The burden of multimorbidity-associated acute hospital admissions in Malawi and Tanzania: a prospective multicentre cohort study.

Background: The global burden of multimorbidity-the coexistence of two or more long-term conditions-is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania.

Acceptability of pulmonary rehabilitation in Malawi: a qualitative study.

Background: Pulmonary rehabilitation (PR) is an effective non-pharmacological intervention for people with chronic respiratory diseases (CRDs), but its acceptability in Malawi was unknown.

Objectives: To explore patients' acceptability of PR at Queen Elizabeth Central Hospital, Blantyre, Malawi.

Methods: This was a pre-post cohort study where participants were offered a two times per week hospital-based PR programme for 6 weeks, consisting of endurance and strengthening exercises.

Aetiologies, neuroradiological features, and risk factors for mortality and long-term neurosequelae of febrile coma in Malawian children: a prospective cohort study.

Background: Children in febrile coma in Africa are frequently hospitalised, with poorer outcomes than those in high-income settings. Cerebral malaria is historically the most common cause of febrile coma. Due to limited diagnostic and radiological resources and a decrease in malaria prevalence, there might be under-recognition of non-malarial coma.

The aetiologies, mortality, and disability of non-traumatic coma in African children: a systematic review and meta-analysis.

Background: Non-traumatic coma in African children is a common life-threatening presentation often leading to hospital attendance. We aimed to estimate the distribution of non-traumatic coma causes and outcomes, including disease-specific outcomes, for which evidence is scarce.

Methods: We systematically reviewed MEDLINE, Embase, and Scopus databases from inception to Feb 6, 2024.

Recruitment strategies used to enrol healthy volunteers in the first pneumococcal human infection study in Africa: Lessons from Blantyre, Malawi.

Background: Human Infection Studies (HIS) also known as Controlled Human Infection Models (CHIM) are a relatively new concept in African countries to clinicians, scientists, and communities alike. We have introduced HIS/CHIM studies to Malawi during the last four years by developing an experimental human pneumococcal carriage model. This CHIM was used to test the efficacy of a licensed 13-valent Pneumococcal Conjugate Vaccine (PCV13) against experimental nasal pneumococcal carriage.

Association of mucosal neutrophil inflammation and cytokine responses with natural and experimental pneumococcal carriage in a randomised vaccine trial using experimental human pneumococcal carriage.

Background: Mucosal inflammation is associated with increased nasal pneumococcal colonisation, but the specific mechanisms are not fully understood. We aimed to find innate immune factors associated with pneumococcal carriage using a controlled human infection model.

Methods: Healthy Malawian adults participating in a randomised trial of pneumococcal conjugate vaccine (PCV13) were inoculated with one of three doses of Streptococcus pneumoniae 6B.

The Epidemiology and Impact of Hypoxemia in Sub-Saharan Africa: Prevalence, Practices, and Outcomes.

The epidemiology of hypoxemia in sub-Saharan Africa is largely unknown. To determine the prevalence, clinical care, and outcomes for hospitalized hypoxemic adults in sub-Saharan Africa. We prospectively screened all adults admitted to five hospitals in Kenya, Malawi, and Rwanda over four months; identified those with hypoxemia (defined as oxygen saturation as measured by pulse oximetry [Sp] < 90% or receipt of oxygen therapy); and followed hypoxemic patients to discharge.

A pilot study to explore utility of electronic informed consent in a low- income setting; the case of a Controlled human infection study in Blantyre, Malawi.

Background: Electronic informed consent can improve accuracy, workflow, and overall patient experience in clinical research but has not been used in Malawi, owing to uncertainty about availability, utility, patient data security and technical support.

Objectives: We aimed to explore the utility of electronic consent (e-consent) in an ongoing human infection study in Blantyre, Malawi.

Methods: The approved paper consent forms were digitized using Open Data Kit (ODK).

A feasibility study of controlled human infection with intradermal Bacillus Calmette-Guérin (BCG) injection: Pilot BCG controlled human infection model.

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden.

RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding.

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus.

Causes, outcomes and diagnosis of acute breathlessness hospital admissions in Malawi: protocol for a multicentre prospective cohort study.

