Pediatric Vaccines: Global Brands and Country Availability

Immunizations are an essential component of modern medicine and are paramount for global health. International immunization programs for children have many vaccines in common but, depending on the region, may vary slightly. For example, most industrialized nations tend to follow similar primary immunization schedules, as opposed to nonindustrialized countries. Geographic location also contributes to variation in immunization schedules by country. ^{[1, 2]} The choice of specific vaccines can also vary by country (eg, 10-valent pneumococcal vaccine instead of or in addition to the 13-valent pneumococcal vaccine).

Another consideration relating to global immunization is the use of travel vaccines. This is particularly important, as the number of world travelers, including children, continues to increase. In general, preparation for global travel should include an assessment of the traveler’s current vaccination status. This is imperative in children, as they are more susceptible to microbial infection than adults but less likely to receive pre-travel care. Administration of routine childhood vaccinations (eg, hepatitis, polio, and meningococcal vaccines) is often prioritized over specific travel vaccines, as these diseases are still prevalent in many underdeveloped countries. Specific travel vaccines (eg, typhoid fever, yellow fever, Japanese encephalitis) are the next consideration, as these diseases are endemic in many resource-limited countries. ^{[3, 4]}

The following tables describe vaccines for children that are used globally. While an important component of immunization programs, a review of influenza vaccines is beyond the scope of this article. However, it is important to note that the live attenuated influenza vaccine (LAIV) is no longer recommended because of efficacy concerns from past seasons. ^{[5, 6]} See Pediatric Influenza.

Hepatitis B (HBV) vaccine is included in routine childhood immunization vaccines to prevent chronic HBV infection. It is primarily given as a 3-dose immunization series, although exceptions to the 3-dose series exist for specific licensed products. For example, in the United States, Engerix-B is licensed as a 4-dose series, with doses administered at 0, 1, 2, and 12 months, whereas Recombivax HB is licensed as a 2-dose series in children aged 11-15 years. HBV vaccine is also targeted for certain high-risk populations and for travel health. For all products, the first monovalent birth dose is recommended to be administered within the first 24 hours of life in medically stable infants born to hepatitis B surface antigen–negative mothers.

The table below outlines HBV vaccines only, although combination vaccines that include HBV are also available.

Table 1. Hepatitis B Vaccine (HepB) ^[7] (Open Table in a new window)

Various pneumococcal conjugate vaccines (PCVs) are currently available, including 7-valent, 10-valent, and 13-valent vaccines. In the United States, only the pneumococcal 13-valent vaccine is available, whereas both the 10-valent and 13-valent vaccines are available in Canada. As of 2017, recommendations for 7-valent vaccine have been removed from the CDC guidelines. Based on local epidemiology of pneumococcal disease and other factors, countries may follow a 3-dose primary series or a 2-dose primary series plus a booster. Ideally, the same vaccine product should be used to complete a series owing to a lack of data regarding interchangeability of the available vaccines. However, if the initial PCV product is unknown or becomes unavailable, another PCV product can be used in its place.

Table 2. Conjugated Vaccines (PCVs) ^[7] (Open Table in a new window)

Varicella virus vaccine (VAR) is a live attenuated vaccine that protects against varicella-zoster virus. It is given as a 2-dose series in children. In the United States, VAR is recommended in all children younger than 13 years who have not had varicella virus infection, as well as in adolescents and adults without evidence of immunity.

Globally, the World Health Organization (WHO) recommends its inclusion in routine childhood immunization programs only if at least 80% vaccine coverage is sustainable. An alternate strategy for countries with a high average age of infection acquisition is to vaccinate adults and adolescents who lack immunity against the virus. Therefore, available resources and local epidemiology of infection influence country-specific recommendations. Combination vaccines that cover varicella and measles, mumps, and rubella (MMR) are available.

Table 3. Varicella Virus Vaccine Live (VAR) ^[7] (Open Table in a new window)

Some countries may administer the measles, mumps, and rubella (MMR) vaccine separately instead of in combination. The WHO recommends use of a combination vaccine of measles, mumps, and rubella when implemented for childhood immunization programs. A 2-dose series is recommended, the first administered at age 15-18 months and the second given at age 4-6 years. If not administered according to the recommendation, it is essential to provide a 2-dose catch-up regimen.

