Achilleas Tsoumanis

The Global Epidemiology of Syphilis in the Past Century - A Systematic Review Based on Antenatal Syphilis Prevalence.

Background How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. Methods 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990–1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. Results In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3–5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990–1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Conclusions Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa.

Long-term Clinical Outcomes in Visceral Leishmaniasis/Human Immunodeficiency Virus–Coinfected Patients During and After Pentamidine Secondary Prophylaxis in Ethiopia: A Single-Arm Clinical Trial

We conducted a single-arm clinical trial in Ethiopian visceral leishmaniasis/HIV-coinfected patients using pentamidine secondary prophylaxis. The 2-year risk of relapse was 37%. Patients reaching a CD4 count >200 cells/µL after 12 months of prophylaxis can safely discontinue pentamidine.

HIV Prevalence Correlates with High-Risk Sexual Behavior in Ethiopia's Regions

Background HIV prevalence varies between 0.9 and 6.5% in Ethiopia’s eleven regions. Little has been published examining the reasons for this variation. Methods We evaluated the relationship between HIV prevalence by region and a range of risk factors in the 2005 and 2011 Ethiopian Demographic Health Surveys. Pearson’s correlation was used to assess the relationship between HIV prevalence and each variable. Results There was a strong association between HIV prevalence and three markers of sexual risk: mean lifetime number of partners (men: r = 0.87; P < 0.001; women: r = 0.60; P = 0.05); reporting sex with a non-married, non-cohabiting partner (men: r = 0.92; P < 0.001, women r = 0.93; P < 0.001); and premarital sex. Condom usage and HIV testing were positively associated with HIV prevalence, while the prevalence of circumcision, polygamy, age at sexual debut and male migration were not associated with HIV prevalence. Conclusion Variation in sexual behavior may contribute to the large variations in HIV prevalence by region in Ethiopia. Population-level interventions to reduce risky sexual behavior in high HIV incidence regions should be considered.

Partner concurrency and HIV infection risk in South Africa

BACKGROUND The relationship between concurrent sexual partnerships and HIV risk is not fully understood. Evidence on the relationship between partner concurrency (ones sexual partner has another partner) and individual HIV risk is limited. In this study, the relationship between reported sexual partner concurrency and the risk of HIV infection was explored among South Africans. METHODS Data from the third South African national HIV survey were used. In this survey, performed in 2008, questionnaires and HIV tests were administered to a nationally representative sample of 15031 persons. Bivariate analysis and multiple logistic regression were used to evaluate the relationship between partner concurrency and HIV serostatus. Spearmans correlation was used to test the association between the prevalence of HIV and partner concurrency by race in women. RESULTS The relationship between HIV prevalence and partner concurrency varied by race. At a cross-racial level there was a positive association between HIV prevalence and partner concurrency for women (rho=0.95, p=0.05). Among coloured, white, and Indian persons, HIV prevalence and partner concurrency rates were too low to allow further statistical testing. In the bivariate analysis, black African women who reported partner concurrency had a higher prevalence of HIV (36% (95% confidence interval (CI) 29.7-42.0) vs. 23% (95% CI 19.6-26.1), p<0.001). After controlling for demographic, social, biological, and behavioural variables, the association remained statistically significant (adjusted odds ratio (aOR) 1.4, p=0.04). The association was stronger among 15-29-year-old black African women (aOR 1.8, p=0.03) than among women aged 30 years and older (aOR 1.3, p=0.36). CONCLUSIONS These results suggest that partner concurrency may increase the HIV infection risk for black South African women, and in particular, for younger women.

Chikungunya virus infection in Aruba: Diagnosis, clinical features and predictors of post-chikungunya chronic polyarthralgia

