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.
At the time of writing, many people around the world are feeling the pain, disruption, and devastating health consequences driven by climate change. The world has been shocked by the widespread flooding in Europe and the consecutive catastrophic hurricanes in North America. Yet far less attention is given to the impacts of climate change in places where Médecins Sans Frontières (MSF) works, such as Central African Republic, Chad, Côte d’Ivoire, Democratic Republic of Congo, Myanmar, Niger, Nigeria, and South Sudan. In 2024, these populations have likewise been affected by devastating floods, many of them not for the first time.
Although immediate impacts like injury, displacement, and limited access to healthcare may be similar worldwide, the compounding crises that follow and the capacity to recover from these vary significantly. Individuals in low-resource and humanitarian settings face significant health threats while contributing the least to global emissions. These regions are often vulnerable to climate hazards and possess low adaptive capacity, increasing people’s susceptibility to the negative impacts of climate change.
In this brief, drawing on evidence from indicators in the 2024 report of the Lancet Countdown on Health and Climate Change, MSF teams present examples of how climate change and environmental degradation are making provision of assistance more difficult by amplifying health and humanitarian needs and by further complicating interventions. It also highlights activities that respond to the climate crisis using a three-pillar approach: mitigating MSF’s environmental footprint, adapting healthcare delivery and emergency response to the current and future realities of climate change, and advocating for those impacted.
The complexity of climate change and environmental degradation, coupled with highly politicised and siloed global response efforts often make it insufficiently clear to health and humanitarian implementing partners that every issue is part of a continuous process, where each component informs the others. In this brief, MSF staff outline six focus areas where teams are engaged in developing environmentally-informed health and humanitarian interventions, emphasising their interdependence, and how failure to act on one issue not only impedes progress on that specific component but also affects the entire sequence of subsequent actions.
While case confirmation is most of the time not necessary for case management decisions– the measles outbreak response relies on the timely biological confirmation of outbreaks to facilitate a vaccination response. Seroprevalence estimates, on the other hand, can help plan vaccination activities or evaluate them, by quantifying immunization levels in the population. In remote areas where transport of serum or plasma samples is challenging, we ideally would like to use dried blood spots (DBS) which are easy to collect, easy to transport, and theoretically stable in time and temperature. However, the practical use of DBS under field conditions is not as easy as we expect. Based on different examples of measles surveys in the DRC and Niger, we will describe the challenges we are facing regarding interpretation of serology results from DBS for both measles
biological confirmation and seroprevalence surveys.
RESULTS AND DISCUSSION
In the DRC, for biological confirmation , the sensitivity of DBS samples compared to plasma decreases with transport delays and is lower in remote settings. Measles seroprevalence based on DBS was lower than expected, raising questions about the use of the recommended seropositivity threshold and the correlation with seroprotection after vaccination. In Niger, we found that a good quality DBS can be obtain under field conditions, and an adjustment factor for DBS compared to serum is needed but may vary between settings.
CONCLUSION
Serology on DBS is the most acceptable procedure so far for biological confirmation of measles cases and seroprevalence. However, additional investigations are needed to better standardize, test, and interpret DBS samples to help making the most appropriate operational decisions.
Current guidelines for the outpatient treatment of severe acute malnutrition (SAM) recommend the provision of routine medications to all children at admission and prescribed medications as clinically indicated thereafter. The objective of this study was to describe the amount and purpose of medications prescribed during outpatient SAM treatment and explore the effect of routine antibiotics at admission on subsequent medication prescription.
METHODS
Medications prescribed during outpatient treatment were described by medication category, time from admission, and diagnoses among children with SAM in a placebo-controlled, double-blind trial of 7-day amoxicillin use. Total medications were compared by parent trial intervention arm (amoxicillin vs placebo) and differences assessed using Χ^2 and two-sample t-tests.
RESULTS
Of the 2399 children enrolled, 74.6% of children received ≥1 prescribed medication during outpatient treatment. Antipyretics/analgesics (44.1% of children), antimalarials (56.6%) and antibiotics (30.0%) were prescribed most frequently. Children who received placebo in the parent trial received fewer total medications (mean difference: −0.80, 95% CI: −0.96 to –0.65) and oral antibiotics (mean difference: −0.96, 95% CI: −0.99 to –0.92) during treatment compared with children who received routine amoxicillin.
CONCLUSIONS
We found high rates of medication prescription during outpatient treatment for SAM, but fewer total medications and oral antibiotics prescribed to children receiving placebo in the parent trial. Our findings underscore the role of outpatient treatment programmes as an important source of medicine prescription and suggest that provision of antibiotics on a clinically indicated basis for outpatient SAM cases may be a strategy to support prudent antibiotic use in certain settings.
Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.
METHODS
We conducted a secondary analysis of a randomised, double-blinded, placebo-controlled trial (NCT01613547) of amoxicillin in children (aged 6-59 months) with severe acute malnutrition treated as outpatients in Madarounfa, Niger. We randomly selected 161 children from the overall cohort (n=2399) for initial 12-week follow-up from Sept 23, 2013 to Feb 3, 2014. We selected a convenience sample of those 161 children, on the basis of anthropometric measures, for follow-up 2 years later (Sept 28 to Oct 27, 2015). Children provided faecal samples at baseline, week 1, week 4, week 8, week 12, and, for those in the 2-year follow-up cohort, week 104. We conducted metagenomic sequencing followed by microbiome and resistome profiling of faecal samples. 38 children without severe acute malnutrition and six children with severe acute malnutrition matching the baseline ages of the original cohort were used as reference controls.
