Yellow Fever

Yellow Fever (YF) is a mosquito-borne viral disease of humans and other primates, and is currently endemic in over 43 countries in the tropical regions of Africa and The Americas. Infection with the YF virus can be asymptomatic or cause a wide spectrum of disease, from mild symptoms to severe illness with bleeding, jaundice and, ultimately, death. Over 30,000 deaths occur each year and this figure would be much higher without vaccination. Aedes aegypti, is the most important vector. Transmission is complex with different characteristics in different endemic areas.

All currently available yellow fever vaccines are live, attenuated and based on the 17D attenuation variant. Vaccines from four manufacturers are currently prequalified by WHO.

Yellow fever vaccination is carried out for 3 reasons: to protect populations living in areas subject to endemic and epidemic disease; to protect travellers visiting these areas; and to prevent international spread by minimizing the risk of importation of the virus by viraemic travellers.

A single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. In view of the ongoing transmission of YF virus, and the proven efficacy and safety of YF vaccination, WHO recommends that all endemic countries should introduce YF vaccine into their routine immunization programmes. Vaccine should be offered to all unvaccinated travellers aged >9 months, travelling to and from at-risk areas, unless they belong to the group of individuals for whom YF vaccination is contraindicated.

Well designed and adequately powered studies are needed to assess co-administration of YF vaccine with other live vaccines, including MMR, and to assess safety and immunogenicity of YF vaccine in pregnant women, in people aged ≥60 years, and in HIV positive adults with CD4 T cell values >200 per mm(3).

Typhoid

Typhoid fever is an infection caused by the Salmonella typhi bacterium, usually through ingestion of contaminated food or water. The acute illness is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhoea. However, clinical severity varies and severe cases may lead to serious complications or even death. WHO estimates that 21 million typhoid cases and 216 000–600 000 typhoid-related deaths occur annually worldwide. A similar but often less severe disease is caused by Salmonella paratyphi bacteria.

Two typhoid vaccines are available internationally and both are considered safe and effective:

• An injectable polysaccharide vaccine based on the purified Vi antigen (known as Vi-PS vaccine) for children under two years of age.
• A live attenuated oral Ty21a vaccine currently available in capsules for those over five years of age.

WHO recommends the use of the Vi-PS and Ty21a vaccines to control endemic disease and for outbreak control. WHO further recommends that all typhoid fever vaccination programmes should be implemented in the context of other efforts to control the disease, including health education, water quality and sanitation improvements, and training of health professionals in diagnosis and treatment.

Several Vi polysaccharide–protein conjugate vaccine candidates are under development (or are nationally licensed but not on the international market) and anticipated to be available in the future for infant immunization.

Rubella

Under the Global Vaccine Action Plan, measles and rubella are targeted for elimination in 5 WHO Regions by 2020. WHO is the lead technical agency responsible for coordination of immunization and surveillance activities supporting all countries to achieve this goal.

Transmitted in airborne droplets when infected people sneeze or cough, rubella is an acute, usually mild viral disease traditionally affecting susceptible children and young adults worldwide. Rubella infection just before conception and in early pregnancy may result in miscarriage, foetal death or congenital defects known as congenital rubella syndrome (CRS). The highest risk of CRS is found in countries with high rates of susceptibility to rubella among women of childbearing age.

In 1996, an estimated 22 000 babies were born with CRS in Africa, an estimated 46 000 in South-East Asia and close to 13 000 in the Western Pacific. Very few countries in these regions had introduced rubella-containing vaccine by the year 2008, and therefore the current burden of CRS in these settings is thought to be similar to that estimated for 1996.

Rubella vaccines are available either in monovalent formulation or in combinations with other vaccine viruses, as rubella-containing vaccines (RCVs). Commonly used RCVs are combinations with vaccines against measles (MR), measles and mumps (MMR), or measles, mumps and varicella (MMRV).

Large-scale rubella vaccination during the last decade has drastically reduced or practically eliminated rubella and CRS in many developed and in some developing countries. Indeed, the western hemisphere and several European countries have eliminated rubella and CRS.

WHO recommends that countries take the opportunity of accelerated measles control and elimination activities to introduce rubella-containing vaccines. All countries that have not yet introduced rubella vaccine, and are providing two doses of measles vaccine using routine immunization and/or supplementary immunization activities should consider the inclusion of RCV in their immunization programme.

