Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study

The Lancet Infectious Diseases, Volume 16, No. 6, Year 2016

Interprétation

Background Little information is available about the effect of pneumococcal conjugate vaccines (PCVs) in low-income countries. We measured the effect of these vaccines on invasive pneumococcal disease in The Gambia where the 7-valent vaccine (PCV7) was introduced in August, 2009, followed by the 13-valent vaccine (PCV13) in May, 2011. Methods We conducted population-based surveillance for invasive pneumococcal disease in individuals aged 2 months and older who were residents of the Basse Health and Demographic Surveillance System (BHDSS) in the Upper River Region, The Gambia, using standardised criteria to identify and investigate patients. Surveillance was done between May, 2008, and December, 2014. We compared the incidence of invasive pneumococcal disease between baseline (May 12, 2008–May 11, 2010) and after the introduction of PCV13 (Jan 1, 2013–Dec 31, 2014), adjusting for changes in case ascertainment over time. Findings We investigated 14 650 patients, in whom we identified 320 cases of invasive pneumococcal disease. Compared with baseline, after the introduction of the PCV programme, the incidence of invasive pneumococcal disease decreased by 55% (95% CI 30–71) in the 2–23 months age group, from 253 to 113 per 100 000 population. This decrease was due to an 82% (95% CI 64–91) reduction in serotypes covered by the PCV13 vaccine. In the 2–4 years age group, the incidence of invasive pneumococcal disease decreased by 56% (95% CI 25–75), from 113 to 49 cases per 100 000, with a 68% (95% CI 39–83) reduction in PCV13 serotypes. The incidence of non-PCV13 serotypes in children aged 2–59 months increased by 47% (−21 to 275) from 28 to 41 per 100 000, with a broad range of serotypes. The incidence of non-pneumococcal bacteraemia varied little over time. Interpretation The Gambian PCV programme reduced the incidence of invasive pneumococcal disease in children aged 2–59 months by around 55%. Further surveillance is needed to ascertain the maximum effect of the vaccine in the 2–4 years and older age groups, and to monitor serotype replacement. Low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease. Funding GAVI’s Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), Bill & Melinda Gates Foundation, and the UK Medical Research Council. This population-based surveillance study was undertaken in Upper River Region, The Gambia, where the UK Medical Research Council has a field station in the town of Basse. Residents of the Basse Health and Demographic Surveillance System (BHDSS) are served by Basse Health Centre and five smaller health facilities (appendix p 16). We conducted surveillance for all cases of suspected pneumonia, sepsis, and meningitis between May 12, 2008, and Dec 31, 2014. The surveillance population included all residents of the BHDSS aged 2 months or older. The population is enumerated every 4 months, with births, deaths, migrations, and vaccinations recorded. The estimated population in 2014 was 178 510, of whom 32 530 (18%) were children younger than 5 years. Children younger than 6 months who presented at maternal and child health clinics were eligible to receive all three doses of the vaccine, whereas older children who presented at the clinics were eligible to receive one dose. PCV7 was introduced on Aug 19, 2009, and replaced by PCV13 in May, 2011, without catch-up vaccination. The study was approved by the Gambia Government–MRC Joint Institutional Ethics Committee (number 1087) and the ethics committee of the London School of Hygiene & Tropical Medicine (London, UK). Participants or their guardians gave written, informed consent. The surveillance methods used in our population-based study have been described previously.10 In brief, nurses assessed all individuals who presented as an outpatient or who were admitted to one of the six health facilities in the study area (Basse, Gambissara, Demba Kunda, Fatoto, Garawol, and Koina). Enrolment involved standardised screening of patients for referral to a clinician in Basse. Clinicians used standardised criteria to identify patients with suspected pneumonia, sepsis, or meningitis, and requested blood culture, lumbar puncture, or chest radiography according to protocol (appendix pp 7–9, 17). Aspiration of pleural fluid of lung aspiration was performed for patients with a pleural effusion or dense peripheral consolidation radiologically. We defined invasive pneumococcal disease as suspected pneumonia, sepsis, or meningitis with isolation. Vaccine failure was defined as invasive pneumococcal disease following two or more doses of PCV covering the homologous serotype, given more than 14 days before the event.11, 12 Weight was recorded on a digital scale (TANITA, Arlington Heights, IL, USA) and height with a ShorrBoard (Weigh and Measure, Olney, MD, USA). Rapid malaria tests (ICT Diagnostics, Cape Town, South Africa) were done on all patients with suspected pneumonia, sepsis, or meningitis from August to December (the malaria