High HIV prevalence and associated risk factors among female sex workers in Rwanda.

Human immunodeficiency virus (HIV) prevalence is often high among female sex workers (FSWs) in sub-Saharan Africa. Understanding the dynamics of HIV infection in this key population is critical to developing appropriate prevention strategies. We aimed to describe the prevalence and associated risk factors among a sample of FSWs in Rwanda from a survey conducted in 2010. A cross-sectional biological and behavioral survey was conducted among FSWs in Rwanda. Time-location sampling was used for participant recruitment from 4 to 18 February 2010. HIV testing was done using HIV rapid diagnostic tests (RDT) as per Rwandan national guidelines at the time of the survey. Elisa tests were simultaneously done on all samples tested HIV-positive on RDT. Proportions were used for sample description; multivariable logistic regression model was performed to analyze factors associated with HIV infection. Of 1338 women included in the study, 1112 consented to HIV testing, and the overall HIV prevalence was 51.0%. Sixty percent had been engaged in sex work for less than five years and 80% were street based. In multivariable logistic regression, HIV prevalence was higher in FSWs 25 years or older (adjusted odds ratio [aOR] = 1.83, 95% [confidence interval (CI): 1.42-2.37]), FSWs with consistent condom use in the last 30 days (aOR = 1.39, [95% CI: 1.05-1.82]), and FSWs experiencing at least one STI symptom in the last 12 months (aOR = 1.74 [95% CI: 1.34-2.26]). There was an inverse relationship between HIV prevalence and comprehensive HIV knowledge (aOR = 0.65, [95% CI: 0.48-0.88]). HIV prevalence was high among a sample of FSWs in Rwanda, and successful prevention strategies should focus on HIV education, treatment of sexually transmitted infections, and proper and consistent condom use using an outreach approach.

Metabolic dysfunctions in multiple sclerosis: implications as to causation, early detection, and treatment, a case control study.

BACKGROUND: Biochemical changes associated with multiple sclerosis (MS), and its various clinical forms have not been characterized well. Therefore, we investigated the biochemistry of MS in relation to its natural history using targeted lipidomics platforms. METHODS: Cross-sectional serum samples from 24 secondary progressive (SPMS), 100 relapsing remitting (RRMS), 19 primary progressive MS (PPMS), and 55 age-matched control subjects were analyzed by flow injection tandem mass spectrometry for very long chain fatty acid (VLCFA) containing phosphatidyl ethanolamines (PtdEtn), plasmalogen ethanolamines (PlsEtn) and for novel anti-inflammatory gastrointestinal tract acids (GTAs). Changes in analyte levels relative to healthy controls were correlated with the disease stage and disease duration. RESULTS: RRMS subjects having <13 years disease duration had elevated levels (p < 0.05) of anti-inflammatory metabolites (GTAs) and normal levels (p > 0.05) of mitochondrial stress biomarkers (VLCFA-PtdEtn), compared to controls. SPMS subjects had statistically similar levels of anti-inflammatory metabolites (GTAs), elevated mitochondrial stress metabolites (VLCFA-PtdEtn) and elevated peroxisomal metabolites (PlsEtn) compared to controls (p < 0.05). RRMS subjects with > = 13 years disease duration exhibited metabolic profiles intermediate between short-duration RRMS and SPMS, based on statistical significance. Therefore, RRMS cohort appear to comprise of two metabolically distinct subpopulations. The key clinical discriminator of these two groups was disease duration. PPMS patients exhibited metabolic profiles distinct from RRMS and SPMS. CONCLUSIONS: These data indicate that inflammation and mitochondrial stress are intricately involved in the etiology of MS and that progression in MS can potentially be monitored using serum metabolic biomarkers.

Pancreatic cancer serum biomarker PC-594: Diagnostic performance and comparison to CA19-9.

AIM: To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer (PaC) patients, and to compare its performance to CA19-9. METHODS: Using tandem mass spectrometry, we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects. We determined CA19-9 levels by ELISA. Significance between PaC patients and controls, and association with clinical variables was determined by analysis of variance and t-tests. Diagnostic performance was evaluated by receiver-operator characteristic (ROC) curve analysis, and PC-594 correlation with age and CA19-9 determined by regression analysis. RESULTS: Mean PC-594 levels were 3.7 times lower in PaC patients compared to controls (P < 0.0001). The mean level in PaC patient serum was 0.76 ± 0.07 µmol/L, and the mean level in control subjects was 2.79 ± 0.15 µmol/L. There was no correlation between PC-594 and age, disease stage or gender (P > 0.05). Using 1.25 µmol/L as a PC-594 threshold produced a relative risk (RR) of 9.4 (P < 0.0001, 95%CI: 5.0-17.7). The area under the receiver-operator characteristic curve (ROC-AUC) was 0.93 (95%CI: 0.91-0.95) for PC-594 and 0.85 (95%CI: 0.82-0.88) for CA19-9. Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9. Six PaC patients with CA19-9 above 35 U/mL showed normal PC-594 levels, while 24 PaC patients with normal CA19-9 showed low PC-594 levels. Eighty-five of the 99 control subjects (86%) showed normal levels of both markers. CONCLUSION: PC-594 biomarker levels are significantly reduced in North American PaC patients, and showed superior diagnostic performance compared to CA19-9.

Metabolic system alterations in pancreatic cancer patient serum: potential for early detection.

BACKGROUND: The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. METHODS: A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasms (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population. RESULTS: FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long-chain fatty acid), was further validated using an independently-collected US Caucasian population (blinded analysis, n=60, p=9.9E-14, AUC=0.97 ±0.02). PC-594 levels across 1000 reference subjects showed an inverse correlation with age, resulting in a drop in the AUC from 0.99 ±0.01 to 0.90 ±0.02 for subjects aged 30 to 80, respectively. A PC-594 test positivity rate of 5.0% in low-risk reference subjects resulted in a PC sensitivity of 87% and a significant improvement in net clinical benefit based on decision curve analysis. CONCLUSIONS: The serum metabolome of PC patients is significantly altered. The utility of serum metabolite biomarkers, particularly PC-594, for identifying subjects with elevated risk of PC should be further investigated.

HIV Prevalence Comparison Between Antenatal Sentinel Surveillance and Demographic and Health Survey in Rwanda.

OBJECTIVE: To compare HIV prevalence from antenatal surveillance to that of the demographic and health survey (DHS), and to identify factors determining the difference of HIV prevalence between women recruited in these two surveys in Rwanda in 2005. METHODS: Comparative cross-sectional study of HIV prevalence and socio-demographic factors collected by the antenatal survey in 13,745 pregnant women, seen in 30 health centres located throughout the country and those collected by the DHS among 5641 women, aged 15-49 years living in households located throughout the country. Log-binomial regression and direct standardization were used to estimate and compare HIV prevalence between the two surveys. RESULTS: HIV prevalence in the antenatal survey was slightly higher than that in DHS women (4.1% versus 3.6% p=0.103). Socio-demographic characteristics were differently distributed between the two populations. Whereas, 59%, 93%, 53% of pregnant women were aged 20-29 years, married or cohabiting and living in rural areas respectively, the corresponding proportions among DHS women were 35%, 48% and 83% (p<0.001). Simultaneous standardization of antenatal prevalence according to the distribution of socio-demographic characteristics in the DHS gave an overall HIV prevalence estimate of 3.6%, similar to the prevalence measured among DHS women. CONCLUSIONS: HIV prevalence in the antenatal survey overestimated that among women of the general population in Rwanda in 2005. This overestimation could be corrected by standardization of antenatal prevalence according to the distribution of age, geographical area, marital status, parity, and education, in the general population.