B cell, CD8 + T cell and gamma delta T cell infiltration alters alveolar immune cell homeostasis in HIV-infected Malawian adults

HIV infection is associated with increased risk to lower respiratory tract infections (LRTI). However, the impact of HIV infection on immune cell populations in the lung is not well defined. We sought to comprehensively characterise the impact of HIV infection on immune cell populations in the lung. : Twenty HIV-uninfected controls and 17 HIV-1 infected ART-naïve adults were recruited from Queen Elizabeth Central Hospital, Malawi. Immunophenotyping of lymphocyte and myeloid cell populations was done on bronchoalveolar lavage fluid and peripheral blood cells. : We found that the numbers of CD8 T cells, B cells and gamma delta T cells were higher in BAL fluid of HIV-infected adults compared to HIV-uninfected controls (all p<0.05). In contrast, there was no difference in the numbers of alveolar CD4 T cells in HIV-infected adults compared to HIV-uninfected controls (p=0.7065). Intermediate monocytes were the predominant monocyte subset in BAL fluid (HIV-, 63%; HIV+ 81%), while the numbers of classical monocytes was lower in HIV-infected individuals compared to HIV-uninfected adults (p=0.0006). The proportions of alveolar macrophages and myeloid dendritic cells was lower in HIV-infected adults compared to HIV-uninfected controls (all p<0.05). : Chronic HIV infection is associated with broad alteration of immune cell populations in the lung, but does not lead to massive depletion of alveolar CD4 T cells. Disruption of alveolar immune cell homeostasis likely explains in part the susceptibility for LRTIs in HIV-infected adults

A 34-Year-Old Man With a Neck Mass.

CASE PRESENTATION A 34-year-old man presented to Queen Elizabeth Central Hospital in Blantyre, Malawi with multiple enlarged right cervical lymph nodes. He had no associated constitutional symptoms. Fine-needle aspirate (FNA) of one of the lymph nodes was negative for acid-fast bacilli (AFB) by smear microscopy. The FNA specimen was not sent for histological examination. Mycobacterial culture and Xpert MTB/RIF were not available at the time. He tested positive for HIV but CD4 T-cell count was not requested at the time of HIV diagnosis, and he did not start antiretroviral therapy (ART) pending confirmation of the cause of lymphadenopathy. Excision biopsy of the lymph nodes was planned; however, the patient was lost to follow-up before the procedure was performed

“An increase in COVID-19 patients would be overwhelming”: A qualitative description of healthcare workers’ experiences during the first wave of COVID-19 (March 2020 to October 2020) at Malawi’s largest referral hospital.

Background:   COVID-19 is currently a global health threat. Healthcare workers are on the front-line of the COVID-19 outbreak response and therefore at heightened risk of infection. There is a dearth of evidence from Sub-Saharan Africa about healthcare worker experiences in managing COVID-19.  We have reported on healthcare worker responses, experiences, and perspectives on epidemic response strategies at Queen Elizabeth Central Hospital, Malawi’s largest referral hospital.   Methods  We conducted 39 face-to-face in-depth interviews with a purposively selected sample of healthcare workers during the first wave of COVID-19 in Malawi (March 2020 to October 2020). The study included healthcare workers who provided direct and indirect patient care.   Results  During the early phase of the first wave (March to May 2020), healthcare workers expressed concerns with inadequate working space, unconducive infrastructure, delayed and rushed training on the management of COVID-19, and lack of incentives. Additionally, the hospital had staff shortages and limited essential resources such as piped oxygen and personal protective equipment. This increased healthcare worker fears of contracting COVID-19 and they were less willing to volunteer at COVID-19 isolation units. Resource constraints and limited preparedness compromised the care pathway particularly with increased numbers of COVID-19 patients. By the peak of the first wave (June to August 2020) many of these issues had been resolved. The hospital provided refresher training courses, personal protective equipment became available, incentives were offered to healthcare workers working in COVID-19 units and piped oxygen was installed. Staff morale was boosted, and more staff were willing to work at the COVID-19 isolation centres.   Conclusion  Experiences of healthcare workers during the first wave of COVID-19 are critical for improving care in future COVID-19 waves. Response strategies in resource-constrained areas should prioritise timely training of staff, creation of adequate isolation areas, provision of adequate medical supplies and strengthening leadership

The significant gap between international standards and stroke management practices at Queen Elizabeth Central Hospital (Malawi): An audit report

