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

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

Improving inpatient provider-initiated HIV testing and counseling in Sierra Leone.

Background/settingOnly 47% of HIV-positive Sierra Leoneans knew their status in 2017, making expanded HIV testing a priority. National guidelines endorse provider-initiated HIV testing and counselling (PITC) to increase testing coverage, but PITC is rarely provided in Sierra Leone. In response, a Quality Improvement Collaborative (QIC) was implemented to improve PITC coverage amongst adult inpatients.MethodsTen hospitals received the intervention between October 2017 and August 2018; there were no control facilites. Each hospital aimed to improve PITC coverage to ≥ 95% of eligible patients. Staff received training on PITC and QIC methods and a package of PITC best practices and tools. They then worked to identify additional contextually-appropriate interventions, conducted rapid tests of change, and tracked performance using shared indicators and time-series data. Supportive supervision bolstered QI skills, and quarterly meetings enabled diffusion of innovations while spurring friendly competition.ResultsBaseline PITC coverage was 4%. The hospital teams tested diverse interventions using QI methods, including staff training; data review meetings; enhanced workflow processes and supervision; and patient education and sensitization activities Nine hospitals reached and sustained the 95% target, and all saw rapid and durable improvement, which was sustained for a median of six months. Of the 5,238 patients tested for HIV, 311 (6%) were found to be HIV-positive and were referred for treatment. HIV rapid test kit stockouts occurred during the project period, limiting PITC services in some cases.ConclusionsThe intervention led to swift and sustained improvement in inpatient PITC coverage and to the diagnosis of hundreds of people living with HIV. Sierra Leone's Ministry of Health and Sanitation plans to take the initiative to national scale, with close attention to the issue of test kit stockouts

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 p p < 0.001). The second study highlights the potential value of timely assessment of the implementation of recommendations following operational research

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

Abstract 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

Clinicopathological discrepancies in the diagnoses of childhood causes of death in the CHAMPS network: An analysis of antemortem diagnostic inaccuracies

Introduction Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS).Methods We analysed data collected during 2016–2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle.Results CHAMPS enrolled 1454 deceased young children aged 1–59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4–21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV.Conclusions Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills