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The pandemic declaration of Covid-19 disease by World Health Organization (WHO) and subsequent widespread morbidities and mortalities in almost all countries of the world led to the research and development to find out a vaccine against SARS-CoV2 virus. Normally any new vaccine development takes 10-15 y time but the search for vaccine against SARS-CoV2 is going on at a very fast pace resulting in almost breakthrough in vaccine development by several research institutions and vaccine manufacturers. In pandemic situation, however, the entire process of vaccine development including clinical trials gets shortened and may be fast tracked to 15-18 mo time. It is expected that there shall be simultaneous marketing of several vaccines by the beginning of 2021. There are more than 164 candidate vaccines which are in the process of development and among them 24 vaccines are in advanced stages of development. This review aims at highlighting the present stages of development of vaccines and discussing the challenges that may be faced with these novel vaccines.

Introduction: Meningococcal disease caused by Neisseria meningitidis has a high case fatality rate. Of 12 distinct serogroups, A, B, C, W-135 (W) and Y cause the majority of infections. The meningococcal disease burden and epidemiology in India are not reliably known. Hence, we performed a narrative review with a systematically conducted search to summarize information on meningococcal disease burden and epidemiology and vaccination recommendations for meningococcal disease in India., Methods: A search of Medline and Embase databases was undertaken to identify relevant publications published in the last 25 years., Results: Results from 32 original publications, 11 of which were case reports, suggest a significant burden of meningococcal disease and related complications. Meningococcal disease is increasingly reported among adolescents and adults, and large outbreaks have been reported in this population. Meningococcal disease in India is caused almost exclusively by serogroup A; serogroups B, C, W and Y have also been documented. Meningococcal disease burden data remain unreliable because of limited disease surveillance, insufficient laboratory capacity, misdiagnosis and prevalence of extensive antibiotic use in India. Lack of access to healthcare also increases under-reporting, thus bringing the reliability of the data into question. Conjugate meningococcal vaccines are being used for disease prevention by national governments and immunization programs globally. In India, meningococcal vaccination is recommended only for certain high-risk groups, during outbreaks and for international travelers such as Hajj pilgrims and students pursuing studies abroad., Conclusion: Meningococcal disease is prevalent in India but remains grossly underestimated and under-reported. Available literature largely presents outbreak data related to serogroup A disease; however, non-A serogroup disease cases have been reported. Reliable epidemiologic data are urgently needed to inform the true burden of endemic disease. Further research into the significance of meningococcal disease burden can be used to improve public health policy in India. Fig. 1 Plain language summary.

Objective: To compare the risk of hyponatremia between hypotonic and isotonic parenteral maintenance solutions (PMS) administered to children with very severe pneumonia, admitted in the general pediatric ward., Methods: A randomized controlled open label trial was conducted in the pediatrics department of a tertiary care medical college hospital including euvolemic children 2 mo to 5 y of age, fulfilling the WHO clinical definition of very severe pneumonia and requiring PMS. They were randomized to receive either isotonic PMS (0.9% saline in 5% dextrose and potassium chloride 20 meq/L) or hypotonic PMS (0.18% saline in 5% dextrose and potassium chloride 20 meq/L) at standard rates for next 24 h., Results: A total of 119 children were randomized (59: Isotonic; 60: Hypototonic PMS). Nine (15%) children in the isotonic PMS group and 29 (48%) in the hypotonic PMS group developed hyponatremia during the study period, (p <0.001) with a relative risk being 3.16 (95% CI 1.64 to 6.09). Mean serum sodium was significantly lower in the hypotonic group compared to the isotonic group (p < 0.001 each at 6, 12 and 24 h). The difference in mean change in serum sodium from baseline was also significant at 12 and 24 h (5.4 and 5.8 meq/L respectively; p < 0.001 each)., Conclusions: This study demonstrates the rationality of the use of isotonic PMS in children with respiratory infections, a condition regularly encountered by most pediatricians.

