A neonatal pneumococcal conjugate vaccine trial in Papua New guinea: study population, methods and operational challenges (original) (raw)
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Pneumonia (Nathan Qld.), 2017
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. 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. This open randomized-controlled trial was conducted...
PLoS ONE, 2013
Background: Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. Methods: We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration $0.35 mg/ml of VT serotypespecific pneumococcal IgG at age 2 months and one month post-PPV. Results: We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p,0.001) and 9V (p,0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p,0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. Conclusions: PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.
Clinical Infectious Diseases
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. Keywords. pneumococcal conjugate vaccine; S. pneumonia; antibodies; carriage; Papua New Guinea. The global implementation of pneumococcal conjugate vaccine (PCV) in childhood immunization programs has been faster than for any other vaccine in the past, reaching an estimated global coverage of 42% in 2016 [1] and has prevented an estimated 230 000 to 290 000 pneumococcal deaths in children under 5 years of age in low-income countries between 2009 and 2015 [2]. Still, many infants are not being vaccinated against pneumococcal infections. Although supply shortages have delayed PCV introduction in many countries [2], other countries are yet to decide on implementing PCV and which vaccine to choose. Currently, 10-valent (PCV10) and 13-valent (PCV13) vaccines are licensed for immunization of infants. These vaccines differ in composition: PCV13 covers 3 additional serotypes compared to PCV10, whereas PCV10 contains a nontypeable Haemophilus influenzae (NTHi) Protein D carrier [3-5]. Both vaccines are effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes in low-and high-risk populations [6, 7]. Of the 135 countries that introduced PCV by 2016, 69% implemented PCV13, 22% PCV10, and 8% are offering both [8]. In low-income countries this pattern is similar (76% use PCV13 and 23% PCV10), but the actual number of supplied doses of PCV10 and PCV13 is comparable due to different population sizes [2]. Because countries with the highest burden of childhood pneumococcal disease in general also have the lowest national
PloS one, 2017
In an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3-5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination. Circulating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3-5 years of age for a subgroup of study children. Serotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children i...
Maternal immunization with pneumococcal polysaccharide vaccine in the highlands of Papua New Guinea
Vaccine, 2002
In Tari, Southern Highlands Province (SHP), Papua New Guinea (PNG), pneumococcal polysaccharide (Pnc PS) vaccine was offered to women at 28–38 weeks gestation. Blood samples were collected for measurement of pneumococcal antibody titres prior to immunization, from mother and cord at delivery and from their children at ages 1–3 and 4–6 months; samples were also collected in a subset of children before and 1 month after Pnc PS vaccine was given at age 8–9 months. Serum was collected from unimmunized women and their children at delivery and from children of unimmunized women at the same ages in infancy. There were no differences in neonatal or post-neonatal mortality rates or congenital abnormalities in the children of 235 immunized and 202 unimmunized women. There was a significant increase in antibody titres to pneumococcal serotypes 5, 14 and 23F in immunized women but not for serotype 7F. Geometric mean titres (GMTs) of antibodies for serotypes 5 and 23F were significantly higher in children of immunized women than in the unimmunized group up to age 2 months and for serotype 14 significantly higher to age 4 months. Maternal immunization did not significantly affect the children’s capacity to make antibody responses to immunization with Pnc PS vaccine in infancy. The findings of this study and those in several other developing countries provide support for the concept of Pnc PS maternal immunization and justify the planning of large-scale efficacy trials.
Studies of maternal immunisation with pneumococcal polysaccharide vaccine in Papua New Guinea
Vaccine, 2003
In two studies, pneumococcal polysaccharide (Pnc PS) vaccine was given to more than 400 pregnant Papua New Guinean women. No deleterious effects were found. The vaccine prevented acute lower respiratory infection (ALRI) among offspring in utero or aged 1–17 months at the time of maternal immunisation, suggesting protection through breast feeding. Serum IgG antibody titres were higher in vaccinated than unvaccinated groups for 2–4 months after delivery and no immune suppression, evaluated by the response to subsequent Pnc PS vaccination, was detected. Breast milk IgA to four serotypes was 1.1–1.8 times higher in immunised than unimmunised women for 6 months postpartum. Given results from several developing countries, large-scale safety and efficacy trials are now justified. Postpartum maternal immunisation is another intervention under consideration.
