Typhoid fever: Control & challenges in India

Enteric fever is a common but serious disease that affects mostly children and adolescents in the developing countries. Salmonella enterica serovar Typhi remains responsible for most of the disease episodes; however, S. Paratyphi A has also been reported as an emerging infectious agent of concern. The control measures for the disease must encompass early diagnosis, surveillance and vaccine to protect against the disease. Sanitation and hygiene play a major role in reducing the burden of enteric diseases as well. The current status of diagnostics, the surveillance practices in the recent past and the vaccine development efforts have been taken into account for suggesting effective prevention and control measures. However, the challenges in all these aspects persist and cause hindrance in the implementation of the available tools. Hence, an integrative approach and a comprehensive policy framework are required to be in place for the prevention, control and elimination of typhoid fevers.

Probiotic foods: Can their increasing use in India ameliorate the burden of chronic lifestyle disorders.

Probiotics are defined as live microorganisms which, when ingested in adequate amounts, confer health benefits on the host. Chronic diseases such as diabetes, non-alcoholic fatty liver disease, coronary artery disease, a variety of chronic inflammatory disorders with an immune basis, and some forms of cancer are increasing in incidence around the world and in India, and may be attributable in part to rapid changes in our lifestyle. There is considerable public interest in India in the consumption of probiotic foods. This brief review summarizes the background of the gut microbiota, the immunological reactions induced by these, the evidence linking the microbiota to health outcomes, and the evidence linking the use of probiotics for amelioration of chronic lifestyle diseases.

Tackling the malaria problem in the South-East Asia Region: Need for a change in policy.

Malaria is largely neglected in the South-East Asia Region (SEAR), although it has the highest number of people susceptible to the disease. Malaria in the SEAR exhibits special epidemiological characteristics such as “forest malaria” and malaria due to migration across international borders. The Greater Mekong Subregion (GMS) has been a focal-point for the emergence of drug resistant malaria. With the recent emergence of artemisinin resistance, coupled with the limited availability of insecticides, malaria control efforts in the SEAR face a steep challenge. Indirect man-made factors such as climate change, as well as direct man-made factors such as the circulation of counterfeit drugs have added to the problem. Increased monitoring, surveillance, pharmacovigilance as well as cross-border collaboration are required to address these problems. Regional networking and data-sharing will keep all stakeholders updated about the status of various malaria control programmes in the SEAR. Cutting-edge technologies such as GIS/GPS (geographical information system/global positioning system) systems and mobile phones can provide information in “real-time”. A holistic and sustained approach to malaria control by integrated vector management (IVM) is suggested, in which all the stakeholder countries work collaboratively as a consortium. This approach will address the malaria problem in a collective manner so that malaria control can be sustained over time.

ICMR-DBT Guidelines for Evaluation of Probiotics in Food.

There has been an increased influx of probiotic products in the Indian market during the last decade. However, there has been no systematic approach for evaluation of probiotics in food to ensure their safety and efficacy. An initiative was, therefore, taken by the Indian Council of Medical Research (ICMR) along with the Department of Biotechnology (DBT) to formulate guidelines for regulation of probiotic products in the country. These guidelines define a set of parameters required for a product/strain to be termed as ‘probiotic’. These include identification of the strain, in vitro screening for probiotic characteristics, animal studies to establish safety and in vivo animal and human studies to establish efficacy. The guidelines also include requirements for labeling of the probiotic products with strain specification, viable numbers at the end of shelf life, storage conditions, etc., which would be helpful to the consumers to safeguard their own interest.

Multi-center surveillance for pneumonia & meningitis among children (<2 yr) for Hib vaccine probe trial preparation in India.

