A. K. Dutta

A comparison of immunogenicity and safety of indigenously developed liquid (DTwPHB-Hib) pentavalent combination vaccine (Shan 5) with Easyfive (Liq) and Tritanrix + Hiberix (Lyo) in Indian infants administered according to the EPI schedule

The study was planned to assess and compare the immune response and safety of an indigenous DTPwHB-Hib pentavalent liquid combination vaccine (Shan 5) with Easyfive and Tritanrix HB + Hiberix, the two available pentavalent combination vaccines. Four hundred infants were randomized to receive three doses of either Shan 5 or one of the two comparators. Antibody analysis was performed prior to and four to six weeks post third vaccine dose. Solicited local and systemic events upto three days and unsolicited adverse events in the 30 days follow up period after each dose were recorded. A total of 365 subjects completed the study. Four to six weeks after third dose, 98.32% of the subjects in Shan 5 group had seroprotective Anti PRP-T IgG antibody concentrations (≥0.15 µg/mL) as compared to 100% and 98.94% subjects in Tritanrix HB + Hiberix and Easyfive groups respectively. Seroprotective levels for Anti-HBs (≥10 mIU/mL) were observed in 97.77%, 97.83% and 98.94% subjects in Shan 5, Tritanrix HB + Hiberix and Easyfive groups respectively. Comparable immune responses were observed for the three other components (D, T and P) in all the groups. Four Serious Adverse Events (SAEs) were reported (three with Shan 5 and one with Easyfive), all unrelated to the respective vaccines. Most commonly reported adverse events in all the groups were pain at injection site, mild fever (< 103° F) and minor swelling at injection site. The study proved that Shan 5 was safe and immunogenic compared to the two other licensed vaccines.

Pneumococcal Vaccines – How Many Serotypes are Enough?

Streptococcus pneumoniae causes meningitis, pneumonia, septicemia, arthritis, sinusitis and otitis media specially in children and over 65 y age groups. It contributes significantly to under-five mortality and morbidity worldwide as well as in India. Use of pneumococcal vaccine seems to be the most effective measure to decrease the disease burden and reduction of under-five mortality. Many countries have already included Pneumococcal Conjugate Vaccines (PCV) in their National Immunization Programmes (NIP). Government of India has announced recently to include PCV13 in NIP in a phased manner. Superiority of a vaccine over the other depends upon serotype coverage, vaccine efficacy, cost effectiveness and safety profile. These facts will be discussed for the vaccines available in India. Further research is warranted to know the disease burden and develop vaccines to have more serotype coverage.

Patient Safety - Protect Yourself from Medical Errors: Aniruddha Malpani (Ed)

Patient safety is one of the most important aspects of health care deliveries at all levels e.g., primary, secondary and tertiary care. An adverse event in the health care delivery system is not uncommon. Although the exact figure is difficult to ascertain, probably one in ten hospital admissions will have such an event. Many of these are preventable or if remedial actions are taken immediately, can save the lives. Patient safety is one of the most important element of efficient and effective health care system where no harm should be caused to any patient. Every doctor/nurse may recall more than one instance of their experience of committing an error in their patient management. The BPatient Safety Protect Yourself from Medical Errors^ is an excellent and thought provoking book edited by Dr. Aniruddha Malpani who is an eminent personality and has unique distinction of managing world’s largest free patient education Library (HELP). I am touched by the bold confession of the author on his first preventable error in patient management. The same system of non-supervised or ill-supervised management practices are not a rarity even in present day health care delivery system. The educational curriculum of medical and nursing students is devoid of this important subject and probably only a brief mention of the same is a part of undergraduate and postgraduate training program. This book highlights important aspects of patient safety, quality of care, medication error etc. at length. The definitions of patient safety and medical errors, which are not necessarily be intentional and often may be a system error has been expressed in detail by the author. The important points to be taken care of by the medical doctors and nurses to prevent medical errors and safeguard oneself has been described in very simplified manner. The role of policy makers, equipments and pharmaceutical companies in patient safety has been nicely dealt in this book. All the thirty eight chapters in the book are key elements which every health care professional, administrator, policy maker and nurse must know and practice in day to day life. The chapters are written in great style and language which is easy to read and understand. The book shall be of immense benefit and help for all the health care workers and policy makers and should find a place in the desk top of every professional caring for their patients.

