RESUMO
Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement, and demonstrate reduced effectiveness against mucosal colonisation. For Malawi, nasopharyngeal carriage of vaccine-type pneumococci is common in vaccinated children despite national roll-out of 13-valent pneumococcal conjugate vaccine (PCV13) since 2011. Our team has safely transferred an established experimental human pneumococcal carriage method from Liverpool School of Tropical Medicine to the Malawi-Liverpool Wellcome Trust Clinical Research Programme, Malawi. This study will determine potential immunological mechanisms for the differential effects of PCV13 on nasal carriage between healthy Malawian and UK populations. We will conduct a double-blinded randomised controlled trial to vaccinate (1:1) participants with either PCV13 or control (normal saline). After a period of one month, participants will be inoculated with S. pneumoniae serotype 6B to experimentally induce nasal carriage using the EHPC method. Subsequently, participants will be invited for a second inoculation after one year to determine longer-term vaccine-induced immunological effects. Primary endpoint: detection of inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: local and systemic innate, humoral and cellular responses to PCV-13 with and without pneumococcal nasal carriage The primary objective of this controlled human infection model study is to determine if PCV-13 vaccination is protective against pneumococcal carriage in healthy adult Malawian volunteers. This study will help us to understand the observed differences in PCV-13 efficacy between populations and inform the design of future vaccines relevant to the Malawian population. Trial Registration: Pan African Clinical Trial Registry (REF: PACTR202008503507113).
RESUMO
Adults admitted to hospital with critical illness are vulnerable and at high risk of morbidity and mortality, especially in sub-Saharan African settings where resources are severely limited. As life expectancy increases, patient demographics and healthcare needs are increasingly complex and require integrated approaches. Patient outcomes could be improved by increased critical care provision that standardises healthcare delivery, provides specialist staff and enhanced patient monitoring and facilitates some treatment modalities for organ support. In Malawi, we established a new high-dependency unit within Queen Elizabeth Central Hospital, a tertiary referral centre serving the country's Southern region. This unit was designed in partnership with managers, clinicians, nurses and patients to address their needs. In this practice piece, we describe a participatory approach to design and implement a sustainable high-dependency unit for a low-income sub-Saharan African setting. This included: prospective agreement on remit, alignment with existing services, refurbishment of a dedicated physical space, recruitment and training of specialist nurses, development of context-sensitive clinical standard operating procedures, purchase of appropriate and durable equipment and creation of digital clinical information systems. As the global COVID-19 pandemic unfolded, we accelerated unit opening in anticipation of increased clinical requirement and describe how the high-dependency unit responded to this demand.