Background & objectives: Severe clinical pneumonia and meningitis caused by Haemophilus influenzae type b in children less than 5 yr old is preventable by use of Hib vaccine. However, data on Hib burden in India are limited. To support an evidence-based decision for Hib vaccine introduction in India, a vaccine probe study was planned. This paper presents the results of the preparatory phase for such a study, which aimed to determine the feasibility of conducting a randomized vaccine probe study and to estimate the incidence of all causes of pneumonia and meningitis. The preparatory study included population-based, hospital-based and carriage surveillance. Methods: Children aged 18-24 months and were enrolled at PGIMER, Chandigarh, CMC, Vellore and NICED, Kolkata, from July 2005 to December 2006. At the time of enrollment, parents were informed about the signs and symptoms of pneumonia and meningitis, and were encouraged to take the child to study hospitals for treatment. Hospitalized children less than two years of age suspected of having pneumonia and/or meningitis were enrolled in study hospitals, whether or not they were from the cohort population. Patients were examined clinically and received chest radiograph for suspected cases of pneumonia or lumbar puncture for suspected cases of meningitis. Blood culture was done for both pneumonia and meningitis patients. Cerebrospinal fluid (CSF) was tested for biochemistry, culture, latex agglutination test and polymerase chain reaction. Nasopharyngeal swabs were collected from healthy children less than 2 yr of age at immunization clinics to estimate Hib carriage. Results: A cohort of 17,951 children were recruited for the population-based arm. The incidence of severe clinical pneumonia ranged from 2717 to 7890 per 100,000 child-years of observation; suspected meningitis ranged from 1971 to 2433 per 100,000 child-years of observation. In the hospital-based study 7/90 (7.8%), 29/98 (29.6%) and 38/181 (21.0%) of CSF samples with cell count ≥100 WBCs/mm3 were purulent at Chandigarh, Kolkata and Vellore respectively. Of these purulent CSF samples, Hib was detected in 2, 6 and 11 cases, respectively. The Hib nasopharyngeal carriage prevalence ranged from 6.0 - 7.6 per cent. Interpretation & conclusions: Incidence of severe clinical pneumonia is comparable with other studies from India but that of suspected meningitis is higher. Although rates of Hib meningitis cannot be calculated from a hospital-based study, there is evidence of Hib meningitis in these study settings. Hib carriage prevalence indicates that Hib is present and circulating in these study areas. There is a significant burden of pneumonia and meningitis among children in India. Continued strengthening of laboratory capacity and bacterial surveillance systems are necessary.

Epidemiology of group a streptococcal pharyngitis & impetigo: A cross-sectional & follow up study in a rural community of northern India.

Background & objectives: Group A streptococcus (GAS) causes a wide array of human diseases. Epidemiological picture of streptococcal infection in India is not complete. Hence, disease burden due to GAS in 5-15 yr old school children in northern India was studied and emm typing of GAS isolates was carried out to help in designing prevention strategies. Methods: A cross-sectional survey was carried out among 4249 school children (5-15 yr) from Raipur Rani Block of Panchkula district in Haryana during 2000-2002; 334 children were followed up fortnightly for one year. Standard clinical and microbiological procedures were used for collection of swabs from throat and skin and confirmation of GAS and its emm types. Results: Of the 4249 children studied, 658 (15.5%) had pharyngitis; 579 of them could be swabbed, of which 2.8 per cent had GAS. From 3591 children without pharyngitis, 3385 who could be swabbed, GAS was found in 1.3 per cent of them. Impetigo was rare (0.7%), but 7.1 per cent (2/28) children had GAS. In the followup study, 17.4 per cent (776/4447 child-contacts) had pharyngitis, 761 could be swabbed and 2.4 per cent had GAS; among those without pharyngitis, 2016 swabs could be taken and GAS was found in 1.3 per cent; whereas only 2.6 per cent (2/75) of skin sores had GAS. Three children had GAS pharyngitis twice during follow up. Fourteen different GAS emm types were found. emm 71, 77 and 81 constituted 69 per cent of the pharyngeal isolates. GAS pharyngitis and impetigo were more common in winters and summers respectively. Interpretation & conclusions: In north India, pharyngitis was more common than impetigo. Most prevalent emm types of GAS in this region differ from those included in M protein-based vaccines.

Preparedness for AIDS vaccine trials in India.

India bears a heavy disease burden of HIV/AIDS infected and affected people. A safe, effective and accessible preventive AIDS vaccine, used along with other preventive interventions, is urgently needed to stem the epidemic. This review highlights the extensive preparedness activities undertaken from 2002 by the International AIDS Vaccine Initiative (IAVI), its Indian government and non government partners with the Indian scientific, political, media and community stakeholders and the capacity building process, before the conduct of the first ever AIDS vaccine trials in India in early 2005. Issues addressed included mistrust of clinical research due to past history of some unethical trials, transparency, community involvement, stigma and discrimination, provision for care and treatment of participants, informed consent, gender considerations, approval process, and operational aspects. The strong political support along with preparedness activities led to the successful conduct of AIDS vaccine trials enrolling equitably healthy women and men from all sections of society. This has paved the way for future vaccine trials in the country.