Background The Queen Elizabeth Central Hospital (QECH) is preparing to set up the first stroke unit in Blantyre, Malawi. We conducted this audit to assess current stroke management practices and outcomes at QECH and identify priority areas for intervention. Methods From April to June 2018, we prospectively enrolled patients with acute stroke and collected data on clinical presentation, cardiovascular risk factors, investigations and interventions, in-hospital outcomes, and follow-up plans after discharge. The American Heart Association/American Stroke Association (AHA/ASA) guidelines were used as the standard of care for comparison. Results Fifty patients with acute stroke were enrolled (46% women, 54% men). The mean age was 63.1 years (95% CI: 59.7-66.6). The diagnosis of stroke was based on the World Health Organization criteria. The diagnosis was made within 24 hours of admission in 19 patients (38%). Acute revascularisation therapy was not available. Forty-eight patients (96%) had their vital signs checked at baseline and 140/90 mmHg in 34 patients (68%), including 4 with values >220/120 mmHg. Nine patients had an RBS >10 mmol/L and four received insulin. Prophylaxis for deep venous thrombosis was offered to 12 patients (24%). Aspiration pneumonia was reported in 16 patients (32%) and was the most common hospital complication. The mean duration of hospitalisation was 10.4 days (95% CI: 5.6-15.2), and case fatality was 18%. The modified Rankin scale at discharge was ≤2 in 32% of patients. Only four patients (8%) were transferred to a rehabilitation centre. At the time of discharge, only 32% of patients received education on stroke. Conclusion Acute stroke care is less than optimal in this setting. Simple interventions such as reducing the delay in making a stroke diagnosis, early swallow assessments, and closer monitoring of vital signs could make a significant difference in stroke outcome. Furthermore, treating cardiovascular risk factors and setting up health education programmes to improve secondary prevention represent key priorities

Challenges of stroke management in resource-limited settings: A case- based reflection

A 19-year-old man presented with a 1-year history of headache, generalised body weakness, progressive memory loss, and disorientation. One month prior to admission, there was aggravation of the weakness of the right upper limb, with new-onset difficulty with mastication, speech impairment, apathy, and urinary incontinence. On clinical examination, the patient had a motor aphasia and a right-sided hemiparesis with increased muscle tone and hyperreflexia. A noncontrast computed tomography (CT) scan of the brain revealed large ischaemic strokes extending beyond the classical vascular territories. Cerebrospinal fluid analysis showed a mildly increased protein level. The electrocardiogram revealed an irregular sinus bradycardia. The remainder of the cardiovascular and laboratory workup was unremarkable. Considering a working diagnosis of central nervous system vasculitis, the patient was treated with aspirin, prednisolone, and physiotherapy. However, he died suddenly a few weeks later. Based on this case, we discuss the challenges of stroke management in resource-limited settings, provide practical tips for general practitioners, reflect on the potential avenues for short- and long-term action, and introduce the budding collaboration platform between the University College London, the University of Liverpool, the Queen Elizabeth Central Hospital, and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme

Mixed method evaluation of a learning from excellence programme for community health workers in Neno, Malawi

Background: Community Health Workers (CHWs) play an essential role in linking communities to facility-based healthcare. However, CHW programmes have often been hampered by low levels of staff motivation, and new tools aimed at improving staff motivation and work environment are needed. One such intervention is the “Learning from Excellence” (LfE) programme. We aimed to assess feasibility, outputs, and impact of a co-designed LfE programme on CHW motivation, in Neno District. Methods: We conducted a convergent mixed-method evaluation of the LfE programme. Co-design of the programme and forms took place between October 2019 and January 2020. LfE forms submitted between September and November 2020 were analysed using descriptive statistics and memos summarising answers to the open-ended question. To investigate experiences with LfE we conducted in-depth semi-structured interviews with key stakeholders, CHWs, and site supervisors, which were analysed thematically. A pre-post intervention questionnaire was developed to assess the impact of the co-designed LfE intervention on CHW motivation and perceived supervision. Outcomes were triangulated into a logic model. Results: In total 555 LfE forms were submitted, with 34.4% of CHWs in Neno District submitting at least one LfE report. Four themes were identified in the interviews: LfE implementation processes, experience, consequences, and recommendations. A total of 50 CHWs participated in the questionnaire in January 2020 and 46 of them completed the questionnaire in December 2020. No statistically significant differences were identified between pre-and post-LfE measurements for both motivation (Site F: p = 0.86; Site G: p = 0.31) and perceived supervision (Site F: p = 0.95; Site G: p = 0.45). A logic model, explaining how the LfE programme could impact CHWs was developed. Conclusions: Many CHWs participated in the LfE intervention between September 2020 and November 2020. LfE was welcomed by CHWs and stakeholders as it allowed them to appreciate excellent work in absence of other opportunities to do so. However, no statistically significant differences in CHW motivation and perceived supervision were identified. While the intervention was feasible in Neno District, we identified several barriers and facilitators for implementation. We developed a logic model to explain contextual factors, and mechanisms that could lead to LfE outcomes for CHWs in Neno District. The developed logic model can be used by those designing and implementing interventions like LfE for health workers