Table 4. Measles, Mumps, and Rubella Virus Vaccine (MMR) ^[7] (Open Table in a new window)

Haemophilus influenzae type B (Hib) vaccines are an essential component of pneumonia prevention. The WHO recommends 3 different immunization schedules, with the number of primary doses determined based on local epidemiology and available vaccine types. Options include a 3-dose primary series with no booster, 2-dose primary plus a booster, or 3-dose primary plus a booster. The immunization schedule should be initiated at age 6 weeks. Children older than 12 months should receive only a single dose, and it is not indicated in healthy children older than 5 years.

Table 5. Haemophilus influenzae Type B (HIB) Vaccine ^[7] (Open Table in a new window)

Inactivated polio vaccine (IPV), also called Salk vaccine, contains all three polio strains. It is used in industrialized nations that have eradicated polio and have a low risk of polio. It is also being incorporated as one dose in countries that predominantly use oral polio vaccine (OPV). ^[8]

Trivalent OPV (tOPV), also called trivalent oral polio vaccine or Sabin vaccine, contains all 3 strains. As of May 2016, trivalent tOPV is no longer used globally in routine or supplemental immunization activities. The switch to a bivalent OPV (bOPV) that contains types 1 and 3 took place in 155 countries and territories from April 17, 2017, to May 1, 2017. ^{[8, 9]}

During the transition from tOPV to bOPV, the WHO recommended that at least one dose of IPV should be added to the schedule in all countries using tOPV only to maintain eradication of wild poliovirus type 2 (WPV2), with the last case occurring in 1999. Even as the remaining strains of wild poliovirus are being eradicated, the switch from tOPV to bOPV was a major step to combat cVDPV and VAPP. Over 90% of cVDPV cases and approximately 40% of VAPP cases are due to the type 2 component of tOPV. The type 2 component of tOPV also interferes with the immune response to poliovirus types 1 and 3. ^{[8, 9]}

The CDC provides detailed guidance regarding vaccination of children who were immunized outside of the United States. ^[5]

Table 6. Inactivated Polio Vaccine (IVP) ^[7] (Open Table in a new window)

Table 7. Oral Polio Vaccine (OPV) ^[7] (Open Table in a new window)

Immunization with 3 doses of diphtheria, tetanus, and pertussis (DTP) vaccine is recommended for children within the first year of life. In the United States, only acellular pertussis-containing vaccines (DTaP) are available. Two additional booster doses are recommended between ages 1 and 6 years, for a total of five DTaP doses during childhood. This prolongs the duration of protection provided by the vaccine. Tetanus toxin–containing boosters (Td) are subsequently recommended for adolescents and adults, and this product should be used for tetanus and diphtheria boosters in children older than 7 years.

Children aged 7-10 years who receive Tdap for a catch-up series may receive either Tdap or Td for the adolescent dose given at age 11-12 years. ^[5] One dose of Tdap should also be administered to pregnant women during gestation between weeks 27 and 36. ^[5]

Additional boosters may be given and extend the duration of protection provided by the vaccines. In the United States, only acellular pertussis-containing vaccines are available.

Table 8. Diphtheria, Tetanus, and Acellular Pertussis (DTaP) Vaccine ^[7] (Open Table in a new window)

Table 9. Tetanus and Reduced Diphtheria Toxoids/Acellular Pertussis Vaccine (Tdap) ^[7] (Open Table in a new window)

Human papillomaviruses (HPV) are common worldwide, and two HPV vaccines are available—a quadrivalent and nonavalent. The bivalent vaccine (Cervarix) and quadrivalent vaccine (Gardasil) are no longer included on the US immunization schedule, as they have been removed from the market and all available doses have expired.

The quadrivalent vaccine is active against HPV types 6 and 11, which cause genital warts, and types 16 and 18, which can cause precancerous lesions and cervical cancer. The nonavalent vaccine covers an additional five HPV types (ie, 31, 33, 45, 52, and 58). In most countries, adolescent girls are targeted as the primary group for immunization. However, males are also at risk for anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58 and genital warts caused by types 6 and 11. All adolescents aged 11-12 years should receive the vaccination series, although it may be initiated as early as age 9 years, even in the absence of a high-risk condition. A two-dose series is recommended if the first dose is given before age 15 years, whereas a three-dose series is recommended is the first dose is given after age 15. An exception to this is immunocompromised children and adolescents, who require a three-dose series regardless of the age at which the series is initiated. ^[5]  The FDA has approved expanding the age range for the 9-valent HPV vaccine from 9-26 years to include adults through age 45 years. ^[10]

Table 10. Human Papillomavirus (HPV) Vaccines ^[7] (Open Table in a new window)

Rotavirus vaccines protect against rotavirusgastroenteritis, the leading cause of gastroenteritis among children worldwide. The WHO recommends that it be included in all national immunization programs. Rotarix and RotaTeq are the two available vaccines, which follow a 2-dose and 3-dose series, respectively. Vaccination is recommended beginning at age 6 months but is not recommended in children older than 24 months.