Nipah/Hendra virus outbreak in Siliguri, West Bengal, India in 2001.

BACKGROUND & OBJECTIVE: The viral encephalitides caused by animal or human viruses are characterized by sudden outbreaks of neurological disease in both tropical and temperate regions. An outbreak of acute encephalitis occurred in Siliguri (West Bengal) town of India between January 31 and February 23, 2001. This outbreak was investigated by a team of scientists from four major institutions, and the findings are presented here. METHODS: Detailed information about the outbreak was collected with the help of local health authorities. Limited entomological investigations were also done. Samples collected from cases and contacts were sent for analysis. RESULTS: A total of 66 probable cases and 45 deaths were reported. Epidemiological linkages between cases point towards person-to-person transmission and incubation period of around 10 days. There was neither any concurrent illness in animals nor was there any exposure of cases to animals. Centres for Disease Control and Prevention, Atlanta, USA concluded on the basis of tests carried out on serum specimen from four cases and two contacts that the causative pathogen appears to be Nipah/ Hendra or closely related virus. INTERPRETATION & CONCLUSION: This outbreak highlights the importance and urgency of establishing a strong surveillance system supported by a network of state-of-the-art laboratories equipped to handle and diagnose new pathogens and including patient isolation techniques, use of personal protective equipment, barrier nursing and safe disposal of potentially infected material in the prevention and control measures for Nipah/Hendra virus infection.

Priorities in tuberculosis research in India.

India accounts for nearly 30% of all tuberculosis cases in the world today and more adults in India die from TB than from any other infectious disease. The problems of HIV and multidrug resistance will make tuberculosis epidemic in India much worse unless urgent action is taken. DOTS is being applied on individual basis in the country. Maintaining the momentum in order to achieve national coverage in a phased manner, while maintaining the quality of services will require constructive commitment from all sectors, both within and outside government. This much be accompanied by additional research inputs and critical data analysis. Operational research provides programme managers the data and tools they need to analyse continuously improve services they offer, hence this must be strengthened with an overall aim to improve diagnosis and treatment of TB patients by translating the results of research into policy and practice. At the same time one should aim to strengthening biomedical research which promises convenient diagnostic tests, new and cost effective drugs and safe an effective vaccines, shortening of treatment, improved treatment of latest infection and overcoming threat of MDR-TB. The challenge is how to achieve this formidable goal as well as gear up to efficiently handle the growing burden of HIV-TB infected patients. The key to success lies in making available to all what we already have, by strengthening operational aspects of programme and at the same time not focus on the research efforts being done in basic science. The solution lies in the link between basic science and public health.

Effect of vitamin A supplementation on childhood morbidity and mortality.

In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high.

A community-based rheumatic fever/rheumatic heart disease cohort: twelve-year experience.

BACKGROUND: A pilot rheumatic fever and rheumatic heart disease control porject was started in 1988 in blocks of district Ambala (Haryana) to test the feasibility of early detection, treatment and secondary prophylaxis for rheumatic fever/rheumatic heart disease cases. School teachers, students and health workers were trained to identify and refer suspected cases of rheumatic fever/rheumatic heart disease to the community health center where physicians examined the suspected cases and monthly secondary prophylaxis was provided to the confirmed cases. METHODS AND RESULTS: A survey of registered cases was done in 1999 to determine the compliance rate of secondary prophylaxis and to describe clinical and epidemiologic features of the registered cohort of rheumatic fever/rheumatic heart disease patients. A total of 257 patients had been registered till the end of 1999 with 1263 person-years of follow-up. Out of these registered patients, 132 were receiving secondary prophylaxis, 52 had died, 17 had migrated, 8 were lost to follow-up, 18 had stopped prophylaxis and 30 completed the prophylaxis course. The mean age at registration was 18 years. Half of the cases were in the 6-15 years age group at registration. Over half of the patients were registered with a history of rheumatic fever. Fever was the most common symptom (75.9%). Carditis was more common among cases with recurrent attacks of rheumatic fever than after a first attack. The mortality in rheumatic fever/rheumatic heart cases was 32.5/1000 person-years. The mean age at death was 24.4 years. Compliance with secondary prophylaxis was 92% during the past 12 years. CONCLUSIONS: A rheumatic fever/rheumatic heart disease control program can be sustained within the primary health care system and the case registry can be utilized not only for monitoring the program but also to gain insight into the epidemiology of the disease.

