Evaluating the impact of Pneumococcal Conjugate Vaccine (PCV) in Kenya


PCVIS is one of the first population-level studies evaluating the impact of PCV use in a lower-middle income African country

Each year over 650,000 children under age 5 die of pneumonia, an infection of the lungs – that’s more than HIV, tuberculosis and malaria combined.

Streptococcus pneumoniae – aka the pneumococcus bacteria– is amongst the leading causes of childhood pneumonia. It’s commonly carried in the nasopharynx (the back of the nose and throat) in healthy people, mostly children.

Pneumococcal disease occurs when the bacteria move from this harmless location to other more vulnerable parts of the body, including the lungs (pneumonia) or more invasive locations such as the blood (bacteremia and sepsis) or the membranes that surround and protect the brain (meningitis).

Vaccines targeting the outer carbohydrate capsule of Streptococcus pneumoniae have existed since the 1940s; however, these formulations of vaccine were not effective in children, who are most likely to carry the bacteria and therefore most vulnerable to infection and death by pneumococcal disease.

In the last two decades, new scientific technology has allowed for the creation of so-called "conjugate" vaccines against pneumococcus that work very well in children. These PCVs link part of the outer carbohydrate capsule of the pneumococcal bacteria to a protein, which makes it possible for children to mount a strong immune response that can protect against disease.

Because of the high cost of developing and manufacturing PCVs, they are some of the most expensive vaccine products on the market – for example, in the United States it costs over $720 for a child’s recommended four doses.

This extreme cost meant that PCVs were licensed and used almost exclusively in high-income countries for the first decade of their existence; lower-income countries simply could not afford to provide them for poor children. With the help of organizations like Gavi, the Vaccine Alliance, who began subsidizing the cost of PCV for low- and middle-income countries in 2009, the vaccine has now been introduced in nearly every country in the world.

Kenya is one of the pioneering countries who became an early adopter of PCV in 2011. However, before studies like PCVIS, not much was known about whether the vaccine works differently in developing countries than it does in developed countries like the United States, where initial vaccine trials were conducted.

PCVIS is one of the first studies to evaluate the impact of routine PCV use in a lower-middle-income country setting

PCVIS leverages the Kilifi Health and Demographic Surveillance System (KHDSS), an extremely robust demographic and health data collection system established in Kilifi in 2000. Because KHDSS has meticulously documented demographic information about births, deaths, migration, etc., it provides the ideal baseline and contextual data required to measure the impact of health interventions, especially vaccines such as PCV. Each resident has a unique identifier, and this enables the linking of demographic, hospital and laboratory data which provides a powerful means of understanding individual and population level patterns of health and disease.

RESEARCH QUESTIONS

As a large-scale before-after study, PCVIS can answer important questions about the use of pneumococcal conjugate vaccine in Kenya.
How well does the vaccine protect children who have been immunized against pneumococcal disease?
By tracking the incidence of pneumococcal disease (pneumonia, meningitis and sepsis) before and then after PCV was introduced, our study can determine how much disease has been prevented by the use of the vaccine.

RESULTS


The Gavi-supported PCV10 program reduced hospital admissions for pneumonia in children under five by more than one quarter after four years of vaccine use.

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The Gavi-supported PCV10 program virtually eliminated vaccine-type invasive pneumococcal disease after four years of use.

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How well does the vaccine prevent transmission of pneumococcal bacteria within the community?
An important component of pneumococcal disease transmission is the carriage of the bacteria in the nose of healthy children and adults - potential pneumococcal disease is commonly spread by asymptomatic carriers within communities. Because carriage of the bacteria is a necessary first step for a person to become sick with pneumococcal disease and/or spread the bacteria to others, reducing carriage is likely to reduce transmission of the bacteria and therefore the number of cases of disease. Our study is measuring community carriage of pneumococcus in Kilifi along with pneumonia and invasive pneumococcal disease to gain a more comprehensive understanding of vaccine impact, beyond the impact on disease alone.

RESULTS


The Gavi-supported PCV10 program the carriage of vaccine-type bacteria in Kenya, but not to the very low levels seen in middle- and high-income countries.

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How well does the vaccine provide indirect protection for people who haven't been vaccinated?
Although pneumococcal disease is a major cause of disease and death in children, it also affects the rest of the population, especially elderly adults and those who are immunocompromised. Because PCV works largely by reducing transmission via carriage in healthy people, it has the potential to protect even those who haven’t been vaccinated through herd protection. In addition to measuring vaccine impact in vaccinated children, we also looked at the potential impact on disease and transmission in unvaccinated people.



The Gavi supported PCV10 program reduced vaccine-type IPD in unvaccinated populations (those under two months, or too young to be vaccinated, and those over five years or too old to be vaccinated), showing that PCV10 provided substantial population protection/herd immunity.

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Does the use of PCV, which only offers protection against some strains of pneumococcal bacteria, result in an increase in transmission or disease caused by non-vaccine-type strains?
Early use of PCVs in developed country settings have shown evidence that strains not included in the vaccines could begin replacing vaccine-type strains in terms of the amount if transmission and disease they cause. If the magnitude of replacement is high enough, it has the potential to significantly reduce the overall impact of vaccine use. As part of our analysis, we sought to identify and quantify this potential serotype replacement.
How good is the health system at ensuring children are vaccinated?
Because PCVIS is embedded in a robust demographic health system, which includes the Kilifi Vaccine Monitoring Study (KiVMS), we are able to track the number of children who are vaccinated each year, including detailed information about the number of vaccine doses each child receives and the timeliness of each. This allows an in-depth understanding of vaccine coverage in the population, which can offer insights about the functionality of the health system as well as context for interpreting the measured vaccine impact on disease and transmission.
Given that Kenya will begin to fully self-finance the vaccine program upon Gavi graduation, is the PCV vaccine program cost-effective in this middle-income setting?
Because the cost of introducing PCV is substantially subsidized for Gavi-eligible countries, the decision to begin and continue a Gavi-supported PCV program is often an obvious choice. However, as countries like Kenya approach Gavi graduation and the subsequent requirement to fully self-finance their vaccine programs, the exact calculation of the costs and benefits of expensive products such as PCV becomes more complicated. We performed a cost-effectiveness evaluation of the PCV program to inform evidence-based decisions about its continuation without Gavi support, which is projected to end in 2027.

PCVIS RESOURCES


Residual nasopharyngeal carriage of vaccine-type pneumococci in a mature pneumococcal conjugate vaccine immunisation programme in Kenya


Poster, 11th International Symposium on Pneumococci and Pneumococcal Diseases, 15-19 April 2018, Melbourne, Australia.

Epidemiology of serogroup 6 Streptococcus pneumoniae carriage and invasive disease in Kilifi, Kenya, and effect of the 10-valent pneumococcal conjugate vaccine (PCV10)


Poster, 11th International Symposium on Pneumococci and Pneumococcal Diseases, 15-19 April 2018, Melbourne, Australia.

Population impact of 10-valent pneumococcal conjugate vaccine (PCV10) on nasopharyngeal carriage of Streptococcus pneumoniae in Kilifi, Kenya


Poster, 11th International Symposium on Pneumococci and Pneumococcal Diseases, 15-19 April 2018, Melbourne, Australia.

KEY PCVIS PARTNERS

KEMRI-Wellcome Trust Research Programme
Centre for Geographic Medical Research Coast (CGMRC) Hospital Road,
Next to Kilifi County Hospital
P.O. Box 230-80108 Kilifi, Kenya
Email: info@kemri-wellcome.org