Scoping review of post-TB pulmonary vascular disease: Proceedings from the 2nd International Post-Tuberculosis Symposium.

Tuberculosis (TB) may cause significant long-term cardiorespiratory complications, of which pulmonary vascular disease is most under-recognized. TB is rarely listed as a cause of pulmonary hypertension (PH) in most PH guidelines, yet PH may develop at various stages in the time course of TB, from active infection through to the post-TB period. Predisposing risk factors for the development of PH are likely multifactorial, involving active TB disease and post-TB lung disease (PTLD), host-related and environment-related factors. Moreover, post-TB PH should likely be classified in Group 3 PH, with the pathogenesis similarly complex and multifactorial as other Group 3 PH causes. Identifying risk factors that predispose to post-TB PH may aid in developing risk stratification criteria for early identification and referral for confirmatory diagnostic tests. Given that universal screening for PH in TB survivors may be impractical and unfeasible, a targeted screening approach for high-risk individuals would be sensible. In this scoping review of post-TB PH, resulting from the proceedings of the 2nd International Post-Tuberculosis Symposium, we aim to describe the epidemiology, risk factors, and pathophysiology of post-TB PH. We emphasize diagnosing PH with an alternative set of diagnostic guidelines in resource-constrained settings where right heart catheterization may not be feasible. Research to describe the burden and distribution of post-TB PH should be prioritized as there is a current gap in knowledge regarding the prevalence and incidence of post-TB PH among persons with TB.

Critical illness due to infection in people living with HIV.

People living with HIV comprise a substantial number of the patients admitted to intensive care. This number varies according to geography, but all areas of the world are affected. In lower-income and middle-income countries, the majority of intensive care unit (ICU) admissions relate to infections, whereas in high-income countries, they often involve HIV-associated non-communicable diseases diagnoses. Management of infections potentially resulting in admission to the ICU in people living with HIV include sepsis, respiratory infections, COVID-19, cytomegalovirus infection, and CNS infections, both opportunistic and non-opportunistic. It is crucial to know which antiretroviral therapy (ART) is appropriate, when is the correct time to administer it, and to be aware of any safety concerns and potential drug interactions with ART. Although ART is necessary for controlling HIV infections, it can also cause difficulties relevant to the ICU such as immune reconstitution inflammatory syndrome, and issues associated with ART administration in patients with gastrointestinal dysfunction on mechanical ventilation. Managing infection in people with HIV in the ICU is complex, requiring collaboration from a multidisciplinary team knowledgeable in both the management of the specific infection and the use of ART. This team should include intensivists, infectious disease specialists, pharmacists, and microbiologists to ensure optimal outcomes for patients.

Lung outcomes and related risk factors in patients after SARS-CoV-2 infection: a hospitalised single-centre cohort from Johannesburg, South Africa.

Background: Sequelae post-SARS-CoV-2 infection, including lung and functional impairment, pose a significant challenge post-recovery. We explored the burden and risk factors for post-COVID-19 sequelae in an African population with prevalent comorbidities including tuberculosis (TB) and HIV. Methods: We conducted an observational cohort study on hospitalised adults with confirmed SARS-CoV-2 infection from 20 March to 06 October 2021 at Chris Hani Baragwanath Academic Hospital, South Africa. We collected data on comorbidities, and COVID-19 severity using the World Health Organization (WHO) clinical progression scale. Prospectively, we followed up all participants within 40-days post-discharge to assess body mass index (BMI), COVID-19 symptoms and quality of life using St George's Respiratory Questionnaire (SGRQ), 6-min walking-test (6MWT), and spirometry. A subsequent in-depth visit assessed plethysmography, diffusing capacity for the lung for carbon monoxide (DLCO), and high-resolution chest-CT. Findings: We followed up 111 participants, where 65.8% were female, median age 50.5 years, and predominantly black-African (92.8%). Relevant comorbidities included TB disease (18.9%) and HIV infection (36%). SGRQ total scores were elevated in 78.9%, median 6MWT distance was reduced at 300 m (IQR 210-400), and nearly half (49.5%) exhibited spirometry findings below the lower limit of normal (LLN). In-depth pulmonary assessment for 61 participants revealed abnormalities in total lung capacity (31.6% <80% predicted), DLCO (53.4% <80% predicted), and chest-CT (86.7% abnormal). Significant risk factors for individual abnormal outcomes, adjusted for age and sex, were TB disease, HIV with CD4 <200 cells/mm3, BMI <18.5 kg/m2 and >35 kg/m2, and initial COVID-19 severity. Interpretation: This study demonstrates substantial lung and functional morbidity within the first weeks post-COVID-19, particularly in individuals with pre-existing comorbidities including TB, HIV, and low or high BMI. Chest-CT and DLCO show best early potential at reflecting COVID-19-related pathologies. Funding: The Bavarian State Ministry of Science and Arts.

