Incidence of HIV-positive admission and inpatient mortality in Malawi (2012-2019).

Objective: To investigate trends in population incidence of HIV-positive hospital admission and risk of in-hospital death among adults living with HIV between 2012 and 2019 in Blantyre, Malawi.

Design: Population cohort study using an existing electronic health information system ('SPINE') at Queen Elizabeth Central Hospital and Blantyre census data.

Methods: We used multiple imputation and negative binomial regression to estimate population age-specific and sex-specific admission rates over time.

Partner-delivered HIV self-test kits with and without financial incentives in antenatal care and index patients with HIV in Malawi: a three-arm, cluster-randomised controlled trial.

Background: Secondary distribution of HIV self-testing (HIVST) kits by patients attending clinic services to their partners could improve the rate of HIV diagnosis. We aimed to investigate whether secondary administration of HIVST kits, with or without an additional financial incentive, via women receiving antenatal care (ANC) or via people newly diagnosed with HIV (ie, index patients) could improve the proportion of male partners tested or the number of people newly diagnosed with HIV.

Methods: We did a three-arm, open-label, pragmatic, cluster-randomised trial of 27 health centres (clusters), eligible if they were a government primary health centre providing ANC, HIV testing, and ART services, across four districts of Malawi.

Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.

Objective: Cerebral malaria (CM) is a complication of malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case-control study of post-mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post-mortem examination to have 'true-CM' (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death ('faux-CM', no parasite sequestration in blood vessels).

Socio-cultural and economic barriers, and facilitators influencing men's involvement in antenatal care including HIV testing: a qualitative study from urban Blantyre, Malawi.

Background: Male partner involvement in antenatal care (ANC) is associated with positive maternal and neonatal outcomes. However, only a handful of men attend ANC with their partners. This study aimed to understand the underlying barriers and facilitators influencing men's ANC attendance including HIV testing in Blantyre, Malawi.

Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis.

Background: Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis.

Methods: Malawian adults with a first presentation of microbiologically confirmed pulmonary tuberculosis received standard 6-month first-line therapy.

Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria.

Microvascular thrombosis and blood-brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients.

A More Granular View of Neutrophils in Malaria.

Neutrophils are abundant innate immune cells with crucial roles in immunity and vascular inflammation. Recent evidence indicates that neutrophils have a dual role in malaria, contributing to both pathogenesis and control of Plasmodium. We discuss emerging mechanisms behind these opposing functions and identify key outstanding questions.

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

Background: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI.

Methods: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older.

Patient outcomes associated with post-tuberculosis lung damage in Malawi: a prospective cohort study.

Background: Post-tuberculosis lung damage (PTLD) is a recognised consequence of pulmonary TB (pTB). However, little is known about its prevalence, patterns and associated outcomes, especially in sub-Saharan Africa and HIV-positive adults.

Methods: Adult (≥15 years) survivors of a first episode of pTB in Blantyre, Malawi, completed the St George's Respiratory Questionnaire, 6-minute walk test, spirometry and high-resolution CT (HRCT) chest imaging at TB treatment completion.

Gut mucosal colonisation with extended-spectrum beta-lactamase producing Enterobacteriaceae in sub-Saharan Africa: a systematic review and meta-analysis.

: Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) threaten human health; and, in areas of sub-Saharan Africa (sSA) where carbapenems are not available, may render ESBL-E infections untreatable. Gut mucosal colonisation probably occurs before infection, making prevention of colonisation an attractive target for intervention, but the epidemiology of ESBL-E in sSA is poorly described. : Describe ESBL-E colonisation prevalence in sSA and risk factors associated with colonisation.

Population Incidence and Mortality of Sepsis in an Urban African Setting, 2013-2016.

Background: Sepsis is an important cause of mortality globally, although population incidence estimates from low-income settings, including sub-Saharan Africa, are absent. We aimed to estimate sepsis incidence burden using routinely available data from a large urban hospital in Malawi.

Methods: We linked routine-care databases at Queen Elizabeth Central Hospital, Blantyre, Malawi, to provide admission and discharge data for 217 149 adults from 2013-2016.

Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial.

Background: People with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes.

Methods: A pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi.

Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis.

Background: Aetiology and outcomes of sepsis in sub-Saharan Africa (sSA) are poorly described; we performed a systematic review and meta-analysis to summarise the available data.

Methods: Systematic searches of PubMed and Scopus were undertaken to identify prospective studies recruiting adults (> 13 years) with community-acquired sepsis in sSA post-2000. Random effects meta-analysis of in-hospital and 30-day mortality was undertaken and available aetiology data also summarised by random effects meta-analysis.

Evidence of reduction of rotavirus diarrheal disease after rotavirus vaccine introduction in national immunization programs in the African countries: Report of the 11 African rotavirus symposium held in Lilongwe, Malawi.

The 11 African Rotavirus Symposium was held in Lilongwe, Malawi from May 28 to 30 2017. Over 270 delegates (73% from Africa) from 40 countries of which 30 (75%) were from African countries attended the symposium. Participants in this symposium included research scientists, clinicians, immunization managers, public health officials, policymakers and vaccine manufacturers.

HIV self-testing alone or with additional interventions, including financial incentives, and linkage to care or prevention among male partners of antenatal care clinic attendees in Malawi: An adaptive multi-arm, multi-stage cluster randomised trial.

