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IntroductionWhile a large proportion of people with HIV (PWH) have experienced SARS-CoV-2 infections, there is uncertainty about the role of HIV disease severity on COVID-19 outcomes, especially in lower income settings. We studied the association between mortality and characteristics of HIV severity and management, and vaccination, among adult PWH.MethodsWe analysed observational cohort data on all PWH aged ≥15 years experiencing a diagnosed SARS-CoV-2 infection (until March 2022), who accessed public sector healthcare in the Western Cape province of South Africa. Logistic regression was used to study the association of mortality with CD4 cell count, viral load, evidence of ART, time since first HIV evidence, and vaccination, adjusting for demographic characteristics, comorbidities, admission pressure, location and time period.ResultsMortality occurred in 5.7% (95% CI: 5.3,6.0) of 17 831 first diagnosed infections. Higher mortality was associated with lower recent CD4, no evidence of ART collection, high or unknown recent viral load (among those with ART evidence), and recent first HIV evidence, differentially by age. Vaccination was protective. The burden of comorbidities was high, and tuberculosis, chronic kidney disease, diabetes and hypertension were associated with higher mortality, more strongly in younger adults.ConclusionsMortality was strongly associated with suboptimal HIV control, and prevalence of these risk factors increased in later COVID-19 waves. It remains a public health priority to ensure PWH are on suppressive ART and vaccinated, and manage any disruptions in care that occurred during the pandemic. The diagnosis and management of comorbidities, including for tuberculosis, should be optimised.

Highlights • The response to COVID-19 in LMICs is challenged by fragile health systems and poverty. • Expanded access to mobile phones facilitates their use in the COVID-19 response. • Mobile phone technology can improve case reporting and patient referral pathways. • We give examples of initiatives enhancing patient care and public health outcome. • We present a checklist for helpful mobile communication to combat COVID-19., Estimates of health capacities in the context of the 2019 coronavirus (COVID-19) pandemic indicate that most low- and middle-income countries (LMICs) are not operationally ready to manage this health emergency. Motivated by worldwide successes in other infectious disease epidemics and our experience in sub-Saharan Africa, we support mobile phone communication to improve data collection and reporting, communication between healthcare workers, public health institutions and patients and implementation of disease tracking and subsequent risk-stratified isolation measures. Programmatic action is needed for centrally coordinated reporting and communication systems facilitating mobile phones in crisis management plans for addressing the COVID-19 pandemic in LMICs. We summarize examples of worldwide mobile phone technology initiatives that enhanced patient care and public health outcome in previous epidemics and the current COVID-19 pandemic. In addition, we provide an overview of baseline conditions, including transparency about privacy guarantees, necessary for the successful use of mobile phones in assisting in the fight against COVID-19 spread.

ObjectiveIn sub-Saharan Africa, hepatitis B is the principal cause of liver disease. Non-invasive biomarkers of liver fibrosis are needed to identify patients requiring antiviral treatment. We assessed aspartate aminotransferase-to-platelet ratio index (APRI), gamma-glutamyl transferase-to-platelet ratio (GPR) and FIB-4 to diagnose significant fibrosis and cirrhosis in an individual patient data (IPD) meta-analysis.DesignIn total, 3,549 patients from 12 cohorts of HBsAg positive individuals in 8 sub-Saharan African countries were included. Transient elastography was used as a reference test for cirrhosis (>12.2 kPa), excluding patients who were pregnant, had hepatitis C, D, or HIV co-infection, were on hepatitis B therapy, or had acute hepatitis. A bivariate Bayesian IPD model was fitted with patient-level covariates and study-level random effects.ResultsAPRI and GPR had the best discriminant performance (area under receiver operating curve 0.81 and 0.82) relative to FIB-4 (0.77) for cirrhosis. The World Health Organization (WHO) recommended APRI threshold of ≥2.0 was associated with a sensitivity and specificity (95% credible interval) of 16.5% (12.5-20.5) and 99.5% (99.2-99.7) for cirrhosis. For APRI, we identified an optimised rule-in threshold for cirrhosis (cut-off 0.65) with a sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (cut-off 0.36) with a sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8).ConclusionsThe WHO recommended APRI threshold of 2.0 is too high to diagnose cirrhosis in sub-Saharan Africa. We identified new and optimised rule-in and rule-out thresholds for cirrhosis, with direct consequences for treatment guidelines in this setting.

