Andrew Black

Non-infectious mimics of community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common cause of presentation to healthcare facilities. The diagnosis of CAP is usually made in patients with suggestive symptoms, signs, and radiological features. A number of non-infectious conditions, including neoplastic lesions, pulmonary oedema, pulmonary embolism, drug-induced pneumonitis, diffuse alveolar haemorrhage syndromes, cryptogenic organising pneumonia and acute eosinophilic pneumonia, may present in a similar way and mimic CAP. These other conditions are often only thought of after patients that are being treated as CAP fail to respond to therapy. The non-infectious mimics of CAP require early diagnosis and appropriate treatment to decrease patient morbidity and mortality. This article is intended to create an awareness of the non-infectious mimics of CAP and highlight some of the more frequent conditions as well as those that require early diagnosis and treatment to prevent a poor outcome.

Increased Access to Antiretroviral Therapy Is Associated with Reduced Maternal Mortality in Johannesburg, South Africa: An Audit from 2003-2012.

Objective To assess the impact of expanded access to antiretroviral treatment (ART) on maternal mortality in Johannesburg, South Africa between 2003 and 2012. Methods Audit of patient files, birth registers and death certificates at a tertiary level referral hospital. Cause of death was assigned independently, by two reviewers. We compared causes of deaths and the maternal mortality ratios (MMR, deaths/100,000 live births) over three periods corresponding to changes in government policy on ART provision: period one, 2003–2004 (pre-ART); period two, 2005–2009 (ART eligibility with CD4 count <200cells/μL or WHO stage 4 disease); and period three, 2010–2012 (eligibility with CD4 count <350 cells/μL). Results There were 232 deaths and 80,376 deliveries in the three periods. The proportion of pregnant women tested for HIV rose from 43.4% in 2003 to 94.6% in 2012. MMR was 301, 327 and 232 in the three periods, (p = 0.10). The third period MMR was lower than the first and second combined (p = 0.03). Among HIV-positive women, the MMR fell from 836 in the first time period to 431 in the third (p = 0.008) but among HIV negative women it remained unchanged over the three periods, averaging 148. Even in the third period, however, the MMR among HIV-infected women was 3-fold higher than in other women. Mortality from direct obstetric causes such as hemorrhage did not decline over time, but deaths from tuberculosis and HIV-associated malignancy did. In 38.3% of deaths, women had not attended antenatal care. Conclusion Higher coverage of HIV testing and ART has substantially reduced MMR in this hospital setting. Though the gap in MMR between women with and without HIV narrowed, a third of deaths still remain attributable to HIV. Lowering overall MMR will require further strengthening of HIV services, increased antenatal care coverage, and improved care for obstetric emergencies at all levels of care.

Tuberculosis Case Finding: Evaluation of a Paper Slip Method to Trace Contacts

Setting South Africa has the third highest tuberculosis (TB) burden in the world. Intensified case finding, recommended by WHO, is one way to control TB. Objective To evaluate the effectiveness and acceptability of a paper slip method for TB contact tracing. Method TB patients were offered paper slips to give to their contacts, inviting them for TB screening. The number of contacts screened and the proportion diagnosed with TB was calculated. Contacts that returned to the clinic after receiving the slips were interviewed. A focus group discussion (FGD) with TB patients was held to determine their acceptability. Results From 718 paper slips issued, a 26% TB contact tracing rate was found, with a 12% case detection rate. The majority (68%) of contacts were screened within 2 weeks of receiving the slip. Age and gender were not significantly associated with time to screening. 16% of the contacts screened did not reside with the TB patients. 98% of the contacts said the method was acceptable. FGD findings show that this method is acceptable and may prevent stigma associated with TB/HIV. Conclusion This simple, inexpensive method yields high contact tracing and case detection rates and potentially would yield additional benefits outside households.

Community-acquired pneumonia—a clinical approach to assessment and management

Abstract Community-acquired pneumonia (CAP) remains an important cause of morbidity and mortality. The implementation of CAP guidelines can decrease patient mortality and limit antibiotic resistance. The South African Thoracic Society (SATS) has revised its guidelines for the management of CAP in adults. This article reviews the management of CAP and explores the rationale for the recommendations regarding point of care and antibiotic therapy.

Performance of the Abbott RealTi m e MTB and MTB RIF/INH Assays in a Setting of High Tuberculosis and HIV Coinfection in South Africa

ABSTRACT South Africa is a country with a high incidence of tuberculosis (TB), complicated by coinfection with human immunodeficiency virus (HIV). The Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is used in South Africa as the test for the initial diagnosis of TB, and other molecular platforms such as the m2000 (Abbott Molecular, Des Plaines, IL, USA) are widely used for molecular monitoring of HIV load. The latter platform is now also equipped with the RealTime (RT) MTB and RealTime MTB RIF/INH assays for TB and first-line drug resistance screening but has not been evaluated in settings of HIV and TB coinfection. A prospective clinical validation study was conducted at a community health center in Johannesburg, South Africa, and consenting individuals with presumptive pulmonary TB were enrolled. The performance of the Abbott assays was compared with those of the Xpert MTB/RIF, liquid culture, drug susceptibility testing, and clinical case definitions. A statistical analysis was performed on 206 individuals (73% were HIV positive). The sensitivity and specificity of the RT MTB were 82.5% (confidence interval [CI], 67.2 to 92.7) and 93.1% (CI, 86.2 to 97.2) on raw sputum and 77.5% (CI, 61.5 to 89.2) and 95.1% (CI, 88.9 to 98.4) on concentrated sputum, respectively, compared with those from liquid culture. The RT MTB correctly identified 17/35 more smear-negative culture-positive specimens than the Xpert MTB/RIF. Both the RT MTB and the Xpert MTB/RIF displayed sensitivities >70% and specificities >90% in HIV-positive individuals. The available drug resistance results concurred with MTBDRplus and drug susceptibility profiles. The RT MTB assay has similar diagnostic performance to the Xpert MTB/RIF and is suited to testing presumptive TB patients coinfected with HIV. The existing laboratory information system connectivity, training, and technical support make this a viable polyvalent option to scale up TB alongside HIV laboratory testing services in South Africa.