Airway CD8+CD161++TCRvα7.2+ T Cell Depletion During Untreated HIV Infection Targets CD103 Expressing Cells

HIV-infected adults are at an increased risk to lower respiratory tract infections (LRTIs). CD8CD161TCRvα7.2 T cells are an innate-like T cell subset that are thought to play an important role in early defense against pathogens in the respiratory tract. HIV infection leads to irreversible depletion of these cells in peripheral blood, however, its impact on this subset in the human airway is still unclear. Here, we show presence of CD103 expressing CD8CD161TCRvα7.2 T cells in the airway that exhibited a distinct cytokine functional profile compared to their CD103 airway counterparts and those from peripheral blood. These CD103 expressing airway CD8CD161TCRvα7.2 T cells were selectively depleted in untreated HIV-infected adults compared to healthy controls. Their frequency was positively correlated with frequency of airway CD4 T cells. Furthermore, the frequency of airway CD8CD161TCRvα7.2 T cells was also inversely correlated with HIV plasma viral load, while suppressive antiretroviral therapy (ART) resulted in restoration of airway CD8CD161TCRvα7.2 T cells. Our findings show that CD103 expressing airway CD8CD161TCRvα7.2 T cells are functionally distinct and are preferentially depleted during untreated asymptomatic HIV infection. Depletion of CD103 expressing airway CD8CD161TCRvα7.2 T cells, at a major portal of pathogen entry, could partly contribute to the increased propensity for opportunistic LRTIs observed in untreated HIV-infected adults

Establishment of a high-dependency unit in Malawi.

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

Re-Treatment Tuberculosis Cases Categorised as “Other”: Are They Properly Managed?

BACKGROUND: Although the World Health Organization (WHO) provides information on the number of TB patients categorised as "other", there is limited information on treatment regimens or treatment outcomes for "other". Such information is important, as inappropriate treatment can lead to patients remaining infectious and becoming a potential source of drug resistance. Therefore, using a cohort of TB patients from a large registration centre in Lilongwe, Malawi, our study determined the proportion of all TB re-treatment patients who were registered as "other", and described their characteristics and treatment outcomes. METHODS: This retrospective observational study used routine program data to determine the proportion of all TB re-treatment patients who were registered as "other" and describe their characteristics and treatment outcomes between January 2006 and December 2008. RESULTS: 1,384 (12%) of 11,663 TB cases were registered as re-treatment cases. Of these, 898 (65%) were categorised as "other": 707 (79%) had sputum smear-negative pulmonary TB and 191 (21%) had extra pulmonary TB. Compared to the smear-positive relapse, re-treatment after default (RAD) and failure cases, smear-negative "other" cases were older than 34 years and less likely to have their HIV status ascertained. Among those with known HIV status, "other" TB cases were more likely to be HIV positive. Of TB patients categorised as "other", 462 (51%) were managed on the first-line regimen with a treatment success rate of 63%. CONCLUSION: A large proportion of re-treatment patients were categorised as "other". Many of these patients were HIV-infected and over half were treated with a first-line regimen, contrary to national guidelines. Treatment success was low. More attention to recording, diagnosis and management of these patients is warranted as incorrect treatment regimen and poor outcomes could lead to the development of drug resistant forms of TB

Efficacy of sodium bicarbonate (Baking soda) and clove powder (Syzygium aromaticum) as anaesthetic agents for Nile tilapia (Oreochromis niloticus, linnaeus 1758) juveniles

Anaesthetics in aquaculture serve as a stress avoidance mechanism, mitigating stress-related impacts during fish handling and transportation. This study assessed the efficacy of sodium bicarbonate and clove stem powder as anaesthetic agents for Nile Tilapia juveniles. Four hundred and twenty uniform O. niloticus juveniles (5 ± 0.5 g, 74 ± 5 mm) were exposed to varying concentrations of sodium bicarbonate (10, 15, 20, 25, 30, 35, 40 g/L) and clove stem powder (0, 1, 3, 5, 7, 10, 15 g/L) in 20 L transparent plastic tanks. The results showed an inverse relationship between anaesthetic concentration and induction time, a direct relationship with recovery time, and an inverse correlation between induction and recovery times for both agents (P < 0.001). The Appropriate concentrations were determined as 25 g/L for sodium bicarbonate and 10 g/L for clove stem powder. At these levels, induction and recovery times met ideal criteria (3-5 min induction, 5-10 min recovery), with fish exhibiting normal behavior and 100% survival after a week of monitoring