Intussusception after Rotavirus Vaccine Introduction in India.

BACKGROUND: A three-dose, oral rotavirus vaccine (Rotavac) was introduced in the universal immunization program in India in 2016. A prelicensure trial involving 6799 infants was not large enough to detect a small increased risk of intussusception. Postmarketing surveillance data would be useful in assessing whether the risk of intussusception would be similar to the risk seen with different rotavirus vaccines used in other countries. METHODS: We conducted a multicenter, hospital-based, active surveillance study at 27 hospitals in India. Infants meeting the Brighton level 1 criteria of radiologic or surgical confirmation of intussusception were enrolled, and rotavirus vaccination was ascertained by means of vaccination records. The relative incidence (incidence during the risk window vs. all other times) of intussusception among infants 28 to 365 days of age within risk windows of 1 to 7 days, 8 to 21 days, and 1 to 21 days after vaccination was evaluated by means of a self-controlled case-series analysis. For a subgroup of patients, a matched case-control analysis was performed, with matching for age, sex, and location. RESULTS: From April 2016 through June 2019, a total of 970 infants with intussusception were enrolled, and 589 infants who were 28 to 365 days of age were included in the self-controlled case-series analysis. The relative incidence of intussusception after the first dose was 0.83 (95% confidence interval [CI], 0.00 to 3.00) in the 1-to-7-day risk window and 0.35 (95% CI, 0.00 to 1.09) in the 8-to-21-day risk window. Similar results were observed after the second dose (relative incidence, 0.86 [95% CI, 0.20 to 2.15] and 1.23 [95% CI, 0.60 to 2.10] in the respective risk windows) and after the third dose (relative incidence, 1.65 [95% CI, 0.82 to 2.64] and 1.08 [95% CI, 0.69 to 1.73], respectively). No increase in intussusception risk was found in the case-control analysis. CONCLUSIONS: The rotavirus vaccine produced in India that we evaluated was not associated with intussusception in Indian infants. (Funded by the Bill and Melinda Gates Foundation and others.).

Should the chickenpox vaccine be included in the National Immunization Schedule in India?

Varicella (chickenpox) is an acute, highly contagious viral disease with worldwide distribution. The highest prevalence occurs in the 4-10 year age group but tends to be more severe in adults. It may be fatal in neonates, immunocompromised persons, and normal adults, especially smokers. Varicella is usually a benign childhood disease, and rarely rated as an important public health problem, but this can be severe and even fatal in otherwise healthy children (< 1 out of every 10,000 cases). Chickenpox can cause pneumonia (23 out of every 10,000 cases), and is an important risk factor for developing severe invasive "strep" (group A streptococcal disease). Complications of varicella include bacterial infections (up to 5% of cases), decreased platelets, arthritis, hepatitis, pneumonia (more commonly in adults) or encephalitis (1 in 10,000 cases), which may cause a failure of muscular coordination, sometimes resulting in persistent sequelae or death. Varicella is the leading cause of vaccine-preventable death in children. Universal vaccination can cause a dramatic reduction in the incidence of varicella, associated complications, hospitalizations and fatality rates. In India, due to the high cost of the vaccine, it would be difficult to vaccinate a large percentage of the children. The government of India should consider the inclusion of varicella vaccine in the National Immunization Schedule with the help of International agencies.

New generation typhoid vaccines: an effective preventive strategy to control typhoid fever in developing countries.

Typhoid fever is a serious systemic infection, caused by the enteric pathogen Salmonella enterica serovar Typhi, a highly virulent and invasive enteric bacterium. This disease occurs in all parts of world where water supplies and sanitation are substandard. These pathogens then travel to food, drinks and water through house-flies and other vectors. Globally, an estimated 12-33 million cases of enteric fever occur with 216,00-600,000 deaths per year, almost exclusively in the developing countries. Health surveys conducted by the Health Ministry of India in the community development areas indicated a morbidity rate varying from 102-2219/100,000 population in different parts of the country. A limited study in an urban slum showed 1% of children up to 17 years of age suffer from typhoid fever annually. The continued high burden of typhoid fever and the alarming spread of antibiotic resistant strains led the World Health Organization (WHO), almost ten years ago, to recommend immunization using the two new-generation vaccines in school- aged children in areas where typhoid fever posed a significant problem and where antibiotic resistant strains were prevalent. Morbidity and mortality due to high incidence of typhoid fever favors the introduction of typhoid vaccine in routine immunization in India. This vaccine should be given at the age of 2 years with Vi antigen vaccine and at least one more dose be given at 5 years of age.

Haemophilus influenzae type b (Hib) vaccine: an effective control strategy in India.

Haemophilus influenzae type b (Hib) is an encapsulated, non-motile and non-spore-forming Gram-negative coccobacillus which causes severe pneumonia, meningitis and other life threatening illnesses. Hib disease affects almost exclusively (95%) children aged less than 5 years throughout the world. The mean age of onset is 6-24 months after which it declines gradually until age 5 years. The World Health Organization (WHO) estimates that Hib is responsible for 3 million cases of serious illnesses and approximately 386,000 deaths worldwide each year in children aged under 5 years. In the latest position paper on Hib vaccine, WHO recommended the inclusion of Hib conjugate vaccines in all routine infant immunization programs without waiting for local disease-burden data. The WHO and the Global Alliance for Vaccine Immunization (GAVI) have been working to expand supplies of Hib vaccine, reduce vaccine cost, and assist especially low-income countries with vaccine introduction. Hib vaccine is safe, highly effective and readily available in the market. Hib vaccine has been shown to be > 95% efficacious in diverse populations around the world. Globally, hundreds of millions of doses of Hib vaccine have been administered in the last 2 decades. More than 160 countries are using Hib vaccine in national immunization programmes and around 25 countries planning to introduce. Hib vaccination fits into the India's national immunization schedule.

Hepatitis B Vaccine in national immunization schedule: a preventive step in India.

Hepatitis B is a disease of the liver caused by Hepatitis B virus (HBV) infection. HBV is transmitted through contact with infected blood or body fluids, unprotected sexual intercourse and the perinatal route but not through casual contact. About two billion people worldwide have been infected with the virus, an estimated 360 million live with chronic infection, and at least 600,000 people die annually from acute or chronic consequences of Hepatitis B, such that Hepatitis B is a major public health problem worldwide. HBV is 50 to 100 times more infectious than HIV. It has been estimated that, of the 25 million infants born every year in India, over one million run the lifetime risk of developing chronic HBV infection. Every year over 100,000 Indians die due to illnesses related to HBV infection. Following the launch of the Global Alliance for Vaccines and Immunization (GAVI) to intensify National Immunization Programs (NIPs) in developing countries worldwide. World Health Organization (WHO) recommends that Hepatitis B vaccine should be given to all infants. Several cost-effectiveness analyses of inclusion of Hepatitis B vaccine in India's NIP have been performed. These indicate that universal childhood Hepatitis B immunization in India will be highly cost-effective. The Government of India is also supporting planned state programs for introducing new vaccines as part of routine immunization. The current immunization schedule for hepatitis B vaccine includes a dose given as early as possible after birth, preferably within 24 hours for all institutional deliveries because the birth dose of Hepatitis B vaccine is effective in preventing perinatal transmission of Hepatitis B. Irrespective of the birth dose, 3 doses are to be given at 6, 10, 14 weeks at the same time as DPT and OPV.

Introduction of a second dose of measles in national immunization program in India: a major step towards eradication.

Measles is a highly infectious, acute respiratory illness that is caused by a virus of the genus Morbillivirus. The disease infects nearly 30 million children each year, and deaths usually occur from complications related to pneumonia, diarrhea and malnutrition. A systematic review of published Indian literature depicts the median case fatality ratio (CFR) of measles to be 1.6%. Through immunization, measles deaths dropped a remarkable 78% from 733,000 in 2000 to 164,000 in 2008. As of 2008, 192 of 193 Member States of WHO use 2 doses of measles vaccine in their national immunization programs, India being the only exception. The Millennium Development Goal (MDG) 4 aims to reduce by two-thirds between 1990 and 2015 the under-five mortality rate (U5MR) in the world. Per the draft comprehensive Multi Year Strategic Plan (cMYP, 2010­17) for immunization of India, the country aims to reduce measles-related mortality by 90% by 2013 when compared to 2000. As recommended by the National Technical Advisory Group on Immunization (NTAGI), the implementation strategy of the second dose of measles vaccine at the state level is determined by the underlying performance of the routine immunization program. The second dose in the national immunization schedule gives extra immunity against measles infection that renders children more susceptible to secondary pneumonia and diarrheal diseases, which are the primary causes of under-5 child mortality in India.