Identification of SARS-CoV-2 infected individuals is imperative to prevent hospital transmission, but symptom-based screening may fail to identify asymptomatic/mildly symptomatic infectious children and their caregivers.A COVID-19 period prevalence study was conducted between 13 and 26 August 2020 at Tygerberg Hospital, testing all children and their accompanying asymptomatic caregivers after initial symptom screening. One nasopharyngeal swab was submitted for SARS-CoV-2 using real-time reverse-transcription polymerase chain reaction (rRT-PCR). An additional Respiratory Viral 16-multiplex rRT-PCR test was simultaneously done in children presenting with symptoms compatible with possible SARS-CoV-2 infection.SARS-Co-V 2 RT-PCR tests from 196 children and 116 caregivers were included in the analysis. The SARS-CoV-2 period prevalence in children was 5.6% (11/196) versus 15.5% (18/116) in asymptomatic caregivers (Given the poor correlation between SARS-CoV-2 symptoms and RT-PCR test positivity, universal testing of children and their accompanying caregivers should be considered for emergency and inpatient paediatric admissions during high COVID-19 community transmission periods. Universal PPE and optimising ventilation is likely the most effective way to control transmission of respiratory viral infections, including SARS-CoV-2, where universal testing is not feasible. In these settings, repeated point prevalence studies may be useful to inform local testing and cohorting strategies.

Background Over 130 million people have been diagnosed with Coronavirus disease 2019 (COVID-19), and more than one million fatalities have been reported worldwide. South Africa is unique in having a quadruple disease burden of type 2 diabetes, hypertension, human immunodeficiency virus (HIV) and tuberculosis, making COVID-19-related mortality of particular interest in the country. The aim of this study was to investigate the clinical characteristics and associated mortality of COVID-19 patients admitted to an intensive care unit (ICU) in a South African setting. Methods and findings We performed a prospective observational study of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to the ICU of a South African tertiary hospital in Cape Town. The mortality and discharge rates were the primary outcomes. Demographic, clinical and laboratory data were analysed, and multivariable robust Poisson regression model was used to identify risk factors for mortality. Furthermore, Cox proportional hazards regression model was performed to assess the association between time to death and the predictor variables. Factors associated with death (time to death) at p-value < 0.05 were considered statistically significant. Of the 402 patients admitted to the ICU, 250 (62%) died, and another 12 (3%) died in the hospital after being discharged from the ICU. The median age of the study population was 54.1 years (IQR: 46.0–61.6). The mortality rate among those who were intubated was significantly higher at 201/221 (91%). After adjusting for confounding, multivariable robust Poisson regression analysis revealed that age more than 48 years, requiring invasive mechanical ventilation, HIV status, procalcitonin (PCT), Troponin T, Aspartate Aminotransferase (AST), and a low pH on admission all significantly predicted mortality. Three main risk factors predictive of mortality were identified in the analysis using Cox regression Cox proportional hazards regression model. HIV positive status, myalgia, and intubated in the ICU were identified as independent prognostic factors. Conclusions In this study, the mortality rate in COVID-19 patients admitted to the ICU was high. Older age, the need for invasive mechanical ventilation, HIV status, and metabolic acidosis were found to be significant predictors of mortality in patients admitted to the ICU.

