Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

The Evolving Spectrum of Kidney Histology in HIV-Positive Patients in South Africa.

Introduction: Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury. Methods: This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005-2009), tenofovir disoproxil (TDF) introduction (2010-2012), TDF-based fixed dose combination (2013-2015), and ART at HIV diagnosis (2016-2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID). Results: We included 671 participants (median age 36, interquartile range, 21-44 years; 49% female; median CD4 cell count 162 [interquartile range, 63-345] cells/mm3). Over time, ART (31%-65%, P < 0.001), rate of HIV suppression (20%-43%, P < 0.001), nonelective biopsies (53%-72%, P < 0.001), and creatinine at biopsy (242-449 µmol/l, P < 0.001) increased. A decrease in HIVAN (45%-29% P < 0.001) was accompanied by an increase in TID (13%-33%, P < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89-4.73 P < 0.001). Conclusion: As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.

Sputum Color as a Marker for Bacteria in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Rationale: Diagnosing bacterial infection as the etiology in acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) remains challenging. Sputum discoloration is easily measured and often used as a marker of bacterial infection in AECOPD, although high-quality evidence for this practice is lacking. Objectives: To determine the diagnostic accuracy of sputum color as a marker for bacteria in AECOPD. Methods: Articles were searched for in electronic databases, and the gray literature were reviewed. Quality assessment of included articles was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. A meta-analysis was conducted using a bivariate logistic regression model with random effects. Analysis was conducted on individual sputum samples rather than on individual participants so that each sample represented a unique index test. Results: Of the 1,600 candidate studies, 13 eligible studies satisfied the inclusion criteria. These included prospective cohort studies (n = 3), cross-sectional studies (n = 3), and secondary analyses of randomized controlled trials (n = 7). The included studies were all from Europe and North America. Most studies scored high risk of bias in at least one domain. In total, this systematic review and meta-analysis included 5,770 sputum samples. The estimated pooled sensitivity and specificity were 81% (95% confidence interval [CI], 70-88%) and 50% (95% CI, 35-65%), respectively, and these results were not significantly altered in a series of sensitivity analyses. Conclusions: Sputum color has limited value as a stand-alone test in diagnosing bacterial infection as the etiology in AECOPD because of its moderate sensitivity and poor specificity.

Multisystem cytomegalovirus end-organ disease in a patient with advanced HIV.

Cytomegalovirus (CMV) infection is common in people living with HIV, but multisystem CMV end-organ disease (EOD) is rare following the introduction of effective antiretroviral therapy. We present the case of a patient with advanced HIV and multisystem manifestations of CMV EOD. Contributions: This case report highlights the potential morbidity and mortality associated with CMV disease in patients with advanced HIV. Clinicians should be vigilant in considering CMV EOD in patients with advanced HIV and visual, neurological and gastointestinal symptoms.

Rifampicin resistance and mortality in patients hospitalised with HIV-associated tuberculosis.

Background: Patients with HIV and drug-resistant tuberculosis (TB) are at high risk of death. Objectives: We investigated the association between rifampicin-resistant TB (RR-TB) and mortality in a cohort of patients who were admitted to hospital at the time of TB diagnosis. Method: Adults hospitalised at Khayelitsha Hospital and diagnosed with HIV-associated TB during admission, were enrolled between 2013 and 2016. Clinical, biochemical and microbiological data were prospectively collected and participants were followed up for 12 weeks. Results: Participants with microbiologically confirmed TB (n = 482) were enrolled a median of two days (interquartile range [IQR]: 1-3 days) following admission. Fifty-three participants (11.0%) had RR-TB. Participants with rifampicin-susceptible TB (RS-TB) received appropriate treatment a median of one day (IQR: 1-2 days) following enrolment compared to three days (IQR: 1-9 days) in participants with RR-TB. Eight participants with RS-TB (1.9%) and six participants with RR-TB (11.3%) died prior to the initiation of appropriate treatment. Mortality at 12 weeks was 87/429 (20.3%) in the RS-TB group and 21/53 (39.6%) in the RR-TB group. RR-TB was a significant predictor of 12-week mortality (hazard ratio: 1.88; 95% confidence interval: 1.07-3.29; P = 0.03). Conclusion: Mortality at 12 weeks in participants with RR-TB was high compared to participants with RS-TB. Delays in the initiation of appropriate treatment and poorer regimen efficacy are proposed as contributors to higher mortality in hospitalised patients with HIV and RR-TB.

Children in foster care with symptoms of reactive attachment disorder: feasibility randomised controlled trial of a modified video-feedback parenting intervention.

