Vitamin D deficiency: concern for rheumatoid arthritis and COVID-19?

Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.

Intestinal microbiota and vaccine efficacy in children from resource poor settings - potential impact for the usefulness of probiotics?

Developing countries continue to contribute significantly to the global burden of childhood mortality due to infectious diseases. Infections leading to diseases like diarrhoea, pneumonia and meningitis account for millions of deaths annually. Most of these diseases are preventable by vaccination and therefore global vaccination rates have risen substantially with clear benefits. But paradoxically, the vaccines have demonstrated lower immunogenicity in developing countries as compared to their industrialised counterparts. Malnutrition in resource poor settings along with repeated polymicrobial infections at early age are some of the reasons for the differences in vaccine efficacy in different settings. Recent studies indicate that the gastrointestinal microbiota possibly influences maturation of immune system as well as vaccine efficacy. In this review we discuss evidences from in vitro, animal and human studies showing that probiotics can positively modulate gut microbiota composition and exert immunomodulatory effects on the host. We also discuss how they should be evaluated for their ability to improve vaccine performance especially in low resource settings.

Trials of the killed oral cholera vaccine (Shanchol) in India and Bangladesh: Lessons learned and way forward.

Cholera has been endemic in India and Bangladesh for the greater part of recorded history, giving this region the reputation of being the 'homeland of cholera'. The causative organism Vibrio cholerae O1 has been responsible for large epidemics and pandemics. Bangladesh and India have conducted several sequential studies of Oral Cholera Vaccine (OCV) to ascertain its safety, efficacy, effectiveness, field feasibility and acceptance in high-risk urban populations. The objective of this article is to illustrate the experience of OCV use in these endemic settings, its major challenges, and how policymakers can grant vaccine licenses as well as implement its use in the national immunization programme. The relevant aspects of the OCV studies, such as boosting the effect of vaccine, single-dose versus double-dose trials and thermal stability of the vaccine during delivery have generated strong evidence for recommendation of vaccine use in these settings. Studies have shown that a single dose is effective for children of five years of age and older age groups. The locally manufactured vaccine in India is thermostable and can be delivered in field settings without use of cold chain. The vaccine delivery is feasible and the protective efficacy (PE) of this vaccine above five years of age against cholera was 53-65%. Administration of an OCV boosting regimen elicits an immune response similar to those who received a two-dose vaccine five years back. OCV can be used as a preemptive measure in endemic settings, in natural calamities and during political instability when there is total disruption as well as collapse of safe water supply, sanitation and hygiene (WASH) facilities and other control measures. Clear identification of areas and target population (who will gain benefit from the OCVs) is required to be developed in endemic settings.

Malaria control in India: A national perspective in a regional and global fight to eliminate malaria.

Since the declaration of the vision of malaria eradication in 2007, the overall burden of malaria has been reduced substantially in many countries in the endemic world. This progress has, however, recently slowed worldwide and even an increase of morbidity and mortality has been observed in some regions. That reality has led to reflection on the strategy for malaria elimination, noting that focusing only on low transmission sites has competed with the efforts in countries that still have foci with high malaria burdens. This opinion piece outlines the collaboration of the ICMR-National Institute of Malaria Research (ICMR-NIMR) and other partner Institutions in India with the WorldWide Antimalarial Resistance Network (WWARN), one part of a global effort to manage the spread of Plasmodium falciparum parasites associated with antimalarial resistance.

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.

Cholera prevention and control in Asian countries.

Cholera remains a major public health problem in many countries. Poor sanitation and inappropriate clean water supply, insufficient health literacy and community mobilization, absence of national plans and cross-border collaborations are major factors impeding optimal control of cholera in endemic countries. In March 2017, a group of experts from 10 Asian cholera-prone countries that belong to the Initiative against Diarrheal and Enteric Diseases in Africa and Asia (IDEA), together with representatives from the World Health Organization, the US National Institutes of Health, International Vaccine Institute, Agence de médecine préventive, NGOs (Save the Children) and UNICEF, met in Hanoi (Vietnam) to share progress in terms of prevention and control interventions on water, sanitation and hygiene (WASH), surveillance and oral cholera vaccine use. This paper reports on the country situation, gaps identified in terms of cholera prevention and control and strategic interventions to bridge these gaps.

Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

BACKGROUND: Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. METHODS: This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. RESULTS: Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. CONCLUSIONS: Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants.

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.

Epidemiology and prospects for prevention of rotavirus disease in India.