Human genome project: pharmacogenomics and drug development.

Now that all 30,000 or so genes that make up the human genome have been deciphered, pharmaceutical industries are emerging to capitalize the custom based drug treatment. Understanding human genetic variation promises to have a great impact on our ability to uncover the cause of individual variation in response to therapeutics. The study of association between genetics and drug response is called pharmacogenomics. The potential implication of genomics and pharmacogenomics in clinical research and clinical medicine is that disease could be treated according to the interindividual differences in drug disposition and effects, thereby enhancing the drug discovery and providing a stronger scientific basis of each patient's genetic constitution. Sequence information derived from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Detection of these human polymorphisms will fuel the discipline of pharmacogenomics by developing more personalized drug therapies. A greater understanding of the way in which individuals with a particular genotype respond to a drug allows manufacturers to identify population subgroups that will benefit most from a particular drug. The increasing emphasis on pharmacogenomics is likely to raise ethical and legal questions regarding, among other things, the design of research studies, the construction of clinical trials and the pricing of drugs.

Kinetics of humoral & cellular immune responses in experimental cysticercosis in pigs infected with Taenia solium.

Studies were undertaken to assess the kinetics of antibody responses, lymphocyte transformation to Taenia solium larval antigens (crude soluble extract antigen and antigen B), and T cell subpopulation in piglets following experimental infection. Cysticercosis was established in 1-2 month old piglets after feeding 5,00,000 T. solium eggs per pig. The anti-CD4 and anti-CD8 monoclonal antibodies against swine T cells were raised indigenously. It was observed that at 60 days post infection (PI) there was a significant increase (P < 0.01) in CD4+ T cells without any change in CD8+ T cells. Increased 3H-thymidine uptake was found in infected piglets at 45 days PI using both CSE and antigen B. Kinetics of antibody responses indicated significant increase (P < 0.01) at 15 days PI (with CSE antigen) and 30 days PI (with antigen B) by ELISA. This increase persisted till 90 days PI (the time up to which the animals were followed). It was also observed that the cellular mechanisms were triggered in late stage (60 days PI) as compared to humoral responses (15-30 days PI) and may persist longer as seen by both lymphocyte transformation and T cell subpopulation studies. The study suggests that in cysticercosis, both humoral and cellular mechanisms may play a role in the host defences.

Isolation of emetine resistant clones of Entamoeba histolytica by petri dish agar method.

Emetine resistant clones of Entamoeba histolytica strain HM1:IMSS were isolated by using petri dish agar method after mutation with ethyl-methanesulphonate. Two emetine resistant clones were obtained and both were resistant to emetine at a concentration of 24 micrograms/ml of emetine. The 50 per cent inhibitory concentration (IC50) for both emetine sensitive and resistant clones was 5 and 14 micrograms/ml respectively. The colony forming efficiency of E. histolytica strain HM1:IMSS varied from 44 to 54 per cent. This method is useful for isolating clones from different strains of the parasite for molecular and immunological studies.

A monoclonal antibody-based test system for detection of Entamoeba histolytica-specific coproantigen.

BACKGROUND: Diagnosis of amebiasis based on stool microscopy or demonstration of anti-amebic antibodies has limitations. A diagnostic system based on demonstration of the parasite product in clinical specimens holds promise. METHODS: Murine monoclonal antibodies were developed against an Entamoeba histolytica-specific coproantigen. A monoclonal antibody (MoAb) 3D10 was employed in a double-antibody sandwich microELISA system for the detection of amebic coproantigen in fecal specimens. The system was evaluated in three groups of subjects: 63 patients with intestinal amebae, 27 with non-amebic parasitosis, and 57 apparently healthy controls. RESULTS: The MoAb 3D10 belonged to IgG1 isotype and recognized three antigens, with mol. wt. 36, 25 and 17 kDa in the crude extract of E. histolytica (HM1-IMSS), and an amebic coproantigen with MW 36 kDa in the stool supernatant from patients with intestinal amebae. The coproantigen was detected in the stool eluates of 56 (89%) patients with intestinal amebae and in none of the stool eluates from other subjects, thereby giving this system a sensitivity of 89% and specificity of 100% for the detection of intestinal amebae. CONCLUSIONS: This monoclonal antibody recognizes as intact epitope on the E. histolytica-specific coproantigen. The validity of the MoAb-based microELISA system needs to be established.