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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- 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.
Distinct Streptococcus pneumoniae cause invasive disease in Papua New Guinea
- Mellor, Kate, Lo, Stephanie, Yoannes, Mition, Michael, Audrey, Orami, Tilda, Greenhill, Andrew, Breiman, Robert, Hawkins, Paulina, McGee, Lesley, Bentley, Stephen, Ford, Rebecca, Lehmann, Deborah
- Authors: Mellor, Kate , Lo, Stephanie , Yoannes, Mition , Michael, Audrey , Orami, Tilda , Greenhill, Andrew , Breiman, Robert , Hawkins, Paulina , McGee, Lesley , Bentley, Stephen , Ford, Rebecca , Lehmann, Deborah
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 7 (2022), p.
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- Description: Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. © 2022 The Authors.
- Authors: Mellor, Kate , Lo, Stephanie , Yoannes, Mition , Michael, Audrey , Orami, Tilda , Greenhill, Andrew , Breiman, Robert , Hawkins, Paulina , McGee, Lesley , Bentley, Stephen , Ford, Rebecca , Lehmann, Deborah
- Date: 2022
- Type: Text , Journal article
- Relation: Microbial Genomics Vol. 8, no. 7 (2022), p.
- Full Text:
- Reviewed:
- Description: Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. © 2022 The Authors.
Limited impact of neonatal or early infant schedules of 7-valent pneumococcal conjugate vaccination on nasopharyngeal carriage of Streptococcus pneumoniae in Papua New Guinean children: A randomized controlled trial
- Aho, Celestine, Michael, Audrey, Yoannes, Mition, Greenhill, Andrew, Jacoby, Peter, Reeder, John, Pomat, William, Saleu, Gerard, Namuigi, Pioto, Phuanukoonnon, Suparat, Smith-Vaughan, Heidi, Leach, Amanda, Richmond, Peter, Lehmann, Deborah
- Authors: Aho, Celestine , Michael, Audrey , Yoannes, Mition , Greenhill, Andrew , Jacoby, Peter , Reeder, John , Pomat, William , Saleu, Gerard , Namuigi, Pioto , Phuanukoonnon, Suparat , Smith-Vaughan, Heidi , Leach, Amanda , Richmond, Peter , Lehmann, Deborah
- Date: 2016
- Type: Text , Journal article
- Relation: Vaccine Reports Vol. 6, no. (2016), p. 36-43
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- Description: Streptococcus pneumoniae is a leading cause of pneumonia, the most common cause of childhood death. Papua New Guinean children experience high rates of nasopharyngeal pneumococcal colonization within weeks of birth, predisposing them to pneumococcal disease. In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage. Infants were randomized at birth to receive 7vPCV in a 0–1–2-month (n = 101) or a 1–2–3-month (n = 105) schedule or no 7vPCV (n = 106). All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. We cultured nasopharyngeal swabs (NPS) collected at ages 1, 2, 3, 4 weeks and 3, 9, 18 months, and middle ear discharge if present. Pneumococcal serotypes were identified by the Quellung reaction. A total of 1761 NPS were cultured. The prevalence of pneumococcal carriage was 22% at 1 week of age, rising to 80% by age 3 months and remained >70% thereafter, with high-density carriage in 42% of pneumococcuspositive samples. We identified 63 different serotypes; 43% of isolates from controls were 13vPCV serotypes. There were no significant differences in 7vPCV serotype carriage between 7vPCV recipients and controls at any age (22% vs. 31% at 9 months, p = 0.2). At age 9 months the prevalence of non-7vPCV carriage was 17% higher in 7vPCV recipients (48%) than in controls (25%, p = 0.02). More non-7vPCV serotypes were isolated from ear discharge in 16 7vPCV recipients than from 4 controls (48% vs. 25%, p = 0.13). The limited impact of neonatal or accelerated infant 7vPCV schedules on vaccine serotype carriage is probably due to the early onset of dense carriage of a broad range of pneumococcal serotypes. While serotype-independent pneumococcal vaccines are needed in high-risk populations, the underlying environmental factors and sources of infection must be investigated.
- Authors: Aho, Celestine , Michael, Audrey , Yoannes, Mition , Greenhill, Andrew , Jacoby, Peter , Reeder, John , Pomat, William , Saleu, Gerard , Namuigi, Pioto , Phuanukoonnon, Suparat , Smith-Vaughan, Heidi , Leach, Amanda , Richmond, Peter , Lehmann, Deborah
- Date: 2016
- Type: Text , Journal article
- Relation: Vaccine Reports Vol. 6, no. (2016), p. 36-43
- Full Text:
- Reviewed:
- Description: Streptococcus pneumoniae is a leading cause of pneumonia, the most common cause of childhood death. Papua New Guinean children experience high rates of nasopharyngeal pneumococcal colonization within weeks of birth, predisposing them to pneumococcal disease. In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage. Infants were randomized at birth to receive 7vPCV in a 0–1–2-month (n = 101) or a 1–2–3-month (n = 105) schedule or no 7vPCV (n = 106). All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. We cultured nasopharyngeal swabs (NPS) collected at ages 1, 2, 3, 4 weeks and 3, 9, 18 months, and middle ear discharge if present. Pneumococcal serotypes were identified by the Quellung reaction. A total of 1761 NPS were cultured. The prevalence of pneumococcal carriage was 22% at 1 week of age, rising to 80% by age 3 months and remained >70% thereafter, with high-density carriage in 42% of pneumococcuspositive samples. We identified 63 different serotypes; 43% of isolates from controls were 13vPCV serotypes. There were no significant differences in 7vPCV serotype carriage between 7vPCV recipients and controls at any age (22% vs. 31% at 9 months, p = 0.2). At age 9 months the prevalence of non-7vPCV carriage was 17% higher in 7vPCV recipients (48%) than in controls (25%, p = 0.02). More non-7vPCV serotypes were isolated from ear discharge in 16 7vPCV recipients than from 4 controls (48% vs. 25%, p = 0.13). The limited impact of neonatal or accelerated infant 7vPCV schedules on vaccine serotype carriage is probably due to the early onset of dense carriage of a broad range of pneumococcal serotypes. While serotype-independent pneumococcal vaccines are needed in high-risk populations, the underlying environmental factors and sources of infection must be investigated.