Background: Previous reports have highlighted the high prevalence of blood culture negative endocarditis (BCNE) in South Africa.Methods: The Tygerberg Endocarditis cohort (TEC) study is a prospective cohort study of patients with confirmed or suspected IE presenting to Tygerberg Academic Hospital, Cape Town, South Africa. Results: To date, 44 patients have been included in this ongoing study. Fourteen of the 44 patients (31.8%) had BCNE. Further analysis of the patients with BCNE identified Bartonella species as the most common causative organism (n=6; 43%). Other causes included Mycoplasma species (n=2), C. burnetii (n=1), and non-bacterial thrombotic endocarditis due to anti-phospholipid syndrome (n=1). No cause could be identified in 4 of the 44 patients (9%). Bartonella quintana was identified with PCR of valvular tissue as the causative organism in 4 of the 5 patients that underwent urgent surgery. The patients with Bartonella IE (n=6) had an average age of 39 years with equal gender distribution The common clinical features were clubbing (n=5; 83%), anemia (n=4; 66.6%), haematuria (n=3; 50%), acute on chronic severe valvular lesion (n=3; 50%) and acute severe valvular lesion (n=2; 33.3%). The aortic valve was involved in 5 of 6 patients. During a mean follow-up period of 251 days after diagnosis, no major adverse events occurred.Conclusion: Bartonella IE is an important cause of BCNE in the Western Cape of South Africa. Imaging findings of significant valvular destruction with large vegetations on the aortic valve not affected by pre-existing congenital or rheumatic valve disease, should raise the suspicion of Bartonella IE.

Background. South Africa (SA) has a high prevalence of HIV and tuberculosis. Cape Town was the SA metropole most affected in the early stages of the COVID-19 pandemic. Early observational data from Africa may provide valuable insight into what can be expected as the pandemic expands across the continent. Objectives. To describe the prevalence, clinical features, comorbidities and outcome of an early cohort of HIV-positive and HIV-negative patients admitted with COVID-19. Methods. This was a descriptive observational study of an early cohort of adults with COVID-19 pneumonia admitted from 25 March to 11 May 2020. Results. Of 116 patients (mean age 48 years, 61% female) admitted, 24 were HIV-positive (21%). The most common symptoms reported were cough ( n =88; 73%), shortness of breath ( n =78; 69%), fever ( n =67; 59%), myalgia ( n =29; 25%) and chest pain ( n =22; 20%). The most common comorbidities were hypertension ( n =46; 41%), diabetes mellitus ( n =43; 38%), obesity ( n =32; 28%) and HIV ( n =24; 21%). Mortality was associated with older age (mean (standard deviation) 55 (12) years v. 46 (14) years; p

CITATION: Schaaf, H. S. et al. 2020. Bacille Calmette-Guerin (BCG) vaccine and the COVID-19 pandemic : responsible stewardship is needed. International Journal of Tuberculosis and Lung Disease, 4(7):732-734, doi:10.5588/ijtld.20.0267.

The first critically ill patient admitted to our hospital in Cape Town, South Africa, during the COVID-19 pandemic was co-infected with HIV and SARS-CoV-2. Pneumocystis jirovecii pneumonia (PCP) and other respiratory opportunistic infections share many clinical features with severe COVID-19. Our understanding of the nuances of co-management of HIV and COVID-19 is evolving. We describe the diagnostic and therapeutic challenges presented by this case.

BackgroundThe diagnosis of infective endocarditis (IE) is based on the modified Duke/European Society of Cardiology (ESC) 2015 clinical criteria. The sensitivity of the criteria is unknown in South Africa, but high rates of blood culture negative endocarditis (BCNIE), coupled with a change in the clinical features of IE, may limit the sensitivity.MethodsThe Tygerberg Endocarditis Cohort study prospectively enrolled patients with IE between November 2019 and June 2021. A standardised protocol for organism detection, with management of patients by an Endocarditis Team, was employed. Patients with definite IE by pathological criteria were analysed to determine the sensitivity of the current clinical criteria.ResultsEighty consecutive patients with IE were included of which 45 (56.3%) had definite IE by pathological criteria. In patients with definite IE by pathological criteria, 26/45 (57.8%) of patients were classified as definite IE by clinical criteria. BCNIE was present in 25/45 (55.6%) of patients and less than three minor clinical criteria were present in 32/45 (75.6%) of patients. The elevation of Bartonella serology to a major microbiological criterion of the modified Duke/ESC 2015 clinical criteria would increase the sensitivity (57.8% vs 77.8%; p=0.07).ConclusionThe sensitivity of the modified Duke/ESC 2015 clinical criteria is lower than expected in patients with IE in South Africa, primarily due to the high rates of Bartonella-associated BCNIE. The elevation of Bartonella serology to a major microbiological criterion, similar to the status of Coxiella burnetii in the current criteria, would increase the sensitivity. The majority of patients with definite IE by pathological criteria had less than three minor criteria present.