COVID-19: An evaluation of predictive scoring systems in South Africa.

Background: | The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has resulted in more than 700 million cases worldwide. Sepsis and pneumonia severity scores assist in risk assessment of critical outcomes in patients with COVID-19. This allows healthcare workers to triage patients, by using clinical parameters and limited special investigations, thus offering the most appropriate level of care. Methods: | A retrospective cohort study of 605 adult patients hospitalised with moderate to severe COVID-19, at a tertiary state hospital in South Africa. Evaluating the utility of the CURB65, NEWS2 and ISARIC-4C Mortality Score, in predicting critical outcomes, using clinical characteristics on admission. Outcomes included in-hospital mortality, invasive mechanical ventilation, and intensive care unit admission (ICU). Performance of severity scores and risk factors was assessed by area under the receiver operator characteristics (AUROC) analysis and logistic regression. Findings |: A total of 605 records were used, 129 (21 %) non-survivors, 101 (17 %) ICU admissions and 77 (13 %) requiring invasive ventilation. Greater odds of mortality was associated with moderate and severe risk groups of the CURB65, ISARIC-4C and NEWS2 score. Mortality AUROC curve analysis for the CURB65 score was 0·76 (95 % CI: 0·71-0·8), 0·77 (95 % CI: 0·73-0·81) for the ISARIC-4C and 0·77 (95 % CI: 0·73-0·82) for the NEWS2 score. The CURB65 score had a sensitivity of 86 % with 12·8 % mortality, ISARIC-4C score a sensitivity of 87·6 % with 8 % mortality and NEWS2 score a sensitivity of 92·2 % with 8·6 % mortality. Interpretation |: In 605 hospitalised patients with moderate to severe COVID-19, predominantly infected by the ancestral strain, good performance of the NEWS2 and ISARIC-4C score in predicting in-hospital mortality was noted. The CURB65 score had a high mortality rate in its low-risk group suggesting unexplained risk factors, not accounted for in the score, thus limiting its utility in the South African setting.

Clinical Profile of Adult Patients Presenting With Renal Dysfunction to a Tertiary Hospital Emergency Department.

Background Renal dysfunction is a potentially life-threatening condition that is commonly encountered in the emergency department (ED). This study aimed to describe the clinical profile of patients presenting with renal dysfunction to a tertiary-level hospital ED. Methods Medical records of patients presenting to the ED with renal dysfunction over a six-month period (July-December 2017) were reviewed. A descriptive analysis of the data was performed. Results Serum creatinine levels were measured in 7,442 (69.9%) of the 10,642 patients that were triaged into the ED. Of these, 208 (2.8%) were identified with renal dysfunction, of which 192 consented to study participation. The median age of study subjects was 49.5 (IQR 38.8-63.0) years; 108 (56.3%) were male; proteinuria on urine dipsticks was demonstrated in 108 (56.3%); 72 (37.5%) were HIV-positive; 66 (39.6%) required dialysis; 11 (5.7%) were admitted to the ICU; and 59 (30.7%) died prior to hospital discharge. More patients presented with acute kidney injury (AKI) (46.9%) compared to chronic kidney disease (CKD) (27.6%) and acute on chronic kidney disease (AoCKD) (25.5%). Sepsis was the most common precipitant of AKI (42.2%) and AoCKD (30.6%), while chronic hypertension (35.8%) and diabetes mellitus (34.0%) were the most common comorbidities in subjects with CKD. Conclusion Patients presenting to the ED with various risk factors and comorbidities, including HIV, sepsis, hypertension, and diabetes mellitus, may have underlying renal dysfunction. ED clinicians should therefore adopt a low threshold to screen for renal dysfunction in these patients.

Challenges and recommendations for the management of asthma in the Middle East and Africa.

