A review of safety and immunogenicity of a novel measles, mumps, rubella (MMR) vaccine.

Measles, mumps, and rubella (MMR) are highly infectious viral diseases affecting young children and have high secondary attack rates. Present MMR vaccines show consistent seroconversion rates for anti-measles and anti-rubella antibodies with variable responses for anti-mumps antibodies. Most common strains for MMR vaccines, currently available in India, are the Edmonston-Zagreb measles strain, Leningrad Zagreb (L-Z) mumps strain, and the RA 27/3 rubella strain. L-Z strain of mumps virus has been found to be associated with aseptic meningitis by different studies from different parts of the world including India. Recently, a novel freeze-dried MMR vaccine developed by Zydus Lifesciences (Zyvac MMR) contains Edmonston Zagreb measles strain, Hoshino mumps strain, and RA 27/3 rubella strain. The Hoshino strain is WHO approved and was found to induce interferon gamma production. This review article aims to provide a comprehensive appraisal of the data available on the safety and immunogenicity of the novel MMR vaccine.

An in vivo evaluation of different methods of working length determination.

OBJECTIVE: The purpose of this in vivo study was to compare the ability of digital tactile, digital radiographic and electronic methods to determine reliability in locating the apical constriction. MATERIALS AND METHODS: Informed consent was obtained from patients scheduled for orthodontic extraction. The teeth were anesthetized, isolated and accessed. The canals were negotiated, pulp chamber and canals were irrigated and pulp was extirpated. The working length was then evaluated for each canal by digital tactile sensation, an electronic apex locator (The Root ZX) and digital radiography. The readings were then compared with post-extraction working length measurements. RESULTS: The percentage accuracy indicated that EAL method (Root ZX) shows maximum accuracy, i.e. 99.85% and digital tactile and digital radiographic method (DDR) showed 98.20 and 97.90% accuracy respectively. CLINICAL SIGNIFICANCE: Hence, it can be concluded that the EAL method (Root ZX) produced most reliable results for determining the accurate working length.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Effect of propofol titration v/s bolus during induction of anesthesia on hemodynamics and bispectral index.

BACKGROUND: Propofol when given as 2 mg/kg IV bolus for induction of anesthesia is known to cause hypotension requiring vasopressors. The objective of our study was to compare Propofol 2 mg/kg single IV bolus (Precalculated group, PG) with the titration of Propofol (Titration group, TG) to clinical parameters as 10 mg IV increments every 3 seconds on hemodynamic Parameters and Bispectral Index (BIS), during induction. The effect of titration on dose requirement for induction was also evaluated. METHODS: Effects on Hemodynamic parameters [Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)], and vasopressors use were recorded at baseline and every 2 minute intervals for 10 minutes. The percent difference in HR, SBP, DBP, and MAP from baseline at 2, 4, 6, 8 and 10 minutes were calculated, to determine the effect on hemodynamic parameters. BIS was recorded at baseline, after injection of Propofol, at intubation and at 10 minutes. Dose requirement of Propofol in TG was also recorded. RESULTS: At 2 and 4 minutes, SBP decreased in PG by 21% and 18% vs. 11% and 9% in TG (p = .00 & .02); DBP decreased by 17% and 15% in PG vs. 5% and 4% in TG (p = .02 & .03); MAP decreased by 19% and 17% in PG vs. 5% and 4% in TG (p = .00 & .01). Vasopressors were required in 14/43 patients in PG vs. 5/41 in TG (p = .03). Titration resulted in 30% reduction in dose. CONCLUSION: Titration of Propofol reduces hemodynamic changes, dose requirement and is able to achieve same level of BIS as in bolus.

IAP Guideline on Practicing Safely During COVID-19 Era: Clinics and Small Establishments.

JUSTIFICATION: The unprecedented COVID-19 pandemic has had a formidable impact on Indian health care. With no sight of its end as yet, various establishments including the smaller clinics and nursing homes are restarting full operations. Hence, there is the need for recommendations to allow safe practice ensuring the safety of both the heath care worker (HCW) and patients. PROCESS: Indian Academy of Pediatrics organized an online meeting of subject experts on 27 July, 2020. A committee was formed comprising of pediatricians, pediatric and neonatal intensivists, and hospital administrators. The committee held deliberations (online and via emails) and a final consensus was reached by November, 2020. OBJECTIVES: To develop recommendations to provide a safe and practical healthcare facility at clinics and small establishments during COVID times. RECOMMENDATIONS: The key recommendation to practise safely in this setting are enumerated. Firstly, organizing the out-patient department (OPD). Secondly, appropriate personal protective equipment (PPE) to provide protection to the individual. Thirdly, decontamination/disinfection of various common surfaces and equipment to prevent transmission of infection from fomites. Next, maintaining the heating ventilation and air conditioning (HVAC) to provide a stress-free, comfortable, and safe environment for patients and HCWs. Finally, steps to effectively manage COVID-19 exposures in a non-COVID-19 facility. All these measures will ensure safe practice during these unprecedent times in clinics and smaller establishments.

The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.

Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with EasyFourTM in Indian infants administered per EPI schedule: a phase III trial.

The study was planned to assess and compare immunogenicity and safety of an indigenous DTPw-Hib combination vaccine (Shan 4) with EasyFour, the available DTwP-Hib vaccine in India. Overall 210 healthy infants, six to eight weeks of age, were randomized to receive three doses of either Shan 4 or EasyFour at 6, 10 and 14 weeks of age. Antibodies were analyzed prior to and four to six weeks post third vaccine dose. Solicited and unsolicited local and systemic events in the follow up period after each dose were recorded. Post vaccination 100% of the infants in Shan 4 and EasyFour groups had seroprotective concentrations of Anti PRP-T IgG antibodies, IgG anti-diphtheria toxoid antibodies and IgG anti-tetanus toxoid antibodies. Following third dose of vaccination 86.99% subjects in the Shan 4 group and 73.85% subjects in the EasyFour group seroconverted for anti-pertussis antibody titres. Two Serious Adverse Events (SAE s) were reported during the course of the study, all unrelated to the respective vaccine administered. Most commonly reported adverse events in both the groups were pain at injection site, mild fever (<103°F) and minor swelling at injection site. The study proved that Shan 4 was safe and immunogenic compared to the available licensed vaccine.

Review of long term immunogenicity and tolerability of live hepatitis A vaccine.

Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two types of hepatitis A vaccines-live attenuated (H2 strain) and inactivated (killed) are available for use in clinical practice in India with former having advantage of a single-dose compared to two-dose killed vaccine. One of the important characteristic of an ideal vaccine includes its ability to provide life-long protection. In this article we reviewed the available long-term (≥10 years follow-up) published data on live attenuated hepatitis A (H2 strain) vaccine. The data from country of origin of the vaccine (China) and India establish the long-term immunogenicity, protection, and tolerability. Based on the results of several clinical trials showing long-term protection, single dose of live attenuated hepatitis vaccine can be widely used to protect high-risk population against hepatitis A virus infection and related complications.

Clinical Course of Patients With Sickle Cell Anemia and Co-inherited Hematological Disorders: Experience at a Tertiary Hematological Centre.

To study the clinical course of patients with sickle cell anemia and coinherited hematological disorders. Retrospective analysis of clinical data of patients enrolled at our hospital over last 7 years was performed. Eighty four patients of symptomatic sickling disorders were registered during this period, comprising of HbSS (n = 49), HbS-ß thalassemia (n = 28), HbS-HbD disease (n = 5), HbS-ß thalassemia with G6PD deficiency (n = 1) and HbS-hemophilia A (n = 1). Among HbS-ß thalassemia, 18% suffered from occasional pain crises and 27% required occasional blood transfusion. 40% patients with HbS-HbD disease required occasional blood transfusions, one patient was transfusion dependent, while none suffered from crisis episodes. Patient with HbS-ß thalassemia with G6PD deficiency had increased transfusion requirement during first 3 years of life, which decreased after that. Patient with HbS and severe hemophilia A had only one episode of severe bleeding, suffered from 1 crisis episode. In conclusion, HbA reduces severity of HbS in HbS-ß + thalassemia. HbS-HbD disease can manifest as a transfusion dependent illness. HbSS reduces severity of G6PD deficiency after first few years of life. HbSS and hemophilia coinheritance ameliorates symptoms of hemophilia.

Immunogenicity and safety of live attenuated hepatitis A vaccine: a multicentric study.