transmission season) each year and in a 10% random sample from January to July each year. This random sample was chosen by random selection of the final digit of the patients’ surveillance identity number (0–9) and during the dry season any patient whose identity number ended in zero had a malaria test. Samples were not collected between Oct 5 and Nov 3, 2010, when the field station flooded. Blood, lung aspirate, cerebrospinal fluid, pleural fluid, and other microbiological samples were processed in Basse using conventional microbiological culture and identification techniques.13 S pneumoniae was identified by morphology and optochin sensitivity. All pneumococcal isolates were confirmed at the WHO Regional Reference Laboratory (MRC Fajara, The Gambia), and serotyped with a latex agglutination assay using factor and group-specific antisera (Statens Serum Institut, Copenhagen, Denmark). Serotypes 6A and 6B were differentiated from 6C by PCR.14 Serotyping of 10% of isolates was repeated at the National Institute for Communicable Diseases in South Africa (Johannesburg, South Africa). The laboratories in Basse and Fajara submitted to external quality assurance throughout the study (UK National External Quality Assessment Service [Sheffield, UK], the WHO Reference Laboratory in Denmark, and the Royal Australasian College of Pathologists [Sydney, Australia]). The primary outcome of the study was the incidence of invasive pneumococcal disease, in four categories: overall invasive pneumococcal disease; invasive pneumococcal disease caused by PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and cross-reactive 6A);15 invasive pneumococcal disease caused by serotypes in PCV13 but not PCV7 (1, 3, 5, 7F, and 19A, excluding serotype 6A); and invasive pneumococcal disease caused by non-vaccine serotypes. We calculated the incidence of invasive pneumococcal disease by dividing the number of cases by the mid-point population estimates from the BHDSS and multiplying by 100 000. Age groups were prespecified as 2–23 months, 2–4 years, 5–14 years, and 15 years and older (adults). To calculate the incidence in 2008, we extrapolated cases for the unobserved period Jan 1–May 11, 2008. We derived the number of unobserved cases in 2008 by multiplying the number of observed cases from May 12 to Dec 31, 2008, by the average ratio of cases before and after May 12 in each of the years 2009 and 2011–14. The unobserved cases were grouped using the pre-PCV age and serotype distribution from 2008–09. For the flood period in 2010 (Oct 5–Nov 3, 2010), we extrapolated cases using the number of observed cases in 2010 multiplied by the average ratio of cases during the same period in each of the years 2009 and 2011–14. We applied the age and serotype distribution of the observed cases in 2010 to the unobserved cases in 2010. We corrected for age-specific changes in the number of individuals eligible for investigation per unit population by adjusting the counts of annual invasive pneumococcal disease by age group, assuming the same serotype distribution as that of the observed cases each year. We adjusted annual age-specific counts of invasive pneumococcal disease to the mean rate of enrolment of patients eligible for investigation. We assessed the effect of the PCV vaccination programme by calculating the ratio of the incidence of invasive pneumococcal disease in the last 2 years of surveillance (2013–14) compared with the baseline first 2 years (May 12, 2008–May 11, 2010). We used the Poisson distribution to calculate incidence rate ratios (IRRs) and 95% CIs. The widths of the confidence intervals were inflated to allow for overdispersion found in the 2–23-month and 5–14-year age groups, estimated from a patient-level Poisson regression analysis of 2008–09 pre-PCV invasive pneumococcal disease data. Statistical significance was set at a p value less than 0·05. To investigate potential bias caused by temporal changes in health-care seeking, patient investigation, or confounding attributable to secular trends in epidemic serotypes, we did three a-priori stratified analyses, excluding: outpatients, cases identified by lung aspiration alone, and cases caused by serotypes 1 or 5 which exhibit temporal variation in prevalence. To assess the effect of temporal trends in invasive bacterial disease, we analysed the incidence of non-pneumococcal bacteraemia, as a control condition, extrapolating case counts for missing periods in the same manner as for invasive pneumococcal disease. We also analysed temporal changes in the prevalence of contaminated blood cultures, malnutrition, and malaria in patients eligible for investigation. We used Stata version 12.1 and MATLAB version R2015a for our analyses. The study was funded by GAVI’s Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), the Bill & Melinda Gates Foundation, and the UK Medical Research Council. None of the funding sources had any role in collection, analysis, or interpretation of the data. The corresponding author had full access to all the data and was responsible for the final decision to submit for publication.