Nutritional Assessment and its Association with Rotavirus Positivity Among Under Five Children Admitted with Diarrhea in a Tertiary Care Hospital of Southern Haryana, India.

OBJECTIVE: To estimate the burden of undernutrition and its association with rotavirus positivity among under-five children admitted with diarrhea. METHODS: This prospective observational study was carried out in hospital-setting from February 2016 to January 2020. For all cases who met the eligibility criteria, an informed written consent was obtained from parents/caregivers. A case report form was used to collect sociodemographic, anthropometric and clinical data. The anthropometric measurements of children were performed according to World Health Organization (WHO) guidelines. RESULTS: Nutritional assessment revealed that 74.1% study subjects were underweight [Weight-for-Age (WAZ) < -2], 59% were stunted [Height-for-Age (HAZ), < -2] and 52.3% were wasted Body Mass Index (BMIZ) < -2]. Stunting was found to be significantly higher among boys as compared to girls and rotavirus positive diarrhea was significantly less prevalent among stunted children. CONCLUSION: There exists a very high prevalence of underweight, stunting, and wasting among hospitalized children with diarrhea. As the better nutrition has not been shown to guard against rotavirus diarrhea, coverage scale-up of rotavirus vaccination, improved hygiene and sanitation, and focussed nutrition programmes are the need of the hour in India.

Rotavirus Diarrhea and its Determinants Among Under-Five Children Admitted in a Tertiary Care Hospital of Southern Haryana, India.

OBJECTIVE: To estimate the prevalence of rotavirus diarrhea and its demographic, social, and clinical characteristics among children less than five years of age admitted in a rural tertiary care institute. METHODS: This prospective hospital-based observational study was carried out during February 2016 to June 2019. Diarrheal admissions of children aged 0-59 mo were screened and those who met the inclusion criteria were included in the study. Sociodemographic and clinical information was collected using a case report form. Stool samples were collected within 48 h of admission and transported in cold chain every month to the referral laboratory situated at Christian Medical College for testing. RESULTS: Among the children admitted with acute diarrhea, 148 (11.02%) were positive for rotavirus in the study. As per Vesikari scoring system, around three fourth (76.2%) of children were having severe or very severe diarrhea. Severity of diarrhea was more among rotavirus positive cases as assessed by the Vesikari scoring system. The rotavirus diarrhea showed a peak during November to February. CONCLUSION: Rotavirus diarrhea is an issue of public health importance, particularly due to its association with the severe diarrhea. As evidenced from similar settings in the world, rotavirus vaccine introduction and increased coverage is the most important strategy towards prevention and control of rotavirus diarrhea.

Epidemiology of Hospitalized Intussusception Cases from Northern States in India.

OBJECTIVE: To describe epidemiology of intussusception post-introduction of the rotavirus vaccine. METHODS: Hospital-based active surveillance system was set up in three tertiary care hospitals in Chandigarh and Haryana, India, to enroll children <2 y of age admitted with intussusception as per Brighton Collaboration Level-I criteria. The clinical characteristics, treatment modalities, seasonal trends, and outcome of the illness episodes were described. RESULTS: A total of 224 cases were reported. Majority were males (71%) and infants (69.5%). Number of intussusception was more in summer season. Location of intussusception was ileo-colic in 85% of the cases. Nearly 54% cases were treated conservatively and 46% needed surgical intervention. CONCLUSION: Surveillance data provided the epidemiological description of intussusception cases post-introduction of the rotavirus vaccine in northern India. This data could be used to assess the impact of vaccine and safety with a special focus on intussusception.

