Challenges in new vaccine introduction in a national program in India.

Vaccines have a long history dating back to the days of Edward Jenner (1749-1823) and Louis Pasteur (1822-1895). Vaccines can be viewed from a public health perspective as well as scientific perspective. Public health experts would focus epidemiological relevance, immunological competency, and technological feasibility. Scientists however will look for a good immune response as well as long-lived immunity, stability considerations, and safety issues such as danger of reversion to virulence. In India, the vaccine coverage is far from satisfactory, national average for full immunization being only 65%. Presently, nine vaccines are being used in the Universal Immunization Program. However, some more have started in pilot, and some are still in the pipeline. Although administrative, logistic and operational challenges have to be faced when introducing a new vaccine into the public health system; these are solvable and should not be a hindrance to the introduction. A real-life example of nonintroduction of a lifesaving vaccine is - the oral cholera vaccine. This vaccine which is manufactured and licensed in India has been the World Health Organization (WHO) prequalified, and it is being used worldwide. Although the disease is a major threat, the disease has its stigma and has led to its low reporting even from cholera endemic areas of the country. Thus, in spite of the WHO recommendations, the vaccine is not being introduced into the national program which would take it to people who need it the most only because of apparent lack of sufficient disease burden data and political commitment.

Community Participation in Two Vaccination Trials in Slums of Kolkata, India: A Multi-level Analysis.

This study aims at understanding the individual and community-level characteristics that influenced participation in two consecutive vaccine trials (typhoid and cholera) in urban slums of Kolkata, India. The study area was divided into 80 geographic clusters (communities), with 59,533 subjects aged ≥2 years for analysis. A multi-level model was employed in which the individuals were seen nested within the cluster. Rates of participation in both the trials were nearly the same; those who participated in the initial trial were likely to participate in the subsequent cholera vaccine trial. Communities with predominantly Hindu population, lower percentage of households with an educated household head, or lower percentage of households owning a motorbike had higher participation than their counterparts. At individual scale, higher participation was observed among younger subjects, females, and individuals from households with a household head who had no or minimal education. Geographic patterns were also observed in participation in the trials. The results illustrated that participation in the trial was mostly influenced by various individual and community-level factors, which need to be addressed for a successful vaccination campaign.

Treatment Cost for Typhoid Fever at Two Hospitals in Kolkata, India.

The purpose of this study was to estimate treatment cost for typhoid fever at two hospitals in Kolkata, India. This study was an incidence-based cost-of-illness analysis from the providers’ perspective. Microcosting approach was employed for calculating patient-specific data. Unit costs of medical services used in the calculation were directly measured from the study hospital by standard method. The study hospitals were selected based on accessibility to data and cooperation. Eighty-three Widal-positive and/or cultureconfirmed patients with typhoid fever during November 2003–April 2006 were included in the study. Most (93%) patients were children. Eighty-one percent was treated at the outpatient department. The average duration of hospitalization for child and adult patients was 8.4 and 4.2 days respectively. The average cost of treating children, adults, and all patients was US$ 16.72, 72.71, and 20.77 respectively (in 2004 prices). Recalculation based on 80% occupancy rate in inpatient wards (following the recommendation of the World Health Organization) found that the cost of treating children, adults, and all patients was US$ 14.53, 36.44, and 16.11 respectively.

Evaluating Investments in Typhoid Vaccines in Two Slums in Kolkata, India.

New-generation vaccines against typhoid fever have the potential to reduce the burden of disease in areas where the disease is endemic. The case for public expenditure on typhoid Vi polysaccharide vaccines for two low-income, high-incidence slums (Narkeldanga and Tiljala) in Kolkata, India, was examined. Three measures of the economic benefits of the vaccines were used: private and public cost-of-illness (COI) avoided; avoided COI plus mortality risk-reduction benefits; and willingness-to-pay (WTP) derived from stated preference (contingent valuation) studies conducted in Tiljala in 2004. Benefits and costs were examined from a social perspective. The study represents a unique opportunity to evaluate typhoid-vaccine programmes using a wealth of new site-specific epidemiological and economic data. Three typhoid-vaccination strategies (targeting only enrolled school children, targeting all children, and targeting adults and children) would most likely pass a social cost-benefit test, unless benefits are restricted to include only avoided COI. All three strategies would be considered ‘very cost-effective’ using the standard comparisons of cost per disability-adjusted life-year avoided with per-capita gross domestic product. However, at an average total cost per immunized person of ~US$ 1.1, a typhoid-vaccination programme would absorb a sixth of existing public-sector spending on health (on a per-capita basis) in India. Because there appears to be significant private economic demand for typhoid vaccines, the Government could design a financially-sustainable programme with user-fees. The results show that a programme where adults pay a higher fee to subsidize vaccines for children (who have higher incidence) would avoid more cases than a uniform user-fee and still achieve revenue-neutrality

