Considerations for randomized controlled trials during future filovirus outbreaks.

Letter to the Edito

Clinical emergency care research in low-income and middle-income countries: Opportunities and challenges

Disease processes that frequently require emergency care constitute approximately 50% of the total disease burden in low-income and middle-income countries (LMICs). Many LMICs continue to deal with emergencies caused by communicable disease states such as pneumonia, diarrhoea, malaria and meningitis, while also experiencing a marked increase in non-communicable diseases, such as cardiovascular diseases, diabetes mellitus and trauma. For many of these states, emergency care interventions have been developed through research in high-income countries (HICs) and advances in care have been achieved. However, in LMICs, clinical research, especially interventional trials, in emergency care are rare. Furthermore, there exists minimal research on the emergency management of diseases, which are rarely encountered in HICs but impact the majority of LMIC populations. This paper explores challenges in conducting clinical research in patients with emergency conditions in LMICs, identifies examples of successful clinical research and highlights the system, individual and study design characteristics that made such research possible in LMICs. Derived from the available literature, a focused list of high impact research considerations are put forth

Recognising Sepsis as a Health Priority in Sub-Saharan African Country: Learning Lessons from Engagement with Gabon’s Health Policy Stakeholders

Sepsis has been recognised as a global health priority by the United Nations World Health Assembly, which adopted a resolution in 2017 to improve sepsis prevention, diagnosis, and management globally. This study investigated how sepsis is prioritised in Gabon. From May to November 2021, we conducted a qualitative study in healthcare stakeholders at the local, regional, and national levels. Stakeholders included the Ministry of Health (MOH), ethics/regulatory bodies, research institutions, academic institutions, referral hospitals, international funders, and the media. Twenty-three multisectoral stakeholders were interviewed. Respondents indicated that sepsis is not yet prioritised in Gabon due to the lack of evidence of its burden. They also suggest that the researchers should focus on linkages between sepsis and the countries’ existing health sector priorities to accelerate sepsis prioritisation in health policy. Stakeholder awareness and engagement might be accelerated by involving the media in the generation of communication strategies around sepsis awareness and prioritisation. There is a need for local, regional and national evidence to be generated by researchers and taken up by policymakers, focusing on linkages between sepsis and a country’s existing health sector priorities. The MOH should set sepsis reporting structures and develop appropriate sepsis guidelines for identification, management, and prevention

Pathogen Detection Using Metagenomic Next-Generation Sequencing of Plasma Samples from Patients with Sepsis in Uganda

Metagenomic sequencing is a promising new method for pathogen detection. We aimed to detect pathogens from archived plasma using metagenomic sequencing in a previously well-characterized cohort of 254 predominantly HIV-infected patients with sepsis in Uganda. We used Illumina sequencing and the Chan Zuckerberg ID metagenomics platform to sequence and identify pathogens. On average, each plasma sample yielded 3,404,737 ± 2,201,997 reads (mean ± standard deviation), of which 220,032 ± 416,691 (6.3% ± 8.6%) were identified as nonhuman reads. Using a background model filter, 414 genus-specific pathogen identifications were found in the 254 samples. Nineteen pathogens were previously detected positive by quantitative PCR (qPCR), compared to sequencing, which demonstrated 30.2% sensitivity and 99.5% specificity. Sensitivity was higher for viral pathogens than nonviral pathogens (37% versus 5%). For example, HIV viremia was detected in 69% of samples using qPCR, and sequencing revealed 70% sensitivity and 92% specificity. There were 75 genus-specific potential pathogens identified by sequencing in this cohort, including hepatitis B and Epstein-Barr virus (EBV), among several others. qPCR showed a prevalence of hepatitis B and EBV viremia of 17% and 45%, respectively. In-hospital mortality was associated with a lower qPCR threshold cycle value for EBV (adjusted odds ratio, 0.85; P < .001) but not for hepatitis B or HIV. In conclusion, a broad range of potential pathogens were identified by metagenomic sequencing in patients with sepsis in Uganda. Unexpectedly high rates of hepatitis B and EBV viremia were found. Whether these viral infections in HIV patients with sepsis are clinically important requires further study

On Prioritising Global Health’s Triple Crisis of Sepsis, COVID-19 and Antimicrobial Resistance: A mixed-methods study from Malawi

Sepsis causes 20% of global deaths, particularly among children and vulnerable populations living in developing countries. This study investigated how sepsis is prioritised in Malawi’s health system to inform health policy. In this mixed-methods study, twenty multisectoral stakeholders were qualitatively interviewed and asked to quantitatively rate the likelihood of sepsis-related medium-term policy outcomes being realised. Respondents indicated that sepsis is not prioritised in Malawi due to a lack of local sepsis-related evidence and policies. However, they highlighted strong linkages between sepsis and maternal health, antimicrobial resistance and COVID-19, which are already existing national priorities, and offers opportunities for sepsis researchers as policy entrepreneurs. To address the burden of sepsis, we recommend that funding should be channelled to the generation of local evidence, evidence uptake, procurement of resources and treatment of sepsis cases, development of appropriate indicators for sepsis, adherence to infection prevention and control measures, and antimicrobial stewardship