Childhood Vaccines in India

India 2013

By Joanne Manaster

February 12, 2013

Also published at Joanne Loves Science

In 2008, WHO estimated that 1.5 million of deaths among children under 5 years were due to diseases that could have been prevented by routine vaccination. This represents 17% of global total mortality in children under 5 years of age.

Hygiene, proper nourishment and sanitary conditions make for a healthy community, with lowered incidence of infectious disease, but since much of this is lacking in developing countries, vaccination is very helpful to giving the immune system a boost.

We can thank scientists, physicians and engineers for their work in understanding the immune system and how to make it work for us against disease by using vaccinations. 

Famous scientists in the field of vaccine development

Most of you have heard the stories of how vaccinations came about starting with Edward Jenner (cowpox) to Louis Pasteur (rabies) then to Jonas Salk and Albert Sabin (polio). A story you may not have heard in school was about Maurice Hilleman and his team at Merck who developed several dozen of the most common efficacious and cost-effective vaccinations and has saved millions of lives. I highly recommend this book by Paul Offit, Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases.  There are many good books and websites on the lives Jenner, Pasteur, Salk and Sabin as well.

For a quick, fun way to learn about scientists who have made vaccination discoveries, click on this image to go to this matching game of pioneers in vaccine development.

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How Vaccines Work 

Vaccines manipulate the immune system of the recipient. Thus, to understand how vaccines work (or how to create new vaccines), we must first understand how the immune system prevents and fights infections. It is also a good idea to understand how infectious agents cause disease. This to me sounds like an entire college career!

Clicking on the image below will take you to a colorful tutorial to learn more. Go ahead and check it out!

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The goal of vaccination is to stimulate the adaptive immune system to make memory cells that will protect the vaccinated person against future exposure to a pathogen, without causing the symptoms of the disease.

There are several types of vaccines which can stimulate the immune system to provide memory and protect against future exposure to a pathogen.

According to the CDC, the GENERAL RULE is: The more similar a vaccine is to the disease-causing form of the organism, the better the immune response to the vaccine. 

What are the requirements for an effective vaccine?

They vary according to the nature of the infecting organism.

For extracellular organisms, antibodies against the organism (or part of it, some antigen) prove to be the most adaptive mechanism of host defense, whereas, for control if intracellular organisms (such as polio virus) an effective immune cell (CD8 t-lymphocyte) response is also essential.

The ideal vaccination provides host defense at the point of entry of the infectious agent; stimulation of mucosal (these are the moist nose, mouth, eye surfaces) immunity is an important goal.

Effective protective immunity against some organisms requires the presence of pre-existing antibody at the time of exposure to the infection, and booster shots are a great way to boost the presence of antibody.

Features of an effective vaccine


 
Safe  

Vaccine must not itself cause illness or death 

Protective

Vaccine must protect against illness resulting from exposure to live pathogen 

Gives sustained protection

Protection against illness must last for several years 

Induces neutralizing antibody

Some pathogens (such as poliovirus) infect cells that cannot be replaced. Neutralizing antiboody is essential to prevent infection of such cells. 

Induces protective T cells 

Some pathogens, particularly intracellular, are more effectively dealt with by cell-mediated responses 

 Practical considerations

low cost per dose, biological stability, ease of administration, few side-effects

Want to learn more about how vaccines are made? Go to this tutorial by clicking on the image.

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Listed here are the types of vaccines that can be produced based on the organism and type of response required.

1) Inactivated organism vaccines
Whole organism
Viral — polio, hepatitis A, rabies, influenza*
Bacterial — pertussis*, typhoid*, cholera*, plague*

Fractional (portion of the organism)
• protein-based
◦ toxold --diphtheria, tetanus
◦ subunit-- — hepatitis B, influenza, acellular pertussis, human papillomarvirus, anthrax
• polysaccharide-based->induces antibody production against the "sugarcoat" of certain organisms
--pneumococcal, meningococcal, Salmonella Typhi (VI), haemophilus influenzae type B
**polysaccharide based vaccines usually won't work in children younger than 2 years. Boosters are ineffective and the antibody is less functional than with other types of vaccines.