Clinical presentation of asthma is variable, and its diagnosis can be a major challenge in routine health-care practice, especially in low-and-middle-income countries. The aim of asthma management is to achieve optimal asthma control and to reduce the risk of asthma exacerbations and mortality. In the Middle East and in Africa (MEA), several patient- and physician-related factors lead to misdiagnosis and suboptimal management of asthma. A panel of experts comprising of specialists as well as general health-care professionals met to identify challenges and provide recommendations for the management of asthma in MEA. The major challenges identified for diagnosis of asthma were lack of adequate knowledge about the disease, lack of specialized diagnostic facilities, limited access to spirometry, and social stigma associated with asthma. The prime challenges for management of asthma in MEA were identified as overreliance on short-acting ß-agonists (SABAs), underprescription of inhaled corticosteroids (ICS), nonadherence to prescribed medications, and inadequate insurance coverage for its treatment. The experts endorsed adapting the Global Initiative for Asthma guidelines at country and regional levels for effective management of asthma and to alleviate the overuse of SABAs as reliever medications. Stringent control over SABA use, discouraging over-the-counter availability of SABA, and using as-needed low-dose ICS and formoterol as rescue medications in mild cases were suggested to reduce the overreliance on SABAs. Encouraging SABA alone-free clinical practice in both outpatient and emergency department settings is also imperative. We present the recommendations for the management of asthma along with proposed regional adaptations of international guidelines for MEA.

Clinical, radiological, and laboratory predictors of a positive urine lipoarabinomannan test in sputum-scarce and sputum-negative patients with HIV-associated tuberculosis in two Johannesburg hospitals.

BACKGROUND: Tuberculosis (TB) is a major cause of mortality in persons living with HIV (PLWH). Sputum-based diagnosis of TB in patients with low CD4 counts is hampered by paucibacillary disease and consequent sputum scarcity or negative sputum results. Urine lipoarabinomannan (LAM) has shown promise in the point-of-care detection of TB in this patient subset but lacks sensitivity, and its exact role in a diagnostic algorithm for TB in South Africa remains to be clarified. OBJECTIVES: The objective of this study was to better define the patient profile and the TB characteristics associated with a positive urine LAM (LAM+ve) test. METHOD: This multicentre retrospective record review examined the clinical, radiological, and laboratory characteristics of hospitalised PLWH receiving urine LAM testing with sputum-scarce and/or negative sputum GeneXpert ® (mycobacterium tuberculosis/resistance to rifampicin [MTB/RIF]) results. RESULTS: More than a third of patients, 121/342 (35%), were LAM+ve. The positive yield was greater in the sputum-scarce than the sputum-negative group, 66/156 (42%) versus 55/186 (30%), P = 0.0141, respectively. Patients who were LAM+ve were more likely to be confused (odds ratio [OR] = 2.2, 95% confidence interval [CI] = 1.2-3.7, P = 0.0045), have a higher median heart rate (P = 0.0135) and an elevated quick sepsis-related organ failure assessment score (≥ 2), OR = 3.5, 95% CI = 1.6-7.6, P = 0.0014. A LAM+ve test was significantly associated with disseminated TB (dTB), P < 0.0001, TB-related immune reconstitution inflammatory syndrome (IRIS), P = 0.0035, and abdominal TB, P < 0.0001. Laboratory predictors of a LAM+ve status included renal dysfunction, P = 0.044, severe anaemia, P = 0.0116, and an elevated C-reactive protein, P = 0.0131. Of the 12 PLWH with disseminated non-TB mycobacteria cultured from the blood and/or bone marrow, n = 9 (75%) had a LAM+ve result (OR = 5.8, 95% CI = 1.6-20.8, P = 0.0053). CONCLUSION: Urine LAM testing of hospitalised PLWH with suspected active TB had significant diagnostic utility in those that were sputum-scarce or sputum-negative. A LAM+ve result was associated with dTB, clinical and laboratory markers of severe illness, and TB-IRIS. Disseminated non-tuberculous mycobacterial infection of hospitalised PLWH may also yield urine LAM+ve results, and mycobacterial cultures must be checked in those non-responsive to conventional TB treatment. Selective use of the LAM test in the critically ill is likely to maximise the diagnostic yield, improve the test's predictive value, and reduce the time to TB diagnosis and initiation of treatment.

