Estimating the date of origin of an HIV-1 circulating recombinant form

HIV is capable of frequent genetic exchange through recombination. Despite the pandemic spread of HIV-1 recombinants, their times of origin are not well understood. We investigate the epidemic history of a HIV-1 circulating recombinant form (CRF) by estimating the time of the recombination event that lead to the emergence of CRF33_01B, a recently described recombinant descended from CRF01_AE and subtype B. The gag, pol and env genes were analyzed using a combined coalescent and relaxed molecular clock model, implemented in a Bayesian Markov chain Monte Carlo framework. Using linked genealogical trees we calculated the time interval between the common ancestor of CRF33_01B and the ancestors it shares with closely related parental lineages. The recombination event that generated CRF33_01B (t_rec) occurred sometime between 1991 and 1993, suggesting that recombination is common in the early evolutionary history of HIV-1. The proof-of-concept approach provides a new tool for the investigation of HIV molecular epidemiology and evolution.     

Preventing tuberculosis in healthcare workers of the radiology department: a Malaysian perspective

Tuberculosis (TB) is a well recognised occupational hazard for healthcare workers (HCWs). Concerns on the safety of healthcare settings in Malaysia was raised following a report of 25 HCWs working in 11 general hospitals in Malaysia who were infected with TB in 2004 being publicised in the media recently. As the disease burden in general is high in Malaysia, due attention should be given to this disease in our healthcare facilities including the radiology department, an often neglected area in TB infection control programmes. This article focuses on the key control measures that can be implemented in radiology departments in a developing country with limited resources.     

Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV Observational Database

BACKGROUND: The antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on the outcome of this treatment in clinic cohorts in this region. METHODS: We selected patients from the TREAT Asia HIV Observational Database (TAHOD) who started their first ART regimen with d4T/3TC/NVP. Treatment change was defined as cessation of therapy or the addition or change of one or more drugs. Clinical failure was defined as diagnosis with an AIDS-defining illness, or death while on d4T/3TC/NVP treatment. RESULTS: The rate of treatment change among TAHOD patients starting d4T/3TC/NVP as their first antiretroviral treatment was 22.3 per 100 person-years, with lower baseline haemoglobin (i.e. anaemia) associated with slower rate of treatment change. The rate of clinical failure while on d4T/3TC/NVP treatment was 7.3 per 100 person-years, with baseline CD4 cell count significantly associated with clinical failure. After d4T/3TC/NVP was stopped, nearly 40% of patients did not restart any treatment and, of those who changed to other treatment, the majority changed to zidovudine (ZDV)/3TC/NVP and less than 3% of patients changed to a protease inhibitor (PI)-containing regimen. The rates of disease progression on the second-line regimen were similar to those on the first-line regimen. CONCLUSION: These real-life data provide an insight into clinical practice in Asia and the Pacific region. d4T/3TC/NVP is maintained longer than other first-line regimens and change is mainly as a result of adverse effects rather than clinical failure. There is a need to develop affordable second-line antiretroviral treatment options for patients with HIV infection in developing countries.     

Faecal prevalence of extended-spectrum Beta-lactamase (ESBL)-producing coliforms in a geriatric population and among haematology patients

Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly reported worldwide. In the local setting, nosocomial infections with multi-resistant Gram-negative bacilli are not uncommon and are a growing concern. However, there is limited data on the carriage rates of such organisms in the local setting. In May 2001, a prospective study was carried out to determine the enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB) among residents of nursing homes and from in-patients of the geriatric and adult haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram-negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6 were from nursing home residents, 5 from geriatric in-patients and 14 from the haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10) and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta-lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in the haematology ward, the six nursing home residents with CAZ-R GNB were enteric carriers of ESBL-producing coliforms. Prior exposure to antibiotics was associated with carriage of ESBL organisms and to a lesser extent, the presence of urinary catheters.     

Treatment of acute Nipah encephalitis with ribavirin.

Nipah virus, a newly identified paramyxovirus caused a severe outbreak of encephalitis in Malaysia with high fatalities. We report an open-label trial of ribavirin in 140 patients, with 54 patients who were managed prior to the availability of ribavirin or refused treatment as control. There were 45 deaths (32%) in the ribavirin arm; 29 deaths (54%) occurred in the control arm. This represents a 36% reduction in mortality (p = 0.011). There was no associated serious side effect. This study suggests that ribavirin is able to reduce the mortality of acute Nipah encephalitis.     

Induction of hepatic 11beta-hydroxysteroid dehydrogenase type 1 in patients with alcoholic liver disease

Background and aim The alcohol‐induced pseudo‐Cushing's syndrome is an important differential diagnosis of hypercortisolism that is poorly understood. Two isozymes of 11β‐hydroxysteroid dehydrogenase (11β‐HSD) interconvert hormonally active cortisol (F) and inactive cortisone (E). Previously we have shown higher urinary F : E metabolite ratios (a reflection of global 11β‐HSD activity) in patients with alcoholic liver disease (ALD) compared to patients with chronic liver disease (CLD) of other aetiologies, suggesting that the phenotype of alcoholic pseudo‐Cushing's may relate to altered metabolism of F. Subjects and methods We performed selective venous sampling of the hepatic, renal and peripheral veins measuring F and E concentrations (using in‐house radioimmunoassay) in 20 patients with histologically confirmed ALD and 19 patients with CLD. Six patients who also had selective venous sampling for investigation of suspected hyperaldosteronism were used as ‘normal’ controls. Results There was a significant difference in the hepatic F gradient (mean ± SEM) between groups, indicating increased F production in the liver in patients with ALD (34·5 ± 21·7 nmol/l) compared to those with CLD (–21·0 ± 18·5 nmol/l) (P < 0·05) and normals (–19·7 ± 17·2 nmol/l) (P < 0·05). 11β‐HSD1 mRNA expression was increased fivefold in the ALD group compared with normal controls (P < 0·01). Conclusions These results indicate significant induction of HSD11B1 gene expression and activity in patients with ALD during short‐ and long‐term abstinence from alcohol. The mechanism is unknown but might be explained on the basis of alcohol‐induced changes in intracellular redox potential or as a protective mechanism to limit liver inflammation and injury. Selective 11β‐HSD1 inhibitors may offer a novel therapeutic approach to treat alcoholic pseudo‐Cushing's.