Prevalence and Associated Factors of Chronic Obstructive Pulmonary Disease Among Adults in Neno District, Malawi: A Cross-Sectional Analytical Study.

Introduction: Chronic obstructive pulmonary disease (COPD) continues to pose a global public health challenge. However, literature is scarce on the burden of COPD in Malawi. We assessed the prevalence and risk factors for COPD among adults in Neno, Malawi. Methodology: We conducted a population-based analytical cross-sectional study in Neno District between December 2021 and November 2022. Using a multi-stage sampling technique, we included 525 adults aged≥40 years. All participants underwent spirometry according to the American Thoracic Society (ATS) guidelines and were interviewed using the IMPALA questionnaire. For this study, we utilized the definition of COPD as a post-bronchodilator FEV1/FVC <0.70. We collected data using Kobo collect, exported to Microsoft Excel, and analysed using R software. We used descriptive statistics and logistic regression analysis; a p-value of <0.05 was considered statistically significant. Results: Out of 525 participants, 510 participants were included in the final analysis. Fifty-eight percent of the participants were females (n=296), and 62.2% (n=317) were between 40 and 49 years with a median (IQR) age of 46 (40-86). For patient characteristics, 15.1% (n=77) were current smokers, and 4.1% (n=21) had a history of pulmonary tuberculosis (PTB). Cough was the most commonly reported respiratory symptom (n=249, 48.8%). The prevalence of COPD was 10.0% (n=51) and higher (15.0%) among males compared to females (6.4%). Factors significantly associated with COPD were age 60 years and above (adjusted odds ratio [aOR] = 3.27, 95% CI: 1.48-7.34, p<0.004), ever smoked (aOR = 6.17, 95% CI:1.89-18.7, p<0.002), current smoker (aOR = 17.6, 95% CI: 8.47-38.4, p<0.001), and previous PTB (aOR = 4.42, 95% CI: 1.16-15.5, p<0.023). Conclusion: The cross-sectional prevalence of COPD in rural Malawi is high, especially among males. Factors significantly associated were older age (60 years and above), cigarette smoking, and previous PTB. Longitudinal studies are needed to better understand disease etiology and progression in this setting.

Quality of life among type 2 diabetes mellitus patients at Kamuzu Central Hospital in Lilongwe, Malawi: A mixed-methods study.

Type II diabetes mellitus (T2DM) significantly impacts quality of life (QoL) yet data among these patients in Malawi are lacking. This study was conducted to assess QoL among patients with T2DM. A mixed-method cross-section study was conducted at Kamuzu Central Hospital (KCH), Lilongwe, Malawi. Data collection was done using a modified diabetes quality of life (MDQoL)-17 questionnaire for quantitative data while in-depth interviews and diary methods were used for qualitative data. Demographic data were summarized using descriptive statistics and inferential statistics using t-tests and ANOVA. Thematic analysis was utilized for qualitative data. A sample of 339 participants (mean age 50.3±15.5) was recruited. Overall, the mean QoL score was moderate (mean QoL 63.91±19.54). Those on health insurance had better QoL (QoL 76.71, C.I. 69.22-84.19, p-value 0.005) compared to those without health insurance. Furthermore, the absence of comorbidities was associated with having better QoL (QoL 71.18, C.I. 66.69-75.67, p-value < 0.0001). Qualitatively, T2DM was associated with patients' health status, increased stress levels, and loss of independence. There were QoL-promoting factors among T2DM patients such as diabetes health talks, having a supportive family, and following hospital advice. Inhibiting factors include drug shortages, societal perceptions, a sedentary lifestyle, stress, and despising hospital advice. Overall QoL in patients with T2DM receiving treatment at KCH is moderate. QoL of patients with T2DM is influenced by interrelated factors which require multidisciplinary team care to optimize the QoL among these patients. Health workers need to adopt a holistic approach when treating patients with T2DM, such as managing comorbidities and including assessment of QoL, behavioral change measures like physical exercises, and a healthy diet.

TB morbidity estimates overlook the contribution of post-TB disability: evidence from urban Malawi.

INTRODUCTION: Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country. METHODS: Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016-April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George's Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender. RESULTS: At treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment. CONCLUSION: TB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.

Respiratory symptoms and lung function in patients treated for pulmonary tuberculosis in Malawi: a prospective cohort study.

