Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New Guinea in the era of conjugate vaccines: study methods and challenges
- Blyth, Christopher, Ford, Rebecca, Sapura, Joycelyn, Kumani, Tonny, Masiria, Geraldine, Kave, John, Yuasi, Lapule, Greenhill, Andrew, Hwaihwanje, Ilomo, Lang, Amanda, Lehmann, Deborah, Pomat, William
- Authors: Blyth, Christopher , Ford, Rebecca , Sapura, Joycelyn , Kumani, Tonny , Masiria, Geraldine , Kave, John , Yuasi, Lapule , Greenhill, Andrew , Hwaihwanje, Ilomo , Lang, Amanda , Lehmann, Deborah , Pomat, William
- Date: 2017
- Type: Text , Journal article
- Relation: Pneumonia Vol. 9, no. 1 (2017/03/05 2017), p. 5
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- Reviewed:
- Description: Background: Pneumonia and meningitis are common causes of severe childhood illness in Papua New Guinea (PNG). The etiology of both clinical conditions in PNG has not been recently assessed. Changes in lifestyle, provision and access to healthcare, antimicrobial utilization and resistance, and the national childhood vaccination schedule necessitate reassessment. Methods: A prospective case-control study was undertaken, enrolling children <5 years of age to determine the contemporary etiology of clinically defined moderate or severe pneumonia or suspected meningitis. Cases were identified following presentation for inpatient or outpatient care in Goroka town, the major population centre in the Eastern Highlands Province. Following enrolment, routine diagnostic specimens including blood, nasopharyngeal swabs, urine and (if required) cerebrospinal fluid, were obtained. Cases residing within one hour’s drive of Goroka were followed up, and recruitment of healthy contemporaneous controls was undertaken in the cases’ communities. Results: 998 cases and 978 controls were enrolled over 3 years. This included 784 cases (78.6%) with moderate pneumonia, 187 (18.7%) with severe pneumonia and 75 (7.5%) with suspected meningitis, of whom 48 (4.8%) had concurrent pneumonia. The median age of cases was 7.8 months (Interquartile range [IQR] 3.9–14.3), significantly lower than community controls, which was 20.8 months (IQR 8.2–36.4). Half the cases were admitted to hospital (500/998; 50.1%). Recruitment of cases and controls and successful collection of diagnostic specimens improved throughout the study, with blood volume increasing and rates of blood culture contamination decreasing. The overall case fatality rate was 18/998 (1.8%). Of cases eligible for follow-up, outcome data was available from 76.7%. Low but increasing coverage of Haemophilus influenzae type B conjugate vaccines on the national schedule was observed during the study period: three dose DTPw-HepB-Hib coverage in children >3 months increased from 14.9 to 43.0% and 29.0 to 47.7% in cases and controls (both p < 0.001). Despite inclusion in the national immunization program in 2014, 2015 PCV13 three-dose coverage in cases and controls >3 months was only 4.0 and 6.5%. Conclusions: Recruitment of large numbers of pediatric pneumonia and meningitis cases and community controls in a third-world setting presents unique challenges. Successful enrolment of 998 cases and 978 controls with comprehensive clinical data, biological specimens and follow up was achieved. Increased vaccine coverage remains an ongoing health priority.
- Authors: Blyth, Christopher , Ford, Rebecca , Sapura, Joycelyn , Kumani, Tonny , Masiria, Geraldine , Kave, John , Yuasi, Lapule , Greenhill, Andrew , Hwaihwanje, Ilomo , Lang, Amanda , Lehmann, Deborah , Pomat, William
- Date: 2017
- Type: Text , Journal article
- Relation: Pneumonia Vol. 9, no. 1 (2017/03/05 2017), p. 5
- Full Text:
- Reviewed:
- Description: Background: Pneumonia and meningitis are common causes of severe childhood illness in Papua New Guinea (PNG). The etiology of both clinical conditions in PNG has not been recently assessed. Changes in lifestyle, provision and access to healthcare, antimicrobial utilization and resistance, and the national childhood vaccination schedule necessitate reassessment. Methods: A prospective case-control study was undertaken, enrolling children <5 years of age to determine the contemporary etiology of clinically defined moderate or severe pneumonia or suspected meningitis. Cases were identified following presentation for inpatient or outpatient care in Goroka town, the major population centre in the Eastern Highlands Province. Following enrolment, routine diagnostic specimens including blood, nasopharyngeal swabs, urine and (if required) cerebrospinal fluid, were obtained. Cases residing within one hour’s drive of Goroka were followed up, and recruitment of healthy contemporaneous controls was undertaken in the cases’ communities. Results: 998 cases and 978 controls were enrolled over 3 years. This included 784 cases (78.6%) with moderate pneumonia, 187 (18.7%) with severe pneumonia and 75 (7.5%) with suspected meningitis, of whom 48 (4.8%) had concurrent pneumonia. The median age of cases was 7.8 months (Interquartile range [IQR] 3.9–14.3), significantly lower than community controls, which was 20.8 months (IQR 8.2–36.4). Half the cases were admitted to hospital (500/998; 50.1%). Recruitment of cases and controls and successful collection of diagnostic specimens improved throughout the study, with blood volume increasing and rates of blood culture contamination decreasing. The overall case fatality rate was 18/998 (1.8%). Of cases eligible for follow-up, outcome data was available from 76.7%. Low but increasing coverage of Haemophilus influenzae type B conjugate vaccines on the national schedule was observed during the study period: three dose DTPw-HepB-Hib coverage in children >3 months increased from 14.9 to 43.0% and 29.0 to 47.7% in cases and controls (both p < 0.001). Despite inclusion in the national immunization program in 2014, 2015 PCV13 three-dose coverage in cases and controls >3 months was only 4.0 and 6.5%. Conclusions: Recruitment of large numbers of pediatric pneumonia and meningitis cases and community controls in a third-world setting presents unique challenges. Successful enrolment of 998 cases and 978 controls with comprehensive clinical data, biological specimens and follow up was achieved. Increased vaccine coverage remains an ongoing health priority.
Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial
- Orami, Tilda, Aho, Celestine, Ford, Rebecca, Pomat, William, Greenhill, Andrew, Kirkham, Lea-Ann, Masiria, Geraldine, Nivio, Birunu, Britton, Kathryn, Jacoby, Peter, Richmond, Peter, van den Biggelaar, Anita, Lehmann, Deborah
- Authors: Orami, Tilda , Aho, Celestine , Ford, Rebecca , Pomat, William , Greenhill, Andrew , Kirkham, Lea-Ann , Masiria, Geraldine , Nivio, Birunu , Britton, Kathryn , Jacoby, Peter , Richmond, Peter , van den Biggelaar, Anita , Lehmann, Deborah
- Date: 2023
- Type: Text , Journal article
- Relation: Vaccine Vol. 41, no. 37 (2023), p. 5392-5399
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- Description: Background: Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). Methods: Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). Results: S. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC
- Authors: Orami, Tilda , Aho, Celestine , Ford, Rebecca , Pomat, William , Greenhill, Andrew , Kirkham, Lea-Ann , Masiria, Geraldine , Nivio, Birunu , Britton, Kathryn , Jacoby, Peter , Richmond, Peter , van den Biggelaar, Anita , Lehmann, Deborah
- Date: 2023
- Type: Text , Journal article
- Relation: Vaccine Vol. 41, no. 37 (2023), p. 5392-5399
- Full Text:
- Reviewed:
- Description: Background: Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13). Methods: Infants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC). Results: S. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC
Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea
- Lehmann, Deborah, Kirarock, Wendy, van den Biggelaar, Anita, Passey, Megan, Jacoby, Peter, Saleu, Gerard, Masiria, Geraldine, Nivio, Birunu, Greenhill, Andrew, Orami, Tilda, Francis, Jacinta, Ford, Rebecca, Kirkham, Lea-Ann, Solomon, Vela, Richmond, Peter, Pomat, William
- Authors: Lehmann, Deborah , Kirarock, Wendy , van den Biggelaar, Anita , Passey, Megan , Jacoby, Peter , Saleu, Gerard , Masiria, Geraldine , Nivio, Birunu , Greenhill, Andrew , Orami, Tilda , Francis, Jacinta , Ford, Rebecca , Kirkham, Lea-Ann , Solomon, Vela , Richmond, Peter , Pomat, William
- Date: 2017
- Type: Text , Journal article
- Relation: Pneumonia Vol. 9, no. 20 (2017), p.
- Full Text:
- Reviewed:
- Description: Background: Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. Methods: This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG’s accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. Results: This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Conclusion: Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization
- Authors: Lehmann, Deborah , Kirarock, Wendy , van den Biggelaar, Anita , Passey, Megan , Jacoby, Peter , Saleu, Gerard , Masiria, Geraldine , Nivio, Birunu , Greenhill, Andrew , Orami, Tilda , Francis, Jacinta , Ford, Rebecca , Kirkham, Lea-Ann , Solomon, Vela , Richmond, Peter , Pomat, William
- Date: 2017
- Type: Text , Journal article
- Relation: Pneumonia Vol. 9, no. 20 (2017), p.
- Full Text:
- Reviewed:
- Description: Background: Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. Methods: This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG’s accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. Results: This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Conclusion: Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal carriage, antibody production and function, and immune memory. The final data will inform policy on pneumococcal vaccine schedules in countries with children at high risk of pneumococcal disease by providing direct comparison of an accelerated schedule of 10vPCV and 13vPCV and the potential advantages of PPV following PCV immunization
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