[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:
Patients with subclinical tuberculosis, smear-negative tuberculosis, extrapulmonary tuberculosis, multidrug-resistant tuberculosis, and asymptomatic tuberculosis are difficult to diagnose and may be missed at all points of health care. We did an autopsy study to ascertain the burden of tuberculosis at post mortem in medical inpatients at a tertiary care hospital in Lusaka, Zambia.
Between April 5, 2012, and May 22, 2013, we did whole-body autopsies on inpatients aged at least 16 years who died in the adult inpatient wards at University Teaching Hospital, Lusaka, Zambia. We did gross pathological and histopathological analysis and processed lung tissues from patients with tuberculosis through the GeneXpert MTB/RIF assay to identify patients with multidrug-resistant tuberculosis. The primary outcome measure was specific disease or diseases stratified by HIV status. Secondary outcomes were missed tuberculosis, multidrug-resistant tuberculosis, and comorbidities with tuberculosis. Data were analysed using Pearson χ2, the Mann-Whitney U test, and binary logistic regression.
The median age of the 125 included patients was 35 years (IQR 29-43), 80 (64%) were men, and 101 (81%) were HIV positive. 78 (62%) patients had tuberculosis, of whom 66 (85%) were infected with HIV. 35 (45%) of these 78 patients had extrapulmonary tuberculosis. The risk of extrapulmonary tuberculosis was higher among HIV-infected patients than among uninfected patients (adjusted odds ratio 5·14, 95% CI 1·04-24·5; p=0·045). 20 (26%) of 78 patients with tuberculosis were not diagnosed during their life and 13 (17%) had undiagnosed multidrug-resistant tuberculosis. Common comorbidities with tuberculosis were pyogenic pneumonia in 26 patients (33%) and anaemia in 15 (19%).
Increased clinical awareness and more proactive screening for tuberculosis and multidrug-resistant tuberculosis in inpatient settings is needed. Further autopsy studies are needed to ascertain the generalisability of the findings.
UBS Optimus Foundation, EuropeAID, and European Developing Countries Clinical Trials Partnership (EDCTP).
Full-text · Article · May 2015 · The Lancet Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: The World Health Organisation (WHO) estimates that 3 million cases of tuberculosis (TB) are missed every year. Identification and treatment of these are critical to achieving global TB control. Patients with sub-clinical TB, extra-pulmonary TB, and drug-resistant TB are difficult to diagnose and may be missed at all points of healthcare. An autopsy study was conducted to ascertain the burden of TB at post-mortem in adults who died in the inpatient general medical wards at a tertiary care referral center in Lusaka, Zambia.
Full-text · Article · Dec 2014 · International Journal of Mycobacteriology
[Show abstract][Hide abstract] ABSTRACT: Background:
Betaherpesviruses are established causes of morbidity and mortality in immunosuppressed patient groups but have been little studied in sub-Saharan Africa, the epicenter of the human immunodeficiency virus (HIV) pandemic. In this region, primary infections with human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) type 6 are endemic in infancy, but the clinical impact of these infections among pediatric inpatient groups is poorly characterized and assumptive, based largely on data from Western populations.
We used TaqMan polymerase chain reaction to screen sera from a group of 303 pediatric inpatients aged between 3 weeks and 2 years, at the University Teaching Hospital in Lusaka, Zambia. We report the prevalence of DNAemia and viral loads within this patient group, and evaluate possible clinical associations/risk factors for betaherpesvirus infections in these hospitalized children.
We detected betaherpesvirus DNAemia in 59.1% (179/303) of children. HCMV was the most prevalent (41.3%), followed by HHV-6B (20.5%), HHV-7 (20.1%), and HHV-6A (0.3%). HIV infection (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.37-3.90; P = .002), being underweight (OR, 1.82; 95% CI, 1.06-3.12; P = .03), and an admission diagnosis of suspected meningitis (OR, 5.72; 95% CI, 1.07-30.5; P = .041) were independently associated with an increased odds of HCMV DNAemia. Conversely, HHV-6B and HHV-7 DNAemia were not associated with HIV, underweight, or admission diagnosis. Median HCMV viral load was moderately but significantly higher in HIV-infected children.
Highly prevalent HCMV DNAemia was independently associated with HIV infection and being underweight across all age groups, and was also associated with meningitis, with previously underappreciated implications for the health and development of African children.
Full-text · Article · Oct 2014 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Background
A high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis, in a tertiary referral centre.
In this prospective study, newly admitted adult inpatients able to produce sputum at the University Teaching Hospital, Lusaka, Zambia, were screened for pulmonary TB using fluorescent smear microscopy and automated liquid culture. The burden of pulmonary TB, unsuspected TB, TB co-morbidity with NCDs and CDs was determined. Sputum was analysed from 900 inpatients (70.6% HIV infected) 277 (30.8%) non-TB suspects, 286 (31.8%) TB suspects and 337 (37.4%) were already receiving TB treatment. 202/900 (22.4%) of patients had culture confirmed TB. TB co-morbidity was detected in 20/275 (7.3%) NCD patients, significantly associated with diabetes (P = 0.006, OR 6.571, 95%CI: 1.706–25.3). 27/202 (13.4%) TB cases were unsuspected. There were 18 confirmed cases of MDR-TB, 5 of which were unsuspected.
A large burden of unsuspected pulmonary TB co-morbidity exists in inpatients with NCDs and other CDs. Pro-active sputum screening of all inpatients in tertiary referral centres in high TB endemic countries is recommended. The scale of the problem of undiagnosed MDR-TB in inpatients requires further study.
[Show abstract][Hide abstract] ABSTRACT: Background. There were 1.45 million deaths from tuberculosis (TB) in 2011. A substantial proportion of active pulmonary TB cases in countries where tuberculosis, human immunodeficiency virus (HIV) infection, and AIDS are highly endemic remain undiagnosed because of the reliance on sputum-smear microscopy. This study evaluated the performance of the Xpert MTB/RIF assay at a tertiary care referral center in Zambia, a country where the burden of TB and HIV infection is high. Methods. A total of 881 adult inpatients admitted to University Teaching Hospital in Lusaka who were able to produce sputum were enrolled and analyzed in the study, irrespective of admission diagnosis. Sputum specimens were analyzed by fluorescence smear microscopy, the Xpert MTB/RIF assay, mycobacterial growth indicator tube (MGIT) culture, and MGIT drug-susceptibility testing. The sensitivity and specificity of the Xpert MTB/RIF assay were evaluated using culture as the gold standard. Results. Culture-confirmed TB was found in 201 of 881 patients (22.8%). The specificity of the Xpert MTB/RIF assay was 95.0% (95% confidence interval [CI], 92.4%-96.8%), and the sensitivity was 86.1% (95% CI, 80.3%-90.4%). In sputum smear-negative, culture-positive cases, the assay was 74.7% sensitive (95% CI, 64.6%-82.8%), identifying 71 additional TB cases that were not detected by smear microscopy. A total of 18 of 111 patients with TB who were tested (16.2%) had multidrug-resistant (MDR) TB. The sensitivity and specificity of the Xpert MTB/RIF assay for detecting culture-confirmed, rifampicin-resistant TB was 81.3% (95% CI, 53.7%-95.0%) and 97.5% (95% CI, 90.4%-99.6%), respectively. Conclusions. The Xpert MTB/RIF assay performs better than smear microscopy in an inpatient setting in a country where TB and HIV infection are highly endemic. Assessment of its usefulness and cost-effectiveness for increased detection of TB cases missed by sputum smear and for concomitant screening for MDR TB among adult inpatients attending tertiary care referral centers in other countries with a high burden of TB and HIV infection is warranted.