Sensitivity and specificity of the mean corpuscular volume and CD4/CD8 ratio in discriminating between rifampicin resistant and rifampicin sensitive tuberculosis.

BACKGROUND: There is need for simple, cost effective and widely available point of care tests for low level health facilities in developing countries to screen for drug resistant tuberculosis (TB) after bacteriological confirmation of TB by smear microscopy. We evaluated the sensitivity and specificity of the mean corpuscular volume (MCV) and CD4/CD8 ratio in discriminating between rifampicin resistant (RR-TB) and rifampicin sensitive (RS-TB) tuberculosis. METHODS: We performed a secondary analysis of data from a cross sectional study that enrolled adult participants with bacteriologically confirmed pulmonary TB at a national tuberculosis treatment center in Uganda. Blood samples were tested for CD4 and CD8 cell counts, HIV serology and a full hemogram. Rifampicin sensitivity and the bacillary load grade were determined by Xpert MTB/RIF®. Fifty-five participants that had RR-TB (cases) were matched with 110 participants that had RS-TB (controls) for age, sex and HIV status in a ratio of 1:2 respectively. Sensitivity (Se), specificity (Sp), area under curve (AUC) analysis and determination of optimal cut-offs were performed using receiver operating characteristic curves. RESULTS: Cases differed from controls with respect to residence (p = 0.031), bacillary load grade (p < 0.010) and MCV (p = 0.021). The Se, Sp and AUC of the MCV (cut-off of > 74.6 femtolitres (fl)) were 88.9%, 34% and 0.607 (p = 0.021) respectively for RR-TB. Among HIV positive participants, the respective Se, Sp and AUC of the MCV for RR-TB (cut-off of > 72.5 fl) were 97.2%, 22.2% and 0.608 (p = 0.061). The respective Se, Sp and AUC of the CD4/CD8 ratio (cut-off of > 0.40) were 67.3%, 50.0% and 0.559 (p = 0.199) on the overall and 54.1%, 71.6% and 0.628 (p = 0.024) among the HIV positive participants for RR-TB. CONCLUSION: The MCV had a high sensitivity but very low specificity for RR-TB. The CD4/CD8 ratio had a low sensitivity and specificity for RR-TB among HIV positive individuals. The utility of either test is low due to low diagnostic accuracy.

Markers of oxidative stress in umbilical cord blood from G6PD deficient African newborns.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that affects as many as 400 million people worldwide, making it the most common enzymatic defect. Subjects with G6PD deficiency are more likely to develop neonatal hyperbilirubinemia potentially leading to kernicterus and are at increased risk for acute hemolytic anemia when exposed to pro-oxidant compounds such as anti-malarial drugs. We collected umbilical cord blood from 300 males born in Uganda to assess for novel markers of systemic oxidative stress. We determined that 10.7% of the samples collected were G6PD A- deficient (G202A/A376G) and when these were compared with unaffected controls, there was significantly higher 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentration, elevated ferritin, increased leukocyte count and higher small molecule antioxidant capacity. These data suggest increased baseline oxidative stress and an elevated antioxidant response in umbilical cord blood of patients with G6PD deficiency.