HIV-Attributed Causes of Death in the Medical Ward at the Chris Hani Baragwanath Hospital, South Africa

Background There are sparse data in Africa on the association between HIV infection and deaths from underlying medical conditions. Using records from the Chris Hani Baragwanath Hospital (CHBH) in Soweto, South Africa, we determined mortality from medical conditions associated with HIV. Methods From January 2006 to December 2009 AB collected data on 15,725 deaths including age, sex, day of admittance and death, HIV status, ART initiation and CD4+ cell counts and reviewed the underlying cause of death using medical notes. Conditions known to be associated with HIV were cases; conditions not associated with HIV were controls. We calculate the HIV odds-ratios for cases relative to controls and HIV-attributable deaths as the fraction of those with each condition, the disease-attributable fraction (DA), and as the fraction of all deaths, the population-attributable fraction (PAF). Interpretation The high prevalence of HIV among those that died in the medical wards at the CHBH, especially in those below the age of 50 years, demonstrates the impact of the HIV-epidemic on adult mortality and hospital services and the extent to which early antiretroviral treatment would have reduced the burden of both. Of the deaths included in the analysis the prevalence of HIV was 61% and the prevalence of AIDS related conditions was 69%. The HIV-attributable fraction was 36% in the whole sample and 60% in those that were HIV-positive. Cryptococcosis, Kaposi’s sarcoma and Pneumocystis jeroveci are highly predictive of HIV while TB, gastroenteritis and anaemia are very strongly associated with HIV. The greatest number of deaths attributable to HIV was among those dying of TB or of other respiratory conditions. Funding No funding was received for this study.

Exhaled human breath analysis in active pulmonary tuberculosis diagnostics by comprehensive gas chromatography-mass spectrometry and chemometric techniques

Tuberculosis (TB) is the deadliest infectious disease, and yet accurate diagnostics for the disease are unavailable for many subpopulations. In this study, we investigate the possibility of using human breath for the diagnosis of active TB among TB suspect patients, considering also several risk factors for TB for smokers and those with human immunodeficiency virus (HIV). The analysis of exhaled breath, as an alternative to sputum-dependent tests, has the potential to provide a simple, fast, non-invasive, and readily available diagnostic service that could positively change TB detection. A total of 50 individuals from a clinic in South Africa were included in this pilot study. Human breath has been investigated in the setting of active TB using the thermal desorption-comprehensive two-dimensional gas chromatography-time of flight mass spectrometry methodology and chemometric techniques. From the entire spectrum of volatile metabolites in breath, three machine learning algorithms (support vector machines, partial least squares discriminant analysis, and random forest) to select discriminatory volatile molecules that could potentially be useful for active TB diagnosis were employed. Random forest showed the best overall performance, with sensitivities of 0.82 and 1.00 and specificities of 0.92 and 0.60 in the training and test data respectively. Unsupervised analysis of the compounds implicated by these algorithms suggests that they provide important information to cluster active TB from other patients. These results suggest that developing a non-invasive diagnostic for active TB using patient breath is a potentially rich avenue of research, including among patients with HIV comorbidities.

Comparison of empyema thoracis in HIV-infected and non-infected patients with regard to aetiology and outcome

Empyema thoracis remains a problem in developing countries. Human immunodeficiency virus (HIV) is a risk factor for the development of empyema. There is a clinical impression that HIV-infected patients with empyema have worse outcomes. This study was conducted to assess whether HIV infection affected aetiology or outcomes of patients with empyema. A retrospective review was conducted of 172 patients, meeting established criteria for the diagnosis of empyema, who were admitted to Chris Hani Baragwanath Hospital between January 2006 and December 2009. HIV-infected and non-infected patients were evaluated for differences in aetiology and outcomes, including length of stay, surgical intervention and local complications of closed-tube thoracostomy. A sub-analysis of HIV-infected patients stratified according to CD4 cell count and use of antiretrovirals (ARVs) was also performed. Of the 172 patients, 125 (73%) were HIV infected, and 47 (27%) were non-infected. HIV-infected patients with lower CD4 cell counts were more likely to be diagnosed with clinical tuberculosis. More commonly, the aetiology of empyema was not determined in HIV-non-infected patients. HIV-infected patients on ARVs were more likely to have thoracic surgery and had shorter hospital stays than those not on ARVs. This study failed to demonstrate any significant differences in aetiology among HIV-infected vs. non-infected patients with empyema. There was a trend towards more Gram-negative infections in the HIV-infected group. ARV use was associated with improved outcomes with regard to cardiothoracic intervention and length of hospital stay.