Table 11. Rotavirus Vaccine, Live ^[7] (Open Table in a new window)

Hepatitis A vaccine is administered as a routine 2-dose series. The two doses are administered 6-18 months apart. The series may be initiated in children at their first birthday, but anyone who has not received hepatitis A vaccine should receive the series, including adults. Vaccination should occur before international travel. Among international adoptees from countries of high or intermediate endemicity, vaccination should ideally be initiated more than 2 weeks before arrival in the United States. Persons with close contact (household or regular babysitting) to the adoptee should also be vaccinated. ^[2]

Table 12. Hepatitis A (HepA) Vaccine ^[7] (Open Table in a new window)

Meningococcal A vaccines

The Centers for Disease Control and Prevention (CDC) recommends routine vaccination with MenACWY-D (Menactra) or MenACWY-CRM (Menveo) in children at age 11-12 years, with a booster at age 16-18 years. High-risk children (eg, complement deficiencies, asplenia, sickle cell disease, serogroup C/Y meningococcal disease outbreak) may be vaccinated as infants, and the number of doses depends on which vaccine is administered and the age at which the vaccine is initiated. Check local recommendations. ^[2]

Children who travel to or reside in countries in which meningococcal disease is hyperendemic or epidemic, including countries in the African meningitis belt or the Hajj, should receive a 2-dose series. Prior administration of Menhibrix is insufficient, as it does not contain serogroups A or W.

Menhibrix combination vaccine (meningococcal polysaccharide groups C and Y and H influenzae type B–tetanus toxoid conjugate vaccine) may be considered in infants aged 6 weeks to 18 months who are at an increased risk for meningococcal disease.

Table 13. Meningococcal (Groups A, C, Y, and W-135) Vaccines (Open Table in a new window)

Meningococcal B (MenB) vaccines

At age 10 years, routine vaccination with one of the meningococcal group B vaccines is recommended in persons with genetic deficiencies in the complement pathway (eg, C3, properdin, factor D, factor H, C5-C9). Older adolescents and young adults aged 16 through 18 years (and through age 23 years), may be vaccinated with either a 2-dose series of Bexsero or a 2- or 3-dose series of Trumenba vaccine to provide short-term protection against most strains of serogroup B meningococcal disease in the event of an outbreak. The choice of a 2- or 3-dose series of Trumenba should be based on the patient’s exposure and susceptibility risk for meningococcal group B disease. ^[5] Insufficient evidence exists to make a routine public health recommendation that all adolescents be vaccinated with MenB vaccine. When vaccination is indicated, either product may be used; however, the two MenB vaccines are not interchangeable and the same product must be used for all doses. ^[2]

Table 14. Meningococcal Group B (MenB) Vaccines (Open Table in a new window)

The WHO recommends that Japanese encephalitis vaccines should be incorporated into routine childhood immunization schedules in all areas where Japanese encephalitis is a public health priority. ^[1] There are four types of available vaccines: inactivated Vero cell–derived, live attenuated, live recombinant, and mouse brain–derived vaccines. Mouse brain–derived vaccines have largely been replaced by cell culture–based vaccines for various factors, including safety and need for booster doses.

Inactivated Vero cell–derived vaccines (eg, Ixiaro) require two doses, whereas both the live attenuated and live recombinant vaccine products require only a single dose. Recommendations for booster doses may vary based on vaccine type, country, and age of the individual.

Ixiaro is indicated for adults and children aged 2 months or older. For children aged 2 months to younger than 18 years, primary immunization consists of a 2-dose series administered IM 28 days apart. A single 5-mL booster dose (third dose) may be given at least 11 months after completing the primary immunization series if ongoing exposure or reexposure to JEV is expected. ^[11]

Table 15. Japanese Encephalitis (JE) Vaccine (Open Table in a new window)

Currently, 3 oral cholera vaccines are available, Dukoral (manufactured by SBL Vaccines in Canada), ShanChol (manufactured by Shantha Biotec in India), and Vaxchora (manufactured by Paxvax in the United States), which are WHO prequalified. ^[12] Dukoral and ShanChol require 2-3 doses, followed by boosters every 2 years, whereas Vaxchora is a administered as a single oral dose. Vaxchora was approved in June 2016 for adults aged 18-64 years who are traveling to cholera-affected regions. ^[13] An injectable vaccine is still manufactured in some countries but is no longer recommended owing to limited efficacy and short duration of protection.