Background Chikungunya virus (CHIKV) emerged in Aruba for the first time in 2014. We studied the clinical presentation of acute CHIKV infection and the contribution of serologic and molecular assays to its diagnosis. In a cohort of confirmed CHIKV cases, we analysed the frequency, duration and predictors of post-chikungunya chronic polyarthralgia (pCHIK-CPA), defined as joint pains lasting longer than 6 weeks or longer than 1 year. Methodology Patient sera obtained within 10 days of symptom onset were tested for CHIKV, using an indirect immunofluorescence test for the detection of CHIKV-specific Immunoglobulin M (IgM) and post-hoc, by reverse-transcription polymerase chain reaction (RT-PCR). CHIKV was isolated from selected samples and genotyped. For confirmed CHIKV cases, clinical data from chart review were complemented by a Telephone survey, conducted 18–24 months after diagnosis. When joint pain was reported, the duration, presence of inflammatory signs, type and number of joints affected, were recorded. Joint involvement was scored according to the 2010 ‘American College of Rheumatology/ European League Against Rheumatism’ criteria for seronegative rheumatoid arthritis (ACR-score). Risk factors for pCHIK-CPA were identified by logistic regression. Principal findings Acute CHIKV infection was diagnosed in 269 of 498 sera, by detection of IgM (n = 105), by RT-PCR (n = 59), or by both methods (n = 105). Asian genotype was confirmed in 7 samples. Clinical data were complete for 171 of 248 (69.0%) patients, aged 15 years or older (median 49.4 [35.0–59.6]). The female-to-male ratio was 2.2. The main acute symptoms were arthralgia (94%), fever (85%), myalgia (85%), headache (73%) and rash (63%). In patients with arthralgia (n = 160), pCHIK-CPA longer than 6 weeks was reported by 44% and longer than 1 year by 26% of cases. Inflammatory signs, stiffness, edema and redness were frequent (71%, 39% and 21%, respectively). Joints involved were knees (66%), ankles (50%), fingers (52%), feet (46%), shoulders (36%), elbows (34%), wrists (35%), hips (31%), toes (28.1%) and spine (28.1%). Independent predictors of pCHIK-CPA longer than 1 year were female gender (OR 5.9, 95%-CI [2.1–19.6]); high ACR-score (7.4, [2.7–23.3]), and detection of CHIKV-RNA in serum beyond 7 days of symptom onset (6.4, [1.4–34.1]. Conclusions We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014–2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.

Repeat syphilis has a different immune response compared with initial syphilis: an analysis of biomarker kinetics in two cohorts

Objective We aimed to asses if there are differences in the clinical presentation and immune response of repeat as compared with initial syphilis. Methods Prospective study: we prospectively recruited all patients with a new diagnosis of syphilis and tested their plasma for a range of cytochemokines and rapid plasma reagin (RPR) at baseline pretreatment and 6 months following therapy. Retrospective study: we compared RPR assay response kinetics between initial and repeat syphilis in persons attending our HIV/STI clinic from 1993 to 2016. Results Prospective study: a total of 91 individuals, 36 with initial syphilis and 55 with repeat syphilis, were included in the study. At baseline visit, those with initial syphilis were more likely to be symptomatic and have higher levels of interleukin-10 than repeaters. At baseline, median RPR titres were higher in the repeat than the initial infection groups. Repeaters were less likely than those with initial infections to serorevert to a negative RPR and be serofast (<4-fold RPR titre decline) at 6 months. Retrospective study: syphilis was diagnosed in 1027/43 870 individuals tested. At diagnosis, repeaters had higher RPR titres and a stepwise increase in RPR titre with number of syphilis episodes. They had a different RPR test response kinetic: they were less likely to be serofast and to serorevert than initial syphilis at 6 and 12 months. No individuals with four or more previous episodes of syphilis seroreverted. Conclusion Repeat syphilis has a different clinical presentation and immunological response to initial infection.

The Risk and Predictors of Visceral Leishmaniasis Relapse in Human Immunodeficiency Virus-Coinfected Patients in Ethiopia: A Retrospective Cohort Study

In East Africa, data on the risk and predictors of visceral leishmaniasis relapse in HIV coinfected patients are scarce. This study shows high risk of relapse, particularly in those not on antiretroviral therapy or with a high tissue parasite load.

Evaluation of an automated quantitative latex immunoturbidimetric non-treponemal assay for diagnosis and follow-up of syphilis: a prospective cohort study.

Purpose. We evaluated the Sekure rapid plasma reagin (RPR‐S) (Sekisui Diagnostics) automated quantitative latex immunoturbidimetric assay performed on the SK500 clinical chemistry system for clinical appropriateness. Methodology. Syphilis‐infected individuals and controls were recruited into a prospective cohort study conducted at a sexually transmitted infection clinic in Antwerp, Belgium. Sera collected at diagnosis (baseline) and at 3, 6, 9 and 12 months post‐treatment were tested with RPR‐S and Macro‐Vue RPR card (RPR‐C) (Becton Dickinson) assays; RPR‐C was considered the reference test. IgG/IgM enzyme immunoassay and Treponema pallidum polA serum PCR results were consulted by discordancy at baseline. Categorical analyses were performed and correlations were assessed with (non)‐linear regression. Post‐treatment longitudinal serological evolution was evaluated. Results. A total of 463 samples from 120 new syphilis cases from a variety of clinical stages and 30 syphilis‐negative controls were tested. Initially, there was a weak correlation between quantitative RPR‐C/S (r=0.15). In 70 samples there was a strong suspicion of hook effect. Of these, 57/70 sera were retested with an extra dilution step, resulting in an average 12‐fold increase in quantitative RPR‐S results. After the extra dilution, the overall qualitative RPR‐C/S agreement was 78.89%, (&kgr;‐coefficient: 0.484). Of the 92 discordant samples, 9 were from the baseline visit (RPR‐C titre: 1‐8), which could have led to possible missed diagnoses using the RPR‐S. Conclusions. The sensitivity and accuracy of the RPR‐S test requires improvement before it can be used to diagnose syphilis and evaluate treatment efficacy in clinical practice.

Strong Country Level Correlation between Syphilis and HSV-2 Prevalence

Background. Syphilis is curable but Herpes Simplex Virus-2 (HSV-2) is not. As a result, the prevalence of syphilis but not HSV-2 may be influenced by the efficacy of national STI screening and treatment capacity. If the prevalence of syphilis and HSV-2 is found to be correlated, then this makes it more likely that something other than differential STI treatment is responsible for variations in the prevalence of both HSV-2 and syphilis. Methods. Simple linear regression was used to evaluate the relationship between national antenatal syphilis prevalence and HSV-2 prevalence in women in two time periods: 1990–1999 and 2008. Adjustments were performed for the laboratory syphilis testing algorithm used and the prevalence of circumcision. Results. The prevalence of syphilis was positively correlated with that of HSV-2 for both time periods (adjusted correlations, 20–24-year-olds: 1990–99: R 2 = 0.54, P < 0.001; 2008: R 2 = 0.41, P < 0.001 and 40–44-year-olds: 1990–99: R 2 = 0.42, P < 0.001; 2008: R 2 = 0.49, P < 0.001). Conclusion. The prevalence of syphilis and HSV-2 is positively correlated. This could be due to a common set of risk factors underpinning both STIs.

A cross-sectional analysis of Zika virus infection in symptomatic and asymptomatic non-pregnant travellers: Experience of a European reference center during the outbreak in the Americas

BACKGROUND Zika virus (ZIKV) infection a concern to travellers because of potential sexual transmission and adverse pregnancy outcomes. OBJECTIVE To describe our experience in diagnosing ZIKV in travellers returning from endemic territories. METHOD Travellers were evaluated for ZIKV at our clinic in a 12-month period during the outbreak, using ZIKV-specific RT-PCR and anti-ZIKV Immunoglobulin M/G ELISA when symptomatic, and ELISA only for asymptomatic travellers, preferably from 20 days after the last exposure. All positive ELISA results were subject to confirmation by Virus Neutralization Testing. We estimated post-test probabilities of ZIKV in asymptomatic travellers. RESULTS Of 462 travellers, 227 reported symptoms and 235 did not. Asymptomatic travellers had similar baseline characteristics, but were younger (median age 31 vs. 33 years, p = 0.01) and had reproductive concerns more often (75.8% vs. 24.2%). ZIKV infection was confirmed in 49 cases: 46/227 (20.3%) were symptomatic and 3/235 (1.3%) asymptomatic. Rash (positive likelihood ratio (LRP) 5.6) and conjunctivitis (LRP 10.8) predicted ZIKV infection. The post-test probability of a negative ELISA-result at 20-25 days was below 0.1%. CONCLUSION ZIKV infection was frequent in symptomatic, but not in asymptomatic travellers. We consider negative ELISA results at 20-25 days after exposure a safe strategy to rule out ZIKV infection. Testing for ZIKV-specific antibodies within this timeframe could be particularly valuable in the management of returning travellers who wish to conceive.