The Global Meningococcal Initiative (GMI) consists of an international group of scientists and clinicians, with expertise in meningococcal immunology, epidemiology, public health and vaccinology that aims to prevent meningococcal disease worldwide through education, research, cooperation and vaccination. In India, there is no national policy on routine meningococcal vaccination to control the disease. The GMI convened a meeting in India, with local medical leaders and public policy personnel, to gain insight into meningococcal disease burden and current surveillance and vaccination practices in the country. Neisseria meningitidis is the third most common cause of sporadic bacterial meningitis in children <5 years, with higher incidence in temperate northern versus tropical southern India. Incidence is not reliably known due to suboptimal surveillance and insufficient microbiological support for diagnosis. Since 2005, there have been a number of outbreaks, all attributable to serogroup A. Outbreak responses were ad hoc and included mandatory case reporting by hospitals in Delhi, temporary strengthening of laboratory diagnostics, chemoprophylaxis of close contacts/high-risk groups and limited reactive use of polysaccharide vaccine. Although a conjugate serogroup A vaccine (MenAfriVac™) is manufactured in India, it is not presently used in India. Epidemiological data on meningococcal disease in India are sparse. Meningococcal disease control efforts should focus on establishing systematic surveillance and educating physicians and officers of the Immunization Division of the Ministry of Health on the importance of N. meningitidis as a cause of morbidity and mortality. Conjugate vaccine should be used for outbreak control and the immunization of high-risk persons., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Background: In 2010, there was an increase in the severity of malaria admissions to Kalawati Saran Children's Hospital, New Delhi and this report describes the morbidity and mortality profile., Method: A retrospective chart review of patients admitted with parasitologically confirmed malaria between January and December 2010., Results: There were 156 cases: P. vivax 105 (67.3%), P. falciparum 39 (25%) and mixed infections 12 (7.7%). Thrombocytopenia (platelet count <150×10(9)/L) was present in 90 (85.7%) patients with P. vivax mono-infection. There were 91 (58.3%) patients with severe malaria: P. vivax mono-infection 46 (50.5%), P. falciparum mono-infection 35 (38.5%) and mixed 10 (11%). Severe anaemia and severe thrombocytopenia (platelet count <20×10(9)/L) were detected significantly more often in P. falciparum and P. vivax mono-infection, respectively. Complications including cerebral malaria, acute renal failure, shock, acute respiratory distress syndrome (ARDS) and multiple-organ dysfunction syndrome (MODS) were similar in both groups. The mortality rate of around 20% was similar in severe P. vivax and P. falciparum mono-infection. Risk of mortality in vivax malaria was highest in patients with ARDS followed by MODS and shock., Conclusion: Increased morbidity owing to P. vivax malaria was observed and risk of mortality was highest in patients with ARDS and MODS.

Tetanus remains endemic in India. A retrospective hospital-based study was conducted to review the profile of all children admitted with diagnosis of tetanus between January 2009 and December 2010. A total of 140 cases of tetanus were admitted; 45 cases of neonatal tetanus (NT) and 77 cases of post-neonatal tetanus (PNT) were studied. Age of presentation of NT was 9.4 ± 1.2 days. Home-delivered children accounted for 86.7% of cases, with 77.8% being attended by untrained birth attendants. Unimmunized mothers accounted for 93.4%. In PNT, otogenic route of infection and trauma were present in 58.4% and 23.3% of cases, respectively. The rate of hospital admission of tetanus remains high. Unlike previously published reports, otogenic route is the most common mode of PNT infection in this study. Improving immunization, increasing deliveries by skilled birth attendants and prompt treatment of suppurative otitis media are the main areas in which public health initiatives need to be focused.

Background: Serious bacterial infections are a major cause of death in early infancy in developing countries. Inexpensive and accessible interventions that can add to the effect of standard antibiotic treatment could reduce infant mortality. We measured the effect of zinc as an adjunct to antibiotics in infants with probable serious bacterial infection., Methods: In this randomised, double-blind, placebo-controlled trial, we enrolled infants aged 7-120 days with probable serious bacterial infection at three hospitals in New Delhi, India, between July 6, 2005, and Dec 3, 2008. With computer-generated sequences, we randomly assigned infants in permuted blocks of six, stratified by whether patients were underweight or had diarrhoea at enrolment, to receive either 10 mg of zinc or placebo orally every day in addition to standard antibiotic treatment. The primary outcome was treatment failure, which was defined as a need to change antibiotics within 7 days of randomisation, or a need for intensive care, or death at any time within 21 days. Participants and investigators were masked to treatment allocation. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00347386., Findings: 352 infants were randomly assigned to receive zinc and 348 to placebo. 332 given zinc and 323 given placebo could be assessed for treatment failure. Significantly fewer treatment failures occurred in the zinc group (34 [10%]) than in the placebo group (55 [17%]; relative risk reduction 40%, 95% CI 10-60, p=0·0113; absolute risk reduction 6·8%, 1·5-12·0, p=0·0111). Treatment of 15 (95% CI eight to 67) infants with zinc would prevent one treatment failure. Ten infants receiving zinc died compared with 17 given placebo (relative risk 0·57, 0·27-1·23, p=0·15)., Interpretation: Zinc could be given as adjunct treatment to reduce the risk of treatment failure in infants aged 7-120 days with probable serious bacterial infection., Funding: Department of Biotechnology, Government of India; the European Commission; the Meltzer Foundation; and the Research Council of Norway.