2) Live attenuated vaccines
Uses an attenuated (weakened) form of the "wild" virus or bacterium
• Must replicate to be effective
• Immune response similar to natural infection
• Usually produce immunity with one dose

Viral — measles, mumps, rebella, vaccinia, varicella, zoster, yellow fever, rotavirus, intranasal influenza, oral polio
Bacterial — BCG (against TB), oral typhoid

Drawbacks to live attenuated vaccines
• Severe reactions possible
• Interference from circulating antibody
• Fragile — must be store and handled carefully

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Challenges of Vaccination in Developing Countries

Developing countries generally wait an average of 20 years between when a vaccine is licensed in industrialized countries and when it is available for their own populations.Economic, infrastructural and scientific hurdles all contribute to this long delay. The Global Alliance for Vaccines and Immunization (GAVI) is a partnership between many public and private organization, including UNICEF, The WHO, the Bill and Melinda Gates Foundation, members of the vaccine industry and NGOs. GAVI was formed in 1999 to address the long delay between vaccine availability in industrialized countries and developing countries. Scientific advances that would help make more vaccines available in developing countries include the development of temperature stable vaccines, development of vaccines that required less than three doses to immunize and the development of needle free methods to administer vaccines.

Vaccines are complex biological substances and can lose their potency over time. They are sensitive to too cold or too hot temperatures and some are sensitive to exposure to UV light.

The "cold chain system" ensures that vaccines are kept cold from the time they leave the manufacturer all the way through to administration to the patient, but maintaining the cold chain is especially challenging in developing nations where lack of infrastructure can make it difficult to maintain proper storage temperatures. To this end, vaccine manufacturers engineered Vaccine Viral Monitors (VVMs) based on technology used in the food industry. Since March 1996, all polio vaccine through UNICEF carry VVMs, at minimal cost. As of January 2001, ALL of UNICEF's vaccine supplies are required to have VVMs.

As most of us are "painfully" aware, many vaccines must be given by injection. In developing countries, healthcare workers may not have access to an adequate supply of sterile needles, and sometimes disposable syringes are saved and reused. This could lead to the spread of blood borne diseases. This is where bioengineering really shows its strength of creating solutions to problems. I could create a very long list of devices that have been created and are considered as innovative including nasal delivery, needle free, patches with dissolvable microneedles made of sugar embedded with the vaccine. Check out what bioengineers have done for the field of vaccine administration!

"One shot" locks after one use to prevent re-use and spread of blood borne disease. Oral liquid has been used for the OPV (oral polio vaccine) and also for rotavirus Intranasal spray is an excellent way to work at the site most viruses enter This patch has vaccine embedded and moves slowly into the skin  Air gun (BioShot) uses force of air to push liquid into skin rather than needle. Very hygienic Dissolvable needles made of sugar with vaccine embedded are placed on a patch and painlessly deliver the vaccine
 BD_SoloShot.jpg photo_boy_receiving_oral_polio_vaccine.jpg art.marti.vaccine.cnn.jpg patch-vaccine.jpg Bioject1.jpg sugarneedles.jpeg

For India specifically, I found this information related to vaccine production:  "Vaccine production by indigenous manufacturers needs to be encouraged to bring down costs, reduce dependence on imports and ensure availability of vaccines specifically needed by India (e.g. typhoid) and custom made to Indian requirements (rotavirus and pneumococcal vaccines). The recent vaccination related deaths signal a need for improving immunization safety and accountability and setting up of an adverse event monitoring system. Finally setting up a system for monitoring incidence of vaccine preventable diseases and conducting appropriate epidemiological studies is necessary to make evidence based decisions on incorporation of vaccines in the national schedule and study impact of vaccines on disease incidence, serotype replacement, epidemiologic shift, etc." (source)

What are some diseases that do not have a vaccine?

Malaria: Malaria is a protozoan parasite and while tiny it is still much larger than the bacteria or viruses that cause most other diseases.