Adults' perceived prevalence of enteric fever predicts laboratory-validated incidence of typhoid fever in children.

This study was undertaken to develop a model to predict the incidence of typhoid in children based on adults' perception of prevalence of enteric fever in the wider community. Typhoid cases among children, aged 5-15 years, from epidemic regions in five Asian countries were confirmed with a positive Salmonella Typhi culture of the blood sample. Estimates of the prevalence of enteric fever were obtained from random samples of adults in the same study sites. Regression models were used for establishing the prediction equation. The percentages of enteric fever reported by adults and cases of typhoid incidence per 100,000, detected through blood culture were 4.7 and 24.18 for Viet Nam, 3.8 and 29.20 for China, 26.3 and 180.33 for Indonesia, 66.0 and 454.15 for India, and 52.7 and 407.18 for Pakistan respectively. An established prediction equation was: incidence of typhoid (1/100,000= -2.6946 + 7.2296 x reported prevalence of enteric fever (%) (F=31.7, p<0.01; R2=0.992). Using adults' perception of prevalence of disease as the basis for estimating its incidence in children provides a cost-effective behavioural epidemiologic method to facilitate prevention and control of the disease.

A study on smoking habits among slum dwellers and the impact on health and economics.

To assess the impact on health from smoking with economic implications with major emphasis given to see whether passive smoking is an established outcome and if it is, how much additional burden of the disease is put on the smokers' families and consequently how much extra economic cost is put on such families, a study was conducted in a slum area of Howrah Municipal Corporation (HMC) on approximately 3000 families, which were randomly selected. Data was collected in relation to the socio-economic status, family members, housing with water and environmental sanitation, smoking habit, energy used for cooking, health awareness, follow-up of episodes of diseases of all ages, their remedial action taken and estimation of economic burden of the disease due to smoking (active and passive). There was a statistically significant difference in disease pattern between smokers' family and non-smokers' family especially with relation to chronic obstructive pulmonary disease, coronary heart disease, acute respiratory infections, common cold, hypertension and peptic ulcer (p<0.05). Also it was observed that with increasing years (1st, 2nd, 3rd years), the number of cases in each disease group gradually increased. This can be attributed to the effect of passive smoking especially when environmental conditions and socio-economic variants are same in both groups. Cost analysis of the illness episodes in the smokers' and non-smokers' families showed that there was a 3-fold difference in average annual expenditure between the families of the non-smokers and that of smokers and a 8-fold difference in work days lost. There was a 4-fold difference in annual expenditure on these diseases by the families. It is observed that when the total cost of smoking was included in the total expenditure, there was a 12-fold increase in annual expenditure between smokers' and non-smokers' families. The study conclusively proves that there are ill effects on health both from active and passive smoking. It is also demonstrated here that apart from economic implications due to direct smoking, the economic loss has been added to smokers' families due to passive smoking.

Occurrence, significance & molecular epidemiology of cholera outbreaks in West Bengal.