Delayed sexual maturation is a known complication of celiac disease (CD). There is paucity of data regarding the effect of gluten-free diet (GFD) on sexual maturity in patients with CD in India. We did a cross-sectional observational study to assess the sexual maturity in 30 adolescents with CD on GFD for at least 1 year, and evaluated factors which affect their sexual maturity. Sexual maturation was assessed using Tanner's stages of sexual development. All adolescents had completed 2 years of GFD and 53 % had completed 4 years of GFD. Sexual maturation was delayed in 30 %. Age at initiation of GFD was associated with attaining appropriate sexual maturity (p = 0.048). We conclude that delayed sexual maturation is not uncommon in adolescents with CD and may be corrected by early diagnosis and initiation of GFD.

Objective: To look for profile of severe malaria and contribution of vivax infection to malarial morbidity in North Indian children., Methods: Detailed clinical, biochemical and hematological characteristics of children hospitalized with severe malaria over last 3 y were recorded. Presence of malarial parasite on peripheral smear and/or positive antigen test was considered as diagnostic for malaria., Results: A total of 131(55.3%) patients with Plasmodium vivax (Pv), 79 (33.3%) with Plasmodium falciparum (Pf) and 27 (11.4%) with mixed infections were admitted. Cerebral malaria, severe anemia and shock were significantly more frequently observed in Pf group, while hepatic, renal, respiratory, and bleeding complications were more commonly seen in Pv patients. Malaria mortality was highest in mixed infection (11.1%), followed by Pf (7.6%) and Pv (3%) group., Conclusions: Severe and fatal vivax malaria is an emerging recognized entity and challenges the perception of Pv as a benign disease. Further clinical studies and molecular research is required to understand emergence of severe malaria in vivax mono-infection.

Congenital hyperinsulinism (CHI) is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. We report a case of CHI with diffuse pancreatic abnormality diagnosed preoperatively using the 68Ga octreotide (DOTA NOC) positron emission tomography scan. Genetic analysis revealed homozygous ABCC8 splicing mutation. Subtotal (95%) pancreatectomy was done, and the infant remained euglycemic and was discharged on breast feeds. The patient is continuously followed up and is asymptomatic until 9 months.

Objectives: To determine the population at risk, risk factors, and outcome of occupational exposure to blood and body fluids in health care providers., Materials and Methods: Retrospective review of two and half year data of ongoing surveillance of occupational exposure to blood and body fluids in a tertiary care hospital., Results: 103 Health Care Providers (HCP) reported an occupational exposure to blood and body fluids during the period under review. These comprised 72 (69.9%) doctors, 20 (19.4%) nursing personnel, and 11 (10.6%) cleaning staff. Of the doctors, 65% were interns. 53.4% HCP had work experience of less than one year. Circumstances of exposure included clinical procedures (48%), sweeping/handling used sharps (29%), recapping (16%), and surgery (6.9%). 74.3% of the exposures were due to non-compliance with universal precautions and were thus preventable. The device most frequently implicated in causing injury was hollow bore needle (n=85, 82.5%). Human Immunodeficiency Virus (HIV) status of the source was positive in 6.8% cases, negative in 53.4% cases, and unknown in remaining 39.8% cases. Postexposure prophylaxis (PEP) was indicated in 100 (97.08%) cases and was initiated within 2 h of exposure in 26.8% HCP. In 23.2% HCP, PEP initiation was delayed beyond 72 h of exposure due to late reporting. Thirteen HCP received expanded and the remaining received basic regime. Of the 82 HCP followed up, 15 completed the full course, while 55 stopped PEP after the first dose due to negative source status. Twelve HCP with exposure to blood of unknown HIV status discontinued PEP despite counseling. Complete follow-up for seroconversion was very poor among the HCP. HIV status at 6 month of exposure is not known for any HCP., Conclusions: Failure to follow universal precautions including improper disposal of waste was responsible for majority of occupational exposures. HCP need to be sensitized regarding hospital waste management, management of occupational exposure, need for PEP, and continued follow-up.