Active case finding of tuberculosis among household contacts of newly diagnosed tuberculosis patients: A community-based study from southern Haryana.

BACKGROUND: Active case-finding is provider-initiated and implies systematic searching for TB in individuals who would not spontaneously present to a health service, and bringing them into care for diagnosis and treatment. AIM: The present study was carried out with the objective to assess the yield and feasibility of active case finding strategy among household contacts of newly diagnosed pulmonary TB cases and to determine risk factors in household contact. METHODS: This community-based study with cross-sectional design was conducted among the household contacts of all newly diagnosed microbiologically confirmed pulmonary TB patients registered at Tuberculosis Unit (TU), Nuh. Investigator conducted house to house visit and met respective index case and his/her household contacts to build the rapport. RESULTS: In the present study, there were 55 sputum smear-positive index cases and 356 household contacts of index cases. The most common symptom among screening positive household contacts was cough followed by weight loss. A substantial proportion (83.8%) of symptom positive household contacts were investigated for tuberculosis and among them, 18.9% were found to be positive for tuberculosis. The overall prevalence of TB cases among household contacts was found to be 1.97%. CONCLUSION: The present study concludes that household contact screening for active case finding for TB is a feasible and efficient tool that can potentially result in earlier diagnosis and treatment of active TB, thus minimizing the severity and decreasing transmission. It can also contribute toward improving treatment outcomes, health sequelae, and the social and economic consequences of TB.

Association between the socioeconomic determinants and soil-transmitted helminthiasis among school-going children in a rural area of Haryana.

BACKGROUND: WHO indicates that India has the highest burden of soil-transmitted helminthiasis (STH) in the world, contributing to 25% of the total global cases, with 220 million children aged 1-14 estimated to be at risk. AIM AND OBJECTIVE: To study the association between the socioeconomic factors and STHs among primary school children in a rural area of Haryana. METHODOLOGY: The study was conducted among children aged 6-10 years studying in the rural government primary schools in the rural areas of Haryana. A total of 300 children were enrolled from government school. RESULTS: The study found that the prevalence of helminthiasis was 28.7% (86/300) and of these 14.0% children were infected with Ascaris lumbricoides and sex wise association with Helminthic infection was observed as statistically nonsignificant. One third of the (31.39%; 27/86) children were pallor and 5.81% subjects were having Bitot's spot while 13.95% children were having constitutional symptoms such as weakness, 6.97% subjects have fatigue, and 5.81% children have body ache. DISCUSSION: The morbidity can be reduced with appropriate inputs to improve the environmental factors. This may need investment for sanitary latrines, food hygiene, and safe drinking water, anti-helminthic drugs, and health education. CONCLUSION AND RECOMMENDATIONS: The results of the study concluded and recommended that proper implementation of national deworming day and other long-term strategies like sanitation, clean drinking water, adequate sanitation, and also improvement in nutritional status through various nutritional health programmes.

Undernutrition and associated factors among children 1-5 years of age in rural area of Haryana, India: A community based cross-sectional study.

BACKGROUND: Children under five years of age are most vulnerable to the vicious cycles of malnutrition, disease/infection and resultant disability all of which influence the present condition of a child at the microlevel and the future human resource development of the nation at the macrolevel. AIM: The present study was conducted to estimate the prevalence of undernutrition among under-five children; and to determine the associated factors. METHODS: All 112 Anganwadi Centres in block Lakhan Majra were enlisted and 30 Anganwadi Centres were selected by adopting systematic random sampling. From each selected Anganwadi Centre, 20 children of 15 years of age group were selected by simple random sampling, thus, a sample of 600 children was included in the study. RESULTS: Overall prevalence of undernutrition in our study was found as follows: wasted 18.4%; underweight 38.3%; stunted 41.3%. Mothers who had four or more ANC visits and IFA intake for 100 or more days had lower prevalence of wasting, stunting, and underweight than the mothers with three or less ANC visits and inadequate IFA intake. Children with a history of pre-lacteal feeding had higher prevalence of stunting, underweight, and wasting than the children with no history of pre-lacteal feeding. CONCLUSION: Every endeavor should be made to combat the outcomes of undernutrition through multipronged approach such as growth monitoring, nutritional supplementation, etc., Also, present study findings reinforce the importance of proper infant and child feeding practices and appropriate maternal care in prevention of childhood undernutrition.