In January 2015, an application for Euvichol was submitted to obtain WHO prequalification.

In countries where cholera is endemic, the current strategy is to administer vaccinations in high-risk areas and populations, including preschool-aged and school-aged children, pregnant women, and individuals with HIV. Research regarding the role of mass immunization is ongoing.

Table 16. Cholera Vaccine ^[12] (Open Table in a new window)

Typhoid vaccines are recommended in areas where typhoid poses a significant health problem for preschool-aged and school-aged children. Immunization is particularly important where antibiotic-resistant strains of Salmonella typhi are present. Vaccines may be used to control both endemic disease and outbreaks.

The available vaccines include Vi-PS, a parenteral typhoid polysaccharide vaccine that requires 1 dose, and Ty21a, an oral live attenuated typhoid vaccine that requires 3-4 doses. A booster is necessary 3-7 years following completion of the primary immunization series.

Additional Vi polysaccharide-protein conjugate vaccines are currently under development. Some are nationally licensed but not available on the international market.

Table 17. Typhoid Vaccines for Intramuscular Administration (Open Table in a new window)

Table 18. Typhoid Vaccines for Oral Administration (Open Table in a new window)

The WHO recommends that all endemic countries should introduce yellow fever vaccine into their routine immunization schedule for children. The WHO recommends a single yellow fever vaccine to confer sustained life-long immunity. The CDC also adopted this recommendation in February 2015 but recommends a booster dose in certain individuals traveling to endemic areas, including the following: ^[14]

• Women who were pregnant when first vaccinated
• Persons who received a hematopoietic stem cell transplant following their last dose of yellow fever vaccine
• Persons who are HIV-infected
• Travelers who received yellow fever vaccine at least 10 years previously and who will be in a higher-risk setting based on season, location, activities, and duration of travel
• Laboratory workers who routinely handle wild-type yellow fever virus

Table 19. Yellow Fever Vaccine (Open Table in a new window)

The incidence of tick-borne encephalitis varies considerably between and within geographical regions. Because of this, public immunization strategies are based on risk assessments conducted at country, regional, or district level and are guided by the local endemic situation. The WHO recommends immunization of all age groups, including children, in countries with an average incidence of clinical disease of more than 5 cases/100,000 population. ^[1]

For the vaccines manufactured in Austria and Germany (FSME-Immun and Encepur) that can be given at age 1 year or older, an interval of 1-3 months is recommended between the first 2 doses and 5-12 months between the second and third doses. When rapid protection is required (eg, among persons who will be travelling to endemic areas), the interval between the first two doses may be reduced to 1-2 weeks. ^[1]

With the vaccines manufactured in the Russian Federation (TBE-Moscow and EnceVir), the recommended intervals are 1-7 months between the first 2 doses and 12 months between the second and third doses. Booster doses are recommended every 3 years among those at continued risk of exposure. ^[1]

Tick-borne encephalitis is endemic in focal areas of Europe and Asia, extending from eastern France to northern Japan and from northern Russia to Albania.

Table 20. Tick-Borne Encephalitis Vaccines (Open Table in a new window)

Production and use of nerve-tissue rabies vaccines should be discontinued and replaced with cell-culture–based vaccines (CCVs). The WHO recommends immunization with rabies vaccine among anyone who will be at continual, frequent, or increased risk of exposure to the rabies virus as a result of residence or occupation. In particular, those with outdoor exposure in rural high-risk areas where immediate access to appropriate medical care may be limited should also be vaccinated, regardless of the duration of stay. ^[1]

In areas where canine rabies is a public health problem, the WHO encourages studies on the feasibility, cost-effectiveness, and long-term impact of incorporating rabies vaccination into the immunization program for infants and children.

Table 21. Rabies Vaccines (Open Table in a new window)

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a vaccine that has been available for 90 years but that now has limited use against tuberculosis (TB). While not recommended for general use in the United States, BCG vaccine is still used in infants and small children living in countries with a high prevalence of TB. Children who are HIV-positive or have an unknown HIV status should not receive BCG vaccine. BCG can interfere with TB skin test results by causing a false-positive reaction.

Recent studies have shown that mass immunization in latently infected populations, particularly adolescents and young adults, will likely affect new disease transmission. TB vaccine research continues to progress, and two vaccines are in large-scale efficacy studies. This is an important step forward to combat the growing issue of TB-resistant antibiotics. ^[15]

Table 22. BCG Vaccine ^[7] (Open Table in a new window)