Background. The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. Objectives. To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. Methods. We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m 2 ) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. Results. One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n =61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p

RATIONALE: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied. METHODS: We included consecutive patients with COVID-19-related HRF treated with HFNO and awake proning at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO. FINDINGS: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (PaO2/FiO2) was 68 (54-92) in 293 enrolled patients. 137/293 (47%) of patients [PaO2/FiO2 76 (63-93)] were successfully treated with HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p

Highlights • We compared HBV monoinfection with HBV/coinfection in a cross-sectional cohort from South Africa. • HBV/HIV coinfected individuals were more likely to undergo assessment by fibroscan. • HBV monoinfection was less likely to be treated than HBV/HIV coinfection. • Indications of severe liver disease were more common in HBV monoinfection. • Cases of hepatocellular carcinoma all arose in HBV monoinfection., Objectives Prompted by international targets for elimination of hepatitis B virus (HBV), we set out to characterise individuals with HBV monoinfection vs. those coinfected with HBV/HIV, to evaluate the impact of therapy and to guide improvements in clinical care. Methods We report observational data from a real world cross-sectional cohort of 115 adults with chronic hepatitis B infection (CHB), at a university hospital in Cape Town, South Africa. HIV coinfection was present in 39 (34%) subjects. We recorded cross-sectional demographic, clinical and laboratory data. Results Compared to those with HIV coinfection, HBV monoinfected adults were less likely to be HBeAg-positive (p=0.01), less likely to have had assessment with elastography (p

Background. Kaposi’s sarcoma (KS) typically occurs in the setting of immunodeficiency and specifically in the presence of HIV infection, when it is called AIDS-associated KS (AIDS-KS). In spite of impressive gains in the South African (SA) antiretroviral therapy (ART) roll-out programme since 2004, AIDS-KS still causes significant morbidity and mortality, and the treatment of advanced disease can be challenging owing to the centralisation of oncology services and the high incidence of concurrent infections. In 2014, a multidisciplinary AIDS-KS clinic (MKSC) was established at Tygerberg Hospital, Cape Town, with the goal of optimising management of AIDS-KS patients. Objectives. To report on the characteristics and outcomes of patients seen during the first 6 months after the inception of the MKSC. Methods. A retrospective observational study was performed of all new cases referred to the MKSC from February to August 2014. Results. Forty-two patients were included in the study. The median age was 34 years (range 20 - 60). Forty-one patients were on ART at time of diagnosis or were initiated by a median of 3 months after diagnosis. The median CD4+ count before diagnosis was 147 cells/µL (range 4 - 811). The HIV viral load was undetectable in 22 cases (52.4%). Thirty-eight patients (90.5%) were classified as AIDS Clinical Trials Group (ACTG) poor risk, 10 patients (23.8%) had visceral KS, 14 patients (33.3%) were on tuberculosis (TB) treatment at time of presentation, and 22 patients (52.4%) received oncological therapy in addition to ART. After median follow-up of 25.6 months, 2-year overall survival (OS) was 61.1%. On univariate analysis, factors significantly associated with poor 2-year OS included ACTG S1 stage (S = systemic illness), visceral KS, being on TB treatment, and Eastern Cooperative Oncology Group performance status score >2. In the T1 (T = tumour extent) subgroup, receiving chemotherapy was significantly associated with improved 2-year OS. Conclusions. Advanced AIDS-KS significantly affects young people in the Western Cape Province of SA despite 10 years of ART roll-out. There is a high prevalence of concomitant TB infection that could adversely affect adherence and response to treatment. Despite advanced disease at presentation and palliative treatment intent, survival outcomes are encouraging and seem to be positively affected by the increased use of chemotherapy. A multidisciplinary approach to diagnosis, staging and treatment and the exploration of prognostic indices specific to the sub-Saharan setting would be valuable in designing appropriate treatment algorithms.

