Jonathan Peter

There are few prospective data about the incidence and mortality associated with pulmonary tuberculosis in intensive care units (ICUs), and none on the accuracy and clinical effect of the Xpert-MTB/RIF assay in this setting. We aimed to measure the frequency of culture-positive tuberculosis in ICUs in Cape Town, South Africa and to assess the performance and effect on patient outcomes of Xpert MTB/RIF versus smear microscopy for diagnosis of tuberculosis. We did a prospective burden of disease study with a randomised controlled substudy at the ICUs of four hospitals in Cape Town. Mechanically ventilated adults (≥18 years) with suspected pulmonary tuberculosis admitted between Aug 1, 2010, and July 31, 2013 (irrespective of the reason for admission), were prospectively investigated by culture, and by Xpert-MTB/RIF testing or smear microscopy, of tracheal aspirate samples. In the substudy, patients were randomly assigned (1:1), via a computer-generated allocation list, to smear microscopy or Xpert MTB/RIF. Participants, caregivers, and outcome assessors were not masked to group assignment. Only the laboratory staff were blinded to the clinical details of the participants. In November, 2012, Xpert MTB/RIF was adopted as the initial diagnostic test for respiratory samples in Western Cape province. Thereafter, patients received Xpert MTB/MIF and culture as standard of care. For the whole study cohort, the primary outcome was the frequency of bacteriologically confirmed tuberculosis. The primary endpoint of the randomised substudy was the proportion of culture-positive patients on treatment at 48 h after enrolment. The randomised substudy is registered with ClinicalTrials.gov, number NCT01530568. We investigated 341 patients for suspected pulmonary tuberculosis out of a total of 2309 ICU admissions. 46 (15%) of 317 patients included in the final analysis had a positive test for tuberculosis (Xpert MTB/RIF or culture). Culture-positive patients who failed to initiate treatment (adjusted HR 4·49, 95% CI 1·45-13·89) or who received inotropes (4·33, 1·49-12·60) were more likely to die. However, tuberculosis status was not associated with 28-day or 90-day mortality. In the substudy, we randomly assigned 115 patients to smear microscopy and 111 to Xpert MTB/RIF. Smear microscopy detected six (43%) of 14 culture-positive patients, and Xpert MTB/RIF detected 11 (100%) of 11 culture-positive patients (p=0·002). The proportion of culture-positive patients on treatment at 48 h was higher in the Xpert MTB/RIF group than in the smear microscopy group (11 [92%] of 12 vs nine [53%] of 17; p=0·043), although use of Xpert MTB/RIF had no effect on mortality or other patient outcomes. Tuberculosis is fairly common in ICUs in high-burden settings, and clinicians should screen and test patients for tuberculosis with Xpert MTB/RIF where available. This test improves diagnostic yield and rates of treatment initiation, and reduces unnecessary treatment, but might not increase the total number of patients on treatment when empirical treatment is widely used. A suspected diagnosis of pulmonary tuberculosis should not exclude patients from ICU care in resource-limited settings because mortality is unaffected by the presence of this disease. European and Developing Countries Clinical Trials Partnership, South African Medical Research Council, and the Discovery Foundation.

Exogenous antibody therapy to protect patients against infections and toxins is over 100 years old, yet progress continues to be made in the manufacture, administration and application of this type of immunotherapy, known as therapeutic human immunoglobulin. For the majority of patients with primary immunodeficiencies, immunoglobulin replacement is the only life-saving therapy and treatment is life-long, since the vast majority of primary immunodeficiency patients have primary antibody failure. Successful treatment depends on multiple factors: the availability of products, the type of immunodeficiency and any comorbidities of the individual patient. Essential components include long-term follow-up, regular monitoring and a close relationship between the patient and the multidisciplinary clinical immunology team. In this article, we describe the current immunoglobulin products and the types of adverse reactions. We provide evidence for clinical decision-making regarding dosing, route...

