guidelines include presenting manifestations, case definition, laboratory criteria (specific and supportive investigations) and treatment.

An Outbreak of Cholera Associated with an Unprotected Well in Parbatia, Orissa, Eastern India.

In November 2003, an outbreak (41 cases; attack rate–4.3%; no deaths) of severe diarrhoea was reported from a village in Orissa, eastern India. Thirteen of these cases were hospitalized. A matched case-control study was conducted to identify the possible exposure variables. Since all wells were heavily chlorinated immediately after the outbreak, water samples were not tested. The cases were managed symptomatically. Descriptive epidemiology suggested clustering of cases around one public well. Vibrio cholerae El Tor O1, serotype Ogawa was isolated from four of six rectal swabs. The water from the public well was associated with the outbreak (matched odds ratio: 12; 95% confidence interval 1.2-44.1). On the basis of these conclusions, access to the well was barred immediately, and it was protected. This investigation highlighted the broader use of field epidemiology methods to implement public-health actions guided by epidemiologic data to control a cholera epidemic.

Risk factors associated with leptospirosis during an outbreak in Middle Andaman, India.

Background & objectives: Leptospirosis outbreaks occur frequently in North and South Andaman Islands but not in Middle Andaman. In 2002, an outbreak appeared in Middle Andaman for the first time. Although a study on risk factors was conducted in North Andaman, it used seropositivity to define leptospirosis. Since seropositivity might not indicate current leptospiral infection and as no study on risk factors was conducted in Middle Andaman, we carried out this study to identify the risk factors during the outbreak. Methods: A suspected outbreak of leptospirosis occurred in Rangat of Middle Andaman during October - November 2002. Suspected cases were screened for leptospirosis using microscopic agglutination test (MAT). Fifty two patients confirmed to have leptospirosis based on rising titres in MAT on paired sera, and 104 age, sex and neighbourhood seronegative matched controls, were included in the study. A conditional multiple regression by backward elimination process was carried out with acute leptospirosis as the dependent factor and various environmental, occupational and behavioural factors as independent factors. A stratified analysis was also carried out. Results: The presence of cattle in the house, drinking stream water, contact with garbage, walking barefoot and standing in water while working were identified as significant factors associated with leptospirosis. Stratified analysis showed a dose response relationship between number of cattle in the house and the risk of leptospiral infection suugesting that cattle could be a source of infection. Interpretation & conclusions: Identification of the potential risk factors would help understand the transmission dynamics of the disease and formulate public health interventions.

Prevalence and distribution of cardiovascular risk factors in an urban industrial population in south India: a cross-sectional study.

BACKGROUND: Cardiovascular diseases (CVD) are leading cause of death in developing countries including India. The huge burden of CVD in Indian subcontinent is the consequence of the large population and high prevalence of cardiovascular risk factors. This study was done to determine the prevalence of cardiovascular risk factors in two industrial units in Chennai, India. METHODS: Survey of behavioural risk factors using structured questionnaires and anthropometric measurements were done for the study population. Blood samples were collected for the fasting plasma glucose and serum cholesterol. Trend chi-square was employed to test the linear trend. RESULTS: The total study population included 2262 male subjects. Blood samples were collected for 2148 (95.0%) subjects. Age range was 18-69 years. Prevalence of major cardiovascular risk factors was: current smokers 462 (20.2%), body mass index > or = 23 kg/m2 1510 (66.8%), central obesity 1589 (70.2%), hypertension 615 (27.2%), diabetes mellitus 350(16.3%) and total cholesterol > or = 200mg/dl in 650(30.3%). CONCLUSIONS: The study results indicated high prevalence of behavioural risk factors, central obesity, hypertension and diabetes in a select group of middle and high-income young urban males. The long-term follow-up in such settings will provide an opportunity to understand the influence of risk factors on cardiovascular disease outcomes.

Lesional characteristics and histopathology in paucibacillary leprosy patients with 2 or 3 skin lesions: comparison between ROM and PB-MDT regimens.

Paucibacillary (PB) patients form a large segment of newly diagnosed leprosy patients and those who present with only two or three skin lesions could have problems with compliance. With prolonged anti-leprosy drug regimens that last over six months. ROM therapy, a one-dose regimen, offers an attractive alternative in treating such patients. We conducted a longitudinal study of 51 such PB patients, placing them in two groups at random: one receiving the standard PB-MDT regimen, and the other the ROM regimen. Patients were followed up for 2 years, with a comprehensive clinical examination done every six months. 14 patients, 7 in each group, also had their skin biopsies evaluated histopathologically at recruitment, at 6 months and at the end of 2 years. There was a consistent improvement of lesions in both the groups over time. The fall in granuloma fraction and the clearance of the initial bacterial index were seen in the histopathology of both groups. Although the PB-MDT regimen is an effective and robust one, the operational convenience and drug compliance with ROM could make it an acceptable, parallel regimen for PB patients when the disease is localized to 2 or 3 skin lesions.