Pneumonia
Background Maternal immunization with pneumococcal conjugate vaccine (PCV) may protect young infants in high-risk settings against the high risk of pneumococcal infections in early life. The aim of this study was to determine the safety and immunogenicity of 13-valent PCV (PCV13) in healthy women of childbearing age in PNG. Methods As part of this observational study, 50 non-pregnant women of childbearing age (18-45 yrs. old) living in the highlands of PNG were vaccinated with a single dose of PCV13. Local and systemic reactogenicity were assessed 24–48 h after vaccination. Venous blood samples were collected before and 1 month after vaccination to measure PCV13 serotype-specific IgG antibody concentrations. Results No severe adverse effects were reported during the 1-month follow-up period. IgG antibody concentrations significantly increased after vaccination for all PCV13 serotypes. One month after vaccination IgG antibody levels ≥2.5 μg/mL were reached in at least 75% of women fo...
Vaccine, 2020
Introduction: Invasive pneumococcal disease remains a major cause of hospitalization and death in Papua New Guinean (PNG) children. We assessed mucosal IgA and IgG responses in PNG infants vaccinated with pneumococcal conjugate vaccine (PCV) followed by a pneumococcal polysaccharide vaccine (PPV) booster. Methods: Infants received 7-valent PCV (7vPCV) in a 0-1-2 (neonatal) or 1-2-3-month (infant) schedule, or no 7vPCV (control). At age 9 months all children received 23-valent PPV (23vPPV). IgA and IgG to 7vPCV and non-7vPCV (1, 5, 7F, 19A) serotypes were measured in saliva collected at ages 1, 2, 3, 4, 9, 10 and 18 months (131 children, 917 samples). Correlations were studied between salivary and serum IgG at 4, 10 and 18 months. Results: Salivary IgA and IgG responses overall declined in the first 9 months. Compared to non-7vPCV recipients, salivary IgA remained higher in 7vPCV recipients for serotypes 4 at 3 months, 6B at 3 months (neonatal), and 14 at 3 (neonatal), 4 and 9 months (infant); and for salivary IgG for serotypes 4 at 3, 4 and 9 months, 6B at 9 months, 14 at 4 (neonatal) and 9 months, 18C at 3, 4, and 9 (infant) months, and 23F at 4 months. Following 23vPPV, salivary 7vPCV-specific IgA and IgG increased in 7vPCV-vaccinated children but not in controls; and salivary IgA against non-PCV serotypes 5 and 7F increased in 7vPCV recipients and non-recipients. Salivary and serum IgG against 7vPCV-serotypes correlated in 7vPCV-vaccinated children at 4 and 10 months of age. Conclusions: PCV may protect high-risk children against pneumococcal colonization and mucosal disease by inducing mucosal antibody responses and priming for mucosal immune memory that results in mucosal immune responses after booster PPV. Saliva can be a convenient alternative sample to serum to study PCV-induced systemic IgG responses.
2021
BackgroundInvasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants aged <90 days in Blantyre, Malawi over a 14 year period and evaluated the impact of the 12 November 2011 introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population.MethodsWe conducted laboratory-based prospective IPD surveillance in infants aged <90 days admitted to Queen Elizabeth Central Hospital (QECH) in Blantyre between 2005 and 2018, including 7 years pre- and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex PCR and latex agglutination testing.ResultsWe identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005-...
BMJ open, 2018
Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific. We are recruiting cases, defined as children aged 2-59 months admitted to participating hospitals with acute respiratory infection in Lao People's Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using qPCR and serotyped by microarray. Village-level vaccination coverage...