Direct and indirect effect of 10 valent pneumococcal vaccine on nasopharyngeal carriage in children under 2 years of age in Matiari, Pakistan

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Abstract

Background

Pakistan introduced Ten-valent pneumococcal-conjugate-vaccine PCV10 in 2012 as a 3 + 0 schedule without catch-up.

Methods

Children <2 years old in Matiari, Sindh provided nasopharyngeal swabs between 2014 and 2018, which were cultured for pneumococcus and serotyped through multiplex PCR at the Aga Khan University Hospital. Carriage rates over time for Vaccine-Type (VT) and Non-VT (NVT) serotypes were used to estimate direct, indirect, total and overall effects of vaccination. Regression analysis was used to determine factors associated with VT carriage.

Results

Pneumococcus was detected in 2370/3140 (75%). VT carriage decreased overall, 16.1–9.6% (p-trend <0.001); vaccinated (all 3 doses of PCV10 received) 11.3–8.1% (p-trend 0.031) and unvaccinated (no PCV10 dose received) 17.4–10.3% (p-trend 0.003) with a decline in serotypes 6B, 9V/9A and 19F. Immunization increased from 41.0% to 68.4% (p-trend 0.001). Direct effect of vaccine was 32.8% (95% CI 14.7–47.0%) and indirect effect 44.6%(95% CI 40.6–48.6%). Factors associated with decreased VT colonization were education 1–5 years (aOR 0.7, 95%CI 0.6–1.0), history of difficulty breathing (aOR 0.7, 95%CI 0.5–1.0), exposure to smoke (aOR 0.8, 95% CI 0.6–1.0), child fully immunized (aOR 0.7, 95%CI 0.5–1.0) and enrolled in 3rd (aOR 0.6, 95%CI 0.4–0.8) and 4th (aOR 0.6, 95%CI 0.5–0.9) year of the study whereas history of runny nose (aOR 1.5, 95% CI 1.2–1.9) was positively associated.

Conclusions

Decrease in VT pneumococcal carriage in vaccinated and unvaccinated children indicates herd immunity. Sustained increase in vaccine coverage and close long-term surveillance is warranted.

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Most cited references 38

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Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

Tamara Pilishvili, Catherine Lexau, Monica M. Farley … (2010)

Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children. Laboratory-confirmed IPD cases were identified during 1998-2007 by 8 active population-based surveillance sites. We compared overall, age group-specific, syndrome-specific, and serotype group-specific IPD incidence in 2007 with that in 1998-1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations. Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively (P< .01 all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively (P< .01 for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups (P< .05), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006-2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old. Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.

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Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

Brian Wahl, Katherine L O'Brien, Adena Greenbaum … (2018)

Summary Background Pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015. Methods Using WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use. Findings We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015. Interpretation The widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia. Funding Bill & Melinda Gates Foundation.

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Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.

Katherine L O'Brien, Lara J. Wolfson, James P. Watt … (2009)

Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide. However, many countries lack national estimates of disease burden. Effective interventions are available, including pneumococcal conjugate vaccine and case management. To support local and global policy decisions on pneumococcal disease prevention and treatment, we estimated country-specific incidence of serious cases and deaths in children younger than 5 years. We measured the burden of pneumococcal pneumonia by applying the proportion of pneumonia cases caused by S pneumoniae derived from efficacy estimates from vaccine trials to WHO country-specific estimates of all-cause pneumonia cases and deaths. We also estimated burden of meningitis and non-pneumonia, non-meningitis invasive disease using disease incidence and case-fatality data from a systematic literature review. When high-quality data were available from a country, these were used for national estimates. Otherwise, estimates were based on data from neighbouring countries with similar child mortality. Estimates were adjusted for HIV prevalence and access to care and, when applicable, use of vaccine against Haemophilus influenzae type b. In 2000, about 14.5 million episodes of serious pneumococcal disease (uncertainty range 11.1-18.0 million) were estimated to occur. Pneumococcal disease caused about 826,000 deaths (582,000-926,000) in children aged 1-59 months, of which 91,000 (63,000-102,000) were in HIV-positive and 735,000 (519,000-825,000) in HIV-negative children. Of the deaths in HIV-negative children, over 61% (449,000 [316,000-501,000]) occurred in ten African and Asian countries. S pneumoniae causes around 11% (8-12%) of all deaths in children aged 1-59 months (excluding pneumococcal deaths in HIV-positive children). Achievement of the UN Millennium Development Goal 4 for child mortality reduction can be accelerated by prevention and treatment of pneumococcal disease, especially in regions of the world with the greatest burden. GAVI Alliance and the Vaccine Fund.

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Author and article information

Contributors

Muhammad Imran Nisar

Journal

Journal ID (nlm-ta): Vaccine

Journal ID (iso-abbrev): Vaccine

Title: Vaccine

Publisher: Elsevier Science

ISSN (Print): 0264-410X

ISSN (Electronic): 1873-2518

Publication date PMC-release: 22 February 2021

Publication date (Print): 22 February 2021

Volume: 39

Issue: 8

Pages: 1319-1327

Affiliations

[a ]Department of Pediatric and Child Health, Aga Khan University, Karachi, Pakistan

[b ]Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan

[c ]Bill & Melinda Gates Foundation, Seattle, WA, USA

[d ]Emory University, Atlanta, GA, USA

[e ]Yale Institute for Global Health, New Haven, CT, USA

Author notes

[* ]Corresponding author at: Department of Pediatrics and Child health, The Aga Khan University, Karachi, Pakistan. Imran.nisar@ 123456aku.edu

Article

Publisher Item ID: S0264-410X(20)31662-5

DOI: 10.1016/j.vaccine.2020.12.066

PMC ID: 7910277

PubMed ID: 33422379

SO-VID: 853722b6-9aa7-43b8-9fba-df09f2b95a1e

License:

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

History

Date received : 1 September 2020

Date revision received : 21 December 2020

Date accepted : 22 December 2020

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Direct and indirect effect of 10 valent pneumococcal vaccine on nasopharyngeal carriage in children under 2 years of age in Matiari, Pakistan

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Most cited references 38

Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine.

Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates.

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