Tuesday, October 28, 2014

Vaccination FAQ - JE (Japanese Encephalitis Vaccine)

Q: We have given the first dose of Encephalitis some two months ago to our daughter. So do we have to give the second dose now or later?
Ans: Two doses of JE vaccine vaccines are needed at a gap of minimum 28 days.
Hence you should take the second dose of JE vaccine now,
Warm regards

Dr Gupta

Wednesday, October 22, 2014

A New Indian Vaccine for Rotavirus enters final stage of trials

LYON, France: A new made-in-India vaccine against Rotavirus, the most common cause of severe dehydrating diarrhoea in Indian infants, has entered a crucial final stage of trials. 

Hyderabad-based Shantha Biotechnics' investigational Rotavirus vaccine has entered Phase III clinical trials across 12 different sites in India. 

In an interview to TOI, Sanofi Pasteur's associate vice-president of research and development sites and hubs Jacques Volckmann said, "It is a vaccine which is being developed in India for Indians. Close to 1,200 volunteers are being sought at the trial sites to test the safety and efficacy of the vaccine that will specifically protect Indian children against the strains G1, G2, G3 and G4 that circulate extensively across the country". 

Among children under five, Rotavirus has been estimated to be responsible for two million hospitalizations and 500,000 deaths worldwide each year, the majority of which occur in the Indian subcontinent, sub-Saharan Africa and South America. 

It is estimated that one of every 260 children born each year will die from diarrhea caused by rotavirus infection by their fifth birthday. 

Recent studies indicate that rotavirus causes approximately 40% of childhood diarrheal hospitalizations worldwide, 40.7% in Sub Saharan African countries, 33% in Nepal, 34% in Pakistan ,40-50% in Japan and around 39% in India in children less than 5 years of age. 

India, with more than 1 billion people, 11% of whom are less than 5 years of age, has an especially large population at risk of clinically significant infection. 

There is no specific drug approved to cure rotavirus gastroenteritis. Since virtually all infants and young children will suffer at least one rotavirus infection and many will become infected two or more times, even in settings where good hygiene is practiced, universal immunization of infants with a vaccine is clearly the way to reduce rotavirus related morbidity, mortality, and associated medical costs. 

Shantha's investigational vaccine is designed to prevent severe rotavirus gastroenteritis in infants and children when administered as a 3-dose series to infants between the ages of 6 to 32 weeks. 

Each dose is an all-in-one formulation containing an antacid. The vaccine is a live-attenuated bovine-human reassortant comprising four serotypes, G1, G2, G3 and G4, and is targeted to be safe, confer non-inferior immunogenicity to already licensed vaccines and have the ability to prevent rotavirus gastroenteritis. 

The trial is designed to show non-inferiority against a currently licensed vaccine with the use of three, ready-to-use liquid doses administered orally, starting from six-to-eight weeks of age, with the subsequent doses administered at 4 weeks intervals. 

A phase I/II study was carried out with the long-term aim to produce a locally licensed vaccine that is safe and able to protect children against rotavirus gastroenteritis. 

Overall, the results showed that all three doses of the vaccine evaluated in the study were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants. 

"We aim to provide an affordable vaccine to meet the still significant medical need in emerging markets, like India, and through partnerships with organizations like Gavi, the Vaccine Alliance," said Olivier Charmeil, Sanofi Pasteur's President & CEO. 

The World Health Organization (WHO) recommends that vaccination with rotavirus vaccines should be included in all national immunization programs. Gavi, has established an accelerated vaccine introduction initiative with the objective of driving the sustainable introduction of rotavirus vaccine in 30 Gavi-eligible countries by 2015. 

In addition, PATH, an international, non-profit organization to improve public health, is working to accelerate access to rotavirus vaccines and sustain their implementation and use in countries where children need them most urgently. 

Rotavirus infections are prevalent in human populations worldwide. Although the virus can and does infect older individuals, illness caused by rotavirus can be quite severe in infants and young children. In low income countries, the median age at the primary rotavirus infection ranges from 6 to 9 months (80% occur among infants less than 1 year old) whereas in high income countries the first episode may occasionally be delayed until the age of 2-5 years, though the majority still occur in infancy (65% occur among infants less than 1 year old). 

The WHO estimates that in 2008 approximately 453,000 rotavirus gastroenteritis (RVGE) -associated child deaths occurred worldwide. These fatalities accounted for about 5% of all child deaths and a cause-specific mortality rate of 86 deaths per 100,000 population aged less than 5 years. About 90% of all rotavirus-associated fatalities occur in low income countries in Africa and Asia and are related to poor healthcare.


Comment: This is interesting news, since the Bharat Biotech vaccine for Rotavirus (116 E) made in India has already undergone the necessary testing & is likely to be launched in the next couple of months (possibly Jan 2015). Among all the newer vaccines, rotavirus is the only one where we have large amount of Indian data available regarding the disease from India through the IRSN - Indian Rotavirus Surveillance Network. This is probably one of the reasons why we are getting India specific vaccines for this disease. It is important to start vaccinating children early against this disease so as to prevent significant disease burden, since almost EVERY child will suffer from Rotavirus diarrhea if they are not vaccinated, probably by the age of 2 years.

