Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation.

CRADLE-5: a stepped-wedge type 2 hybrid implementation-effectiveness cluster randomised controlled trial to evaluate the real-world scale-up of the CRADLE Vital Signs Alert intervention into routine maternity care in Sierra Leone-study protocol.

BACKGROUND: The CRADLE Vital Signs Alert intervention (an accurate easy-to-use device that measures blood pressure and pulse with inbuilt traffic-light early warning system, and focused training package) was associated with reduced rates of eclampsia and maternal death when trialled in urban areas in Sierra Leone. Subsequently, implementation was successfully piloted as evidenced by measures of fidelity, feasibility and adoption. The CRADLE-5 trial will examine whether national scale-up, including in the most rural areas, will reduce a composite outcome of maternal and fetal mortality and maternal morbidity and will evaluate how the CRADLE package can be embedded sustainably into routine clinical pathways. METHODS: CRADLE-5 is a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care across eight rural districts in Sierra Leone (Bonthe, Falaba, Karene, Kailahun, Koinadugu, Kono, Moyamba, Tonkolili). Each district will cross from control to intervention at six-weekly intervals over the course of 1 year (May 2022 to June 2023). All women identified as pregnant or within six-weeks postpartum presenting for maternity care in the district are included. Primary outcome data (composite rate of maternal death, stillbirth, eclampsia and emergency hysterectomy) will be collected. A mixed-methods process and scale-up evaluation (informed by Medical Research Council guidance for complex interventions and the World Health Organization ExpandNet tools) will explore implementation outcomes of fidelity, adoption, adaptation and scale-up outcomes of reach, maintenance, sustainability and integration. Mechanisms of change and contextual factors (barriers and facilitators) will be assessed. A concurrent cost-effectiveness analysis will be undertaken. DISCUSSION: International guidance recommends that all pregnant and postpartum women have regular blood pressure assessment, and healthcare staff are adequately trained to respond to abnormalities. Clinical effectiveness to improve maternal and perinatal health in more rural areas, and ease of integration and sustainability of the CRADLE intervention at scale has yet to be investigated. This trial will explore whether national scale-up of the CRADLE intervention reduces maternal and fetal mortality and severe maternal adverse outcomes and understand the strategies for adoption, integration and sustainability in low-resource settings. If successful, the aim is to develop an adaptable, evidence-based scale-up roadmap to improve maternal and infant outcomes. TRIAL REGISTRATION: ISRCTN 94429427. Registered on 20 April 2022.

Assessing Changes in Surgical Site Infections and Antibiotic Use among Caesarean Section and Herniorrhaphy Patients at a Regional Hospital in Sierra Leone Following Operational Research in 2021.

Surgical site infections (SSIs) are a major public health threat to the success of surgery. This study assessed changes in SSIs and use of antibiotics among caesarean section (CS) and herniorrhaphy patients at a regional hospital in Sierra Leone following operational research. This was a comparative before and after study using routine hospital data. The study included all the CS and herniorrhaphy patients who underwent surgery between two time periods. Of the seven recommendations made in the first study, only one concerning improving the hospital's records and information system was fully implemented. Three were partially implemented and three were not implemented. The study population in both studies showed similar socio-demographic characteristics. The use of postoperative antibiotics for herniorrhaphy in both studies remained the same, although a significant increase was found for both pre- and postoperative antibiotic use in the CS patients, 589/596 (98.8%) in 2023 and 417/599 (69.6%) in 2021 (p < 0.001). However, a significant decrease was observed in the overall incidence of SSIs, 22/777 (2.8%) in 2023 and 46/681 (6.7%) in 2021 (p < 0.001), and the incidence of SSIs among the CS patients, 15/596 (2.5%) in 2023 and 45/599 (7.5%) in 2021 (p < 0.001). The second study highlights the potential value of timely assessment of the implementation of recommendations following operational research.

Antibiotic use and consumption in Freetown, Sierra Leone: A baseline report of prescription stewardship in outpatient clinics of three tertiary hospitals.

Objective: As there are no country-representative data on bacterial sensitivities to guide antimicrobial stewardship (AMS) interventions, an AMS programme was established in the outpatient clinics of three tertiary hospitals in Freetown, Sierra Leone. Methods: The study employed a cross-sectional design to collect antibiotic prescribing data from 370 pregnant women and lactating mothers, 314 children and 229 regular patients in the outpatient clinics of the Princess Christian Maternity Hospital (PCMH), Ola During Children's Hospital and Connaught Hospital (CH), respectively, in April 2022. All data were analysed using Stata Version 16. Results: Of 913 patients, most were female (n=635, 69.5%), treated at PCMH (n=370, 40.5%) and had a bacterial infection (n=661, 72.4%). The indication for prescribing antibiotics was inappropriate in 252 (27.6%) patients. Of the 1236 prescriptions, 393 (31.8%) were made at CH. The duration of antibiotic use was not stated in 230 (18.6%) prescriptions. Overall antibiotic consumption was 55.3 defined daily doses per 1000 outpatient-days. Conclusion: Gaps in antibiotic prescriptions were identified in the outpatient clinics of three national referral hospitals in Sierra Leone. In order to combat antimicrobial resistance, AMS interventions are needed to reduce the prescription of antibiotics for inappropriate indications or without specified duration.