Foraging theory and the propensity to be obese: an alternative to thrift.

The evolutionary origin of obesity is classically believed to be genetic or developmentally induced thrift, as an adaptation to ancestral feast and famine conditions. However, recently the thrift family of hypotheses have attracted serious criticism necessitating alternative thinking. Optimization of foraging behaviour is an important aspect of behavioural evolution. For a species evolved for optimizing nutritional benefits against predation or other foraging risks, reduction in foraging risk below a threshold dramatically increases the steady-state body weight. In modern life where feeding is detached from foraging, the behavioural regulation mechanisms are likely to fail resulting into escalation of adiposity. At a proximate level the signalling pathways for foraging optimization involve fear induced signal molecules in the brain including Cocaine and Amphetamine Regulated Transcript (CART) interacting with adiposity signals such as leptin. While leptin promotes the expression of the fear peptides, the fear peptides promote anorectic action of leptin. This interaction promotes foraging drive and risk tolerance when the stored energy is low and suppresses hunger and foraging drive when the perceived risk is high. The ecological model of foraging optimization and the molecular model of interaction of these peptides converge in the outcome that the steady state adiposity is an inverse square root function of foraging risk. The foraging optimization model is independent of thrift or insurance hypotheses, but not mutually exclusive. We review existing evidence and suggest testable predictions of the model. Understanding obesity simultaneously at proximate and ultimate levels is likely to suggest effective means to curb the obesity epidemic.

Inferring causal pathways among three or more variables from steady-state correlations in a homeostatic system.

Cross-sectional correlations between two variables have limited implications for causality. We examine here whether it is possible to make causal inferences from steady-state data in a homeostatic system with three or more inter-correlated variables. Every putative pathway between three variables makes a set of differential predictions that can be tested with steady state data. For example, among 3 variables, A, B and C, the coefficient of determination, [Formula: see text] is predicted by the product of [Formula: see text] and [Formula: see text] for some pathways, but not for others. Residuals from a regression line are independent of residuals from another regression for some pathways, but positively or negatively correlated for certain other pathways. Different pathways therefore have different prediction signatures, which can be used to accept or reject plausible pathways using appropriate null hypotheses. The type 2 error reduces with sample size but the nature of this relationship is different for different predictions. We apply these principles to test the classical pathway leading to a hyperinsulinemic normoglycemic insulin-resistant, or pre-diabetic, state using four different sets of epidemiological data. Currently, a set of indices called HOMA-IR and HOMA-ß are used to represent insulin resistance and glucose-stimulated insulin response by ß cells respectively. Our analysis shows that if we assume the HOMA indices to be faithful indicators, the classical pathway must in turn be rejected. In effect, among the populations sampled, the classical pathway and faithfulness of the HOMA indices cannot be simultaneously true. The principles and example shows that it is possible to infer causal pathways from cross sectional correlational data on three or more correlated variables.

HIV vaccine: Can it be developed in the 21st century?

HIV infection is a major public health problem especially in the developing countries. Once a person infects with HIV, it remained infected for lifelong. The advanced stage developed after 10-15 y of HIV infection that stage is called acquired immunodeficiency syndrome (AIDS). From 1990 to 2000 the number of people living with HIV rose from 8 million to 27 million; since the beginning of the HIV/AIDS epidemic, AIDS has claimed almost 39million lives so far. Till now, there is no cure for HIV infection; however, after the introduction of effective treatment with antiretroviral (ARV) drugs the HIV individual can enjoy healthy and productive lives. Vaccine is safe and cost-effective to prevent illness, impairment, disability and death. Like other vaccines, a preventive HIV vaccine could help save millions of lives. All vaccines work the same way i.e. the antigen stimulate the immune system and develop antibodies. The ultimate goal is to develop a safe and effective vaccine that protects people worldwide from getting infected with HIV. However, some school of thought that vaccine may protects only some HIV people, it could have a major impact on the rates of transmission of HIV and this will help in control of epidemic, especially in populations where high rate of HIV transmission. In the past, some scientist doubted on the development of an effective polio vaccine, but now we are near to eradicate the polio from the world this is possible because of successful vaccination programmes. HIV vaccine research is aided by the not-for-profit International AIDS/HIV vaccine Initiative (IAVI), which helps to support and coordinate vaccine research, development, policy and advocacy around the world. Although the challenges for scientist are intimidating but scientists remain hopeful that they can develop safe and effective HIV vaccines for patients in future.