Age significantly influences the sensitivity of SARS-CoV-2 rapid antibody assays.

BACKGROUND: Point-of-care serological assays are a promising tool in COVID-19 diagnostics but do have limitations. Our study evaluated the sensitivity of five rapid antibody assays and explored factors influencing their sensitivity in detecting SARS-CoV-2-specific IgG and IgM antibodies. METHODS: Finger-prick blood samples from 102 participants, within 2-6 weeks of PCR-confirmed COVID-19 diagnosis, were tested for IgG and IgM using five rapid serological assays. The assay sensitivities were compared, and patient factors evaluated in order to investigate potential associations with assay sensitivity. RESULTS: Sensitivity ranged from 36% to 69% for IgG and 13% to 67% for IgM. Age was the only factor significantly influencing the likelihood of a detectable IgG or IgM response. Individuals aged 40 years and older had an increased likelihood of a detectable IgG or IgM antibody response by rapid antibody assay. CONCLUSION: Rapid serological assays demonstrate significant variability when used in a real-world clinical context. There may be limitations in their use for COVID-19 diagnosis among the young.

Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19.

BACKGROUND: South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa. METHODS: Data was collected on all adult patients with known HIV status and COVID-19, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), admitted to the medical wards and intensive care unit (ICU) between 6 March and 11 September 2020. The data included demographics, co-morbidities, laboratory results, severity of illness scores, complications and mortality, and comparisons were made between the HIV-positive and HIV negative groups. RESULTS: Three-hundred and eighty-four patients, 108 HIV-positive and 276 HIV-negative, were included in the study. Median 4C score was significantly higher in the HIV-positive patients compared to the HIV-negative patients, but there was no significant difference in mortality between the HIV-positive and HIV-negative groups (15% vs 20%, p = 0.31). In addition, HIV-positive patients who died were younger than their HIV-negative counterparts, but this was not statistically significant (47.5 vs 57 years, p = 0.06). CONCLUSION: Our findings suggest that HIV is not a risk factor for moderate or severe COVID-19 disease neither is it a risk factor for mortality. However, HIV-positive patients with COVID-19 requiring admission to hospital are more likely to be younger than their HIV-negative counterparts. These findings need to be confirmed in future, prospective, studies.

Artesunate for the treatment of severe malaria: A retrospective review of patients admitted to two tertiary hospital intensive care units in Johannesburg, South Africa.

BACKGROUND: Globally, malaria is one of the six major causes of deaths from communicable diseases. In South Africa, malaria is known to be endemic in three provinces. Two large trials, AQUAMAT and SEAQUAMAT, demonstrated the superiority of intravenous (IV) artesunate compared to quinine. A systematic review (including the above trials) demonstrated a mortality benefit for adult patients treated with artesunate, but included studies that were conducted in Asia with no adult data available for Africa. Given the lack of local data, we conducted this study to investigate the use of artesunate for the treatment of severe malaria at two academic adult intensive care units (ICUs) in Johannesburg. METHODS: We undertook a retrospective patient record review. All patients admitted to the two ICUs and treated for severe malaria using artesunate were included. The study period extended from April 2010 to April 2014. The primary outcome was to determine the observed mortality and relate it to the predicted mortality based on the Acute Physiology and Chronic Health Evaluation (APACHE II) severity of illness score. The ratio of the observed mortality to the expected mortality based on the APACHE II severity of illness score provides a standardised mortality ratio (SMR). Clinical and laboratory parameters data were analysed. RESULTS: There were 56 patients included in the study, of which 40 were male (71.4%). The mean APACHE II score was 19 (standard deviation 5.4). We observed a lower than predicted mortality rate of 21.4% (SMR 0.66). Human immunodeficiency virus (HIV) was the most prevalent comorbidity (32%). There was no travel history in 26.8% of patients. Heart rate, respiratory rate and Glasgow Coma Scale (GCS) all improved significantly from admission to the time of discharge (p ≤ 0.01). Acidaemia, bilirubin, urea and bleeding risk (platelet count) also improved (p ≤ 0.01). Mechanical ventilation was associated with an increased risk of death (OR 35; CI 7.0-182). CONCLUSION: In this retrospective two-centre study, IV artesunate was associated with a lower than predicted mortality in adult patients with severe malaria requiring ICU admission.