Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization's routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries.
METHODS
An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes.
RESULTS
Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2 ug/ml and 0.35 ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality.
DISCUSSION
PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to effectively implement extended age vaccinations, access to affordably-priced PCV is critical.
Information on Streptococcus pneumoniae nasopharyngeal (NP) carriage before the pneumococcal conjugate vaccine (PCV) introduction is essential to monitor impact. The 10-valent PCV (PCV10) was officially introduced throughout Ugandan national childhood immunization programs in 2013 and rolled-out countrywide during 2014. We aimed to measure the age-specific Streptococcus pneumoniae carriage and serotype distribution across all population age groups in the pre-PCV10 era in South Western Uganda.
METHODS
We conducted a two-stage cluster, age-stratified, cross-sectional community-based study in Sheema North sub-district between January and March 2014. One NP swab was collected and analyzed for each participant in accordance with World Health Organization guidelines.
RESULTS
NP carriage of any pneumococcal serotype was higher among children <2years old (77%; n=387) than among participants aged ≥15years (8.5%; n=325) (chi2 p<0.001). Of the 623 positive cultures, we identified 49 serotypes among 610 (97.9%) isolates; thirteen (2.1%) isolates were non-typeable. Among <2years old, serotypes 6A, 6B, 14, 15B, 19F and 23F accounted for half of all carriers. Carriage prevalence with PCV10 serotypes was 29.4% among individuals aged <2years (n=387), 23.4% in children aged 2-4years (n=217), 11.4% in 5-14years (n=417), and 0.4% among individuals ≥15years of age (n=325). The proportion of carried pneumococci serotypes contained in PCV10 was 38.1% (n=291), 32.8% (n=154), 29.4% (n=156), and 4.4% (n=22) among carriers aged <2years, 2-4years, 5-14years and ≥15years, respectively.
DISCUSSION
In Sheema district, the proportion of PCV10 serotypes was low (<40%), across all age groups, especially among individuals aged 15years or older (<5%). PCV10 introduction is likely to impact transmission among children and to older individuals, but less likely to substantially modify pneumococcal NP ecology among individuals aged 15years or older.
BACKGROUND
In settings with low Pneumoccocal Conjugate Vaccine (PCV) coverage, mass campaigns targeting multi-age cohorts (MAC) might accelerate herd protection but ould be costly. Campaigns using fractional dose PCV would decrease cost and increase access.
METHODS
We conducted a cluster-randomized trial in Niger to evaluate the effect of a mass campaign targeting children aged 1-9 years on pneumococcal carriage. 63 villages were randomized in a 3:3:1 ratio to receive campaigns with a single full dose of a 10-valent PCV (Pneumosil®), a single 1/5th fractional dose, or no campaign. We conducted two independent carriage surveys among a total of 2268 households 6 months before and 6 months after vaccination, collecting a nasopharyngeal swab from a child aged 1-9 years for culture and serotyping. If the full-dose campaign was shown superior to control in carriage reduction, the non-inferiority of fractional-dose campaign was to be evaluated, with the lower bound of the 95%CI > -7.5%. Registration: NCT05175014, PACTR20211257448484
RESULTS
Surveys were conducted between December 22, 2021, and 18 March, 2022, and December 12, 2022, and March 9, 2023. The vaccination campaign was June 15-August 2, 2022. Participant characteristics were similar between the two surveys and across arms. Pre-vaccination, vaccine-type (VT) carriage was 15.6% in the full-dose arm, 17.9% in the fractional dose arm, and 18.8% in the control arm. Post-
vaccination, VT carriage was 4.6% in the full-dose arm, 8.0% in the fractional dose arm, and 16.5% in the control arm. In the primary analysis, the risk difference between the full dose and the control arms was -12.0% [-19.0; -5.0], p=0.001, and between the full dose and fractional dose arms it was -3.5% [-5.8; -1.1], meeting the prespecified non-inferiority criterion. Similar results were seen after adjustment for age, vaccine coverage and other factors.
CONCLUSION
MAC campaigns had a marked impact on VT carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection.
Tuberculosis diagnosis might be delayed or missed in children with severe pneumonia because this diagnosis is usually only considered in cases of prolonged symptoms or antibiotic failure. Systematic tuberculosis detection at hospital admission could increase case detection and reduce mortality.