Association of rotavirus strains and severity of gastroenteritis in Indian children

ABSTRACT Rotavirus is the leading cause of severe and dehydrating diarrhea in children aged under 5 years. We undertook this hospital-based surveillance study to examine the possible relationship between the severity of diarrhea and the various G-group rotaviruses circulating in India. Stool samples (n = 2,051) were systematically collected from 4,711 children aged <5 years admitted with severe acute gastroenteritis to 12 medical school centers from April 2011 to July 2012. Rotavirus testing was undertaken using a commercially available enzyme immunoassay kit for the rotavirus VP6 antigen (Premier Rotaclone Qualitative ELISA). Rotavirus positive samples were genotyped for VP7 and VP4 antigens by reverse-transcription polymerase chain reaction at a central laboratory. Of the stool samples tested for rotavirus antigen, 541 (26.4%) were positive for VP6 antigen. Single serotype infections from 377 stool samples were compared in terms of gastroenteritis severity. Among those with G1 rotavirus infection, very severe diarrhea (Vesikari score ≥ 16) was reported in 59 (33.9%) children, severe diarrhea (Vesikari score 11–15) in 104 (59.8%), moderate (Vesikari score 6–10) and mild diarrhea (Vesikari score 0–5) in 11 (6.3%). Among those with G2 infection, very severe diarrhea was reported in 26 (27.4%) children, severe diarrhea in 46 (48.4%), and moderate and mild diarrhea in 23 (24.2 %). Among those with G9 infection, very severe diarrhea was reported in 47 (54.5%) children, severe diarrhea in 29 (33.6%), and moderate and mild diarrhea in 10 (11.9%). Among those with G12 infection, very severe diarrhea was reported in 9 (40.9%) children and severe diarrhea in 13 (59.1%). The results of this study indicate some association between rotavirus serotypes and severity of gastroenteritis.

Safety and immunogenicity of diphtheria-tetanus-pertussis vaccine and hepatitis B vaccine as a new tetravalent combination (DTwP/HB) administered alone and at separate sites (DTwP & HB) including comparison with standard commercially available combination vaccine in Indian infants 6-14 weeks of age

An open, comparative study was conducted at two tertiary care hospitals in India to assess immunogenicity and reactogenicity following administration of the DTwP/HB combination vaccine (Q-Vac) alone and DTwP and HB (Genevac B) vaccines at separate sites. These vaccines manufactured by Serum Institute of India Ltd (SIIL), Pune were compared with DTwP/HB vaccine (Tritanrix HB) manufactured by Glaxo SmithKline (GSK) in infants aged 6 - 14 weeks. The sample size comprised 447 infants who received DTwP/HB vaccine (Group A – 150, SIIL) or DTPw & HB (Group B – 147, SIIL) vaccines at separate sites or DTPw/HB vaccine (Group C – 150, GSK), in a dose of 0.5 ml intra-muscularly. Pre and postvaccination IgG antibodies were determined by ELISA. Postvaccination, in Group A sero-protection was 99.3%, 100%, 96%, and 100% to Diphtheria, Tetanus, Pertussis and HBs components respectively. In Group B (n=147) it was 98.6%, 100%, 95.9% and 99.3% and in Group C (n=150), it was 96%, 99.3%, 93.3% and 98.6% to D, T, P and HBs component of the vaccine. Postvaccination, geometric mean titres for each component were comparable across three groups by analysis of variance (ANOVA). Adverse events observed were within the range quoted in literature and no Serious Adverse Event (SAE) was observed. Reactogenicity profile in all three groups was comparable. Q-Vac vaccine manufactured by SIIL was found to be safe and immunogenic. Hepatitis B component did not interfere with the immune response to DTwP components of the vaccine.