Wednesday, October 15, 2014

What is causing the deaths in Muzaffarnagar children due to brain fever - is it an infection or a toxin in Lychee?

Written by Pritha Chatterjee | New Delhi | Posted: October 13, 2014 4:20 am
A two-year-long investigation into the “mystery” disease termed Acute Encephalitis Syndrome (AES) that kills tens of young children in Muzaffarpur, Bihar, every year has found no evidence of infectious microbes in the victims.
Instead, the investigators have said, their findings suggest “toxin mediated illness”, with a hypothesis of a toxin in the prevalent litchi fruit in the area.
The joint report, by the Centers for Disease Control (CDC), Atlanta, and National Centre for Disease Control (NCDC), under the Union Health Ministry, compares the outbreak to ackee fruit poisoning reported in the Carribean islands and West Africa.

Correction of hypoglycemia, or low blood glucose, in patients as per their recommendations, adds the report, has helped reduce mortality from 44 per cent last year to 26 per cent in 2014.
In an article in the latest internal newsletter of the NCDC, Dr Padmini Srikantiah of the CDC’s India wing and Dr Aakash Shrivastava of the NCDC’s epidemiology division say, “Based on the 2013 findings, we concluded that the outbreak appeared to be more consistent with a non-inflammatory encephalopathy rather than infectious encephalitis.”
Encephalopathy is a general term used to describe neurological symptoms while encephalitis indicates infection as a cause for the same. Explained a scientist, “We are saying the presentation indicates a generalised cause rather than an infection.”
Comparing the annual disease to ackee fruit poisoning, the authors have suggested the “potential presence of a toxin, Methylene Cyclopropyl Glycine (MCPG), with hypoglycemic activity that is found in the litchi seed”.
The CDC-NCDC team points out that hypoglycemia, not identified as a common symptom till now, was present in a majority of the cases, which the authors have said could be sparking the neurological symptoms.
In 2013, of the 303 children tested, including the control group, “hypoglycemia in 94 per cent of the children trended towards an increased risk of death”, according to the findings.
This year, 63 per cent of the 390 patients between May 26 and July 17 showed blood glucose less than 70 mg/dL.
However, various studies, including by the National Research Centre for Litchi (NRCL) in Muzaffarpur, have discounted any toxins in the litchi fruit pulp, root of the crop, seeds and skin as causing the symptoms. Litchi is a common fruit in the area.
According to the CDC-NCDC authors, “It is possible that exposure or ingestion of this toxin (MCPG) may have the potential to lead to acute hypoglycemia and precipitate the seizures that seem to be the clinical hallmark of this illness… Animal studies suggest that ingestion of MCPG may have the potential to cause acute hypoglycemia and encephalopathy, similar to ackee food poisoning described in the Carribean and West Africa.”
The investigators have advised the Bihar government to supply glucometers to hospitals to monitor sugar levels of affected children, ensure rapid treatment of hypoglycemia, and conduct a “detailed field study” to evaluate potential toxins.
The joint NCDC investigation team is, meanwhile, conducting a field study to identify toxins in pesticides, heavy metals, naturally occurring plant or fruit-based agents in Muzaffarpur area. Laboratory samples from patients are also being tested for toxin metabolites and residues.
AES affects young children between the ages of one and five, resulting in fever, sudden seizures and altered mental status. It was earlier characterised by over 90 per cent mortality.
This year, a team of the National Vector Borne Disease Control Programme had found a pesticide, Alphacyphermethrin, to be above minimum safe limits in a chemical analysis of litchi samples in Malda in West Bengal, but said it was too early to “confirm its toxicity in humans”.
Researchers, however, continue to deny the presence of any toxins in litchis. According to Dr Vishal Nath, director of the National Centre for Litchi under the Indian Council of Agricultural Research, based in Muzaffarpur, “We have been working on investigating a corelation between litchi and AES cases for years, and have performed hundreds of toxicology studies. We have established no association between the two.”
He adds that every year AES cases start surfacing in June, by when 90 per cent of the litchi crop in Muzaffarpur has already been “picked, sold and disposed of”.
Comment: We see a large number of patients from poor socio-economic status coming to PGI Chandigarh as well. Many of them die, while others are left paralysed. If we can find the root cause of these symptoms, this may help in avoiding these fatalities. Trying to find the pieces of this fascinating medical jig saw puzzle is also a great challenge. I am hopeful that Indian scientists will be able to rise above their egos, and together find the reasons for these cases of 'brain fever'

Tuesday, October 14, 2014

Updated Influenza vaccine policy by the AAP - any relevance to India?

