No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda.

BACKGROUND: Vascular endothelial growth factor A (VEGFA) is a major angiogenic factor that plays an important role in the formation of blood vessels during embryonic development. VEGFA has been implicated in the pathophysiology of pre-eclampsia (PE), since pre-eclamptic women present with reduced levels of free circulating VEGFA. The 3' untranslated region (3'-UTR) of the VEGFA gene consists of elements that regulate the transcription and hence expression of the VEGFA protein in circulation. Hence it is suggested that variations thereof could underlie the reduced VEGFA levels observed in pre-eclamptic women. The purpose of this study was to investigate presence of the + 936C/T polymorphism, a common single nucleotide polymorphism (SNP) in the 3'-UTR of the VEGFA gene, and determine its association with PE among pregnant women in Uganda. RESULTS: There was no significant difference observed in the allele and genotype frequencies of the + 936C/T 3' UTR-VEGFA polymorphism between pre-eclamptic and normotensive pregnant women (P > 0.05). Additionally, there was no significant difference in the median plasma levels of free VEGFA among women with the wild type, CT and TT genotypes of the + 936C/T VEGFA polymorphism (median = 0.84 pg/mL (IQR = 0.39-1.41) Vs 1.05 (0.61-1.18) Vs 1.05 (1.05-1.05) respectively, p-value = 0.7161). CONCLUSIONS: These study findings indicate that the + 936C/T 3' UTR-VEGFA polymorphism had no significant association with increased susceptibility to PE among women in Uganda. Further studies with a larger sample size are recommended.

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.

Translational research in Uganda: linking basic science to bedside medicine in a resource limited setting.

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.

Complete ciprofloxacin resistance in gonococcal isolates in an urban Ugandan clinic: findings from a cross-sectional study.

Antimicrobial resistance (AMR) 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 AMR patterns of Neisseria gonorrhoeae clinical isolates to antimicrobial agents in patients with HIV or high risk of HIV acquisition, to compare the concordance of disk diffusion and agar dilution as methods for determining AMR to N. gonorrhoeae, and to describe methodological challenges to carrying out AMR testing. 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 polymerase chain reaction (PCR)-based assay. Samples positive for gonorrhoea were cultured. Antimicrobial susceptibility testing was performed using disk diffusion and isolates were sent to a reference laboratory for agar dilution direct susceptibility testing. Five hundred and seventy-five patients were screened. There were 33 (5.7%) patients with gonorrhoea detected 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. 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. AMR testing of N. gonorrhoeae isolates is needed to ensure optimal treatment and prevention of antibiotic resistance progression.

Very low sensitivity of wet mount microscopy compared to PCR against culture in the diagnosis of vaginal trichomoniasis in Uganda: a cross sectional study.

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. RESULTS: The 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. CONCLUSION: Among 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.