Hospitalisation for medical illness has ongoing impact on individuals, healthcare services and society beyond discharge. This study's objective was to determine the 12-month mortality and functional outcomes of patients admitted to the acute medical service at Groote Schuur Hospital (GSH). Follow-up, using the hospital records system and provincial death registry, together with telephonic interviews or home visits, was attempted for 465 medical inpatients admitted to GSH between 14 September and 16 November 2009. Functional outcomes were assessed using the Katz activities of daily living (ADL) score and Barthel index (BI). Outcome measures. The major study outcomes included: 12-month mortality (overall and unexpected), changes in functional status and pre- and post-admission employment rates. Inpatient mortality was 11%. At 12-month follow-up, 35% (145/415) were deceased and 30% (125/415) could not be traced; 38% (55/145) of deaths were considered expected and unexpected mortali...

University of Cape Town, Cape Town, South Africa, All India Institute of Medical Sciences, New Dehli, India, University of KwaZulu-Natal, 1 ... Corresponding author's email: grant.theron@uct.ac.za ... The performance of conventional diagnostics in high HIV ...

Although interferon-γ release assays (IGRAs) are intended for diagnosing latent tuberculosis (TB), we hypothesised that in a high-burden setting: 1) the magnitude of the response when using IGRAs can distinguish active TB from other diagnoses; 2) IGRAs may aid in the diagnosis of smear-negative TB; and 3) IGRAs could be useful as rule-out tests for active TB. We evaluated the accuracy of two IGRAs (QuantiFERON®-TB Gold In-tube (QFT-GIT) and T-SPOT®.TB) in 395 patients (27% HIV-infected) with suspected TB in Cape Town, South Africa. IGRA sensitivity and specificity (95% CI) were 76% (68-83%) and 42% (36-49%) for QFT-GIT and 84% (77-90%) and 47% (40-53%) for T-SPOT®.TB, respectively. Although interferon-γ responses were significantly higher in the TB versus non-TB groups (p<0.0001), varying the cut-offs did not improve discriminatory ability. In culture-negative patients, depending on whether those with clinically diagnosed TB were included or excluded from the analysis, the negative predictive value (NPV) of QFT-GIT, T-SPOT®.TB and chest radiograph in smear-negative patients varied between 85 and 89, 87 and 92, and 98% (for chest radiograph), respectively. Overall accuracy was independent of HIV status and CD4 count. In a high-burden setting, IGRAs alone do not have value as rule-in or -out tests for active TB. In smear-negative patients, chest radiography had better NPV even in HIV-infected patients.

Abstract: Liver function test abnormalities are prevalent in patients with HIV, and in particular advanced HIV. Opportunistic infections, drug hepatotoxicity and viral hepatitis co-infections are frequently encountered. We present a patient with advanced HIV and abnormal liver ...

Jonathan Peter completed his training as a specialist in internal medicine in 2009. Currently he is a full-time PhD student with the UCT Lung Infection and Immunity unit and an NIH Fogarty International Clinical Research Fellow. His PhD research is focused on the utility of sputum induction and novel emerging tools for the diagnosis of TB in high HIV-prevalent primary care settings. Additionally, he is the clinical co-ordinator and co-investigator for a number of ongoing multicentre TB diagnostic trials and a part-time lecturer in the ...

Light-emitting diode (LED) microscopy has recently been endorsed by the World Health Organization (WHO). However, it is unclear whether LED is as accurate and cost-effective as Ziehl–Neelsen (ZN) microscopy or mercury vapour fluorescence microscopy (MVFM) in tuberculosis (TB)–HIV-co-infected subjects.

... cost of diagnosis in a resource-poor setting? Grant Theron1, Anil Pooran1, Jonny Peter1, Richard van Zyl-Smit1,Hridesh Kumar Mishra2, Richard Meldau1, Greg Calligaro1, Brian Allwood1, Surendra Kumar Sharma2, Rod Dawson1, Keertan Dheda1, 3* ...