Rotavirus Vaccination in India – Need for Surveillance of Intussusception

Intussusception is an acute surgical emergency characterized by sudden onset of severe intermittent abdominal pain (excessive crying and irritability in small infants), vomiting, bleeding per recturm (red current jelly stool) and presence of abdominal mass on palpation. It occurs due to invagination of a bowel segment by amore proximal segment. Due to peristaltic movement the intussusception can be propelled distally leading to obstruction and ischemia of the gut. For the purpose of definitions and reporting as an adverse event following rotavirus vaccine, Brighton’s classification is followed as described by Bines et al. [1]. Rotavirus vaccine has the dubious distinction of its association with intussusception and therefore poses a risk and safety concern in National Immunization Program of any country. The first causal relationship of intussusception and rotavirus vaccine was noticed in USA in post marketing surveillance of a human-rhesus reassortant pentavalent rota vaccine (Rotashield) in 1998. In the vaccine adverse event reporting system (VAERS) which is a passive National reporting of any adverse events following vaccination, it was observed that there was an increase in cases of intussusception among the vaccine recipients. This resulted in an immediate institution of a case control study by the licensing authority which confirmed a causal relationship between rota vaccine (Rotashield) and intussusception. In the cohort study, it was observed that there was 37 times higher risks of an intussusception following rota vaccine after 3–7 d of first dose and a very small increase in second week. Overall the study showed an excess risk of one case of intussusception per 10,000 recipients. Based on the findings of the study the manufacturing company itself withdrew this formulation from the market in 1999 [2]. Almost at the same time two other vaccine manufacturing companies MSD and GSK were in the process of advance stages of development of live oral rotavirus vaccine. Based on earlier safety concern with Rotashield, both Rotateq (MSD vaccine) and Rotarix (GSK vaccine) trials had taken large human candidates in USA and Europe for assessment of the adverse reactions especially intussusception. Rotateq is a pentavalent human-bovine reassorted live attenuated vaccine and approximately 70,000 infants were administered three doses at 2, 4 and 6mo schedule. The Rotarix which is a human strain of monovalent live attenuated vaccine has been tried in over 60,000 infants in Europe in a two dose schedule at 2 and 4 mo of age. Both the vaccines were found to have only a slight increase in risk of intussusception than the control groups and the results were statistically not significant [3, 4]. Since then both these vaccines are used extensively and millions of doses are being used in National immunization program of many countries of the world [5]. Following the introduction of rota vaccine in National immunization program (NIP), many studies have been undertaken as a part of post marketing active surveillance to find out the causal relationship with the vaccine and intussusception. Carlin et al. from Australia have observed an increased risk with both monovalent and pentavalent vaccines which were used in the country. In their case series and case control study, there was an increased risk of intussusception in the first 3 wk after the first dose and after 1 wk of the second dose. The greatest risk was after first week following first dose [6]. Similar results were reported in other studies using RV-1 in Australia and Mexico and Brazil [7–10]. The use of RV-5 also * Ashok Kumar Dutta drdutta@gmail.com