Background. Community-acquired pneumonia (CAP) is a common condition, with mortality increasing in patients who require intensive care unit (ICU) admission. A better understanding of the current aetiology of severe CAP will aid clinicians in requesting appropriate diagnostic tests and initiating appropriate empiric antimicrobials. Objective. To assess the comorbidities, aetiology and mortality associated with severe CAP in a tertiary ICU in Cape Town, South Africa. Methods. We retrospectively analysed a prospective registry of all adults admitted to the medical intensive care unit at Tygerberg Hospital with severe CAP over a 1-year period. Results. We identified 74 patients (mean (SD) age 40.0 (15.5) years; 44 females). The patients had a mean (SD) APACHE II score of 21.4 (7.9), and the mean ICU stay was 6.6 days. Of the 74 patients, 16 (21.6%) died in ICU. Non-survivors had a higher mean (SD) APACHE II score than survivors (28.3 (6.8) v. 19.4 (7.1); p

SETTING Data on the determinants of tuberculosis (TB) mortality in the intensive care unit (ICU) are scarce. OBJECTIVE To describe factors influencing outcomes of patients admitted with TB requiring mechanical ventilation. DESIGN All TB patients admitted to the ICU of an academic hospital in South Africa from January 2012 to May 2013 were enrolled. Disease severity was graded according to the Acute Physiology And Chronic Health Evaluation (APACHE II) score. Comorbid diagnoses, clinical features, radiological and laboratory investigations and outcomes were recorded. RESULTS Of 83 patients (mean age 36.5 ± 12.9 years; 45 females; 44 human immunodeficiency virus [HIV] positive) admitted with pulmonary (n = 69) and/or extra-pulmonary (n = 37) TB, 39 died in the ICU (mortality 44.2%), and a further 10 died during hospitalisation (in-hospital mortality 59.0%). Few clinical parameters, special investigations or other ancillary tests predicted outcome. Only CD4 count

Background Skin lesions are common in advanced HIV infection and are sometimes caused by serious diseases like systemic mycoses (SM). AIDS-related SM endemic to Western Cape, South Africa, include emergomycosis (formerly disseminated emmonsiosis), histoplasmosis, and sporotrichosis. We previously reported that 95% of patients with AIDS-related emergomycosis had skin lesions, although these were frequently overlooked or misdiagnosed clinically. Prospective studies are needed to characterize skin lesions of SM in South Africa and to help distinguish these from common HIV-related dermatoses. Methods We prospectively enrolled HIV-infected adult patients living in Western Cape, South Africa, with CD4 counts ≤100 cells/μL and widespread skin lesions present ≤6 months that were deemed clinically compatible with SM. We obtained skin biopsies for histopathology and fungal culture and collected epidemiological and clinical data. Results Of 34 patients enrolled and in whom a diagnosis could be made, 25 had proven SM: 14 had emergomycosis, and 3 each had histoplasmosis and sporotrichosis; for 5 additional patients, the fungal species could not be identified. Antiretroviral therapy (ART) had been initiated in the preceding 4 weeks for 11/25 (44%) patients with SM (vs no patients without SM). Plaques and scale crust occurred more frequently in patients with SM (96% vs 25%, P = .0002; and 67% vs 13%, P = .01, respectively). Conclusions Recent ART initiation and presence of plaques or scale crust should make clinicians consider SM in patients with advanced HIV infection in this geographic area. Clinical overlap between SM and other dermatoses makes early skin biopsy critical for timely diagnosis and treatment.