Rotavirus

Rotaviruses are the most common cause of severe diarrhoeal disease in young children throughout the world. According to WHO 2008 estimates, about 450 000 children aged <5 years die each year from vaccine-preventable rotavirus infections; the vast majority of these children live in low-income countries.

Two oral, live, attenuated rotavirus vaccines, Rotarix™ (derived from a single common strain of human rotavirus) and RotaTeq™ (reassorted bovine-human rotavirus), are available internationally; and both vaccines are considered highly effective in preventing severe gastrointestinal disease. In low income countries, vaccine efficacy can be lower than in industrialized settings, similar to other live oral vaccines, but even with this lower efficacy a greater reduction in absolute numbers of severe gastroenteritis and death was seen, due to the higher background rotavirus disease incidence.

WHO recommends that rotavirus vaccines should be included in all national immunization programmes and considered a priority particularly in countries in South and Southeast Asia and sub-Saharan Africa. WHO continues to recommend that the first dose of either RotaTeq™ or Rotarix™ be administered as soon as possible after 6 weeks of age, along with DTP vaccination. Apart from a low risk of intussusception (about 1-2 per 100 000 infants vaccinated) the current rotavirus vaccines are considered safe and well tolerated.

The public health impact of rotavirus vaccination has been demonstrated in several countries. For example, in the USA, a measurable decrease was seen in the number of rotavirus gastroenteritis hospitalizations accompanied by a suggested herd effect protecting older non-vaccinated children, while in Mexico a decline of up to 50% in diarrhoeal deaths in children < 5 years of age was attributed directly to the use of the vaccine.

WHO reiterates that the use of rotavirus vaccines should be part of a comprehensive strategy to control diarrhoeal diseases with the scaling up of both prevention (promotion of early and exclusive breastfeeding, handwashing with soap, improved water and sanitation) and treatment packages (including low-osmolarity ORS and zinc).

Rabies

Rabies is a zoonotic viral disease which infects domestic and wild animals. It is transmitted to other animals and humans through close contact with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans.

Approximately 60 000 people die from rabies each year. The vast majority of these deaths occur in Asia and Africa. Children are at particular risk.

Two types of vaccines to protect against rabies in humans exist - nerve tissue and cell culture vaccines. WHO recommends replacement of nerve tissue vaccines with the more efficacious, safer vaccines developed through cell culture as soon as possible. Cell culture vaccines which are more affordable and require less vaccine have been developed in recent years.

Intradermal immunization using cell-culture-based rabies vaccines is an acceptable alternative to standard intramuscular administration. Intradermal vaccination has been shown to be as safe and immunogenic as intramuscular vaccination, yet requires less vaccine, for both pre- and post-exposure prophylaxis, leading to lower direct costs. This alternative should thus be considered in settings constrained by cost and/or supply issues.

Pre-exposure prophylaxis is recommended for anyone at continual, frequent or increased risk of exposure to rabies virus, either by nature of their residence or occupation.

Periodic booster injections are recommended as an extra precaution only for people whose occupation puts them at continual or frequent risk of exposure. If available, antibody monitoring of personnel at risk is preferred to the administration of routine boosters.

Recommendations for post-exposure depend on the type of contact with the suspected rabid animal. For category I exposure (touching or feeding animals, licks on intact skin), no prophylaxis is required; for category II (nibbling of uncovered skin, minor scratches or abrasions without bleeding), immediate vaccination; and for category III (single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks, licks on broken skin, exposures to bats), immediate vaccination and administration of rabies immunoglobulin are recommended.

Poliomyelitis

Polio (poliomyelitis) is a highly infectious disease caused by a virus. It invades the nervous system and can cause irreversible paralysis in a matter of hours. Polio is spread through person-to-person contact. When a child is infected with wild poliovirus, the virus enters the body through the mouth and multiplies in the intestine. It is then shed into the environment through the faeces where it can spread rapidly through a community, especially in situations of poor hygiene and sanitation. If a sufficient number of children are fully immunized against polio, the virus is unable to find susceptible children to infect, and dies out.

Most infected people (90%) have no symptoms or very mild symptoms and usually go unrecognized. In others, initial symptoms include fever, fatigue, headache, vomiting, stiffness in the neck and pain in the limbs.