Learnings from Pentavalent Vaccine Introduction in India

Vaccination is one of the most cost-effective methods of intervention for prevention of disease without improving the overall socio-economic development of a country. The greatest example is global small pox eradication and now, eradication of poliomyelitis from almost all the countries in the world. The organized way of vaccination in India was started with expanded program of immunization which was launched in 1978 by Govt of India. There has been significant progress by reduction of mortality and morbidity due to neonatal tetanus, paralytic poliomyelitis, measles, diphtheria and pertussis. India, is a vast country with difficult geographical terrain with natural calamities occurring every year and having varying socio-economic and literacy rates in various states. This is reflected in overall health delivery system, disease burden including immunization coverage in some of the high disease and mortality burdened states in India. Vaccine preventable diseases still continue to be among five major killers in under five children in most of the developing countries. The under fivemortality in India is at present 49/1000 live birth as per the latest report from Registrar General of India [1]. However we are still far from reaching the Millennium Development Goal of less than 30/1000 live birth as per the deadline of 2015. United Nations in the program of sustainable development goal declared under Goal no 3 (Good Health and Well Being) target by 2030, the under five mortality rate should be brought down from the present global rate of 43 to 25. In this direction, one of the most important activities includes research and development of vaccines besides substantial increase in health financing [2, 3]. World Health Organization has recommended inclusion of Hemophilus influenza b vaccine (Hib) to prevent invasive Hib disease about a decade ago, however due to logistic problems and lack of sufficient data on Hib disease in India, the vaccine could not be launched in time. However, now Hib vaccine has been incorporated in the National schedule starting from Kerala and Tamil Nadu and gradually, in a phased manner, in other states in the country as a combination pentavalent vaccine. Since DPT, Hepatitis B and Hib vaccines are administered at the same time schedule, combination pentavalent vaccine incorporating all the five antigens is used in the country. By using pentavalent combination vaccine, instead of three separate injections only one shot is given which is beneficial for the infant as well as advantageous for the program in the country. It shall lessen the burden of pain at the injection site, parental anxiety, reduce burden in the maintenance of cold chain system and successful implementation of the immunization program in the country with increased coverage and less dropout rates. However, the quality of combination vaccine and close vigilance on adverse event reporting system has to be addressed simultaneously [4]. Introduction of any new health intervention in the country requires scientific, logistic and economic considerations.Most often, lack of scientific epidemiological data on disease burden, poor health system, procurement of sufficient quantity of vaccines, lack of trained manpower, poor vaccine coverage of the infants are cited as important stumbling blocks in the introduction of new vaccines in the National program. Based on the strong recommendations of National Technical Advisory Group on Immunization, pentavalent vaccine containing DPT+Hib + Hepatitis B has been introduced in December 2011 in Kerala and Tamil Nadu states [5]. Both these states * A. K. Dutta drdutta@gmail.com

IAP Textbook of Vaccines: IAP Committee on Immunization (IAPCOI), 2011–13 (eds)

Vaccination is one of the most cost effective method of prevention of infectious diseases. Since the invention of Small Pox vaccine by Sir Edward Jenner, a large number of vaccines are available in the world which have prevented several million of deaths, disabilities and morbidities in children. Successful immunization practices have led to eradication of Small Pox from the world and in near future, Poliomyelitis would be a disease of the past. In developed countries of the world, many diseases are in control because of inclusion of the vaccines in the country program. Immunization program of a country depends on disease burden, availability of vaccines, feasibility of implementation and cost effectiveness. Based on the above issues, every country decides its own immunization schedule. However, there are several vaccines which are not included in the national schedule but are available in the country for private use. Indian Academy of Pediatrics has time to time given guidelines for all the members to use the additional vaccines which are to be used for children under their care. It has been observed in the past that there is always debate regarding various aspects of immunization practices and the continuing medical education on vaccination attracts most captive audiences. Most of the time it becomes difficult for the organizer as well the speaker to satisfy the delegates. The IAP text book of vaccines is a long awaited prized publication which shall serve as a reference book for every pediatrician and physician practicing immunization. The book has been edited by eminent personalities in the field of vaccination and all contributors from India and abroad are experts in this field. The book includes excellent chapters from basics of vaccination to details of individual vaccines covering epidemiology, clinical presentations and vaccine administration. The chapter on history of vaccination is very interesting to read. The initial chapters e.g., immunological correlates of protection induced by vaccine, epidemiology in relation to vaccinology, general recommendations on immunization, scheduling of vaccine, mucosal immunology and vaccination are very informative. The section 3 on new vaccines in development, contains important vaccines which are in the pipeline and latest and most recent developments in individual vaccine development has been nicely written by all the authors. It is very heartening to find one of the most important chapter on vaccine safety and adverse reaction to vaccination and what needs to be done in case of such an event including management in the community and media. The book is complete in respect of its usefulness to all spheres of medical profession e.g., in government set up, as policy makers, for all pediatricians and physicians and also to the vaccine manufacturing industry. The book is an excellent reference publication by Indian Academy of Pediatrics with very good editing, covering all aspects of vaccination. I am sure this book should find place in the library of each medical college, referral hospitals in the country and also in the desk of every pediatrician and physician practicing immunization.