BACKGROUND: Looked-after children are at risk of suboptimal attachment patterns and reactive attachment disorder (RAD). However, access to interventions varies widely, and there are no evidence-based interventions for RAD. AIMS: To modify an existing parenting intervention for children with RAD in the UK foster care setting, and test the feasibility of conducting a randomised controlled trial (RCT) of the modified intervention. METHOD: The intervention was modified with expert input and tested on a case series. A feasibility and pilot RCT compared the new intervention with usual care. Foster carers and children in their care aged ≤6 years were recruited across nine local authorities, with 1:1 allocation and blind post-treatment assessments. The modified intervention was delivered in-home by trained mental health professionals over 4-6 months. Children were assessed for RAD symptoms, attachment quality and emotional/behavioural difficulties, and foster carers were assessed for sensitivity and stress. RESULTS: Minimal changes to the intervention programme were necessary, and focused on improving its suitability for the UK foster care context. Recruitment was challenging, and remained below target despite modifications to the protocol and the inclusion of additional sites. Thirty families were recruited to the RCT; 15 were allocated to each group. Most other feasibility outcomes were favourable, particularly high numbers of data and treatment completeness. The revised intervention was positively received by practitioners and foster carers. CONCLUSIONS: A large-scale trial may be feasible, but only if recruitment barriers can be overcome. Dedicated resources to support recruitment within local authorities and wider inclusion criteria are recommended.

SARS-CoV-2 infection in public hospital medical doctors in an Eastern Cape metro.

Background: Evidence-based Infection Prevention and Control (IPC) measures are critical in protecting medical doctors from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Concerns surrounding access to personal protective equipment (PPE), compliance with IPC measures and the quality of available PPE have been raised as possible causes for high rates of SARS-CoV-2 infection in medical doctors in high transmission settings. This study aimed to determine the prevalence of SARS-CoV-2 infection and the risk factors for occupational infection in doctors in the hospitals in Nelson Mandela Bay (NMB). Methods: We conducted a cross-sectional study wherein we electronically surveyed medical doctors in public-sector NMB hospitals from 01 March 2020 to 31 December 2020. We collected demographic, health, occupational and SARS-CoV-2 infection and exposure data. Categorical data were described as proportions and a multiple variable logistic regression model was used to identify risk factors for SARS-CoV-2 infection. Results: The survey was distributed amongst 498 doctors, 141 (28%) of whom replied. Forty-three (31%) participants reported that they had tested positive for SARS-CoV-2 during the study period. Eighty-nine participants (64%) reported inadequate access to PPE whilst only 68 (49%) participants adhered to PPE recommendations when interacting with patients with confirmed or suspected SARS-CoV-2 infection. We were unable to identify any significant predictors of SARS-CoV-2 infection. Conclusion: This study demonstrates a high prevalence of SARS-CoV-2 infection in public hospital doctors in NMB. Most participants reported inadequate access to PPE and poor compliance with IPC protocols. These findings suggest an urgent need for the improved implementation of IPC measures to protect doctors from SARS-CoV-2 infection.

Sputum colour as a marker for bacteria in acute exacerbations of COPD: protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of years of life lost globally. Acute exacerbations of COPD (AECOPD) drive disease progression, reduce quality of life and are a source of mortality in COPD. Approximately 50% of AECOPD are due to bacterial infections. Diagnosing bacterial infection as the aetiology of AECOPD however remains challenging as investigations are limited by practicality, accuracy and expense. Clinicians have traditionally used sputum colour as a marker of bacterial infection in AECOPD, despite the lack of high-quality evidence for this practice. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of sputum colour in the diagnosis of bacterial causes of AECOPD. METHODS: Articles will be searched for in electronic databases (MEDLINE, Google Scholar Scopus, Web of Science, Africa-Wide, CINAHL and Health Source Nursing Academy) and we will conduct a review of citation indexes and the grey literature. Two reviewers will independently conduct study selection, against pre-defined eligibility criteria, data extraction and quality assessment of included articles using the QUADAS-2 tool. We will perform a meta-analysis using a bivariate logistic regression model with random effects. We will explore heterogeneity through the visual examination of the forest plots of sensitivities and specificities and through the inclusion of possible sources of heterogeneity as covariates in a meta-regression model if sufficient studies are included in the analysis. We also perform a sensitivity analysis to explore the effect of study quality on our findings. The results of this review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and will be submitted for peer-review and publication. DISCUSSION: The findings of this review will assist clinicians in diagnosing the aetiology of AECOPD and may have important implications for decision making in resource-limited settings, as well as for antimicrobial stewardship. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019141498.

Concept and development of an interactive tool for trial recruitment planning and management.