Highlights of updated AAP policy on influenza

  1. Henry H. Bernstein, D.O., M.H.C.M., FAAP

The beginning of autumn reminds us that it is time to prepare for the 2014-’15 influenza season. The Academy’s updated recommendations for the prevention and treatment of influenza in children are available atwww.pediatrics.org/cgi/doi/10.1542/peds.2014-2413and will be published in the November issue of Pediatrics.
The 2013-’14 influenza season was less severe than the 2012-’13 one, with a lower percentage of outpatient visits for influenza-like illness, lower rates of hospitalization, and fewer deaths attributed to pneumonia and influenza. Still, providers must remain vigilant since the influenza virus is unpredictable.
The influenza season may start early in the fall/winter, have more than one disease peak in a community and even extend into late spring. Therefore, as soon as the seasonal influenza vaccine is available locally, health care personnel should be immunized, parents and caregivers should be notified about vaccine availability, and immunization of all children 6 months and older, especially children at high risk of complications from influenza, should begin.
Dr. Bernstein
Following are key messages from the updated policy statement.


The 2014-’15 influenza vaccine will be available in both trivalent and quadrivalent formulations. (Neither the Centers for Disease Control and Prevention [CDC] nor the Academy has a preference.)
The trivalent vaccine contains the following three virus strains:
  • A/California/7/2009 (H1N1)-like virus
  • A/Texas/50/2012 (H3N2) virus
  • B/Massachusetts/2/2012-like virus (B/Yamagata lineage)
The quadrivalent influenza vaccine includes the same three strains as the trivalent vaccine plus an additional B strain: B/Brisbane/60/2008-like virus (B/Victoria lineage).


Optimal protection is achieved through annual immunization. Antibody titers wane to 50% of their original levels six to 12 months after vaccination. Although the vaccine strains for the 2014-’2015 season are unchanged from last season, a repeat dose this season is critical for maintaining protection in all populations.
Outreach efforts should be made to vaccinate people in the following groups:
  • all children 6 months of age and older, especially those with conditions that increase the risk of complications from influenza (e.g., asthma, diabetes mellitus, hemodynamically significant cardiac disease, immunosuppression or neurologic and neurodevelopmental disorders);
  • children of American Indian/Alaska Native heritage;
  • all household contacts and out-of-home care providers of:
    • children with high-risk conditions, and
    • children younger than 5 years, especially infants younger than 6 months;
  • all health care personnel;
  • all child care providers and staff; and
  • all women who are pregnant, are considering pregnancy, are in the postpartum period or are breastfeeding during the influenza season.


This consideration is based on a Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis done by the CDC, which concluded that there is an increased relative efficacy of LAIV as compared with inactivated influenza vaccine (IIV) against laboratory-confirmed influenza among younger children.
If LAIV is not readily available, IIV should be used; vaccination should not be delayed in order to obtain LAIV.


  • Children 6 months through 8 years of age receiving the seasonal influenza vaccine for the first time should receive a second dose this season at least four weeks after the first dose.
  • Children 6 months through 8 years of age need only one dose of vaccine in 2014-’15 if they have received it according to any one of the following scenarios (otherwise they need two doses):
    • At least one dose of 2013-’14 seasonal influenza vaccine.
    • Two or more doses of seasonal vaccine since July 1, 2010.
    • Two or more doses of seasonal influenza vaccine from any prior season and at least one clearly documented dose of a pH1N1-containing vaccine (i.e., any seasonal vaccine since July 1, 2010, or a monovalent pH1N1 vaccine during the 2009-’10 season).


Treatment should be offered for:
  • any child hospitalized with presumed influenza or with severe, complicated or progressive illness attributable to influenza, regardless of influenza immunization status or whether onset of illness has been greater than 48 hours prior to admission; and
  • influenza infection of any severity in children at high risk of complications of influenza, such as children younger than 2 years.
Treatment should be considered for:
  • any otherwise healthy child with influenza infection for whom a decrease in duration of clinical symptoms is felt to be warranted by his or her pediatrician. The greatest impact on outcome will occur if treatment can be initiated within 48 hours of illness onset but still should be considered if later in the course of illness.
The neuraminidase inhibitors oral oseltamivir and inhaled zanamivir are the only antiviral medications routinely recommended for treatment or chemoprophylaxis of influenza for the 2014-’15 season. Chemoprophylaxis should never be a substitute for immunization.
Given preliminary pharmacokinetic data and limited safety data, oseltamivir can be used to treat influenza in both term and preterm infants from birth as benefits of therapy are likely to outweigh possible risks of treatment. Chemoprophylaxis should be considered only in term infants.


  • Dr. Bernstein is Red Book Online associate editor and an ex officio member of the AAP Committee on Infectious Diseases.

Comments: As far as India is concerned, we are using Influenza vaccine for selected 'high risk' cases. These would include children between 6 months to 2 years ( & possibly up to 5 years), and children with chronic illnesses like diabetes, heart, lung, liver & kidney problems. Since the LAIV (nasal flu vaccine) called Nasovac S has recently become available, it is preferable to use this vaccine in children between 2-8 years age as it is found to be more effective in many western studies.