BACKGROUND & OBJECTIVE: Diarrhoeal disease outbreaks are causes of major public health emergencies in India. We carried out investigation of two cholera outbreaks, for identification, antimicrobial susceptibility testing, phage typing and molecular characterization of isolated Vibrio cholerae O1, and to suggest prevention and control measures. METHODS: A total of 22 rectal swabs and 20 stool samples were collected from the two outbreak sites. The V. cholerae isolates were serotyped and antimicrobial susceptibility determined. Pulsed- field gel electrophoresis (PFGE) was performed to identify the clonality of the V. cholerae strains which elucidated better understanding of the epidemiology of the cholera outbreaks. RESULTS: Both the outbreaks were caused by V. cholerae O1 (one was caused by serotype Ogawa and the other by serotype Inaba). Clinically the cases presented with profuse watery diarrhoea and dehydration. All the tested V. cholerae isolates were sensitive to tetracycline, gentamycin and azithromycin but resistance for ampicillin, co-trimoxazole, nalidixic acid, and furazolidone. PFGE pattern of the isolates from the two outbreaks revealed that they were clonal in origin. Stoppage of the source of water contamination and chlorination of drinking water resulted in terminating the two outbreaks. INTERPRETATION & CONCLUSION: The two diarrhoeal outbreaks were caused by V. cholerae O1 (Inaba/Ogawa). Such outbreaks are frequently seen in cholera endemic areas in many parts of the world. Vaccination is an attractive disease (cholera) prevention strategy although long-term measures like improvement of sanitation and personal hygiene, and provision of safe water supply are important, but require time and are expensive.

Phage typing, biotyping & antimicrobial resistance profile of Salmonella enterica serotype Typhi from Kolkata.

BACKGROUND & OBJECTIVE: Kolkata and its suburbs in eastern India are known to be endemic for typhoid fever. The objective of this study was to determine phage types, biotypes and antimicrobial resistance patterns of Salmonella enterica serotype Typhi isolated during the period 2003-2005 from a prospective surveillance for typhoid fever in two urban slums in Kolkata. METHODS: A total of 195 Salmonella enterica serotype Typhi isolated from blood cultures were phage typed, biotyped and tested for their antimicrobial susceptibility profile. RESULTS: Phage type E1 was the most common (60.3%) followed by phage type A among five phage types identified. Biotype I (95%) was predominant, 28 isolates were multidrug resistant (MDR) and most of the MDR strains belonged to phage type E1 and biotype I. INTERPRETATION & CONCLUSION: A single phage type and biotype were prevalent among the Salmonella enterica serotype Typhi isolates studied from Kolkata, India.

Acute diarrhoeal diseases--an approach to management.

Acute diarrhoeal diseases rank second amongst all infectious diseases as a killer in children below 5 years of age worldwide. Globally, 1.3 billion episodes occur annually, with an average of 2-3 episodes per child per year. The important aetiologic agents of diarrhoea and the guidelines for management are discussed. Management of acute diarrhoea is entirely based on clinical presentation of the cases. It includes assessment of the degree of dehydration clinically, rehydration therapy, feeding during diarrhoea, use of antibiotic(s) in selected cases, micronutrient supplementation and use of probiotics. Assessment of the degree of dehydration should be done following the WHO guidelines. Dehydration can be managed with oral rehydration salt (ORS) solution or intravenous fluids. Recently WHO has recommended a hypo-osmolar ORS solution for the treatment of all cases of acute diarrhoea including cholera. Feeding during and after diarrhoea (for at least 2-3 weeks) prevents malnutrition and growth retardation. Antibiotic therapy is not recommended for the treatmentof diarrhoea routinely. Only cases of severe cholera and bloody diarrhoea (presumably shigellosis) should be treated with a suitable antibiotic. Pilot studies in several countries have shown that zinc supplementation during diarrhoea reduces the severity and duration of the disease as well as antidiarrhoeal and antimicrobial use rate. Probiotics may offer a safe intervention in acute infectious diarrhoea to reduce the duration and severity of the illness.

Childhood visceral leishmaniasis.

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half of the VL cases occur in children (childhood or paediatric VL). The clinical manifestations of childhood VL are more or less same as in the adults. Prolonged fever with anorexia and loss of appetite are the major presenting features. Marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anaemia and changes in hair take place. Bacterial infection is a common coinfection and intestinal parasitic infestations are very common in children with VL. Liver function tests, blood, urine and stool may show abnormalities. Confirmation of diagnosis is made by demonstration of parasite by microscopic examination and culture of materials obtained by bone marrow aspiration or splenic puncture. Sodium antimony gluconate (stibogluconate) has been the drug of choice for over past 50 yr. Pentamidine isothionate, though effective is relatively toxic. Amphotericin B is the most effective drug for the treatment of VL. Miltefosine is the first-ever oral drug, is highly effective. Post kala-azar dermal leishmaniasis (PKDL) in children poses a therapeutic challenge. In the absence of an ideal vaccine for VL, control measures would essentially include prevention of transmission through vector control and community awareness.