This guideline provides a rational and cost-effective approach to patients with acute meningitis, which causes considerable morbidity and mortality, predominantly in children.There are many aetiologies, but a small number of bacteria and viruses account for the majority of cases. There should be a low threshold for suspecting acute meningitis, which is a medical emergency and antibiotics should not be delayed. Blood culture and cerebrospinal fluid (CSF) analysis are the most important diagnostic tests and should be performed whenever it is safe and practical. Contraindications to lumbar puncture are discussed and an algorithm is given regarding administering empiric antibiotics and antivirals, performing blood cultures, computer tomography brain scanning and cerebrospinal fluid analysis, depending on the clinical features and availability of resources. Administration of steroids is not recommended. Guidelines are provided for definitive therapy whenever a causative organism is identified. When no organism is identified, treatment and further investigation should be guided by laboratory results and clinical response. An approach to this process is outlined in a second algorithm. The epidemiology of resistance to common pathogens is described and advice given regarding special groups, including those with recurrent meningitis or base-of-skull fractures. Advice regarding infection control, post-exposure prophylaxis and vaccination is provided.

Background: The novel influenza A (H1N1) pandemic affected South Africa late during the 2009 Southern hemisphere winter and placed an extra burden on a health care system already dealing with a high prevalence of chronic lung diseases and human immunodeficiency virus (HIV) infection. Aim: The aim of this study was to describe the epidemiological characteristics, clinical features, management and outcomes of patients with confirmed influenza A (H1N1) infection complicated by respiratory failure. Methods: We included all adult patients with confirmed influenza A (H1N1) infection that were referred to the medical intensive care unit of a large academic hospital in Cape Town for ventilatory support in this prospective observational study. Results: A total of 19 patients (39.5 ± 14.8 years) needed ventilatory support over a 6-week period. Of these, 15 were female and 16 had identifiable risk factors for severe disease, including pregnancy ( n = 6), type 2 diabetes mellitus ( n = 6), obesity ( n = 4), HIV infection ( n = 3), immunosuppressive therapy ( n = 3) and active pulmonary tuberculosis ( n = 2). The most frequent complications were acute renal failure ( n = 13), acute respiratory distress syndrome ( n = 12) and ventilator associated pneumonia ( n = 10). Thirteen patients died (mortality: 68.4%). Fatal cases were significantly associated with an APACHE II score ⩾20 ( P = 0.034), but not with a PaO2/FIO2

Hepatitis B virus (HBV) infection affects around 240 million people worldwide, with the highest prevalence of disease in Africa and Asia. Hepatocellular carcinoma (HCC) is the second most common cancer in men in Africa, and in around 75% of cases is associated with chronic HBV infection. HIV disproportionately affects sub-Saharan Africa. HIV/HBV co-infection is associated with worse outcomes than HBV monoinfection. Identifying patients who are co-infected enables assessment of liver health and the institution of HCC surveillance. HBV rapid tests are available and could be performed alongside HIV screening. Suppression of HBV viral load reduces complications and improves outcomes. Tenofovir has potent activity against HBV and is becoming increasingly available across sub-Saharan Africa as first-line therapy for HIV. HIV/HBV co-infected patients should be started on HBV active therapy, irrespective of CD4 count. Lifestyle modification, including weight management, avoidance of traditional herbal medication and alcohol restriction, improves liver health and should be encouraged. Confirmation of hepatitis A immunity is prudent. While access to more sensitive tests is limited in sub-Saharan Africa, alpha-fetoprotein and ultrasound scanning is advised for HCC surveillance. Screening and if necessary HBV vaccination of susceptible household and sexual contacts is indicated.

The first 54 cases are reported of disseminated emmonsiosis, a newly described endemic mycosis in South Africa. Most patients were profoundly immunocompromised. Disease most commonly involved the skin and lungs. Nearly half of all patients died, often undiagnosed.Methods.aEuro integral We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015. Results.aEuro integral Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/A mu L [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed. Conclusions.aEuro integral Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients.