Trends in case detection influenced by leprosy elimination campaigns in certain areas of China.

LECs were carried out from 1998 to 2000 in eight counties of west China. The number of cases detected during the year of LECs was much higher than that detected by routine methods before the year of the LEC. However, the annual number of cases detected during the year after the LEC showed different patterns. One pattern is that the number of new cases detected in the year after the LEC declined to the level similar to that before the year of the LEC. The second pattern is that the number of new cases detected in the year after the LEC declined steeply to less than that detected before the year of the LEC. Following peak case-detection during the year of the LEC, a gradual decrease in the number of new cases was observed in the subsequent years. The repeat LEC brought a weakly rebounding peak case-detection during the year following the first LEC carried out 3 years earlier. The operational, epidemiological and technical factors influencing the trends of case-detection during the LECs are discussed.

An institutional outbreak of leptospirosis in Chennai, South India.

The emergence of an outbreak of leptospirosis in a nurses' hostel in Chennai presented a challenge to identify and control the source of the outbreak. Sixty-nine residents and staff members were interviewed to assess exposure factors. Blood samples from the acute and convalescent patients were tested with the Microscopic Agglutination Test using the serovars prevalent in Chennai. Polymerase Chain Reaction (PCR) was conducted on serum and water samples. Based on preliminary investigation, control measures with standard hygienic measures were instituted. The attack rate was 35%. The epidemic curve suggested continuous or intermittent exposure to infection over a five-week period. Twenty residents (three asymptomatic) developed laboratory confirmed Leptospira icterohemorrhagiae. Residents collected water from an underground storage tank that was filled twice weekly from a mobile water tanker with a bucket on a rope, and the tank was usually left open. PCR tests confirmed the presence of leptospires from this water. Other control measures included cleaning the large backyard with its many stray dogs and rats, chlorinating water supplies, boiling drinking water and health education. No further cases occurred twelve days after implementing control measures. Access to clean water, not only for drinking but also for bathing, brushing and washing is essential to prevent water-borne outbreaks.

Epidemiological profile of India: historical and contemporary perspectives.

Knowledge and understanding of the epidemiological profile is an essential pre-requisite to assess and address public health needs in the country and to enable efficient programme planning and management. The need for adequate and accurate health information and data to undertake such an exercise cannot be over-emphasized. The present effort is a modest attempt to critically analyse the epidemiological profile of India from the historical and contemporary perspective. In order to assess the successes achieved as well caution against the daunting challenges awaiting the country, parameters such as disease burden and health status indicators, are increasingly being used. Changes in the population age structure, improvements in the nation's economic status, altered life-styles of people and duality of disease burden testify to the demographic, development and health transition occurring in the country. Population stabilization, poverty alleviation, life-style modification, surveillance and control of communicable and non-communicable diseases constitute the major challenges demanding urgent attention in the future.

Prevalence of known diabetes in Chennai City.

AIM: To determine prevalence of known diabetes in those more than 20 years of age in Chennai city. METHODOLOGY: Urban population was selected for the survey. Assuming the prevalence of known diabetes as 5.0% in those aged > 20 years, the cluster sample size calculated to estimate it with 95% CI and +/- 10% precision, was 25800 individuals of all ages. This population obtained from 200 households in each of 30 randomly selected corporation divisions of the city, was surveyed by social workers by house to house enquiry. General information and health status of every member of the household were recorded on prescribed forms. This survey was conducted during January-July, 1998. RESULTS: Among 26,066 individuals of all ages 779 had known diabetes and 99.4% of them had type 2 diabetes. The prevalence of known diabetes was 2.9% for all ages and both sexes combined. Crude and age-standardized prevalence was 4.9% (95% CI 4.6-5.2) for those aged > 20 years. The standardized prevalence was 10.5% (95% CI 9.8 - 11.2) in those aged > or = 40 years. The prevalence was significantly high (P < 0.05) in females. CONCLUSION: The prevalence of known diabetes was low in total population but increased in those aged > 20 and further increased in those aged > or = 40 years. The causes for high prevalence in > or = 40 year age group needs to be explored in this population.

Lot quality assurance sampling (LQAS) for monitoring leprosy elimination in an endemic district in Tamilnadu.

This paper examines whether the health administration can use lot quality assurance sampling (LQAS) for identifying high prevalence areas for leprosy for initiating necessary corrective measures. The null hypothesis was that leprosy prevalence in the district was at or above ten per 10,000 and the alternative hypothesis was that it was at or below five per 10,000. A total of 25,500 individuals were to be examined with 17 as an acceptable maximum number of cases (critical value). Two-stage cluster sample design was adopted. The sample size need not be escalated as the estimated design effect was 1. During the first phase, the survey covered a population of 4,837 individuals out of whom 4,329 (89.5%) were examined. Thirty-five cases were detected and this number far exceeded the critical value. It was concluded that leprosy prevalence in the district should be regarded as having prevalence of more than ten per 10,000 and further examination of the population in the sample was discontinued. LQAS may be used as a tool by which one can identify high prevalence districts and target them for necessary strengthening of the programme. It may also be considered for certifying elimination achievement for a given area.