Résumé de l’IA

Study Justification:

This study aimed to investigate the impact of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease in The Gambia, a low-income country. Little information was available about the effectiveness of PCVs in low-income countries, so this study was conducted to fill this knowledge gap.

Highlights:

– The study was conducted in The Gambia, where PCV7 was introduced in August 2009, followed by PCV13 in May 2011.
– Population-based surveillance was conducted between May 2008 and December 2014 to identify and investigate cases of invasive pneumococcal disease.
– The study found that after the introduction of PCV13, the incidence of invasive pneumococcal disease decreased by 55% in children aged 2-23 months and by 56% in children aged 2-4 years.
– The reduction in disease incidence was mainly due to a significant decrease in serotypes covered by the PCV13 vaccine.
– However, there was an increase in the incidence of non-PCV13 serotypes in children aged 2-59 months.
– The study concluded that the Gambian PCV program led to a substantial reduction in invasive pneumococcal disease in children and recommended further surveillance to monitor the vaccine’s impact in older age groups and to track serotype replacement.

Recommendations:

– Further surveillance is needed to assess the long-term effectiveness of PCV13 in reducing invasive pneumococcal disease in older age groups.
– Monitoring of serotype replacement is crucial to understand the changing epidemiology of pneumococcal disease.
– Low-income and middle-income countries planning to introduce PCV13 can expect significant reductions in invasive pneumococcal disease.

Key Role Players:

– Researchers and scientists involved in conducting surveillance and analyzing the data.
– Healthcare professionals and clinicians responsible for implementing and monitoring the PCV program.
– Government officials and policymakers involved in decision-making and funding for vaccination programs.
– Community leaders and organizations involved in promoting vaccination and raising awareness among the population.

Cost Items for Planning Recommendations:

– Vaccine procurement and distribution costs.
– Training and capacity building for healthcare professionals.
– Surveillance system setup and maintenance costs.
– Communication and awareness campaigns.
– Monitoring and evaluation activities.
– Research and data analysis costs.
– Administrative and logistical expenses.

Force de la preuve

The strength of evidence for this abstract is 8 out of 10.
The evidence in the abstract is strong because it is based on a population-based surveillance study conducted over a significant period of time. The study compares the incidence of invasive pneumococcal disease before and after the introduction of pneumococcal conjugate vaccines (PCVs) in The Gambia. The study includes a large number of patients and provides specific data on the reduction in incidence of invasive pneumococcal disease in different age groups. However, to improve the evidence, the abstract could provide more information on the study design, such as the methodology used for case ascertainment and the statistical analysis performed. Additionally, it would be helpful to include information on any limitations of the study and recommendations for future research.