Increased pleural fluid adenosine deaminase (ADA) activity is classically associated with tuberculous pleuritis. However, increased activity can also occur in a number of other diseases and this may negatively affect the diagnostic utility of ADA measurements and decrease its specificity for the diagnosis of tuberculosis (TB). The presence of ADA in pleural fluids reflects the cellular immune response in the pleural cavity and in particularly, the activation of T lymphocytes. Different disease entities are typically associated with the presence of particular types of leukocytes. Objective To determine whether the combined use of ADA activity and differential cell counts would provide a more efficient means for diagnosing tuberculous pleurisy than the use of ADA levels alone. Methods Biochemistry, cytology, and microbiology studies were performed on 472 consecutive pleural fluids. ADA and differential cell counts were determined on all exudative effusions. Results ADA activity in tuberculous effusions was significantly higher than in any other diagnostic group (p Conclusion ADA, especially when combined with differential cell counts and lymphocyte/neutrophil ratios, remains a useful test in the diagnosis tuberculous pleuritis.

Objective. To determine the prevalence and specificity of anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) for rheumatoid arthritis (RA) in human immunodeficiency virus (HIV) infection and to evaluate the effect of immune reconstitution on these markers.Methods. Patients with advanced HIV infection without arthritis were enrolled. CD4+ T lymphocyte counts (CD4), anti-CCP, and RF were determined before initiating antiretroviral therapy (ART) and repeated after 6 months. Results were compared to those of healthy controls. Patients were followed for the development of RA for 1 year.Results. Sixty patients and 26 controls were studied. Six-month followup results were available on 49 patients. Mean (SD) levels of anti-CCP were higher in patients with HIV compared to controls: respectively, 9.50 (11.41) versus 0.80 (1.32) units (p < 0.001). Mean (SD) levels decreased to 4.85 (8.12) units (p = 0.006) after 6 months of ART (HIV-infected group). Fifteen percent of patients initially tested positive for anti-CCP, 4% after 6 months versus no controls (p = 0.031). Forty-seven percent of patients initially tested positive for RF, 18% after 6 months versus 8% of controls (p < 0.001). Decreases in RF and anti-CCP after ART were accompanied by increased mean (SD) CD4: from 129 (56) to 278 (140) cells/mm3 (p < 0.001). Anti-CCP and RF positivity was not associated with the development of RA.Conclusion. Increased titers of anti-CCP and RF occur in advanced HIV infection. Although more specific than RF, before immune reconstitution, anti-CCP is an unreliable diagnostic marker for RA and does not necessarily predict future RA. After immune reconstitution, the specificity of anti-CCP approaches that of a control group.

Bone turnover and calcium homeostasis in man can only be modelled validly in Old World nonhuman primates. In order to interpret the models it is necessary to establish endocrine and biochemical parameters of bone mineral metabolism. This report is probably the first description of acute phase parathyroid responses to manipulations of blood ionised calcium, and of reference values for potentially interacting variables, in vervet monkeys. Plasma parathyroid hormone concentrations were measured in vervets under defined conditions, and ranges reported as normal for other nonhuman primates and man are summarised.

Tuberculosis is the major cause of morbidity and mortality in HIV-infected patients in sub-Saharan Africa. HIV infection is often first diagnosed following a diagnosis of tuberculosis, with many patients needing antiretroviral therapy (ART). Starting ART in HIV-infected patients with tuberculosis (TB) may be associated with complications, including side-effects from co-administration of multiple drugs with many overlapping toxicities, reductions in concentrations of certain antiretroviral drugs following the induction of metabolising enzymes and drug transporters by rifampicin, and paradoxical deterioration due to the immune reconstitution inflammatory syndrome (IRIS). Furthermore, the high pill burden of co-treatment could reduce adherence, resulting in poor treatment outcomes for both diseases. These potential harms must be weighed against the high mortality rates in patients with HIV-associated tuberculosis who do not receive ART, especially those with low CD4 counts. The optimal time to initiate ART in patients with tuberculosis is an important research question, and randomised controlled trials are addressing this issue.