METHODS
We did a stepped-wedge cluster-randomised trial in 16 hospitals from six countries (Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Uganda, and Zambia) with high incidence of tuberculosis. Children younger than 5 years with WHO-defined severe pneumonia received either the standard of care (control group) or standard of care plus Xpert MTB/RIF Ultra (Xpert Ultra; Cepheid, Sunnyvale, CA, USA) on nasopharyngeal aspirate and stool samples (intervention group). Clusters (hospitals) were progressively switched from control to intervention at 5-week intervals, using a computer-generated random sequence, stratified on incidence rate of tuberculosis at country level, and masked to teams until 5 weeks before switch. We assessed the effect of the intervention on primary (12-week all-cause mortality) and secondary (including tuberculosis diagnosis) outcomes, using generalised linear mixed models. The primary analysis was by intention to treat. We described outcomes in children with severe acute malnutrition in a post hoc analysis. This study is registered with ClinicalTrials.gov (NCT03831906) and the Pan African Clinical Trial Registry (PACTR202101615120643).
FINDINGS
From March 21, 2019, to March 30, 2021, we enrolled 1401 children in the control group and 1169 children in the intervention group. In the intervention group, 1140 (97·5%) children had nasopharyngeal aspirates and 942 (80·6%) had their stool collected; 24 (2·1%) had positive Xpert Ultra. At 12 weeks, 110 (7·9%) children in the control group and 91 (7·8%) children in the intervention group had died (adjusted odds ratio [OR] 0·986, 95% CI 0·597-1·630, p=0·957), and 74 (5·3%) children in the control group and 88 (7·5%) children in the intervention group had tuberculosis diagnosed (adjusted OR 1·238, 95% CI 0·696-2·202, p=0·467). In children with severe acute malnutrition, 57 (23·8%) of 240 children in the control group and 53 (17·8%) of 297 children in the intervention group died, and 36 (15·0%) of 240 children in the control group and 56 (18·9%) of 297 children in the intervention group were diagnosed with tuberculosis. The main adverse events associated with nasopharyngeal aspirates were samples with blood in 312 (27·3%) of 1147 children with nasopharyngeal aspirates attempted, dyspnoea or SpO2 less than 95% in 134 (11·4%) of children, and transient respiratory distress or SpO2 less than 90% in 59 (5·2%) children. There was no serious adverse event related to nasopharyngeal aspirates reported during the trial.
INTERPRETATION
Systematic molecular tuberculosis detection at hospital admission did not reduce mortality in children with severe pneumonia. High treatment and microbiological confirmation rates support more systematic use of Xpert Ultra in this group, notably in children with severe acute malnutrition.
Continuous Positive Airway Pressure (CPAP) is recommended for neonates with respiratory distress. CPAP is widely used in high-income countries, but less so in low- and middle-income settings. Here we assess key aspects of implementing CPAP in a humanitarian setting and describe the initial cohort of neonates treated, along with their clinical outcomes.
METHODS
MSF implemented CPAP in a basic neonatal unit in Mosul following the request of the local medical team. Implementation of two bubble CPAP machines included initial training and refresher training one year later. Clinical data was recorded over 16 months (13 April 2021- 21 July 2022). Descriptive statistics were used to assess the feasibility and outcomes of using CPAP in this setting.
RESULTS
CPAP was well accepted by most healthcare workers and parents. 93 neonates were placed on CPAP. 98% of patients had a birthweight >1.5Kg. The main indications were respiratory distress syndrome, pneumonia, transient tachypnoea, and meconium aspiration (46%, 22%, 16%, and 14% respectively). Average duration on CPAP was 53 hours. 63% of patients recovered, 8% were discharged against medical advice, 9% were referred, and 15% died. Among the 15 patients who died at our facility or at the referral facility, 7 had a contraindication to CPAP, and the initiation of CPAP was delayed in 9 patients. Complications included minor nasal lesions (17%), irritability (8%), and pneumothoraces (5%).
DISCUSSION
Most patients improved with CPAP and were discharged home. 5% of patients developed pneumothoraces, which is in keeping with other reports. However, among patients who did not improve, a significant proportion had contraindications to CPAP initiation and/or were placed on CPAP in extremis, highlighting the importance of clear indication criteria and training. Using CPAP in a humanitarian setting may be feasible but is associated with high human resource needs for both training and practice.