There is no cure for polio, only treatment to alleviate the symptoms. Heat and physical therapy is used to stimulate the muscles and antispasmodic drugs are given to relax the muscles. While this can improve mobility, it cannot reverse permanent polio paralysis.

Polio can be prevented through immunization. Polio vaccine, given multiple times, almost always protects a child for life. The development of effective vaccines to prevent paralytic polio was one of the major medical breakthroughs of the 20th century. With the development and evaluation of bivalent oral polio vaccine in 2009, the Global Polio Eradication Initiative now has an armory of five different vaccines to stop polio transmission:

• Oral polio vaccine (OPV)
• Monovalent oral polio vaccines (mOPV1 and mOPV3)
• Bivalent oral polio vaccine (bOPV)
• Inactivated polio vaccine (IPV)

If enough people in a community are immunized, the virus will be deprived of susceptible hosts and will die out. High levels of vaccination coverage must be maintained to stop transmission and prevent outbreaks occurring.

In May 2012, the World Health Assembly declared the completion of polio eradication a programmatic emergency for global public health and requested the Director-General to rapidly finalize a comprehensive eradication and endgame strategy for the period 2013-2018. The draft strategic plan and current status of the global polio eradication program were presented to SAGE. Noting the substantive progress made in implementing polio emergency action plans in the remaining polio infected countries, detailed attention to oral polio vaccine (OPV) campaign planning in the field, and new evidence in improving performance, SAGE was alarmed by the considerable funding shortfalls at a time when eradication is in sight, with OPV campaigns already cancelled or scaled back in over 25 high risk countries in 2012.

In November 2012, SAGE endorsed the four major objectives and milestones in the new strategic plan. SAGE also recommended that all countries should introduce at least one dose of inactivated polio vaccine (IPV) in their routine immunization program to mitigate the risks and consequences associated with the eventual withdrawal of the type 2 component of OPV (OPV2). SAGE will review progress on achieving the pre-requisites for OPV2 withdrawal, including the availability of affordable IPV products, every six months to ensure the earliest possible date for OPV2 withdrawal but with sufficient advance notification to ensure programmatic readiness and vaccine availability.

In the new Eradication and Endgame strategy, research is a vital component of the Global Polio Eradication Initiative, providing the necessary evidence to guide the final steps to a lasting polio-free world and beyond. The Global Polio Eradication Initiative coordinates and supports an extensive program of research from a wide range of core scientific disciplines. The research program has two broad objectives:

• to identify, develop and evaluate new tools and tailored approaches to maximize the impact of eradication efforts
• to inform long-term policy for the post-eradication era.

Malaria

Malaria is a preventable and treatable mosquito-borne illness. In 2013, 97 countries had ongoing malaria transmission. There were an estimated 207 million cases of malaria in 2012 (uncertainty range: 135 – 287 million) and an estimated 627 000 deaths (uncertainty range: 473 000 – 789 000). 90% of all malaria deaths occur in sub-Saharan Africa, and 77% occur in children under five. Between 2000 and 2012, an estimated 3.3 million lives were saved as a result of a scale-up of malaria interventions. 90%, or 3 million, of these lives saved are in the under-five age group, in sub-Saharan Africa.

There is currently no commercially available malaria vaccine, despite many decades of intense research and development effort. The most advanced vaccine candidate against Plasmodium falciparum is RTS,S/AS01. A large clinical trial with 15 460 children is ongoing in the following seven countries in sub-Saharan Africa: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and the United Republic of Tanzania.

The clinical trial data for WHO to consider making a policy recommendation is expected to be made available to WHO in late 2014. Depending on these full phase 3 results, the first WHO policy recommendations on use may occur in 2015. The policy timings depend on the outcome of the regulatory process with the European Medicines Agency.

Originally launched in 2006, The Malaria Vaccine Technology Roadmap has been updated in November 2013. The updated Roadmap represents a blueprint for second generation malaria vaccine development, including a new Vision, two new Strategic Goals and 13 priority activities, funding of which will be critical for successful development of a next generation of malaria vaccines by 2030.

HIV / AIDS

HIV/AIDS is a disease caused by the Human Immunodeficiency Virus (HIV), which targets the immune system and weakens people's surveillance and defense systems against infections and some types of cancer. As the virus destroys and impairs the function of immune cells, infected individuals gradually become immunodeficient. Immunodeficiency results in increased susceptibility to a wide range of infections and diseases that people with healthy immune systems can fight off.