Abstrait

This population-based surveillance study was undertaken in Upper River Region, The Gambia, where the UK Medical Research Council has a field station in the town of Basse. Residents of the Basse Health and Demographic Surveillance System (BHDSS) are served by Basse Health Centre and five smaller health facilities (appendix p 16). We conducted surveillance for all cases of suspected pneumonia, sepsis, and meningitis between May 12, 2008, and Dec 31, 2014. The surveillance population included all residents of the BHDSS aged 2 months or older. The population is enumerated every 4 months, with births, deaths, migrations, and vaccinations recorded. The estimated population in 2014 was 178 510, of whom 32 530 (18%) were children younger than 5 years. Children younger than 6 months who presented at maternal and child health clinics were eligible to receive all three doses of the vaccine, whereas older children who presented at the clinics were eligible to receive one dose. PCV7 was introduced on Aug 19, 2009, and replaced by PCV13 in May, 2011, without catch-up vaccination. The study was approved by the Gambia Government–MRC Joint Institutional Ethics Committee (number 1087) and the ethics committee of the London School of Hygiene & Tropical Medicine (London, UK). Participants or their guardians gave written, informed consent. The surveillance methods used in our population-based study have been described previously.10 In brief, nurses assessed all individuals who presented as an outpatient or who were admitted to one of the six health facilities in the study area (Basse, Gambissara, Demba Kunda, Fatoto, Garawol, and Koina). Enrolment involved standardised screening of patients for referral to a clinician in Basse. Clinicians used standardised criteria to identify patients with suspected pneumonia, sepsis, or meningitis, and requested blood culture, lumbar puncture, or chest radiography according to protocol (appendix pp 7–9, 17). Aspiration of pleural fluid of lung aspiration was performed for patients with a pleural effusion or dense peripheral consolidation radiologically. We defined invasive pneumococcal disease as suspected pneumonia, sepsis, or meningitis with isolation. Vaccine failure was defined as invasive pneumococcal disease following two or more doses of PCV covering the homologous serotype, given more than 14 days before the event.11, 12 Weight was recorded on a digital scale (TANITA, Arlington Heights, IL, USA) and height with a ShorrBoard (Weigh and Measure, Olney, MD, USA). Rapid malaria tests (ICT Diagnostics, Cape Town, South Africa) were done on all patients with suspected pneumonia, sepsis, or meningitis from August to December (the malaria transmission season) each year and in a 10% random sample from January to July each year. This random sample was chosen by random selection of the final digit of the patients’ surveillance identity number (0–9) and during the dry season any patient whose identity number ended in zero had a malaria test. Samples were not collected between Oct 5 and Nov 3, 2010, when the field station flooded. Blood, lung aspirate, cerebrospinal fluid, pleural fluid, and other microbiological samples were processed in Basse using conventional microbiological culture and identification techniques.13 S pneumoniae was identified by morphology and optochin sensitivity. All pneumococcal isolates were confirmed at the WHO Regional Reference Laboratory (MRC Fajara, The Gambia), and serotyped with a latex agglutination assay using factor and group-specific antisera (Statens Serum Institut, Copenhagen, Denmark). Serotypes 6A and 6B were differentiated from 6C by PCR.14 Serotyping of 10% of isolates was repeated at the National Institute for Communicable Diseases in South Africa (Johannesburg, South Africa). The laboratories in Basse and Fajara submitted to external quality assurance throughout the study (UK National External Quality Assessment Service [Sheffield, UK], the WHO Reference Laboratory in Denmark, and the Royal Australasian College of Pathologists [Sydney, Australia]). The primary outcome of the study was the incidence of invasive pneumococcal disease, in four categories: overall invasive pneumococcal disease; invasive pneumococcal disease caused by PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and cross-reactive 6A);15 invasive pneumococcal disease caused by serotypes in PCV13 but not PCV7 (1, 3, 5, 7F, and 19A, excluding serotype 6A); and invasive pneumococcal disease caused by non-vaccine serotypes. We calculated the incidence of invasive pneumococcal disease by dividing the number of cases by the mid-point population estimates from the BHDSS and multiplying by 100 000. Age groups were prespecified as 2–23 months, 2–4 years, 5–14 years, and 15 years and older (adults). To calculate the incidence in 2008, we extrapolated cases for the unobserved period Jan 1–May 11, 2008. We derived the number of unobserved cases in 2008 by multiplying the number of observed cases from May 12 to Dec 31, 2008, by the average ratio of cases before and after May 12 in each of the years 2009 and 2011–14. The unobserved cases were grouped using the pre-PCV age and serotype distribution from 2008–09. For the flood period in 2010 (Oct 5–Nov 3, 2010), we extrapolated cases using the number of observed cases in 2010 multiplied by the average ratio of cases during the same period in each of the years 2009 and 2011–14. We applied the age and serotype distribution of the observed cases in 2010 to the unobserved cases in 2010. We corrected for age-specific changes in the number of individuals eligible for investigation per unit population by adjusting the counts of annual invasive pneumococcal disease by age group, assuming the same serotype distribution as that of the observed cases each year. We adjusted annual age-specific counts of invasive pneumococcal disease to the mean rate of enrolment of patients eligible for investigation. We assessed the effect of the PCV vaccination programme by calculating the ratio of the incidence of invasive pneumococcal disease in the last 2 years of surveillance (2013–14) compared with the baseline first 2 years (May 12, 2008–May 11, 2010). We used the Poisson distribution to calculate incidence rate ratios (IRRs) and 95% CIs. The widths of the confidence intervals were inflated to allow for overdispersion found in the 2–23-month and 5–14-year age groups, estimated from a patient-level Poisson regression analysis of 2008–09 pre-PCV invasive pneumococcal disease data. Statistical significance was set at a p value less than 0·05. To investigate potential bias caused by temporal changes in health-care seeking, patient investigation, or confounding attributable to secular trends in epidemic serotypes, we did three a-priori stratified analyses, excluding: outpatients, cases identified by lung aspiration alone, and cases caused by serotypes 1 or 5 which exhibit temporal variation in prevalence. To assess the effect of temporal trends in invasive bacterial disease, we analysed the incidence of non-pneumococcal bacteraemia, as a control condition, extrapolating case counts for missing periods in the same manner as for invasive pneumococcal disease. We also analysed temporal changes in the prevalence of contaminated blood cultures, malnutrition, and malaria in patients eligible for investigation. We used Stata version 12.1 and MATLAB version R2015a for our analyses. The study was funded by GAVI’s Pneumococcal vaccines Accelerated Development and Introduction Plan (PneumoADIP), the Bill & Melinda Gates Foundation, and the UK Medical Research Council. None of the funding sources had any role in collection, analysis, or interpretation of the data. The corresponding author had full access to all the data and was responsible for the final decision to submit for publication.