Adult immunization in India: Importance and recommendations.

Vaccination is recommended throughout life to prevent infectious diseases and their sequelae. Vaccines are crucial to prevent mortality in that >25% of deaths are due to infections. Vaccines are recommended for adults on the basis of a range of factors. Substantial improvement and increases in adult vaccination are needed to reduce the health consequences of vaccine-preventable diseases among adults. Incomplete and inadequate immunization in India against these communicable diseases results in substantial and unnecessary costs both in terms of hospitalization and treatment. The government of India as well as the World Health Organization (WHO) consider childhood vaccination as the first priority, but there is not yet focus on adult immunization. Adult immunization in India is the most ignored part of heath care services. The Expert Group recommended that data on infectious diseases in India should be updated, refined, and reviewed periodically and published regularly. This group suggested that the consensus guidelines about adult immunization should be reviewed every 3 years to incorporate new strategies from any emerging research from India. There is an immediate need to address the problem of adult immunization in India. Although many issues revolving around efficacy, safety, and cost of introducing vaccines for adults at the national level are yet to be resolved, there is an urgent need to sensitize the health planners as well as health care providers regarding this pertinent issue.

Recommended vaccines for international travelers to India.

India's tourism industry generated 6.6% of the nation's Gross Domestic Product (GDP) during 2012. International travel to India is predicted to grow at an average annual rate of ∼ 8% over the next decade. The number of foreign tourists has increased by 9% to 5.8 million. Approximately 8% of travelers to developing countries require medical care during or after travel; the main diagnoses are vaccine-preventable diseases. Travelers to India can be exposed to various infectious diseases; water-borne, water-related, and zoonotic diseases may be imported to India where the disease is not endemic. The World Health Organization (WHO) emphasizes that all international travelers should be up to date with routine vaccinations. The recommended vaccinations for travelers to India vary according to the traveler's age, immunization history, existing medical conditions, duration, legal requirements for entry into countries being visited, travelers preferences, and values. Travelers should consult with a doctor so that there is sufficient time for completion of optimal vaccination schedules. No matter where traveling, one should be aware of potential exposure to certain organisms that can cause severely illnesses, even death. There is no doubt that vaccines have reduced or virtually eliminated many diseases that killed or severely disabled children and adults just a few generations ago. Thus, travelers must take recommended vaccines per schedule before traveling to India.

Adolescent vaccines: Need special focus in India.

WHO defines adolescence age between 10 to 19 years. In India, there are 243 million adolescents which constitute 21 per cent of the total population. The global burden of disease in adolescents (2011) reports that the total number of disability adjusted life years (DALYs) worldwide among adolescents were 230 million which constitutes 15.5% of total DALYs. The immunization is one of the most important, most beneficial and cost-effective disease prevention measures that can be provided for adolescents. The adolescent vaccination protects most of the world's adolescents from a number of infectious diseases that previously claimed millions of lives each year. In India, thousands of adolescents die and thousands are hospitalized every year due to communicable diseases that could have been prevented by vaccination. Main aims of adolescent vaccinations are: to boost immunity status that is waning after completion of primary immunization or absence of "natural" boosting due exposure to the particular disease. The recommendations for the immunization of adolescents are to improve vaccination coverage among them. The adolescent vaccinations also help in accelerate disease control or elimination effort. Improvement in adolescent immunization coverage in India, will require strengthening of health care delivery system and also require significant improvements in the health care functionaries ability and willingness to provide and deliver vaccines to adolescents.