HIV can be transmitted via the exchange of a variety of body fluids from infected individuals, such as blood, breast milk, semen and vaginal secretions but not by ordinary day-to-day contact such as kissing, hugging, shaking hands or sharing personal objects, food or water. The symptoms of HIV vary depending on the stage of infection. Though people living with HIV tend to be most infectious in the first few months, many are unaware of their status until later stages. The first few weeks after initial infection, individuals may experience no symptoms or an influenza-like illness including fever, headache, rash or sore throat. As the infection progressively weakens the person's immune system, the individual can develop other signs and symptoms such as swollen lymph nodes, weight loss, fever, diarrhoea and cough. Without treatment, HIV/AIDS invariably leads to the death of the infected individual.

There is currently no vaccine against HIV/AIDS. However, there are a number of very encouraging leads towards the development of a HIV vaccine. Thus, a combination of two vaccines, a modified poxvirus expressing HIV antigen and a so-called protein subunit vaccine, was shown to provide over 30% protection against HIV infection in a human clinical trial, the “RV144 protocol”, in Thailand, in 2009. The current vaccine development effort is therefore two-pronged: to improve on the results of the RV144 protocol, in trials planned in Thailand and South Africa and to develop a whole range of “second generation” products to address challenges such as the extreme variability of the HIV virus, which is recognized as an important bottleneck to HIV vaccine development.

In the absence of a licensed vaccine, WHO recommends prevention of HIV infection through:

• male and female condom use,
• testing and counselling for HIV and Sexually Transmitted Infections,
• voluntary medical male circumcision,
• anti-retroviral (ARV) drug-based prevention, including pre- and post-exposure prophylaxis,
• harm reduction for injecting drug users and (f) elimination of mother-to-child transmission of HIV.

The development of an HIV vaccine is a high priority and WHO supports this effort through technical guidance and advice.

Hepatitis E

Hepatitis E is a viral liver infection which is usually self-limiting, but may develop into fulminant hepatitis (acute liver failure). Annually, there are an estimated 20 million hepatitis E infections, over 3 million acute cases of hepatitis E, and over 57,000 hepatitis E-related deaths.

Hepatitis E virus is transmitted mainly via the faecal/oral route through ingestion of contaminated drinking water. Other, less common, transmission routes have been identified including through ingestion of food products derived from infected animals and shellfish; transfusion of infected blood products; and vertical transmission in pregnancy.

Currently, there are no WHO pre-qualified vaccines against hepatitis E. In 2011, the first vaccine to prevent hepatitis E infection was registered in China.

A Strategic Advisory Group of Experts (SAGE) on Immunization Working Group on Hepatitis E was established in October 2013 to review the existing data on the safety, immunogenicity, efficacy, and cost-effectiveness of the hepatitis E vaccine. The target date for publication of the WHO position paper on hepatitis E vaccine is early 2015.

In the absence of internationally available vaccines, WHO recommends prevention of hepatitis E infection and transmission by maintaining quality standards for public water sources and proper disposal of sanitary waste, as well as maintenance of personal hygiene practice and avoiding drinking water and/or ice of unknown purity while in areas of high endemicity.

Hepatitis B

 

Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. It is a major global health problem, and the most serious type of viral hepatitis. It is estimated that about 780,000 people die each year due to consequences of hepatitis B, such as liver cirrhosis and liver cancer.

The virus is highly contagious and is transmitted through contact with the blood or other body fluids of an infected person. Hepatitis B virus can survive outside the body for at least 7 days, and is an important occupational hazard for health workers.

Hepatitis B is preventable with currently available safe and effective vaccines.

WHO recommends that all infants should receive their first dose of vaccine as soon as possible after birth, preferably within 24 hours. Delivery of hepatitis B vaccine within 24 hours of birth should be a performance indicator for all immunization programmes. The birth dose should be followed by 2 or 3 doses to complete the primary series.

There is no evidence to support the need for a booster dose of hepatitis B vaccine. Protection lasts at least 20 years, and is possibly life-long.

WHO strongly recommends that all regions and associated countries develop goals for hepatitis B control appropriate to their epidemiological situation.