Matériaux

https://efashare.b-cdn.net/materials/a07e29c512948461124c0e35c79816796c4f4443ad316e2d86751817107b6bc0/mmc1.pdf

Innovations

The study titled “Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study” investigated the impact of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease in The Gambia. The study found that the introduction of PCV7 and PCV13 vaccines resulted in a significant reduction in the incidence of invasive pneumococcal disease in children aged 2-59 months. The incidence of invasive pneumococcal disease decreased by 55% in the 2-23 months age group and by 56% in the 2-4 years age group. This decrease was primarily due to a reduction in serotypes covered by the PCV13 vaccine. However, there was an increase in the incidence of non-PCV13 serotypes in children aged 2-59 months. The study concluded that low-income and middle-income countries that introduce PCV13 can expect substantial reductions in invasive pneumococcal disease.

AI Innovations Description

The study described in the provided text focuses on the effect of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease in The Gambia. The study found that the introduction of PCV13 resulted in a significant reduction in the incidence of invasive pneumococcal disease in children aged 2-59 months. The incidence decreased by 55% in the 2-23 months age group and by 56% in the 2-4 years age group. This decrease was primarily due to a reduction in serotypes covered by the PCV13 vaccine.

Based on these findings, a recommendation to improve access to maternal health could be to introduce and promote the use of PCV13 vaccination for pregnant women. This would help protect both the mother and the newborn from invasive pneumococcal disease, which can have severe consequences for maternal and child health. By integrating PCV13 vaccination into routine antenatal care services, pregnant women can easily access the vaccine and receive the necessary doses to ensure protection.