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
Respiratory viral pathogens associated with lower respiratory tract disease among young children in the highlands of Papua New Guinea
- Chidlow, Glenys, Laing, Ingrid, Harnett, Gerald, Greenhill, Andrew, Phuanukoonnon, Suparat, Siba, Peter, Pomat, William, Shellam, Geoffrey, Smith, David, Lehmann, Deborah
- Authors: Chidlow, Glenys , Laing, Ingrid , Harnett, Gerald , Greenhill, Andrew , Phuanukoonnon, Suparat , Siba, Peter , Pomat, William , Shellam, Geoffrey , Smith, David , Lehmann, Deborah
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Clinical Virology Vol. 54, no. 3 (2012), p. 235-239
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- Description: Background: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. Objectives: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. Study design: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. Results: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p< 0.01) or C (p< 0.05), influenza A (p< 0.0001) or respiratory syncytial virus (p< 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p< 0.0001). Conclusions: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands.
- Authors: Chidlow, Glenys , Laing, Ingrid , Harnett, Gerald , Greenhill, Andrew , Phuanukoonnon, Suparat , Siba, Peter , Pomat, William , Shellam, Geoffrey , Smith, David , Lehmann, Deborah
- Date: 2012
- Type: Text , Journal article
- Relation: Journal of Clinical Virology Vol. 54, no. 3 (2012), p. 235-239
- Full Text:
- Reviewed:
- Description: Background: Acute lower respiratory tract infections (ALRI) commonly result in fatal outcomes in the young children of Papua New Guinea (PNG). However, comprehensive studies of the viral aetiology of ALRI have not been conducted in PNG for almost 30 years. Objectives: To determine the viruses associated with ALRI among children living in the PNG highlands using sensitive molecular detection techniques. Study design: Pernasal swabs were collected routinely between 1 week and 18 months of age and also during episodes of ALRI, as part of a neonatal pneumococcal conjugate vaccine trial. A tandem multiplex real-time PCR assay was used to test for a comprehensive range of respiratory viruses in samples collected from 221 young children. Picornavirus typing was supported by DNA sequence analysis. Results: Recognized pathogenic respiratory viruses were detected in 198/273 (73%) samples collected from children with no evidence of ALRI and 69/80 (86%) samples collected during ALRI episodes. Human rhinoviruses (HRV) species A, B and C were detected in 152 (56%) samples from non-ALRI children and 50 (63%) samples collected during ALRI episodes. Partial structural region sequences for two new species C rhinoviruses were added to the GenBank database. ALRI was associated with detection of adenovirus species B (p< 0.01) or C (p< 0.05), influenza A (p< 0.0001) or respiratory syncytial virus (p< 0.0001). Multiple viruses were detected more often during ALRI episodes (49%) than when children displayed no symptoms of ALRI (18%) (p< 0.0001). Conclusions: The burden of infection with respiratory viruses remains significant in young children living in the PNG highlands.
Safety and immunogenicity of pneumococcal conjugate vaccines in a high-risk population : A randomized controlled trial of 10-valent and 13-valent pneumococcal conjugate vaccine in Papua New Guinean infants
- Pomat, William, Van Den Biggelaar, Anita, Wana, Sandra, Francis, Jacinta, Solomon, Vela, Greenhill, Andrew, Ford, Rebecca, Orami, Tilda, Passey, Megan, Jacoby, Peter, Kirkham, Lea-Ann, Lehmann, Deborah, Richmond, Peter
- Authors: Pomat, William , Van Den Biggelaar, Anita , Wana, Sandra , Francis, Jacinta , Solomon, Vela , Greenhill, Andrew , Ford, Rebecca , Orami, Tilda , Passey, Megan , Jacoby, Peter , Kirkham, Lea-Ann , Lehmann, Deborah , Richmond, Peter
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 68, no. 9 (2019), p. 1472-1481
- Full Text:
- Reviewed:
- Description: Background. There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. Methods. PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. Results. One month after the third dose of PCV10 or PCV13, 80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. Conclusions. Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. Clinical Trials Registration. NCT01619462.
- Authors: Pomat, William , Van Den Biggelaar, Anita , Wana, Sandra , Francis, Jacinta , Solomon, Vela , Greenhill, Andrew , Ford, Rebecca , Orami, Tilda , Passey, Megan , Jacoby, Peter , Kirkham, Lea-Ann , Lehmann, Deborah , Richmond, Peter
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 68, no. 9 (2019), p. 1472-1481
- Full Text:
- Reviewed:
- Description: Background. There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. Methods. PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. Results. One month after the third dose of PCV10 or PCV13, 80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. Conclusions. Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. Clinical Trials Registration. NCT01619462.
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