Hepatitis A

Hepatitis A is a viral liver disease that can cause mild to severe illness. Globally, there are an estimated 1.4 million cases of hepatitis A every year. Unlike hepatitis B and C, hepatitis A infection does not cause chronic liver disease and is rarely fatal, but can cause debilitating symptoms and lead to acute liver failure, which is associated with high mortality.

Hepatitis A virus is transmitted primarily via the faecal/oral route through ingestion of contaminated food and water, or through direct contact with an infectious person. Improved sanitation and vaccination are the most effective ways to combat the disease.

Several hepatitis vaccines are available internationally. Both inactivated and live attenuated hepatitis A vaccines are highly immunogenic and immunization will generate long-lasting, possibly life-long, protection against hepatitis A in children as well as in adults.

Vaccination against hepatitis A should be part of a comprehensive plan for the prevention and control of viral hepatitis, including measures to improve hygiene and sanitation and measures for outbreak control.

WHO recommends that vaccination against hepatitis A virus be integrated into the national immunization schedule for children aged 1 year or older, if indicated on the basis of local factors, including incidence of acute hepatitis A, level of endemicity, and consideration of cost-effectiveness.

The use of hepatitis A vaccine, rather than passive prophylaxis with immune globulin, is recommended for pre-exposure prophylaxis for individuals considered at increased risk, such as travellers to areas of higher hepatitis A endemicity, men who have sex with men, and people with chronic liver diseases. The vaccine can also be given as post-exposure prophylaxis to close contacts of acute cases of hepatitis A.

Dengue

Dengue is a mosquito-borne flavivirus found in tropical and sub-tropical regions of the world, mostly in urban and semi-urban settings. Day-biting Aedes mosquitos spread disease. It is the fastest spreading vector-borne viral disease and is now endemic in over 100 countries, resulting in 40% of the world’s population living in an area at risk for dengue. It is caused by one of four distinct serotypes (dengue 1-4). While the first infection with one of the four dengue serotypes is typically non-severe or asymptomatic, individuals who are subsequently exposed in later years to one of the other serotypes are more likely to develop severe dengue. Non-severe dengue illness often presents as flu-like illness, with symptoms included high fever, severe headache, pain behind the eyes, muscle and joint pains, nausea, vomiting, swollen glands, or rash. Severe dengue, including dengue hemorrhagic fever or dengue shock syndrome, is characterized by severe abdominal pain, persistent vomiting, rapid breathing, bleeding gums, fatigue, restlessness, and blood in vomit, and may be fatal due to plasma leakage, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. Although there is no specific treatment for dengue, case fatality rates can be below 1% with proper case management. In its absence, the case fatality rate can be has high at 20% in patients with severe dengue.

There are currently no licensed dengue vaccines available. Several vaccine candidates are in clinical or pre-clinical development. The most advanced candidate, a chimeric tetravalent vaccine based on the yellow fever 17d backbone, is currently under evaluation in Phase III clinical trials.

In the absence of a licensed vaccine, WHO recommends prevention of dengue through vector control methods such as mosquito habitat removal and use of insecticides. Integrated vector control, surveillance, case management, and future vaccines are the technical elements of WHO’s dengue control strategy.

The development of a dengue vaccine is a high priority and WHO supports this effort through technical guidance and advice.

Immunization Vaccines and Biologicals

Cholera

Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholera. It is a disease of poverty, closely linked to poor sanitation and lack of clean drinking water. It has a short incubation period of a few hours to five days, and is characterized in the majority of cases by acute, profuse watery diarrhoea lasting from one to a few days. In its extreme form, cholera can be rapidly fatal. The disease occurs in both endemic and epidemics patterns. Cholera incidence worldwide has increased steadily since 2005 with outbreaks affecting several continents.

Two types of oral cholera vaccines (OCVs) are currently recommended for use by WHO. The first, a monovalent vaccine based on formalin and heat-killed whole cells of V. cholerae O1 plus recombinant cholera toxin B subunit, provides short-term protection in all age groups evaluated at 4-6 months following vaccination. It also provides short-term protection against enterotoxigenic E coli (ETEC). The second type is a bivalent vaccine based on V. cholerae serogroups O1 and O139 for which evidence of efficacy persisting over 5 years follow-up in children under five years of age at vaccination has been reported (2013).