CONTEXT: With rotavirus vaccines now available globally, it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India, in order to weigh the urgency of introducing a vaccine to help control rotavirus disease. EVIDENCE ACQUISITION: We reviewed published studies on rotavirus infection and genotype distribution in India, as well as safety and immunogenicity studies of currently available vaccines. PubMed was searched for papers published after 1990, and several authors who are experts in the field recommended papers of known significance. RESULTS: Rotavirus accounts for close to 40% of hospitalizations for diarrhea in India, with more recent studies showing an increased proportion compared with older studies. There is substantial serotype diversity in India, although there is less intra-country variation than previously thought. Two genotypes, G1P[8] and G2P[4], account for roughly 50% of symptomatic infections in non-neonates. Currently licensed vaccines are safe, and although the efficacy appears lower in developing countries, given the extremely high incidence of diarrhea these could still be cost-effective interventions. CONCLUSIONS: The epidemiology and burden of rotavirus diarrhea is fairly well characterized in India. Introducing rotavirus vaccine into the UIP, along with adequate surveillance, should be an important part of efforts to reduce diarrhea mortality, the third leading cause of death among Indian children, and achieve the country's MDG goals.

Natural prevalence of antibody titers to glucosyltransferase of Streptococcus mutans in serum in high and low caries active children.

In this investigation, serum immunoglobulin G (IgG) and immunoglobulin A (IgA) titers, as well as total immunoglobulin concentration (IgG + IgA + IgM), were found to be raised with the increase in the number of dental caries. Only the total serum antibody titer in high dental caries (HDC) group was found to be significantly raised as compared to no dental carries (NDC) group. Although the IgG and IgA titers were raised in blood with the increased number of caries, the results were not statistically significant. However, we could not find any correlation between serum antibodies and dental caries except that there was an increased trend of serum antibodies to GTF with the increased number of carious lesions.

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 > or =100 WBCs/mm(3); 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.

Low-dose cidofovir in the treatment of symptomatic BK virus infection in patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective analysis of an algorithmic approach.

BK virus (BKV) reactivation occurs in 50% of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Standardized antiviral management of BKV infection has not been established. In order to develop a uniform guideline, a treatment algorithm for the management of symptomatic BKV replication was implemented for our allo-HSCT population. This is a retrospective analysis of patients treated according to the protocol between January 2008 and January 2009. Eighteen patients developed symptomatic BKV replication a median of 43 days after allo-HSCT. All patients had BK viruria and 12 patients had BK viremia in addition to viruria. Patients with isolated viruria were treated with intravenous (IV) low-dose cidofovir (0.5-1mg/kg IV weekly) until symptom resolution. In patients with BK viremia, therapy was continued until virological clearance was achieved in the blood. Four patients also received intravesical instillation of cidofovir per physician discretion. Thirteen of 18 (72%) patients with viruria and 8 of 12 (75%) patients with viremia responded to treatment. Three patients developed transient renal dysfunction. Low-dose cidofovir is safe and effective in allo-HSCT recipients. In absence of randomized prospective data, an institutional algorithmic protocol removes variance in practice pattern and derives data that may be used for research and improved patient care.

Natural prevalence of antibody titres to GTF of S. mutans in saliva in high and low caries active children.

The present study was conducted to find out the role of natural immunity against dental caries. Whole stimulated saliva of various caries from active children was collected. Antigen glucosyltransferase (GTF) was prepared from Streptococcus mutans serotype C and the antibody titre was estimated using ELISA. Salivary IgG, s-IgA and total immunoglobulins (IgG + s-IgA+ IgM) concentration were assayed. The result showed an increased level of salivary IgG concentration with the increased number of dental caries, which was not statistically significant. But there were significant decrease of s-IgA titre as well as total immunoglobulin concentration in saliva with the increased number of dental caries. This study showed that because of lack of local immunity the children are more prone to dental caries.

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

BACKGROUND & OBJECTIVE: 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 & CONCLUSION: 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.

Giant anal condylomatosis after allogeneic bone marrow transplantation: a rare complication of human papilloma virus infection.

Condyloma acuminata or genital warts are caused by human papilloma virus (HPV). Ongoing proliferation of HPV in patients with congenital or acquired immunodeficiency states leads to the development of rapidly progressive and sometimes locally invasive tumor with or without dysplasia. Aggressive treatment, diagnostic immuno-typing, and follow-up are necessary in patients with ongoing immunosuppression. We report a case of giant ano-genital condylomatosis due to HPV types 6 and 11 in a patient with chronic myeloid leukemia after allogeneic bone marrow transplantation. The tumor was successfully treated with surgical excision and local application of 5% imiquimod cream.