BACKGROUND--A statistical audit of adenosine deaminase (ADA) in pleural effusions was undertaken. METHODS--ADA analysis, cytological and microbiological examinations, and differential cell counts were performed on 462 pleural fluid samples. RESULTS--ADA activity in tuberculous effusions was higher than in any other diagnostic group. At a level of 50 U/l the sensitivity and specificity for the identification of tuberculosis was 90% and 89%, respectively. CONCLUSIONS--ADA activity remains a useful test in the evaluation of pleural effusions.

Summary Objectives Hepatitis B virus (HBV), hepatitis C virus (HCV), and the human immunodeficiency virus (HIV) are endemic in Africa. However, hepatitis co-infection rates among HIV-infected individuals remain controversial. The aim of this review was to determine the prevalence of HBV and HCV in HIV-infected patients in sub-Saharan Africa and to analyze whether HIV is associated with a higher HBV/HCV prevalence in that region. Design and methods We performed a systematic review and meta-analysis. Studies reporting HBV and HCV prevalence data amongst HIV-infected patients in sub-Saharan Africa were included. Weighted means and medians across studies were calculated. Studies including an HIV-negative control group were used for meta-analysis. Risk ratios (RRs) were calculated using a random effects model. Results Sixty studies were included. Among HIV-infected individuals, mean HBsAg and anti-HCV prevalence rates were 15% and 7%, respectively. RRs for a positive HBsAg and a positive anti-HCV were 1.40 (95% confidence interval (CI) 1.16–1.69) and 1.60 (95% CI 1.05–2.45) for HIV-infected, as compared to HIV-uninfected, patients. Conclusions Many HIV-positive individuals in sub-Saharan Africa are HBV or HCV co-infected. HIV is associated with a higher prevalence of both HBV and HCV in this region. However, this association is less evident than that observed in Western countries and varies between studies.

Table S1. Serum LPB concentration according to patient group (Îźg/ml). Table S2. Proportions of fibrosis scores according to the HBV genotype. Table S3. Multiple correlation analysis of all patients ungrouped. Statistically significant correlations appear in red font. Figure S1. Gating strategy for Immune Activation panel. Plot A shows the singlet population gating while Plot B represents the SSC against FSC plot indicating the position of the singlet cells of the lymphocyte population. Plot C shows the lymphocyte population as shown by less complexity (SS) and intense staining for CD45-KO in a plot of side scatter against CD45-KO. Plot D shows the CD3+ population (Gate G) as gated from Gate F shown in Plot C. Using colour precedence and back gating, Plot D also shows the non-lymphocyte population (red colour) that is included within gate F based on use of complexity (SS INT) and staining for CD45. Picture E shows the CD4+ in the blue colour (gate H) and the CD8+ lymphocytes in the magenta colour (gate I). Plot F shows the CD8+ population staining for CD38-PE and HLA-DR-APC gated from gate I. The gate placement was based on defined fluorescence minus one (FMO) settings. Figure S2. Scatter plot of % CD8/CD38+/HLA-DR+ in the co-infected group. The plot only includes HBV/HIV co-infected patients. All patients with undetectable HIV viral load are assigned values of zero and appear on the y-axis as dots corresponding with the percentage expression CD8/CD38+/HLA-DR. Frequency of HBV genotypes according to HBV and HIV infection status. Among the 13 co-infected patients whose HBV was successfully sequenced, 8 (62%) were infected with HBV genotype A, 3 (23%) with D and 2 had HBV genotype E (15%). The distribution of genotypes among the HBV mono-infected patients was- 16/29 (55%) A, 11/29 (38%) D and 2/29 (7%) E. The red columns represent HBV genotype A, green is for genotype D and the blue corresponds to genotype E. Genotyping was frequently more successful in the HBV mono-infected group compared to the co-infected group. (DOCX 475Â kb)