According to "Professor Adrian Hill, ... at the University of Oxford, whose group is working on malaria vaccines. "You can't really use the whole malaria parasite to make a vaccine, but you still need to generate immunity to it. That means that we have to design a subunit vaccine, which is always difficult, and in this case the major problem is to induce a big enough immune response to kill the parasite." (source)

Tuberculosis: There has been a TB vaccine for nearly 100 years, the BCG vaccine. It is not highly effective. There are several types of TB. Most of us think of the TB that affects the lungs but it can also affect bone, the bladder, and the gastrointestinal tract. The life cycle of Mycobacterium is complex and the disease can lay dormant and sequester itself in the human body for quite some time, making it difficult for the body to launch an immune attack even if it is given a boost with a vaccine. The vaccine works well in some populations but not others and is not effective in infants. Essentially the complexity of the disease and its manifestations is outfoxing our own knowledge of how to create a vaccine. You can read a story about the work on new vaccines here at NPR.

HIV: There are many reasons that a vaccine has proven so difficult to develop. HIV represents a unique challenge: our body can eliminate most acute viral infections. In contrast, our natural immune system does not destroy HIV. In fact, HIV infection results in the production of large amounts of virus, even in the presence of killer T cells and antibody. In developing a vaccine, we are faced with the challenge of tyring to elicit an dimmune response that does not exist in nature. Therefore, we don't know exactly what type of immune response a vaccine should develop. In addition, HIV virus mutates at a high rate and allows it to escape destruction by the immune system.

A note about polio eradication in India

Thankfully India has been declared Polio free for two years thanks to a very strong initiative, but there are still countries that struggle with its eradication.

Polio is a highly infectious disease caused by a virus. It invades the nervous system, and can cause total paralysis in a matter of hours. The virus enters the body through the mouth and multiplies in the intestine. Initial symptoms are fever, fatigue, headache, vomiting, stiffness in the neck and pain in the limbs. One in 200 infections leads to irreversible paralysis (usually in the legs). Among those paralysed, 5% to 10% die when their breathing muscles become immobilized. Polio mainly affects children under five years of age.

Treatment: There is no cure for polio, it can only be prevented. Polio vaccine, given multiple times, can protect a child for life.

Books: A very popular book about Polio is not about it's worldwide impact but its effect on America in Polio: An American Story by David M. Oshinsky. 

You may also check out Splendid Solution: Jonas Salk and the Conquest of Polio

Famous Scientists: Jonas Salk and Albert Sabin both made great strides towards the development of the polio vaccine. Their feud was famous as to whether a live of killed virus was the best way to inoculate against polio.

If we were able to eradicate smallpox and are on our way to eradicating polio, why can't we do this with every disease?

We were able to eradicate smallpox because its virulence was specific to humans only. If enough people are vaccinated, there will not enough of a threshold level of hosts (us) to sustain the pathogen. Once vaccination strtegies can be implemented more forcefully in areas that still have polio, it can be eradicated fully.

Diseases caused by organisms that live in the environment, like Clostridium tetani, that causes tetanus, could never be eradicated, even though we have an effective vaccine unless we were able to eliminate all Clostridium tetani from the planet. Not easily done.

Any disease that is zoonotic, meaning, can jump from animal to animal to human and back again will never be eradicated. If you want to learn about zoonotic diseases like Ebola, hantavirus, influenza and more, I HIGHLY recommend Spillover: Animal Infections and the Next Human Pandemic by David Quammen.  

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Resources

An excellent source about everything vaccine related is at the CDC 2012 Epidemiology & Prevention of 
Vaccine-Preventable Diseases

Learn more about vaccinations in India at this very comprehensive website.

A great educational site explaining vaccines in complete details is A History of Vaccines  by the College of Physicians in Philadelphia. It has games, interactive timelines, videos and more. I highly recommend this site!

The WHO maintains an excellent website related to vaccinations for most infectious diseases in developing countries here and definitely check out their massive Immunization Profile page for India

Joanne Manaster is a university-level cell and molecular biology lecturer with an insatiable passion for science outreach to all ages. Joanne traveled to India as a Fellow with IRP in February 2013 to report on child survival. Enjoy her quirky videos at www.joannelovesscience.com, on her Facebook page at JoanneLovesScience, and on Twitter @sciencegoddess.