India has the world's greatest burden of neonatal and under- five mortality. In 2008, approximately 1.8 million under five children, including 1 million neonates, died. At the current rate of progress, India will not be able to achieve the MDG 4 target of reduction of under- five mortality to 38 per 1,000 live births by 2015. The Reproductive and Child Health programme (RCH) II under the National Rural Health Mission (NRHM) comprehensively integrates interventions that improve child health and addresses factors contributing to infant and under-five mortality. Under the RCH II National Programme-Implementation Plan, IMNCI approach is the major instrument of newborn and child health strategy. IMNCI clinical guidelines focus on assessment, classification and providing treatment according to disease severity. Severe illnesses (red classification) require urgent referral after pre-referral treatment. Further diagnosis and management is dependent on the skills of health workers of the referral hospital. Therefore, capacity building of professionals for providing optimum care for sick children in referral units is an obvious path to optimize the benefits of IMNCI on child survival. With these objectives, F-IMNCI (Facility based IMNCI) package was developed by a committee of experts constituted by the Ministry of Health and Family welfare, Government of India.

The health related indices in our country are far from satisfactory and the country still bears an enormous share of the global disease burden. The lack of accessibility, scarce availability and the poor quality of health services and personnel in the remote rural and underdeveloped urban areas have been the major obstacles to the delivery of quality health care services in a vast and culturally diverse country with inter- and intra-regional variations and inequalities. The already over-stretched public health care system has been grappling with the deficiencies in linkage with the collateral health determinants, gross shortage and non utilization of infrastructure, financial and human resources. Revitalizing the existing primary health care infrastructure under the National Rural Health Mission (NRHM) will bring about the long overdue architectural corrections in the health care sector and be able to provide accessible, affordable, accountable, effective and reliable health care especially to the under-privileged sections of the society. NRHM is based on the principles of decentralisation of the health system, empowerment of the community and the panchayati raj institutions. Effective integration of health concerns with other health determinants like sanitation, hygiene and nutrition through district health plan is being made.

Malaria is a major vector borne disease in India with significant morbidity and mortality. The official figure of 1.5 million cases annually is a gross under-estimation of the true incidence and the actual figures are estimated to be 10-100 times higher. The National Vector Borne Disease Control Programme (NVBDCP) directorate is the main body responsible for malaria control in India. Newer strategies including insecticide treated bednets, longlasting insecticidal bednets and rapid diagnostic tests have been used for malaria control in the last decade. Global assistance has come from the World Bank and Global fund in the form of Enhanced Malaria Control Programme(EMCP) and Intensified Malaria Control Programme(IMCP) respectively. Despite years of concerted global and national efforts, control of malaria continues to be a challenge. The emergence of drug resistance to anti-malarial drugs has been a major hurdle in its control. The NVBDCP has formulated new treatment guidelines for malaria in 2010 which recommend artemisinin based combination therapy (ACT) as the first-line drugs for P. falciparum malaria in the country. The article discusses the recent national drug policy for malaria and the rationale for its use.

Kala-azar or visceral leishmaniasis is a disseminated protozoal infection caused by parasites of the genus Leishmania (Leishmania donovani in India). Conventional therapy for visceral leishmaniasis continues to be pentavalent antimony (sodium antimony gluconate [SAG]). Amphotericin B is widely used for SAG-unresponsive cases and sometimes even as a first-line drug, especially in endemic areas. With the conventional regimen of SAG, cardiac toxicity has been reported in 8% to 17% of cases with 5% to 7% of them having fatal toxicity. Cardiac toxicity is uncommon with amphotericin B with only few isolated reports. We report some patients with kala-azar in whom coadministration of SAG and amphotericin B led to arrhythmia and sudden death.

Objectives: To describe our experience in children hospitalized with the pandemic Influenza A (H1N1) from Northern India., Methods: The retrospective case study was conducted at the Pediatric ward and Pediatric Intensive Care Unit (PICU) dedicated to the children (aged 18 years or younger) with influenza-like illness (ILI) with positive laboratory test results for pandemic H1N1 by reverse-transcriptase polymerase-chain-reaction assay., Results: Between August 2009 and January 2010, a total of 100 children were hospitalized with suspected 2009 H1N1 influenza with Category "C" as described by the Government of India. Twenty five patients were positive for H1N1 and 9 for seasonal influenza A. The most common presentation (H1N1 positive) was with fever (100%), cough (100%), coryza (52%), respiratory distress (88%), vomiting (28%) and diarrhea (16%). One child presented with hypernatremic dehydration and seizures (Serum sodium 174 meq/l). Of the H1N1 positive hospitalized children, 7 (28%) had respiratory failure and required PICU admission, 4 (16%) required mechanical ventilation, and 3 (12%) died. The major radiological findings were bilateral pulmonary infiltrates and consolidation. All patients were treated with oral Oseltamivir suspension or capsule as per appropriate weigh band and supportive care as required. Two deaths were caused by refractory hypoxemia and one by refractory shock., Conclusions: The exact incidence of Pandemic 2009 H1N1 influenza on morbidity and mortality is difficult to calculate since only Category "C" patients were screened.