Modelling epidemiology of leprosy.

A simulation model for leprosy transmission and control has been developed with specific objectives. Several sensitivity experiments have been carried out by altering the various inputs based on empirical data combined with intelligent guessing. The outputs generated through these exercises were on the expected lines. While incremental exercises would improve the model, it can be used even at the existing stage as a tool for programme managers.

Quality control tests for vaccines in leprosy vaccine trial, Avadi.

All the vaccines supplied for the large scale comparative leprosy vaccine trial of ICRC bacilli, M.w, BCG plus killed M. leprae (candidate vaccines), BCG and normal saline (control arms) at CJIL Field Unit, Chennai were tested for quality control by the suppliers following the procedures laid down in the WHO protocol for killed M. leprae. Quality control for BCG was carried out at BCG vaccine laboratory as per protocol. Toxicity and sterility tests were done on all the vaccine batches/lots received. As part of the quality control, bacterial count, and protein estimation were also done. Studies showed that the bacterial content and protein concentration were comparable with the original preparations. Vaccines were free from micro-organisms, toxic materials and safe for human use. Thus the quality of all vaccine preparations was satisfactory.

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.

Tuberculin sensitivity and skin lesions in children after vaccination with two batches of BCG vaccine.

BCG is one of the vaccines used, as control arm, in an ongoing large scale comparative leprosy vaccine trial in South India. The objective of the present study was to examine, in the local population, the sensitizing ability, as measured by skin test reactions to tuberculin, and reactogenecity, in terms of skin lesions at the site of vaccination, for the two batches of BCG vaccine used in the above trial. The study was undertaken in 816 tuberculin-negative, previously not vaccinated school children, aged five to 14 years. Each child received one of the two batches of BCG vaccine or normal saline (control), by random allocation. At 12 weeks from vaccination, character and size of local response, at the vaccination site, were recorded. At the same time, the children were retested with tuberculin and post-vaccination reactions to the test were measured after 72 hours. At three years after vaccination all available children were re-examined for the presence and size of BCG scar at the site of vaccination. It was found that healing of vaccination lesions was uneventful, with both batches of BCG. The mean size of the lesion was similar for the two batches, the overall mean being 6.3 mm. The mean size of post-vaccination tuberculin sensitivity increased with age, and it was 14.5 mm and 15.6 mm. The sensitizing effect attributable to the vaccine was 11 mm and 12 mm, for the two batches of BCG respectively. This study showed that the two batches of BCG, in a dose of 0.1 mg, used in the ongoing leprosy vaccine trial were acceptable in terms of vaccination lesion and were highly satisfactory in terms of development of hypersensitivity.

Underutilization of the available services by the needy disabled leprosy patients in Government Leprosy Control Unit Puttoor, Chittoor district, Andhra Pradesh, South India.

This study was undertaken to find out the deformity profile, utilization of disability care services, factors associated with underutilization and the impact of educating leprosy patients with visible disabilities in self-care practices in the area covered by the LCU Chittoor. The disability prevalence rate in the area was 15 per 10,000 population. Training of the staff and teaching leprosy patients in self-care practices has shown a remarkable improvement in skin texture and ulcer situation of disabled leprosy patients.

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.

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.

Post-vaccination sensitization with ICRC vaccine.

ICRC vaccine is one of the candidate anti-leprosy vaccines under test in a large scale comparative vaccine in trial. The objectives of the present study was to study the sensitization potential, as measured by Rees' MLSA and lepromin, and reactogenicity of this vaccine preparation in the local population. The study included 368 'healthy' individuals aged 1-70 years. Each individual received either ICRC vaccine or normal saline (control) by random allocation. They were also tested with Rees' MLSA and lepromin-A, 12 weeks after vaccination. Reactions to Rees' MLSA were measured after 48 hours and those to lepromin-A after 48 hours and three weeks. Character and size of local response, at the vaccination site, were recorded at 3rd, 8th and 15th week after vaccination. The results of the study showed that healing of vaccination lesion was uneventful, the mean size of the lesion being 10.3 mm. The mean sizes of post-vaccination reactions, to Rees' MLSA and lepromin (both early and late reactions), were significantly higher in the vaccine group compared to that in the normal saline group; the sensitizing effect attributable to the vaccine was of the order of 3.5 mm, 1.7 mm and 2.2 mm respectively. In conclusion, the study has demonstrated that ICRC vaccine was 'safe' and produced significant sensitizing effect as measured by post-vaccination sensitization to Rees' MLSA and lepromin, in the local population.