Background: Hospital admission due to breathlessness carries a significant burden to patients and healthcare systems, particularly impacting people in low-income countries. Prompt appropriate treatment is vital to improve outcomes, but this relies on accurate diagnostic tests which are of limited availability in resource-constrained settings. We will provide an accurate description of acute breathlessness presentations in a multicentre prospective cohort study in Malawi, a low resource setting in Southern Africa, and explore approaches to strengthen diagnostic capacity.

Natural Carriage of Streptococcus pneumoniae Is Associated With Increased Experimental Pneumococcal Carriage but Reduced Conjugate Vaccine Efficacy in a Human Challenge Model.

Background: In Malawi, the national 13-valent pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than in the United States, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy.

Review of Current Tuberculosis Human Infection Studies for Use in Accelerating Tuberculosis Vaccine Development: A Meeting Report.

Tools to evaluate and accelerate tuberculosis (TB) vaccine development are needed to advance global TB control strategies. Validated human infection studies for TB have the potential to facilitate breakthroughs in understanding disease pathogenesis, identify correlates of protection, develop diagnostic tools, and accelerate and de-risk vaccine and drug development. However, key challenges remain for realizing the clinical utility of these models, which require further discussion and alignment among key stakeholders.

Experimental pneumococcal carriage in people living with HIV in Malawi: the first controlled human infection model in a key at-risk population.

As well as suffering a high burden of pneumococcal disease people living with HIV (PLHIV) may contribute to community transmission in sub-Saharan African (sSA) settings. Pneumococcal vaccination is not currently offered to PLHIV in sSA but may prevent disease and reduce transmission. More evidence of vaccine effectiveness against carriage in PLHIV is needed.

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3).

Introduction: Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed.

Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study.

Background: The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage.

Use of hospital services by patients with chronic conditions in sub-Saharan Africa: a systematic review and meta-analysis.

Objective: To estimate the prevalence of individual chronic conditions and multimorbidity among adults admitted to hospital in countries in sub-Saharan Africa.

Methods: We systematically searched MEDLINE®, Embase®, Global Index Medicus, Global Health and SciELO for publications reporting on patient cohorts recruited between 1 January 2010 and 12 May 2023. We included articles reporting prevalence of pre-specified chronic diseases within unselected acute care services (emergency departments or medical inpatient settings).

A Randomized Controlled Clinical Trial of Nasal Immunization with Live Virulence Attenuated Strains Using Human Infection Challenge.

Pneumococcal pneumonia remains a global health problem. Pneumococcal colonization increases local and systemic protective immunity, suggesting that nasal administration of live attenuated (Spn) strains could help prevent infections. We used a controlled human infection model to investigate whether nasopharyngeal colonization with attenuated strains protected against recolonization with wild-type (WT) Spn (SpnWT).

A health systems approach to critical care delivery in low-resource settings: a narrative review.

There is a high burden of critical illness in low-income countries (LICs), adding pressure to already strained health systems. Over the next decade, the need for critical care is expected to grow due to ageing populations with increasing medical complexity; limited access to primary care; climate change; natural disasters; and conflict. In 2019, the 72nd World Health Assembly emphasised that an essential part of universal health coverage is improved access to effective emergency and critical care and to "ensure the timely and effective delivery of life-saving health care services to those in need".

Comprehensive review of safety in Experimental Human Pneumococcal Challenge.

Introduction: Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.

Methods: A single-centre review of all EHPC studies performed 2011-2021.

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances.

Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi.

Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome.

'Why would they spend all this money and give us these items for free?': Exploring precarity and power in a cleaner cookstove intervention in rural Malawi.

We carried out a qualitative study to gain a deeper understanding of the social context of the Cooking and Pneumonia Study (CAPS) and implications for implementation of clean cooking and similar interventions. Such initiatives are recognised as complex, power-laden processes, which has consequences for outcomes and uptake. However, understanding of how precarious livelihoods and unequal power differentials impact on trials of technology is limited and potentially hampers the achievement of the SDGs including SDG 7, Affordable and Clean Energy.