SummaryBackgroundThe Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance.MethodsIn this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection.FindingsBetween Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance.InterpretationFor tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity.FundingGovernment of Netherlands, Government of Australia, Bill & Melinda Gates Foundati...
Objectives Antimicrobial resistance to gonorrhoea is a threat to global health security. There have been concerns expressed that countries with high rates of disease have poor surveillance. The objectives of the study were: to determine the antimicrobial resistance patterns of N. gonorrhoeae clinical isolates to antimicrobial agents in patients with HIV or high risk of HIV acquisition; to compare the concordance of disc diffusion and agar dilution as methods for determining antimicrobial resistance to N. gonorrhoeae, and to describe methodological challenges to carrying out AMR testing. Methods The study was conducted at an HIV outpatient service for at-risk populations and an outreach clinic for commercial sex workers in Kampala. Patients were offered a sexually transmitted infection screen using a PCR-based assay. Samples positive for gonorrhoea were cultured. Antimicrobial susceptibility testing was performed using disc diffusion and isolates were sent to a reference laboratory for agar dilution direct susceptibility testing. Results Five hundred and seventy five patients were screened. There were 33 (5.7%) patients with gonorrhoea by PCR. Of the 16 viable N. gonorrhoeae isolates, 100% were resistant to ciprofloxacin and tetracycline by disk diffusion; and 31% exhibited reduced susceptibility to ceftriaxone and cefixime. By agar dilution, 100% of isolates were resistant to ciprofloxacin and all isolates were susceptible to ceftriaxone and cefixime. Conclusions One hundred percent resistance to ciprofloxacin was identified. There was concordance between disk diffusion and agar dilution for ciprofloxacin and tetracycline resistance and a significant discordance for third generation cephalosporins. More than half the women with gonorrhoea were asymptomatic, and represent a potential reservoir for ongoing transmission. Antimicrobial resistance testing of N.gonorrhoeae isolates is needed to ensure optimal treatment and prevention of antibiotic resistance progression.
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.
Background Trichomonas vaginalis (TV) causes the Trichomoniasis Syndrome composed of vaginitis in women, urethritis in men and tube infection in both sexes. This infection is strongly associated with premature rupture of membranes, preterm delivery, low birth weight, promoting HIV sexual transmission and infertility. Prevention of these complications requires accurate early detection and effective treatment of infected individuals. In the resource limited settings, the wet mount microscopy (WMM) is often the only available test for laboratory detection of TV, but its accuracy and that of polymerase chain reaction (PCR) tools in Uganda remain poorly studied. The aim of this cross-sectional study was to compare the diagnostic accuracy of the WMM and PCR against culture as reference standard for the direct diagnosis of TV among symptomatic women. Three high vaginal swabs were collected from each of one hundred fifty women presenting with symptoms suggestive of active vaginal trichomoniasis at the sexually transmitted diseases clinic of Mulago National Referral Hospital Kampala, Uganda. The swabs were tested for TV with WMM, in-house PCR and TV culture. Results were analysed using excel 2007, SPSS v16, and Meta-disc software to determine the diagnostic accuracy of the tests.ResultsThe sensitivity, specificity and kappa agreement of the WMM was 25% (95% CI 5.5–57.2%), 100% (95% CI 97–100) and 0.38, respectively. Corresponding values for the PCR were 91.7% (95% CI 61.5–99.8), 99.3% (95% CI 96–100) and 0.91, respectively.ConclusionAmong the TV symptomatic women, the sensitivity of the WMM was very low, with two-thirds of the patients missing a diagnosis while the in-house PCR was highly sensitive and specific. Feasibility studies aimed at incorporating PCR tools in algorithms for diagnosis of TV infection in resource-limited settings are recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2581-1) contains supplementary material, which is available to authorized users.
Background Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. Main body In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. Conclusion Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.
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