FINDINGS
In the 12-week follow-up group, amoxicillin led to an immediate decrease in gut microbiome richness from 37·6 species (95% CI 32·6-42·7) and Shannon diversity index (SDI) 2·18 (95% CI 1·97-2·39) at baseline to 27·7 species (95% CI 22·9-32·6) species and SDI 1·55 (95% CI 1·35-1·75) at week 1. Amoxicillin increased gut antibiotic resistance gene abundance to 6044 reads per kilobase million (95% CI 4704-7384) at week 1, up from 4800 (3391-6208) at baseline, which returned to baseline 3 weeks later. 35 children were included in the 2-year follow-up; the amoxicillin-treated children (n=22) had increased number of species in the gut microbiome compared with placebo-treated children (n=13; 60·7 [95% CI 54·7-66·6] vs 36·9 [29·4-44·3]). Amoxicillin-treated children had increased Prevotella spp and decreased Bifidobacterium spp relative to age-matched placebo-treated children, indicating a more mature, adult-like microbiome.
INTERPRETATION
Amoxicillin treatment led to acute but not sustained increases in antimicrobial resistance genes and improved gut microbiome maturation 2 years after severe acute malnutrition treatment.
Antibiotic resistance is a significant public health problem and is responsible for high mortality in children and new-borns. Strengthening the rational use of antibiotics and improving the quality and access to existing antibiotics are important factors in the fight against antibiotic resistance. This study aims to provide knowledge on the use of antibiotics in children in resource-limited countries in order to identify problems and possible avenues for improvement of antibiotics use.
METHODS
We conducted a retrospective study in July 2020 and collected quantitative clinical and therapeutic data on antibiotic prescriptions between January and December 2019 in 4 hospitals or health centres in both Uganda and Niger, respectively from January to December 2019. Semi-structured interviews and focus groups were conducted among healthcare personnel and carers for children under 17 years of age, respectively.
RESULTS
A total of 1,622 children in Uganda and 660 children in Niger (mean age of 3.9 years (SD 4.43)) who received at least one antibiotic were included in the study. In hospital settings, 98.4 to 100% of children prescribed at least one antibiotic received at least one injectable antibiotic. Most hospitalized children received more than one antibiotic in both Uganda (52.1%) and Niger (71.1%). According to the WHO-AWaRe index, the proportion of prescriptions of antibiotics belonging to the Watch category was 21.8% (432/1982) in Uganda and 32.0% (371/1158) in Niger. No antibiotics from the Reserve category were prescribed. Health care provider’s prescribing practices are rarely guided by microbiological analyses. Prescribers are faced with numerous constraints, such as lack of standard national guidelines, unavailability of essential antibiotics at the level of hospital pharmacies, the limited financial means of the families, and pressure to prescribe antibiotics from caregivers as well as from drug company representatives. The quality of some antibiotics provided by the National Medical Stores to the public and private hospitals has been questioned by some health professionals. Self-medication is a widespread practice for the antibiotic treatment of children for economic and access reasons.
CONCLUSION
The study findings indicate that an intersection of policy, institutional norms and practices including individual caregiver or health provider factors, influence antibiotic prescription, administration and dispensing practices.
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Patients with advanced HIV disease (AHD), defined as WHO clinical stage 3 or 4 and/or CD4<200, have a high risk of death. One common cause of death is invasive bacterial infection (IBI, i.e., septicemia or meningitis). The global increase of antibiotic resistance threatens current treatments against bacterial infections. This study aims to describe the burden of IBI among patients with AHD to guide empirical treatment protocols.
METHODS
This is a prospective, descriptive study implemented at Kabinda General Hospital in Kinshasa, Democratic Republic of Congo (DRC). All patients with AHD and a blood or cerebrospinal fluid (CSF) culture collected because of: 1) fever/hypothermia and/or signs of shock, on admission or during hospitalization, and/or 2) previous exposure to care (<30 days), were eligible to participate. Clinical and bacteriological data were collected. An IBI was defined as a positive blood or CSF culture, and then categorized as: 1) community-acquired or healthcare-associated, if occurring =48 hours since hospitalization, and contingent on previous exposure to care (<30 days), or 2) hospital-acquired, if occurring >48 hours after hospitalization.
RESULTS
From August 2021 to July 2022, we included 997 patients, corresponding to 1198 hospitalizations with =1 blood and/or CSF culture. The proportions of community-acquired, healthcare-associated, and hospital-acquired IBI among hospitalizations were 5.9% (71/1198), 9.2% (110/1198), and 3.5% (42/1198), respectively. The main bacterial agents responsible for community-acquired and healthcare-associated IBI were non-Typhi Salmonella followed by Gram-positive Cocci, while K. pneumoniae was most common in hospital-acquired IBI. The levels of antibiotic susceptibility among Enterobacterales were similar between community-acquired and healthcare-associated IBI, with low susceptibility to ceftriaxone and ciprofloxacin, but high susceptibility to carbapenems and azithromycin.
CONCLUSION
We confirmed alarming levels of antibiotic resistance among patients with ADH in the DRC. Discussions are ongoing to translate results into practice, in particular to target broad spectrum empirical antibiotics.
KEY MESSAGE
Invasive bacterial infections among hospitalized patients with advanced HIV in Kinshasa showed high levels of antibiotic resistance regardless of their recent, previous exposure to care.
This abstract is not to be quoted for publication.