Prevalence of thalassaemia trait in the state of West Bengal.

From three districts namely, Burdwan, Midnapur (undivided) and 24-Parganas North of the state of West Bengal, a total of 2045 blood samples were drawn to test for the presence or absence of thalassaemia trait. Out of the total samples, 621 samples were from general population, 807 from focus group (Muslims and ST/SC), 370 from antenatal mothers and 247 from relatives of cases. The blood samples were first subjected to screening test ie, red cell indices and the presence of trait was confirmed by gel-electrophoresis of the samples positive in screening test. Results showed that thalassaemia trait is prevalent in the population of the state in the magnitude of 11.25%. It is mostly prevalent in close relatives of cases (thalassaemia major) in the magnitude of 55.26%, followed by scheduled tribe (29.87%) and among the Muslim population it was predominantly more. General population has a prevalence of 3.6% (males) and 5.95% in antenatal mothers. High prevalence rate is associated with illiterates (19.23%) than literates (5.55%). Highest prevalence rate ie, 20.47% (overall prevalence) is associated with age group between 0-9 years. The findings of the study are considered to be very valuable as far as future action programme is considered to reduce the prevalence rate of thalassaemia trait in the community. The action programmes like intensive counselling and IEC maybe instituted to the groups, which show high prevalence rate rather than general population to make the programme not only cost-effective but cost-efficient as well.

Epidemiological, microbiological & electron microscopic study of a cholera outbreak in a Kolkata slum community.

BACKGROUND & OBJECTIVE: Epidemics of cholera caused by Vibrio cholerae O1 or O139 have been reported from different parts of India. Factors such as unsafe water supply, poor environmental sanitation, indiscriminate defaecation and lack of personal hygiene are mainly responsible for continued transmission of this disease. We report here epidemiological and microbiological findings of a localized outbreak of cholera, which occurred during March and April 2004 in the eastern part of Kolkata city. METHODS: The affected slum area has a population of 4409, predominantly muslims. Patients suffering from acute watery diarrhoea attended the health outposts organized by National Institute of Cholera and Enteric Diseases, Kolkata and International Vaccine Institute, South Korea as part of a routine surveillance programme at the locality as well as the emergency medical camp organized by the Kolkata Municipal Corporation. Stool and water samples were collected and tested for diarrhoeagenic pathogens in the laboratory. Bacteriophages specific for V. cholerae were isolates and studied electron microscopically for morphology. RESULTS: A total of 89 diarrhoea cases were reported giving an attack rate of 2 per cent. V. cholerae O1 biotype ElTor, serotype Ogawa was isolated as a sole pathogen from 15 (15.8%) of 89 stool samples screened. Water samples (2 from tube wells, 3 from municipal taps and 1 from well) showed presence of coliform bacilli with high MPN (Most Probable Number) count. Bacteriophages specific to V. cholerae were isolated from 2 of 6 water samples examined. A leakage was detected in the main pipeline supplying drinking water to that area. INTERPRETATION & CONCLUSION: The outbreak was caused by V. cholerae O1 (Ogawa) biotype ElTor. The presence of phages in the water samples was an additional indicator for V. cholerae contamination in this community. Occurrences of such outbreaks support vaccination against cholera as an alternative strategy.

Shigellosis : challenges & management issues.

