BACKGROUND
In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.
METHODS
In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than -7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484).
FINDINGS
Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of -16·2% (95% CI -28·6 to -3·0) between the full-dose group and control group (p=0·002 for superiority), and -3·8% (-6·1 to -1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination.
INTERPRETATION
Multi-age cohort campaigns had a marked effect on vaccine-type 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.
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.
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.
Improved vaccination coverage after two rounds of multi-antigenic catch-up vaccination in Mauritania
Despite a likely high burden of disease caused by Streptococcus pneumoniae in humanitarian crises, pneumococcal conjugate vaccines (PCV’s) are rarely used in such settings. Routine immunisation is rarely feasible in crises, and there is little evidence on alternative delivery strategies for PCV. We used modelling to evaluate the effects of different vaccination strategies within humanitarian crisis settings, aiming to identify those which could quickly reduce and sustain low transmission of vaccine serotypes.
METHODS
We conducted a nested carriage and contact survey in a camp for internally displaced people (IDP) in Somaliland to parameterise a transmission model and used it to assess the potential impact and optimal age targeting of PCV campaigns. We extrapolated this model to other representative humanitarian crisis settings: an acute-phase IDP camp, a protracted crisis in a rural setting, and an urban setting with mixed IDP and host communities. For each we explored the impact and efficiency of campaigns with different target age groups and dosing strategies.
ETHICS
This study was approved by the Ethics Review Boards of the London School of Hygiene and Tropical Medicine and the Republic of Somaliland Ministry of Health Development.
RESULTS
We found high prevalence of nasopharyngeal carriage of Streptococcus pneumoniae; 37% (95% confidence interval (CI), 32-42) in all ages, and 76% (95% CI, 70-82) in children <5 years in the Somaliland IDP camp. 53% (95% CI, 45-61) of serotypes are included in the PCV13 vaccine. People had, on average, 9 (9-10) contacts per day, with high mixing rates between children and intergenerational contacts in older age groups. Our model projects that, for the Somaliland IDP camp, a single PCV campaign including children <5 years can temporarily establish substantial herd protection, averting 37% (95% credible interval (CrI) 24-48) of invasive pneumococcal disease cases in the 2 years following the campaign. Extending age eligibility to children up to 10 or 15 years old could further increase this impact by 49% (95% CrI, 39-50) and 53% (95% CrI, 40-64) respectively. Increased migration rates and close contact with unvaccinated host populations reduces the impact. These factors might require wider age targeting and more frequent repeat campaigns until routine services could be re-established.
CONCLUSION
We show that PCV campaigns could be an effective option to reduce the burden of pneumococcal disease in humanitarian crises until routine immunisation can be implemented. Our results are based on modelled estimates, intervention studies are needed to evaluate their feasibility and effectiveness in real settings.
CONFLICTS OF INTEREST
None declared