OBJECTIVE: To evaluate immunogenicity and tolerability of single dose live attenuated injectable hepatitis A vaccine in four metropolitan cities of India. METHODS: Live attenuated hepatitis A vaccine was administered to 505 children aged 18 to 60 months in four centers across India. Immunogenicity of the vaccine was assessed by estimation of anti-HAV antibody titer at 6 weeks and 6 months following administration of the vaccine. Safety evaluation of the vaccine was also done during the visits. RESULTS: At 6 weeks, 480 subjects (95%) came for the follow-up and 411 (81.4%) subjects reported at the end of 6 months. The geometric mean titer (GMT) of anti-HAV antibody of the subjects who did not have the seroprotective titer at the baseline were assessed at 6 weeks and 6 months which was 81.04 mIU/ml and 150.66 mIU/ml respectively. At 6 weeks, 95.1 % seroconverted and at the end of 6 months, 97.9 % had seroconverted. Both solicited and unsolicited vaccine-induced local and systemic adverse events were insignificant at all the centers, except swelling and induration in a few. CONCLUSION: Live attenuated injectable hepatitis A vaccine was immunogenic and tolerable with minimal reactogenecity, in this study of single dose schedule. Safety profile was also satisfactory in the study population.

Laparoscopic Management of Post-Cesarean Section Uterocutaneous Fistula.

A uterocutaneous fistula is a rare clinical presentation that occurs following cesarean section or any other pelvic surgery. We describe a case of uterocutaneous fistula with successful surgical management. A 25-year woman was referred to our hospital with complaints of cyclical bleeding from lower segment cesarean section scar (LSCS scar). It was diagnosed as uterocutaneous fistula on ultrasonography and computed tomography. The fistula tract was excised. Histopathology report was suggestive of sinus tract due to tuberculous etiology. Patient was started on antituberculous treatment. Recovery was uneventful.

Immunization of Children with Cancer in India Treated with Chemotherapy - Consensus Guideline from the Pediatric Hematology-Oncology Chapter and the Advisory Committee on Vaccination and Immunization Practices of the Indian Academy of Pediatrics.

JUSTIFICATION: Children with cancer need to be immunized against the common vaccine-preventable diseases after completion and sometimes during ongoing treatment of cancer. However, the immunization schedule for these children needs to be altered due to disease and treatment related immune-suppression. Consequently, there are many guidelines/practice statements from around the world to address this issue, however, there is no such comprehensive guideline from India catering to the need of Indian children with cancer. PROCESS: A guideline was drafted after reviewing the available literature. The draft guideline was discussed and modified in a meeting attended by pediatric oncologists from the PHO chapter and vaccine experts from the ACVIP of the IAP. Subsequently, the modified draft was reviewed and recommendations were finalized. OBJECTIVES: To review the current evidence and generate a nationally relevant guideline for immunization of children receiving chemotherapy for cancer. RECOMMENDATIONS: Live vaccines are contraindicated during and up to 6 months after end of chemotherapy. Non-live vaccines are also best given after 6 months from the end of treatment for durable immunity. Annual inactivated influenza vaccine is the only vaccine recommended for all children during chemotherapy whereas hepatitis B vaccine is recommended only for previously unimmunised children with risk of transfusion associated transmission of infection. Post-treatment re-immunization/catch-up schedule largely depends on the pre-chemotherapy immunization status. Sibling immunization should continue uninterrupted except for oral polio vaccine which needs to be substituted by the injectable vaccine. Inactivated influenza vaccine is recommended and varicella vaccine is encouraged for all contacts including siblings.

Lymphopenia and Severe Combined Immunodeficiency (SCID) - Think Before You Ink.

OBJECTIVES: Severe combined immunodeficiency (SCID) represents one of the most severe forms of Primary immunodeficiency (PID) disorders, characterized by T cell lymphopenia (TCL) and lack of cellular and humoral immune responses. However, not all patients with low T cell lymphocyte counts may have an abnormal T cell immunity and the observed TCL may be a temporary suppression resulting from transient lymphopenia secondary to severe infections. In such cases, it is necessary to estimate the severity of the observed TCL by assessing thymic capabilities. METHODS: In this study, patients clinically suspected of SCID were evaluated for lymphocyte subsets analysis, naïve T cells and T cell receptor excision circles (TREC). RESULTS: Patients with transient lymphopenia had detectable TREC levels and normal naïve T cells subsets. Normalization of absolute lymphocyte counts, and T cells was seen in the patients after a short duration. CONCLUSIONS: The authors highlight the importance of detailed immunological investigations in an infant with severe infections and lymphopenia before labeling the infant as SCID.

