Baseline Xpert MTB/RIF ct values predict sputum conversion during the intensive phase of anti-TB treatment in HIV infected patients in Kampala, Uganda: a retrospective study.

BACKGROUND: In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB. METHODS: A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity. RESULTS: A total of 81 patients (58.7%) were males, median age 34 (IQR 29  ̶ 40) years, median CD4 cell count of 180 (IQR 68  ̶ 345) cells/µL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0  ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04  ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03  ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74  ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79  ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8. CONCLUSION: Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.

Circulating levels of angiogenic factors and their association with preeclampsia among pregnant women at Mulago National Referral Hospital in Uganda.

Preeclampsia (PE) is a major cause of maternal and new-born morbidity and mortality. Angiogenic factors contribute a major role in the vascular dysfunction associated with PE. We investigated the circulating levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble Feline McDonough Sarcoma (fms)-like tyrosine kinase-1 (sFlt1), their association with PE and diagnostic performance of disease among pregnant women in Uganda. Using a case-control study design, 106 women with PE and 106 with normal pregnancy were enrolled. Demographic and clinical characteristics, and anticoagulated blood samples were collected from participants. Plasma VEGF, PlGF and sFlt1 levels were measured using Luminex and enzyme linked immunosorbent assays (ELISA). Conditional logistic regression was used to explore association of angiogenic factors with PE and receiver operating characteristic analysis was performed to investigate PE diagnostic performance. Levels of VEGF and PIGF were significantly lower in cases compared to controls (VEGF: median = 0.71 pg/ml (IQR = 0.38-1.11) Vs 1.20 pg/ml (0.64-1.91), p-value<0.001 and PlGF: 2.20 pg/ml (1.08-5.86) Vs 84.62 pg/ml (34.00-154.45), p-value<0.001). Plasma levels of sFlt1 were significantly higher in cases than controls (median = 141.13 (71.76-227.10) x103 pg/ml Vs 19.86 (14.20-29.37) x103 pg/ml). Increasing sFlt1 levels were associated with increased likelihood of PE (aOR = 4.73; 95% CI, 1.18-19.01; p-value = 0.0287). The sFlt1/PlGF ratio and sFlt1 had a better performance for diagnosis of PE, with AUC = 0.95 (95% CI, 0.93-0.98) followed by PlGF with AUC = 0.94 (95% CI, 0.91-0.97). Therefore, sFlt1, sFlt1/PlGF ratio and PlGF are potential candidates for incorporation into algorithms for PE diagnosis in the Ugandan population.

Carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii at Mulago Hospital in Kampala, Uganda (2007-2009).

BACKGROUND: Multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii are common causes of health care associated infections worldwide. Carbapenems are effective against infections caused by multidrug resistant Gram-negative bacteria including Pseudomonas and Acinetobacter species. However, their use is threatened by the emergence of carbapenemase-producing strains. The aim of this study was to determine the prevalence of carbapenem-resistant P. aeruginosa and A. baumannii at Mulago Hospital in Kampala Uganda, and to establish whether the hospital environment harbors carbapenem-resistant Gram-negative rods. RESULTS: Between February 2007 and September 2009, a total of 869 clinical specimens were processed for culture and sensitivity testing yielding 42 (5 %) P. aeruginosa and 29 (3 %) A. baumannii isolates, of which 24 % (10/42) P. aeruginosa and 31 % (9/29) A. baumannii were carbapenem-resistant. Additionally, 80 samples from the hospital environment were randomly collected and similarly processed yielding 58 % (46/80) P. aeruginosa and 14 % (11/80) A. baumannii, of which 33 % (15/46) P. aeruginosa and 55 % (6/11) A. baumannii were carbapenem-resistant. The total number of isolates studied was 128. Carbapenemase genes detected were bla IMP-like (36 %, 9/25), bla VIM-like (32 %, 8/25), bla SPM-like (16 %, 4/25); bla NDM-1-like (4 %, 1/25) in carbapenem-resistant P. aeruginosa, and bla OXA-23-like (60 %, 9/15), bla OXA-24-like (7 %, 1/15), bla OXA-58-like (13 %, 2/15), and bla VIM-like (13 %, 2/15) in carbapenem-resistant A. baumannii. Furthermore, class 1 integrons were detected in 38 % (48/128) of P. aeruginosa and Acinetobacter, 37 % (26/71) of which were in clinical isolates and 39 % (22/57) in environment isolates. Gene cassettes were found in 25 % (12/48) of integron-positive isolates. These were aminoglycoside adenylyltransferase ant(4')-IIb (3 isolates); trimethoprim-resistant dihydrofolate reductase dfrA (2 isolates); adenyltransferase aadAB (3 isolates); QacE delta1 multidrug exporter (2 isolates); quinolone resistance pentapeptide repeat protein qnr (1 isolate); and metallo-ß-lactamase genes bla VIM-4-like, bla IMP-19-like, and bla IMP-26-like (1 isolate each). Gene cassettes were missing in 75 % (36/48) of the integron-positive isolates. CONCLUSIONS: The prevalence of carbapenem-resistant P. aeruginosa and Acinetobacter among hospitalized patients at Mulago Hospital is low compared to rates from South-East Asia. However, it is high among isolates and in the environment, which is of concern given that the hospital environment is a potential source of infection for hospitalized patients and health care workers.