Additionally, efforts should be made to raise awareness among healthcare providers and communities about the benefits of PCV13 vaccination during pregnancy. This can be done through educational campaigns and training programs for healthcare workers. By increasing knowledge and understanding about the importance of PCV13 vaccination, more pregnant women can make informed decisions and take advantage of this preventive measure.

Furthermore, it is crucial to ensure the availability and affordability of PCV13 vaccines in maternal health settings. This can be achieved through partnerships with vaccine manufacturers, international organizations, and governments to negotiate favorable pricing and secure a sustainable supply of vaccines. By addressing these barriers, access to PCV13 vaccination for pregnant women can be improved, leading to better maternal and child health outcomes.

AI Innovations Methodology

The provided description is a summary of a study conducted in The Gambia to measure the effect of pneumococcal conjugate vaccines (PCVs) on invasive pneumococcal disease. The study aimed to assess the impact of PCV7 and PCV13 vaccines on the incidence of invasive pneumococcal disease in different age groups.

To improve access to maternal health, it is important to consider innovations that can address barriers and challenges faced by pregnant women in accessing healthcare services. Here are some potential recommendations:

1. Mobile Health (mHealth) Applications: Develop mobile applications that provide pregnant women with information on prenatal care, nutrition, and common pregnancy complications. These apps can also offer appointment reminders, medication reminders, and access to telemedicine consultations.

2. Community Health Workers: Train and deploy community health workers who can provide antenatal care, education, and support to pregnant women in remote or underserved areas. These workers can also facilitate referrals to healthcare facilities when necessary.

3. Telemedicine Services: Establish telemedicine services that allow pregnant women to consult with healthcare providers remotely. This can be particularly useful for women in rural areas who may have limited access to healthcare facilities.

4. Maternal Health Vouchers: Implement voucher programs that provide pregnant women with financial assistance to cover the costs of maternal healthcare services, including prenatal care, delivery, and postnatal care.

To simulate the impact of these recommendations on improving access to maternal health, a methodology could be developed as follows:

1. Define the target population: Identify the specific group of pregnant women who would benefit from the innovation, such as women in rural areas or low-income communities.

2. Collect baseline data: Gather information on the current state of access to maternal health services in the target population, including factors such as distance to healthcare facilities, availability of healthcare providers, and utilization rates.

3. Develop a simulation model: Create a mathematical or computational model that simulates the impact of the recommended innovations on access to maternal health. The model should consider factors such as the number of women reached, the reduction in barriers to access, and the increase in utilization rates.

4. Input data and parameters: Input relevant data and parameters into the simulation model, including the characteristics of the target population, the implementation scale of the innovations, and the expected effectiveness of each recommendation.

5. Run simulations: Run multiple simulations using different scenarios and assumptions to assess the potential impact of the innovations on improving access to maternal health. This could include variations in the scale of implementation, the coverage of the target population, and the level of utilization.

6. Analyze results: Analyze the simulation results to determine the projected impact of the recommendations on access to maternal health. This could include metrics such as the increase in the number of women accessing prenatal care, the reduction in maternal mortality rates, or the improvement in health outcomes for both mothers and infants.

7. Refine and validate the model: Continuously refine and validate the simulation model based on real-world data and feedback from stakeholders. This will help ensure the accuracy and reliability of the model’s predictions.

By following this methodology, policymakers and healthcare providers can gain insights into the potential impact of innovative interventions on improving access to maternal health and make informed decisions regarding their implementation.

Auteur

Dima Health

Statistics:

Citations: 120

Identifiers:

DOI: 10.1016/S1473-3099(16)00054-2

ISSN: 14733099

Research Areas:

Food Security, Health System and Policy, Infectious Diseases, Maternal and Child Health, Quality of Care, Social Determinants

Study Countries:

Gambia, Multi-Countries, South Africa

Study Design:

Cohort Study, Cross Sectional Study

Study Approach:

Mixed-methods, Quantitative, Systematic Review

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