RATIONALE: Pulmonary tuberculosis (PTB) can cause post-TB lung disease (PTLD) associated with respiratory symptoms, spirometric and radiological abnormalities. Understanding of the predictors and natural history of PTLD is limited. OBJECTIVES: To describe the symptoms and lung function of Malawian adults up to 3 years following PTB-treatment completion, and to determine the evolution of PTLD over this period. METHODS: Adults successfully completing PTB treatment in Blantyre, Malawi were followed up for 3 years and assessed using questionnaires, post-bronchodilator spirometry, 6 min walk tests, chest X-ray and high-resolution CT. Predictors of lung function at 3 years were identified by mixed effects regression modelling. MEASUREMENT AND MAIN RESULTS: We recruited 405 participants of whom 301 completed 3 years follow-up (mean (SD) age 35 years (10.2); 66.6% males; 60.4% HIV-positive). At 3 years, 59/301 (19.6%) reported respiratory symptoms and 76/272 (27.9%) had abnormal spirometry. The proportions with low FVC fell from 57/285 (20.0%) at TB treatment completion to 33/272 (12.1%), while obstruction increased from and 41/285 (14.4%) to 43/272 (15.8%) at 3 years. Absolute FEV1 and FVC increased by mean 0.03 L and 0.1 L over this period, but FEV1 decline of more than 0.1 L was seen in 73/246 (29.7%). Higher spirometry values at 3 years were associated with higher body mass index and HIV coinfection at TB-treatment completion. CONCLUSION: Spirometric measures improved over the 3 years following treatment, mostly in the first year. However, a third of PTB survivors experienced ongoing respiratory symptoms and abnormal spirometry (with accelerated FEV1 decline). Effective interventions are needed to improve the care of this group of patients.

Antibiotic guideline adherence by Clinicians in medical wards at Queen Elizabeth Central Hospital (QECH), Blantyre Malawi.

Antimicrobial resistance (AMR) is a major concern in health care worldwide. In Malawi rates of AMR, in particular third-generation cephalosporin-resistant (3GC-R) Enterobacterales have rapidly increased since 2003. Antibiotic guidelines are a key component of antimicrobial stewardship (AMS). As part of stewardship, Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi developed an antibiotic guideline in the form of a smart phone application in June 2016. Aim: We conducted a study to assess clinicians adherence to the local antibiotic guideline on the adult medical wards, two years after it was introduced. Specifically assessing choice of antibiotic, time of blood culture collection and 48-hour review. Methods: A cross-sectional study was carried out using purposive sampling method. 230 case files of adult patients were audited against the antibiotic guideline. Adherence to the guideline in terms of indication for antibiotic, choice of antibiotic and antibiotic review time was reviewed. Statistical analysis was done using IBM SPSS and presented with descriptive statistics. Results: 194 (84% [95% CI 79.0-88.8]) antibiotic prescriptions were adherent to the guideline, 28 (12% [95% CI 8.2-17.1]) non-adherent and 8 (3.5% [95% CI 1.5-6.7]) antibiotic indication was not clear. The most common indication for antibiotic prescriptions was pneumonia, as documented in 89 (39% [95 % CI 32.4-45.3]) case files. 191(76% [95% CI 70.3-81.2]) of prescriptions were for ceftriaxone. There was evidence of utilising blood culture to adjust therapy as 88/230 (38% [95% CI 32.0-44.9]) had culture taken. 175(76% [95 % CI 70.0-81.4]) of files had antibiotics reviewed within 48 hours. Conclusion: There is still need to work on rational prescribing of antibiotics as ceftriaxone usage was high during this study period. Scheduled audits and point prevalence surveys should be implemented quickly to reduce the impact of antibiotic resistance and improve individual patient care.

A feasibility study of controlled human infection with Streptococcus pneumoniae in Malawi.

BACKGROUND: Persistent carriage of pneumococcal vaccine serotypes has occurred after introduction of PCV13 vaccination in Africa but the mechanisms are unclear. We tested the feasibility of using a human pneumococcal challenge model in Malawi to understand immune correlates of protection against carriage and to trial alternative vaccine candidates. We aimed to identify a dose of Streptococcus pneumoniae serotype 6B sufficient to establish nasopharyngeal carriage in 40% of those nasally inoculated and evaluate nasal mucosal immunity before and after experimental inoculation. METHODS: Healthy student volunteers were recruited and inoculated with saline, 20,000 CFU/naris or 80,000 CFU/naris of Streptococcus pneumoniae serotype 6B Post inoculation carriage was determined by nasal sampling for bacterial culture and lytA PCR. Immunological responses were measured in serum and nasal mucosal biopsies before and after bacterial inoculation. FINDINGS: Twenty-four subjects completed the feasibility protocol with minimal side effects. pneumococcal carriage was established in 0/6, 3/9 and 4/9 subjects in the saline, 20,000 CFU/naris and 80,000 CFU/naris groups, respectively. Incidental (natural) serotype carriage was common (7/24 participants carried non-6B strains, 29.2%. Experimentally induced type 6B pneumococcal carriage was associated with pro-inflammatory nasal mucosal responses prior to inoculation and altered mucosal recruitment of immune cells post bacterial challenge. There was no association with serum anti-capsular antibody. INTERPRETATION: The serotype 6B experimental human pneumococcal carriage model is feasible in Malawi and can now be used to determine the immunological correlates of protection against carriage and vaccine efficacy in this population. FUNDING: None.

The influence of pneumococcal conjugate vaccine-13 on nasal colonisation in a controlled human infection model of pneumococcal carriage in Malawi: a double-blinded randomised controlled trial protocol.

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).

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.

A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi - A feasibility study.

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.  As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants. We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice. The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.