Herd Effects

Key Evidence: The introduction of PCV-10, along with a “catch-up” campaign for 1-4 year olds, led to dramatic reductions in the rates of pneumococcal pneumonia in adults (≥18 years old) in a rural area of Kenya with high rates of both adult pneumococcal pneumonia and HIV. Over five years following the vaccine introduction, the incidence rates among adults were 47-94% lower each year than in the pre-vaccine period, with similar declines for HIV-infected and HIV-uninfected adults.

Key Evidence: Children with cancer often rely on herd immunity as protection from vaccine-preventable diseases, so vaccinating family members and health workers is critical. Herd effects may be the only source of protection against diseases for which the vaccines are not recommended for immunosuppressed children, such as measles.

Key Evidence: Several studies in the U.S. have shown that hospitalizations due to rotavirus fell sharply in children too old to be vaccinated as well as in adults after rotavirus vaccines were introduced, indicating herd protection. In one large study, rotavirus hospitalizations in 2008 — two years after the first vaccine was introduced — declined by 71% in 5-14 year old children and by 65% in 15-24 year olds compared to the pre-vaccine period.

From the VoICE Editors: For more information also see Lopman 2011. https://academic.oup.com/jid/article/204/7/980/810889

Key Evidence: A modelling simulation study in Germany found that routine influenza vaccination coverage of 55% in children of 6 months to 17 years indirectly reduces influenza infections by 26% in the general population through pronounced herd effects. The study authors conclude that targeting children in influenza vaccination campaigns may not only reduce their individual disease burden, but also that of non-vaccinated individuals.

Key Evidence: Two years after the introduction of 10-strain pneumococcal conjugate vaccine (PCV-10) in Mozambique, the percent of unvaccinated children under five years of age who carried pneumococcal strains in the vaccine declined 30% among HIV-infected children, while no significant decline in unvaccinated HIV-negative children was seen.

Key Evidence: A study in rural Kenya, over a 4-year period following the introduction of the 10-strain pneumococcal conjugate vaccine for infants, that included a catch-up vaccination campaign for children 12-59 months of age, suggests that the catch-up vaccination for older birth cohorts may have been a key factor in protecting unvaccinated individuals and speeding up the reduction of the disease in the community. In contrast, a study in The Gambia, where no catch-up campaign took place, found no herd effects during the first three years following the introduction of PCV-13 for infants.

From the VoICE Editors: The Gambia study publication referenced can be found at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909992/ 

Key Evidence: Several countries have seen a significant decrease in the number of rotavirus-related hospital admissions in rotavirus unvaccinated children ages 2-5 years who were not age eligible to receive the vaccine post introduction. The US had a 41-92% decrease, Australia had a 30-70% decrease, Belgium had a 20-64% decrease, Austria had a 35% reduction and El Salvador had a 41-81% decrease. In addition, there was a reduction in hospitalizations due to gastroenteritis of any cause by 17-51% in the US and 40% in Australia.

From the VoICE Editors: This data is from a review article of multiple studies that evaluated the benefits of rotavirus vaccine following vaccine introduction.

Key Evidence: While there have been concerns that vaccinating infants against varicella (chicken pox) would shift the disease to older age groups, numerous studies in countries that have introduced the vaccine have shown a decrease in varicella incidence or in hospitalizations in older age groups of 80% or greater. Indirect protection from vaccination has been reported in individuals not eligible for live vaccines and those who may be at higher risk of complications from chicken pox, such as children <1 year of age, pregnant women and immuno-compromised individuals.

Key Evidence: HPV vaccine given to young women may also protect similarly-aged men against oropharyngeal cancers, which have been rising in incidence in the U.S. and Western Europe. In a small study in the UK, rates of oral HPV infections caused by HPV-16 were similar for males 12-24 years of age and vaccinated females (0% vs. 0.5%). This was considerably lower than the rates for unvaccinated females (5.6%) and men ≥25 years old (7.1%).

From the VoICE Editors: HPV-16 is the main HPV type linked to oropharyngeal cancers

Key Evidence: There is evidence that the 4-strain HPV vaccine protects people who haven’t been vaccinated from getting HPV infection. A study in the U.S. of sexually active 13-26 year old women found that, as the vaccination rate of these women climbed from 0% to 84% over an 11-year period, the rate of infection with any of the four vaccine strains fell 40% among those who had not been vaccinated.

Key Evidence: According to some studies, hospitalizations from all causes of pneumonia declined in 18-39 year old adults in the U.S. by 26% 4 years after PCV7 vaccine was included in the infant vaccination schedule and by a further 12% with the first 2 years after PCV13 replaced PCV7. Though reductions in older age groups were not statistically significant, other U.S. studies showed significant reductions in pneumonia hospitalization rates in all adult age groups, including the elderly.

Key Evidence: In Nagoya, Japan, hospitalizations due to rotavirus (RV) decreased sharply in children 2-4 years of age once the percent of infants vaccinated against RV climbed to around 80%. Few of these older children had likely received the vaccine, suggesting that they were protected as a result of herd immunity.

Key Evidence: In a major children’s hospital in the Indian state of Tamil Nadu, meningitis cases caused by Haemophilus influenzae type b (Hib) in children under two years declined by 79% within two years of the introduction of Hib vaccine. This decline was greater than expected given a vaccination coverage of ~70% for one dose of the vaccine and much greater than expected with a 53% coverage rate for three doses. This suggests that the vaccine protected unvaccinated children through herd immunity.