Clinical, Immunological, and Molecular Findings in 57 Patients With Severe Combined Immunodeficiency (SCID) From India.

Severe combined immunodeficiency (SCID) represents one of the most severe forms of primary immunodeficiency (PID) disorders characterized by impaired cellular and humoral immune responses. Here, we report the clinical, immunological, and molecular findings in 57 patients diagnosed with SCID from India. Majority of our patients (89%) presented within 6 months of age. The most common clinical manifestations observed were recurrent pneumonia (66%), failure to thrive (60%), chronic diarrhea (35%), gastrointestinal infection (21%), and oral candidiasis (21%). Hematopoietic Stem Cell Transplantation (HSCT) is the only curative therapy available for treating these patients. Four patients underwent HSCT in our cohort but had a poor survival outcome. Lymphopenia (absolute lymphocyte counts/µL <2,500) was noted in 63% of the patients. Based on immunophenotypic pattern, majority of the cases were T-B- SCID (39%) followed by T-B+ SCID (28%). MHC class II deficiency accounted for 10.5% of our patient group. A total of 49 patients were molecularly characterized in this study and 32 novel variants were identified in our cohort. The spectrum of genetic defects in our cohort revealed a wide genetic heterogeneity with the major genetic cause being RAG1/2 gene defect (n = 12) followed by IL2RG (n = 9) and JAK3 defects (n = 9). Rare forms of SCID like Purine nucleoside phosphorylase (PNP) deficiency, reticular dysgenesis, DNA-Protein Kinase (DNA-PKcs) deficiency, six cases of MHC class II deficiency and two ZAP70 deficiency were also identified in our cohort. Fourteen percent of the defects still remained uncharacterized despite the application of next generation sequencing. With the exception of MHC class II deficiency and ZAP70 deficiency, all SCID patients had extremely low T cell receptor excision (TRECs) (<18 copies/µL).

Protecting Indian schoolchildren against rabies: pre-exposure vaccination with purified chick embryo cell vaccine (PCECV) or purified verocell rabies vaccine (PVRV).

Although rabies can be effectively prevented by means of preexposure or post-exposure prophylaxis, in India, an estimated 17,000 to 20,000 human rabies deaths occur annually. Tragically, 50% of these victims are children under the age of 15. In addition to immediate post-exposure prophylaxis measures, including active and passive immunization, pre-exposure vaccination using tissue culture vaccines is a safe and effective but highly underutilized method of preventing rabies in humans living or working in areas at risk. This study assessed the safety and immunogenicity of Purified Chick Embryo Cell Vaccine (PCECV) and Purified Verocell Rabies Vaccine (PVRV), administered as a three-dose intramuscular pre-exposure regimen on days 0, 7 and 28 in 175 healthy schoolchildren. PCECV was administered after reconstitution using either 1.0 mL or 0.5 mL (half the diluent volume) and PVRV was given after reconstitution with 0.5 mL. Vaccine safety was assessed observer-blind, including pain assessment with a validated visual analogue scale for children. Rabies virus neutralizing antibody (RVNA) concentrations were measured on day 49 by RFFIT. All children developed adequate RVNA concentrations above 0.5 IU/mL. Solicited local and systemic reactions were within the range expected, pain after vaccination was reported in 2 to 12% of study subjects, fever was reported in 2 to 5%. There was no statistical difference by vaccination group or vaccination day. No unexpected or serious adverse event was reported during the study. In conclusion, PCECV and PVRV are safe and immunogenic when administered intramuscularly for pre-exposure prophylaxis of rabies in children. A 1.0 mL dilution volume for PCECV was as well tolerated as PVRV or PCECV reconstituted in half the volume.

Carbon dioxide absorber as a cause of high airway pressures.

We investigate an incident in which a carbon dioxide absorber caused difficulty with ventilation. The problem as it developed throughout the anesthetic, and clues that led to the determination that the carbon dioxide canister was the problem, is discussed.