Awareness among the general population of the risk factors and warning symptoms of stroke is essential for preventative purposes and for immediate effective treatment. The aim of the present study was to assess the awareness, among the general population and stroke survivors, of the risk factors and warning symptoms of stroke, to develop an educational strategy for its prevention and immediate effective treatment. Six hundred and sixty stroke patients (370 male, 290 female) and 4000 people from the general population who accompanied the patients (2800 male, 1200 female) were interviewed, using three sets of questionnaires, on the risk factors and warning symptoms of stroke. Poor knowledge or awareness of the risk factors and warning symptoms of stroke was found in both groups. Both groups suggested educational programs for stroke using printed information, audiovisual programs and community survey programs using simple and understandable information for the prevention and immediate effective treatment of stroke. Poor awareness of stroke contributes to a delay in the arrival of patients in hospital emergency departments for immediate effective treatment. Multifaceted programs regarding stroke, including printed information, audiovisual programs and stroke service programs, are advocated by both patients and the general population to improve stoke treatment and prevention.

Objective: To evaluate simple clinical signs of illness in young infants (0 to 2 months) and to correlate with WHO IMCI algorithm (7 days-2 months)., Design: Prospective observational. Study conducted in the outpatient department and emergency room of a pediatric tertiary level hospital., Methods: Four hundred and ninety seven young infants (0 to 2 months) presenting to outpatient department or emergency room were recruited. Detailed history, clinical examination including all signs in IMCI algorithm was recorded in the pre-designed proforma. The study subjects were investigated and managed according to the protocol of treating unit, which served as gold standard. The diagnostic and therapeutic agreement between the gold standard and IMCI was computed. The study subjects were analyzed as one age group (0 to 2 months) and also after de- segregating into early and late neonatal age group (0 to 7 days and 7 days to 2 months age)., Results: Mean number of illnesses in 0 to 7 days, 7 days-2 months and 0-2 months groups were 1.97, 2.0 and 2.02 respectively. Those who required referral as per IMCI algorithm had higher proportion of co-morbidities. The referral criteria were fairly sensitive (78 to 85 percent) in predicting hospitalization with moderately high specificity (78 percent). Diagnostic agreement between gold standard and IMCI module was complete in 57 to 68 percent. Amongst diagnostic mismatch, under-diagnosis was found more frequently (72 to 82 percent) than over-diagnosis (17 to 29 percent). The sensitivity of algorithm to identify serious bacterial infections was quite high (96 to 98 percent) with moderately good specificity (80 to 92 percent). Jaundice was single most important complaint accounting for 47 to 62 percent of diagnostic mismatch., Conclusion: IMCI algorithm appears to be a promising, feasible and useful intervention strategy to triage and treat young infants in 7 days-2 months age group. This tool remains effective even when extended to 0 to 7 days age group. However a further increase in its sensitivity can be achieved by including yellowness of lower extremities/ palms/ soles as a criterion.

Pancytopenia is a common occurrence in pediatric patients. Though acute leukemias and bone marrow failure syndromes are usual causes of pancytopenia, etiologies such as infections and megaloblastic anemia also contribute. The aim of this study was to evaluate the clinico-hematological profile of varying degrees of childhood cytopenias with special reference to the non-malignant presentations. This is a retrospective study carried out in a tertiary care children's hospital. We retrospectively analyzed 109 pediatric patients who presented with pancytopenia for different etiologies. Acute leukemia (including ALL, AML and myelodysplastic syndrome) and aplastic anemia accounted for 21 per cent and 20 per cent cases respectively. Megaloblastic anemia was found in 31 (28.4 per cent) patients and was single most common etiological factor. Severe thrombocytopenia (platelet < or = 20 x 10(9)/l) occurred in 25.2 per cent of these patients. Various skin and mucosal bleeding occurred in 45.1 per cent of patients with megaloblastic anemia. Infections accounted for 23 (21 per cent) patients who presented with pancytopenia. Amongst infections, enteric fever occurred in 30 per cent patients. Malaria, kala-azar and bacterial infections were other causes of pancytopenia at presentation. The study focuses on identifying easily treatable causes such as megaloblastic anemia and infections presenting with pancytopenia. These conditions though look ominous but respond rapidly to effective therapy.