Immunization in Practice - Clearing the Cobwebs: Author’s Reply

To the Editor: I wish to congratulate Dr Chandra Mohan Kumar and Dr Preeti Sharma for reading the article in great details and pointing errors in the manuscript [1]. However I do not totally agree with their views on all points and condemning the article as misleading. In the abstract there is no mention of MMR and why there is mention for Hib. In fact Hib is being given in more states (9) thanMMR vaccine (4). MMR vaccine is not recommended in routine Govt of India vaccination schedule. GoI recommends only measles as second dose. Therefore in GoI schedule, MMR which has been mentioned should be omitted. MMR vaccine is being used with state funds in Delhi, Goa, Sikkim and Puducherry. [Personal communication, Deputy Commissioner Child Health GoI]. In scheduling of vaccination, it is well known that two or more live vaccines can be given on the same day and only when it cannot be given on the same day, an interval of 28 d should be adhered to. This point has been missed in the text and needs to be incorporated. There has been a typographical error where one full column of 6 mo schedule with OPV 1 dose and Hep B 2 dose is missing in IAP schedule which also needs correction. However in the text when hepatitis B is described, there is mention about the second dose of Hep-B. In Rotavirus vaccine, no doses schedule has beenmentioned and therefore the question of 2 vs. 3 doses does not arise and always the vaccine doses are given as per the guidelines of the manufacturer. Regarding maximum age for administering the last dose it has been mentioned as 32 wk. I do not find any difference between 32 wk and 8 mo. In the article of a general concept every detail of individual vaccine, especially the contra indications cannot be addressed and therefore in Rota vaccine, there is no mention of intussuception as contraindication. The two typographical errors are regretted and require correction. In the keywords again IPV is inactivated polio vaccine and PCV is pneumococcal conjugate vaccine which needs correction.

Bringing up Preterm Babies—A Guide for Parents: Krisha Krishnani and Umesh Vaidya (eds)

Preterm babies contribute a huge burden of sick newborns in the world. Many of them require prolonged stay in level II and III care newborn units for treatment and later, for a long term follow-up by a multispeciality team of doctors, developmental specialists and lactational management experts. During hospital stay, the parents and familymembers of the preterm babies undergo tremendous psychological and financial stress resulting in feeling of guilt and helplessness. Most often, the treating neonatologists and nurses are too preoccupied by their busy work schedule and always may not be in a position to explain and counsel the family in the right manner which leads to a sense of dissatisfaction among the family members. The book “Bringing up preterm babies—A guide for parents” written by Ms Krisha Krishnani and Dr Umesh Vaidya clarifies most of the problems and queries of the parents and families who are faced with a situation of having a preterm baby admitted in one of the neonatal units. The book highlights, in very simple language, the terminologies used in newborn care including different levels of care, how to cope up with stress, the follow up care, special feeding technique, including importance of breast milk and lactational management. The chapter on parenting your neonatal intensive care unit (NICU) baby at home, parental participation in NICU care and financial aspects of neonatal care are excellently written and are of great use for the parents and family. The book covers a wide spectrum of the medical complications including problems in growth and development and assessment depicting various charts for monitoring. The chapters are very well written in a simple language for the parents. However, many of these topics appear to be difficult to understand by ordinary parents without any background knowledge of medical sciences unless they are explained by the doctors. It shall be heartening for all the parents of preterm babies to know about famous preemies of the world. I congratulate the authors of all the chapters who have done excellent work by simplifying the subject in simple and understandable language. The book shall be a useful knowledge bank for not only parents but also for all nurses and doctors caring for the newborn babies.