Universal Immunization Programme

Universal Immunization Programme is a vaccination program launched by the Government of India in 1985. It became a part of Child Survival and Safe Motherhood Programme in 1992 and is currently one of the key areas under National Rural Health Mission(NRHM)since 2005. The program consists of vaccination for seven diseases- tuberculosis, diphtheria, pertussis (whooping cough), tetanus, poliomyelitis, measles and Hepatitis B. Hepatitis B was added to the UIP in 2007. Thus, UIP has 7 vaccine preventable diseases in the program. 

On 2014 it was announced that four vaccines will be added to the program, namely rotavirus, rubella and Japanese encephalitis, as well as the injectable polio vaccine.

ROUTINE IMMUNIZATION IN INDIA

The Universal Immunization Programme is possibly the longest and one of the biggest public health intervention measures undertaken in India. To improve immunization coverage in the country various initiatives have been undertaken since the inception of the programme in 1985; key inputs being strengthening and expanding the cold chain system, establishing a network of outreach immunization sites, alternate vaccine delivery model, capacity building of health functionaries and medical officers and intensified polio control measures. Introduction of new and underutilized vaccines, drafting of the national vaccine policy, tracking of beneficiaries through the Maternal and Child Tracking system are some of the recent developments. However in spite of more than 25 years since inception the programme is still adversely impacted by challenges across key thematic areas of programme management, cold chain and vaccine management, recording and reporting and injection safety. To further strengthen and improve service delivery 2012-13 has been declared as the “Year of Intensification of Routine Immunization” with the objective of improving immunization coverage rates across poor performing districts and states so as to attain Global Immunization Vision and Strategy goals of 90% coverage at national and more than 80% coverage at district level. Key activities planned during the year include sustained advocacy at all levels, improved communication and social mobilization, robust and regular program reviews, comprehensive microplanning, strengthening cold chain and vaccine logistics system, special catch up rounds through immunization weeks, piloting the teeka express, improved surveillance systems, strengthened partnerships and operational research activities. The current review pertains to the existing scenario of Universal Immunization Program in the country with impetus on the existing challenges, progress achieved till date as a result of various measures and initiatives undertaken and activities lined up as a part of year of intensification of Routine Immunization.

ROUTINE IMMUNIZATION :-

A vaccination schedule is a series of vaccinations, including the timing of all doses, which may be either recommended or compulsory, depending on the country of residence.

A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or reduce the effects of infection by any natural or "wild" pathogen. Many vaccines require multiple doses for maximum effectiveness, either to produce sufficient initial immune response or to boost response that fades over time. For example, tetanus vaccine boosters are often recommended every 10 years. Vaccine schedules are developed by governmental agencies or physicians groups to achieve maximum effectiveness using required and recommended vaccines for a locality while minimizing the number of health care system interactions. Over the past two decades, the recommended vaccination schedule has grown rapidly and become more complicated as many new vaccines have been developed.

Some vaccines are recommended only in certain areas (countries, subnational areas, or at-risk populations) where a disease is common. For instance, yellow fever vaccination is on the routine vaccine schedule of French Guiana, is recommended in certain regions of Brazil but in the United States is only given to travelers heading to countries with a history of the disease. In developing countries, vaccine recommendations also take into account the level of health care access, the cost of vaccines and issues with vaccine availability and storage. Sample vaccinations schedules discussed by the World Health Organization show a developed country using a schedule which extends over the first five years of a child's life and uses vaccines which cost over $700 including administration costs while a developing country uses a schedule providing vaccines in the first 9 months of life and costing only $25. This difference is due to the lower cost of health care, the lower cost of many vaccines provided to developing nations, and that more expensive vaccines, often for less common diseases, are not utilized.

In 1900, the smallpox vaccine was the only one administered to children. By the early 1950s, children routinely received three vaccines, for protection against (diphtheria, pertussis, tetanus and smallpox), and as many as five shots by two years of age. Since the mid-1980s, many vaccines have been added to the schedule. As of 2009, the US Centers for Disease Control and Prevention (CDC) now recommends vaccination against at least fourteen diseases. By two years of age, U.S. children receive as many as 24 vaccine injections, and might receive up to five shots during one visit to the doctor. The use of combination vaccine products means that, as of 2013, the United Kingdom's immunization program consists of 10 injections by the age of two, rather than 25 if vaccination for each disease was given as a separate injection.