Key Evidence: Hospitalization rates for pneumococcal pneumonia in adults 65 and older in Portugal — which had been increasing on average by 16% per year before pneumococcal conjugate vaccines became available — began to reverse once PCVs became available for infants. The reduction in the elderly, over expected rates, was greatest after the introduction of PCV13.

Key Evidence: The rate of invasive pneumococcal disease (IPD) in children too old to be vaccinated (≈1.5 – 10 years old) fell by 33% over a five-year period following the introduction of PCV-10 vaccines in Finland. The rate of IPD caused by serotypes in the vaccine fell by 58% in these children.

Key Evidence: School-aged children (5-18 years old) experience the highest attack rates of influenza of any age group and are thus the most important means of spread of infection in the community, making them crucial targets for influenza vaccination. In a study of school-based influenza vaccination in Los Angeles County, California, schools that offered flu vaccine to their students reduced the risk of any child getting the flu by 30% (regardless of vaccination status) compared to schools that did not offer flu vaccine to students.

Key Evidence: Data obtained through active surveillance pre and post introduction of PCV in the US showed that the vaccine averted an estimated 38,000 cases of invasive pneumococcal disease within its first five years of use. Additionally, 71,000 cases of disease were estimated to be prevented by herd effects.

Key Evidence: Following the introduction of PCV-10 for infants in Brazil, which included catch-up vaccination for children 7-23 months old and achieved high coverage (82% increasing to 94% within 5 years), hospitalization rates for pneumonia from any cause declined over the next five years by 11-27% in persons 5-49 years of age, after adjusting for trends with other causes of hospitalization.

From the VoICE Editors: Note that the rate for the elderly (65+) increased by 15% over this period —  a trend that preceded the introduction of the vaccine. 

Key Evidence: Assuming 90% coverage, a program in The Gambia using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs over the first 5 years of life of a birth cohort. The estimated cost would be $670 per DALY averted in The Gambia.

Key Evidence: In one of the first studies of real-world use of pneumococcal conjugate vaccine (PCV) in Africa, the 10-strain vaccine introduced in Kenya for infants and provided to all children under five in “catch-up” campaigns reduced the incidence of any cause of pneumonia confirmed by a chest X-ray by nearly half (48%) in children 2-59 months of age over a five-year period. This sharp reduction in radiological-confirmed pneumonia is more than twice the reduction seen in several clinical trials of PCV in Africa and Latin America which was around 20-23%.

From the VoICE Editors: The sharp reduction in radiological-confirmed pneumonia as a result of immunization in this study is likely because – unlike in some clinical trials – the herd effects of the vaccine on unvaccinated children were prospectively captured in the study.

Key Evidence: In Rwanda, the number of hospital admissions for diarrhea and rotavirus fell substantially after rotavirus vaccine (RVV) introduction, including among older children age-ineligible for vaccination. This suggests indirect protection through reduced transmission of rotavirus. Two years after RVV introduction, the country had nearly 400 fewer hospital admissions for diarrhea among young children.

Key Evidence: After PCV13 replaced PCV7 in the U.S. infant immunization program in 2010, the incidence of invasive pneumococcal disease (IPD) caused by the 6 additional serotypes in the new vaccine declined by 75% in children too old to be vaccinated (5-17 years) by the third year following the switch, and by 58-72% in adults, compared to the expected incidence if PCV7 alone had been continued. This led to overall reductions in IPD incidence of 53% in 5-17 year olds and of 12-32% in adults within three years of the switch from PCV7 to PCV13.

Key Evidence: According to a study using local epidemiological data in China, vaccinating infants with pneumococcal conjugate vaccine (PCV-13), using a 3+1 schedule, would prevent more than 10 times as many deaths from invasive pneumococcal disease and pneumonia in unvaccinated individuals (147,500 per year) than it would prevent directly in those vaccinated (12,800 per year). This would be due mainly to a reduction in hospitalizations for pneumonia.

Key Evidence: A meta-analysis of studies measuring the impact of rotavirus vaccine (RVV) on severe gastroenteritis morbidity and mortality, found a 22% herd immunity effect for severe rotavirus gastroenteritis in children less than one year of age in US and El Salvador.  In Latin America, severe gastroenteritis due to any cause was reduced by 25%.

Key Evidence: A large study in Norway found that the overall incidence of invasive pneumococcal disease (IPD) declined significantly in individuals on immunosuppressive drugs following the introduction of PCVs for infants — and most significantly in people undergoing chemotherapy. These findings underscore the benefits that childhood vaccination with PCVs affords the entire population.

Key Evidence: According to a modeled data study on cholera transmission in Bangladesh, a cholera vaccination program for 1-14 year olds in the slums of Dhaka, Bangladesh involving periodic (every 3 years) campaigns would reduce cholera incidence in adults living in these areas by 40% due to the herd effects of oral cholera vaccines.

Key Evidence: A Swedish-Finnish study conducted between 2007-2014 found that vaccinating both girls and boys against HPV (a gender-neutral vaccination strategy) could lead to the eradication of the most common cancer-causing types of the virus through stronger herd immunity. The study randomized HPV vaccination interventions across 33 towns (gender neutral HPV, girls-only HPV, and a control non-HPV vaccination), including 80,000 adolescents between ages 12 and 15. Results of general HPV screening at the age of 19 showed that gender-neutral vaccination prevented HPV infections much more effectively than vaccinating girls only.