Infectious diseases kill about 11 million children each year while acute diarrhoeal diseases account for 3.1 million deaths in children under 5 yr of age, of which 6,00,000 deaths annually are contributed by shigellosis alone. Shigellosis, also known as acute bacillary dysentery, is characterized by the passage of loose stools mixed with blood and mucus and accompanied by fever, abdominal cramps and tenesmus. It may be associated with a number of complications of which haemolytic uraemic syndrome is the most serious. Shigellosis is caused by Shigella spp. which can be subdivided into four serogroups namely S.sonnei, S.boydii, S.flexneri and S.dysenteriae. Organisms as low as 10-100 in number can cause the disease. Shigellosis can occur in sporadic, epidemic and pandemic forms. Epidemics have been reported from Central American countries, Bangladesh, Sri Lanka, Maldives, Nepal, Bhutan, Myanmar and from the Indian subcontinent, Vellore, eastern India and Andaman and Nicobar islands. Plasmid profile of shigellae in Kolkata has shown a correlation between presence of smaller plasmids and shigellae serotypes- indicating epidemiological changes of the species. Diagnosis of shigellosis is essentially clinical. Laboratory diagnosis includes stool culture and polymerase chain reaction (PCR). Treatment includes use of an effective antibiotic, rehydration therapy (if there is dehydration) and appropriate feeding during and after an episode of shigellosis. Hand-washing is the single most important strategy for prevention of transmission of shigellosis from person to person. A safe and effective vaccine should be developed against the more important circulating strains i.e., S. dysenteriae type 1 and S. flexneri 2a.

Factors associated with reported diarrhoea episodes and treatment-seeking in an urban slum of Kolkata, India.

In an urban slum in eastern Kolkata, India, reported diarrhoea rates, healthcare-use patterns, and factors associated with reported diarrhoea episodes were studied as a part of a diarrhoea-surveillance project. Data were collected through a structured interview during a census and healthcare-use survey of an urban slum population in Kolkata. Several variables were analyzed, including (a) individual demographics, such as age and educational level, (b) household characteristics, such as number of household members, religious affiliation of the household head, building material, expenditure, water supply and sanitation, and (c) behaviour, such as hand-washing after defecation and healthcare use. Of 57,099 study subjects, 428 (0.7%) reported a diarrhoea episode sometime during the four weeks preceding the interview. The strongest independent factors for reporting a history of diarrhoea were having another household member with diarrhoea (adjusted odds ratio [OR]=3.8; 95% confidence interval [CI] 3.3-4.4) and age less than 60 months (adjusted OR=3.7; 95% CI 3.0-4.7). The first choice of treatment by the 428 subjects was as follows: 151 (35%) had self- or parent-treatment, 150 (35%) consulted a private allopathic practitioner, 70 (16%) went directly to a pharmacy, 29 (7%) visited a hospital, 14 (3%) a homoeopathic practitioner, 2 (0.5%) an ayurvedic practitioner, and 12 (3%) other traditional healers. The choices varied significantly with the age of patients and their religion. The findings increase the understanding of the factors and healthcare-use patterns associated with diarrhoea episodes and may assist in developing public-health messages and infrastructure in Kolkata.

Gender differences in healthcare-seeking during common illnesses in a rural community of West Bengal, India.

This follow-up observational study examined gender disparities in seeking healthcare and in home management of diarrhoea, acute respiratory infections, and fever among 530 children (263 boys and 267 girls) aged less than five years in a rural community of West Bengal, India, from June 1998 to May 1999. Of 790 episodes detected by a weekly surveillance, 380 occurred among boys and 410 among girls. At the household level, girls were less likely to get home fluids and oral rehydration solutions (ORS) during diarrhoea. Qualified health professionals were consulted more often (p = 0.0094) and sooner for boys than for girls (8.3 +/- 4.5 hours vs 21.2 +/- 9.5 hours), for which parents also travelled longer distances (3.3 km for boys vs 1.6 km for girls). Expenditure per treated episode (Rs 76.76 +/- 69.23 in boys and Rs 44.73 +/- 67.60 in girls) differed significantly (p = 0.023). Results of logistic regression analysis showed that chance of spending more money was 4.2 [confidence interval (CI) 1.6-10.9] times higher for boys. The boys were 4.9 (CI 1.8-11.9) times more likely to be taken early for medical care and 2.6 (CI 1.2-6.5) times more likely to be seen by qualified allopathic doctors compared to girls. Persistence of gender disparities calls for effective interventions for correction.