Advancing maternal and perinatal health in low- and middle-income countries: A multi-country review of policies and programmes.

The Sustainable Development Goals prioritize maternal mortality reduction, with a global average target of < 70 per 100,000 live births by 2030. Current pace of reduction is far short of what is needed to achieve the global target. It is estimated that globally there are 300,000 maternal deaths, 2.4 million newborn deaths and 2 million stillbirths annually. Majority of these deaths occur in low-and-middle-income countries. Global initiatives like, Ending Preventable Maternal Mortality (EPMM) and Every Newborn Action Plan (ENAP), have outlined the broad strategies for maternal and newborn health programmes. A set of coverage targets and ten milestones were launched to support low-and-middle-income countries in accelerating progress in improving maternal, perinatal and newborn health and wellbeing. WHO, UNICEF and UNFPA, undertook a scoping review to understand how country strategies evolved in different contexts over the past two decades to improve maternal survival and wellbeing, and how countries in similar settings could accelerate progress considering the changing epidemiology and demography. Case studies were conducted to inform countries in similar settings and various global initiatives. Six countries were selected based on standard criteria-Cambodia, Democratic Republic of the Congo, Georgia, Guatemala, Pakistan and Sierra Leone representing different stages of the obstetric transition. A conceptual framework, encapsulating the interrelated factors impacting maternal health outcomes, was used to organize data collection and analysis. While all six countries made remarkable progress in improving maternal and perinatal health, the pace of progress and the factors influencing the successes and challenges varied across the countries. The context, opportunities and challenges varied from country to country. Two strategic directions were identified for next steps including the need to implement and evaluate innovative service delivery models using an updated obstetric transition as an organizing framework and expanding our vision to address equity and well-being.

Incidence of Surgical Site Infection and Use of Antibiotics among Patients Who Underwent Caesarean Section and Herniorrhaphy at a Regional Referral Hospital, Sierra Leone.

Surgical site infections (SSIs) are common postoperative complications. Surgical antibiotic prophylaxis (SAP) can prevent the occurrence of SSIs if administered appropriately. We carried out a retrospective cohort study to determine the incidence of SSIs and assess whether SAP were administered according to WHO guidelines for Caesarean section (CS) and herniorrhaphy patients in Bo regional government hospital from November 2019 to October 2020. The analysis included 681 patients (599 CSs and 82 herniorrhaphies). Overall, the SSI rate was 6.7% among all patients, and 7.5% and 1.2% among CS patients and herniorrhaphy patients, respectively. SAP was administered preoperatively in 85% of CS and 70% of herniorrhaphy patients. Postoperative antibiotics were prescribed to 85% of CS and 100% of herniorrhaphy patients. Ampicillin, metronidazole, and amoxicillin were the most commonly used antibiotics. The relatively low rate of SSIs observed in this study is probably due to improved infection prevention and control (IPC) measures following the Ebola outbreak and the current COVID-19 pandemic. A good compliance rate with WHO guidelines for preoperative SAP was observed. However, there was a high use of postoperative antibiotics, which is not in line with WHO guidelines. Recommendations were made to ensure the appropriate administration of SAP and reduce unnecessary use of antibiotics.

Prevalence of use of highly concentrated oxytocin or "pepper injection" in labor among clinicians undergoing emergency obstetric training in Sierra Leone.

OBJECTIVE: To examine the awareness, prevalence of use, and knowledge of risks of pepper injection (PI), an injection of highly concentrated oxytocin used to augment or induce labor, among clinicians. METHODS: An anonymous pre- and post-workshop evaluation conducted among 227 clinicians participating in emergency obstetric and newborn care training in Sierra Leone from June to October 2018. RESULTS: Overall, 225 participants completed the surveys. Of these, 198 (88.0%) of clinicians reported awareness of PI, and 123 (54.7%) self-reported prior use, which was highest among midwives (94/129; 72.9%). Before EmONC training, 82 (36.4%) clinicians reported that they were likely to use PI; this decreased to 39 (17.3%) after training (P<0.05). The mean number of participants correctly identifying risks of PI increased from 149 (66.2%) to 204 (90.7%) after training (P<0.05). CONCLUSION: There was widespread awareness of PI use among clinicians, and prevalent self-reported prior use among midwives. Risk awareness improved after EmONC training, and the proportion of clinicians reporting likelihood of future use decreased. Improper use of oxytocin may be a major contributor to maternal and newborn morbidity and mortality in Sierra Leone. Initiatives to educate clinicians and to regulate and stop the practice are needed.

Prevalence and mortality of cryptococcal disease in adults with advanced HIV in an urban tertiary hospital in Sierra Leone: a prospective study.

BACKGROUND: The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/µl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone. METHODS: A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm3 from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables. RESULTS: A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm3 (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks. CONCLUSION: A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.