BACKGROUND: Predicting and monitoring recruitment in large, complex trials is essential to ensure appropriate resource management and budgeting. In a novel partnership between clinical trial investigators of the South African Medical Research Council and industrial engineers from the Stellenbosch University Health Systems Engineering and Innovation Hub, we developed a trial recruitment tool (TRT). The objective of the tool is to serve as a computerised decisions-support system to aid the planning and management phases of the trial recruitment process. METHOD: The specific requirements of the TRT were determined in several workshops between the partners. A Poisson process simulation model was formulated and incorporated in the TRT to predict the recruitment duration. The assumptions underlying the model were made in consultation with the trial team at the start of the project and were deemed reasonable. Real-world data extracted from a current cluster trial, Project MIND, based in 24 sites in South Africa was used to verify the simulation model and to develop the monitoring component of the TRT. RESULTS: The TRT comprises a planning and monitoring component. The planning component generates different trial scenarios for predicted trial recruitment duration based on user inputs, e.g. number of sites, initiation delays. The monitoring component uses and analyses the data retrieved from the trial management information system to generate different levels of information, displayed visually on an interactive, user-friendly dashboard. Users can analyse the results at trial or site level, changing input parameters to see the resultant effect on the duration of trial recruitment. CONCLUSION: This TRT is an easy-to-use tool that assists in the management of the trial recruitment process. The TRT has potential to expedite improved management of clinical trials by providing the appropriate information needed for the planning and monitoring of the trial recruitment phase. This TRT extends prior tools describing historic recruitment only to using historic data to predict future recruitment. The broader project demonstrates the value of collaboration between clinicians and engineers to optimise their respective skillsets.

Predictors and Prognosis of HIV-Associated Nephropathy on Kidney Biopsy in South Africa.

INTRODUCTION: South Africa has the highest prevalence of HIV in the world. The epidemiology of kidney disease among people with HIV infections is well-described in the United States. However, there are limited data coming from South Africa, particularly that involve kidney biopsies. The purpose of this study was to determine what, if any, patient factors are predictive of HIV-associated nephropathy (HIVAN) on kidney biopsy in a South African kidney biopsy cohort. METHODS: This study prospectively collected data of all patients infected with HIV referred to the Groote Schuur Hospital (GSH) renal unit for a kidney biopsy from 2002 to 2018. RESULTS: There were 419 patients included in the study. Mean age was 36.5 years (SD, 9.4); 219 (52.3%) were women; and all were black. Seventy-nine patients (18.9%) were on dialysis at the time of biopsy; the mean estimated glomerular filtration rate among the remainder was 41.4 ml/min per 1.73 m2 (SD, 39.2). Only 163 patients (47.1%) were known to be taking antiretroviral therapy (ART) at the time of biopsy. There were 246 (58.7%) cases of HIVAN detected, and they were comparable on age, sex, kidney function, and kidney size to those with kidney disease of other causes but were less likely to be taking ART (P < 0.001). Biopsy confirmed HIVAN was associated with mortality (adjusted hazard ratio, 1.77; 95% confidence interval [CI]: 1.07-2.91; P = 0.025), and the use of ART at biopsy was protective (adjusted hazard ratio, 0.52; 95% CI, 0.32-0.84, P = 0.008). The proportion of HIVAN on biopsy decreased and the proportion taking ART increased from 2002 to 2018 (P for trend for both < 0.001). CONCLUSION: In summary, HIVAN was the most common etiology of kidney disease in this biopsy cohort from South Africa; however, the proportion with biopsy-proven HIVAN declined over time, perhaps in the setting of greater ART availability.

Kidney disease in Africans with HIV and tuberculosis.

OBJECTIVE: To describe the spectrum of kidney disease in African patients with HIV and tuberculosis (TB). METHODS: We used data from three cohorts: consecutive patients with HIV/TB in South London (UK, 2004-2016; n = 95), consecutive patients with HIV/TB who underwent kidney biopsy in Cape Town (South Africa, 2014-2017; n = 70), and consecutive patients found to have HIV/TB on autopsy in Abidjan (Cote d'Ivoire, 1991; n = 100). Acute kidney injury (AKI) was ascertained using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. In the Cape Town cohort, predictors of recovery of kidney function at 6 months were assessed using Cox regression. RESULTS: In the London cohort, the incidence of moderate/severe AKI at 12 months was 15.1 (95% CI 8.6-26.5) per 100 person-years, and the prevalence of chronic and end-stage kidney disease (ESKD) 13.7 and 5.7%, respectively. HIV-associated nephropathy (HIVAN) was diagnosed in 6% of patients in London, and in 6% of autopsy cases in Abidjan. Evidence of renal TB was present in 60% of autopsies in Abidjan and 61% of kidney biopsies in Cape Town. HIVAN and acute tubular necrosis (ATN) were also common biopsy findings in Cape Town. In Cape Town, 40 patients were dialyzed, of whom 28 (70%) were able to successfully discontinue renal replacement therapy. Antiretroviral therapy status, CD4 cell count, estimated glomerular filtration rate (eGFR) at biopsy and renal histology, other than ATN, were not predictive of eGFR recovery. CONCLUSION: Kidney disease was common in Africans with HIV/TB. Monitoring of kidney function, and provision of acute dialysis to those with severe kidney failure, is warranted.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.