Background: Conventional HIV testing services have been less comprehensive in reaching men than in reaching women globally, but HIV self-testing (HIVST) appears to be an acceptable alternative. Measurement of linkage to post-test services following HIVST remains the biggest challenge, yet is the biggest driver of cost-effectiveness. We investigated the impact of HIVST alone or with additional interventions on the uptake of testing and linkage to care or prevention among male partners of antenatal care clinic attendees in a novel adaptive trial.

The effect of demand-side financial incentives for increasing linkage into HIV treatment and voluntary medical male circumcision: A systematic review and meta-analysis of randomised controlled trials in low- and middle-income countries.

Introduction: Linkage to HIV treatment is a vital step in the cascade of HIV services and is critical to slowing down HIV transmission in countries with high HIV prevalence. Equally, linkage to voluntary medical male circumcision (VMMC) has been shown to decrease HIV transmission by 60% and increasing numbers of men receiving VMMC has a substantial impact on HIV incidence. However, only 48% of newly diagnosed HIV positive people link to HIV treatment let alone access HIV prevention methods such as VMMC globally.

A systematic review of clinical outcomes on the WHO Category II retreatment regimen for tuberculosis.

Objective: To assess the clinical outcomes of patients prescribed the World Health Organization (WHO) Category II retreatment regimen for tuberculosis (TB).

Design: A systematic review of the literature was performed by searching Medscape, Embase and Scopus databases for cohort studies and clinical trials reporting outcomes in adult patients on the Category II retreatment regimen.

Results: The proportion of patients successfully completing the retreatment regimen varied from 27% to 92% in the 39 studies included in this review.

A qualitative evaluation of hospital versus community-based management of patients on injectable treatments for tuberculosis.

Background: Patients being treated for recurrent or multidrug-resistant tuberculosis (TB) require long courses of injectable anti-tuberculous agents. In order to maintain strong TB control programmes, it is vital that the experiences of people who receive long-term injectables for TB are well understood. To investigate the feasibility of a novel model of care delivery, a clinical trial (The TB-RROC Study) was conducted at two central hospitals in Malawi.

A Systematic Review of the Prevalence and Pattern of Imaging Defined Post-TB Lung Disease.

Background: Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment are well described, but the structural abnormalities underlying these changes remain poorly defined, limiting our ability to phenotype post-TB lung disease in to meaningful categories for clinical management, prognostication, and ongoing research. The relationship between post-TB lung damage and patient-centred outcomes including functional impairment, respiratory symptoms, and health related quality of life also remains unclear.

Monocyte unresponsiveness and impaired IL1β, TNFα and IL7 production are associated with a poor outcome in Malawian adults with pulmonary tuberculosis.

Background: Early death during TB treatment is associated with depressed TNFα response to antigenic stimulation and propensity to superadded bacterial infection. Hypothesising the role of monocyte unresponsiveness, we further compared the immunological profile between patients who died or suffered a life-threatening deterioration ('poor outcome') during the intensive phase of TB treatment with patients who had an uneventful clinical course ('good outcome') who had been recruited as part of a larger prospective cohort study of Malawian TB patients.

Methods: Using Luminex, IL1β, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12, IL13, IL17, GCSF, GMCSF, MCP1, MIP1b, IFNγ and TNFα were measured in whole blood assay supernatants (stimulated with Mycobacterium tuberculosis H37Rv and LPS) and serum from 44 Malawian adult TB patients (22 of each outcome) immediately prior to commencing treatment, after 7 days and on day 56 of TB treatment.

Chronic Household Air Pollution Exposure Is Associated with Impaired Alveolar Macrophage Function in Malawian Non-Smokers.

Background: Household air pollution in low income countries is an important cause of mortality from respiratory infection. We hypothesised that chronic smoke exposure is detrimental to alveolar macrophage function, causing failure of innate immunity. We report the relationship between macrophage function and prior smoke exposure in healthy Malawians.

Laboratory evidence of disseminated intravascular coagulation is associated with a fatal outcome in children with cerebral malaria despite an absence of clinically evident thrombosis or bleeding.

Background: A procoagulant state is implicated in cerebral malaria (CM) pathogenesis, but whether disseminated intravascular coagulation (DIC) is present or associated with a fatal outcome is unclear.

Objectives: To determine the frequency of overt DIC, according to ISTH criteria, in children with fatal and non-fatal CM.

Methods/patients: Malawian children were recruited into a prospective cohort study in the following diagnostic groups: retinopathy-positive CM (n = 140), retinopathy-negative CM (n = 36), non-malarial coma (n = 14), uncomplicated malaria (UM), (n = 91), mild non-malarial febrile illness (n = 85), and healthy controls (n = 36).

Sepsis carries a high mortality among hospitalised adults in Malawi in the era of antiretroviral therapy scale-up: a longitudinal cohort study.

Objective: To assess mortality risk among adults presenting to an African teaching hospital with sepsis and severe sepsis in a setting of high HIV prevalence and widespread ART uptake.

Methods: Prospective cohort study of adults (age ≥16 years) admitted with clinical suspicion of severe infection between November 2008 and January 2009 to Queen Elizabeth Central Hospital, a 1250-bed government-funded hospital in Blantyre, Malawi. Demographic, clinical and laboratory information, including blood and cerebrospinal fluid cultures were obtained on admission.

HIV associated neurocognitive disorders (HAND) in Malawian adults and effect on adherence to combination anti-retroviral therapy: a cross sectional study.

Background: Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART.

Methods: HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment.