The sensitivity and specificity of Lassa virus IgM by ELISA as screening tool at early phase of Lassa fever infection

Background: Early diagnosis, prompt treatment, and disease containment are vital measures in the management of Lassa fever (LF), a lethal and contagious arenaviral hemorrhagic disease prevalent in West Africa. Lassa Virus (LAV)‑specific Reverse Transcriptase Polymerase Chain Reaction (RT‑PCR) test, the gold standard for diagnosis, is unavailable in most centers. Serologic detection of LAV IgM is a more accessible tool and this work was to investigate its adequacy as an early marker for LF. Patients and Methods: A prospective case–control study conducted July 2007‑March 2011 in a tertiary referral health center in Nigeria. Blood samples for test and control were evaluated for Lassa specific antigens and IgM using RT‑PCR (primers S36+ and LVS 339) and indirect ELISA (Lassa Nucleo‑protein (NP)‑Antigen) respectively. RT‑PCR outcome was used as standard to test for the sensitivity and specificity of IgM. Results: Of the 37 confirmed cases of LF infection by RT‑PCR, 21 (57%) were IgM positive. Amongst the 35 confirmed negative cases (control group), eight were IgM positive. The diagnostic sensitivity and specificity of the IgM assay were 57% and 77% respectively. The negative and positive predictive values of the IgM serological assay were 63% and 72%, respectively, while the efficiency of the test was 67%. Conclusion: The specificity and sensitivity of IgM as a screening tool for early detection of LF appear weak and, hence, the need for a reliable LF “rapid screening kit” since RT‑PCR is unavailable in most centers. In the interim, “high clinical index of suspicion,” irrespective of IgM status, requires urgent referral to confirmatory centers.Keywords: Immunoglobulin M, Lassa fever, reverse transcriptase polymerase chain reaction test, serologyNigerian Medical Journal | Vol. 53 | Issue 4 | October-December | 201

Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish

BACKGROUND: The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. METHODS: In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). RESULTS: In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P < 0.05). The risk of ECG-LVH increased more with office and home BP in Blacks than Whites. CONCLUSIONS: Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range.status: publishe

Prevalence and Determinants of Masked Hypertension Among Black Nigerians Compared With a Reference Population

Hitherto, diagnosis of hypertension in sub-Saharan Africa was largely based on conventional office blood pressure (BP). Data on the prevalence of masked hypertension (MH) in this region is scarce. Among individuals with normal office BP (<140/90 mm Hg), we compared the prevalence and determinants of MH diagnosed with self-monitored home blood pressure (≥135/85 mm Hg) among 293 Nigerians with a reference population consisting of 3615 subjects enrolled in the International Database on Home Blood Pressure in Relation to Cardiovascular Outcomes. In the reference population, the prevalence of MH was 14.6% overall and 11.1% and 39.6% in untreated and treated participants, respectively. Among Nigerians, the prevalence standardized to the sex and age distribution of the reference population was similar with rates of 14.4%, 8.6%, and 34.6%, respectively. The mutually adjusted odds ratios of having MH in Nigerians were 2.34 (95% confidence interval, 1.39-3.94) for a 10-year higher age, 1.92 (1.11-3.31) and 1.70 (1.14-2.53) for 10- or 5-mm Hg increments in systolic or diastolic office BP, and 3.05 (1.08-8.55) for being on antihypertensive therapy. The corresponding estimates in the reference population were similar with odds ratios of 1.80 (1.62-2.01), 1.64 (1.45-1.87), 1.13 (1.05-1.22), and 2.84 (2.21-3.64), respectively. In conclusion, MH is as common in Nigerians as in other populations with older age and higher levels of office BP being major risk factors. A significant proportion of true hypertensive subjects therefore remains undetected based on office BP, which is particularly relevant in sub-Saharan Africa, where hypertension is now a major cause of death.status: publishe

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

BACKGROUND: Genetic factors play an important role in prostate cancer (PCa) susceptibility. OBJECTIVE: To discover common genetic variants contributing to the risk of PCa in men of African ancestry. DESIGN, SETTING, AND PARTICIPANTS: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness. RESULTS AND LIMITATIONS: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4). CONCLUSIONS: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry. PATIENT SUMMARY: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups