Prevalence and risk factors for Betaherpesvirus DNAemia in children >3 weeks and <2 years of age admitted to a large referral hospital in sub-Saharan Africa

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. Methods. 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. Results. 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. Conclusions. 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

Tuberculosis at post-mortem in inpatient adults at a tertiary referral centre in sub-Saharan Africa - A prospective descriptive autopsy study

Background: 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. Methods: Complete whole body autopsies were performed on 125 adult inpatients. Pathological examination involved two stages: (1) Gross pathology was recorded, and samples were taken from all organs for histopathology and cryopreservation; and (2) Histopathological examination of tissue after appropriate staining. Specific pathology and diseases identified on examination were recorded. Lung tissues were processed using the GeneXpert MTB/RIF Assay. Primary outcome measures were specific diseases stratified by HIV status. Secondary outcomes were missed TB and drug-resistant TB cases. Findings: Of 125 adults, median age 35. years (IQR: 29-43), 80 (64%) were male and 101 (80.8%) were HIV-positive. Tuberculosis was the most common finding at autopsy with 78/125 cases (62.4%), of which 66/78 (84.6%) were HIV-infected. There were 35/78 cases (44.9%) with extra-pulmonary TB, the odds of which were higher among HIV-infected cases (aOR 5.14 (95% CI: 1.04-25.4), p=. 0.045); 25.6% (20/78) of the TB cases were not diagnosed ante-mortem; and 13/78 (16.7%) of the TB cases had undiagnosed MDR-TB. Other autopsy findings included: pyogenic pneumonia 36.8% (46/125); bacterial meningitis 7.2% (9/125); cardiac failure 7.2% (9/125); and malignancies 8.8% (11/125). Prevalence of HIV did not differ between TB and non-TB cases (84.6% vs. 74.5%: p=. 0.163). Interpretation: TB remains an important cause of death in adult inpatients. A substantial number of inpatients with TB and MDR-TB are not diagnosed by the current cascade of healthcare. Inpatient settings in high TB endemic countries should be included in WHO 'high risk' groups, and heightened clinical awareness and more proactive screening for TB and MDR-TB in all inpatients should be required

Evaluation of the Xpert MTB/RIF Assay at a Tertiary Care Referral Hospital in a Setting Where Tuberculosis and HIV Infection Are Highly Endemic.

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. © 2012 Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved