All-oral direct-acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV-coinfected subjects in real-world practice: Madrid coinfection registry findings.

We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients treated with interferon-free direct-acting antiviral agent-based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%-93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12-2.41), a baseline cluster of differentiation 4-positive (CD4+) T-cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. CONCLUSION: In this large real-world study, direct-acting antiviral agent-based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus-related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct-acting antiviral agent-based regimens. (Hepatology 2018;68:32-47).

The Maritime Declaration of Health (MDH) as a tool to detect maritime traffic-related health risks: analysis of MDH forms submitted to Spanish ports, October 2014 to March 2015.

The international maritime traffic of people and goods has often contributed to the spread of pathogens affecting public health. The Maritime Declaration of Health (MDH), according to the International Health Regulations (IHR) (2005), is a document containing data related to the state of health on board a ship during passage and on arrival at port. It is a useful tool for early detection of public health risks. The main objective of our study was to evaluate compliance with the model provided in the IHR, focusing on the format and degree of completion of MDH forms received at Spanish ports. We reviewed the content of 802 MDH forms submitted to nine Spanish ports between October 2014 and March 2015. Study results show that 22% of MDH forms presented did not comply with the recommended model and 39% were incomplete. The proportion of cargo ships with correct and complete MDH forms was lower than passenger ships; thus, the nine health questions were answered less frequently by cargo ships than passenger ships (63% vs 90%, p value < 0.001). The appropriate demand and usage of MDH forms by competent authorities should improve the quality of the document as a tool and improve risk assessment.

Effectiveness and economic analysis of the whole cell/recombinant B subunit (WC/rbs) inactivated oral cholera vaccine in the prevention of traveller's diarrhoea.

BACKGROUND: Nowadays there is a debate about the indication of the oral whole-cell/recombinant B-subunit cholera vaccine (WC/rBS) in traveller's diarrhoea. However, a cost-benefit analysis based on real data has not been published. METHODS: A cost-effectiveness and cost-benefit study of the oral cholera vaccine (WC/rBS), Dukoral for the prevention of traveller's diarrhoea (TD) was performed in subjects travelling to cholera risk areas. The effectiveness of WC/rBS vaccine in the prevention of TD was analyzed in 362 travellers attending two International Vaccination Centres in Spain between May and September 2005. RESULTS: The overall vaccine efficacy against TD was 42,6%. Direct healthcare-related costs as well as indirect costs (lost vacation days) subsequent to the disease were considered. Preventive vaccination against TD resulted in a mean saving of 79.26 euro per traveller. CONCLUSION: According to the cost-benefit analysis performed, the recommendation for WC/rBS vaccination in subjects travelling to zones at risk of TD is beneficial for the traveller, regardless of trip duration and visited continent.

Reinfection by hepatitis C virus following effective all-oral direct-acting antiviral drug therapy in HIV/hepatitis C virus coinfected individuals.

OBJECTIVES: We analysed hepatitis C virus (HCV) reinfection among participants in a prospective registry of HIV/HCV-coinfected patients treated with all-oral direct-acting antiretroviral (DAA)-based therapy in the region of Madrid. DESIGN: An observational cohort study. METHODS: The study period started on the date sustained viral response (SVR) was confirmed. The censoring date was 31 December 2017. SVR was defined as negative HCV-RNA 12 weeks after completion of treatment. Reinfection was defined as a positive HCV-RNA test result after achievement of SVR. RESULTS: Reinfections were detected in 17 of 2359 HIV/HCV-coinfected patients (0.72%) overall, in 12 out of 177 (6.78%) MSM and in five out of 1459 (0.34%) people who inject drugs (PWID). The incidence of reinfection [95% confidence interval (95% CI)] per 100 person-years was 0.48 (0.30-0.77) overall, 5.93 (3.37-10.44) for MSM and 0.21 (0.09-0.52) for PWID. Reinfections were detected a median of 15 weeks (interquartile range 13-26) after SVR. In 10 (58.82%) patients, the reinfection was caused by a different HCV genotype. All 12 MSM with reinfection acknowledged unprotected anal intercourse with several partners, seven used chemsex, six reported fisting and four practiced slamming. A concomitant STI was detected in five patients. Four IDU with reinfection reported injecting drugs following SVR. CONCLUSION: HCV reinfection is a matter of concern in HIV-positive MSM treated with all-oral DAA therapy in the region of Madrid. Our data suggest that prevention strategies and frequent testing with HCV-RNA should be applied following SVR in MSM who engage in high-risk practices.

HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1.

BACKGROUND: The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)-monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. METHODS: We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. RESULTS: Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27-4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13-4.38; P = .020). CONCLUSIONS: The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.

[Transverse vaginal septum diagnosed in sisters. Cases report]. / Tabique vaginal transverso diagnosticado en dos hermanas. Reporte de dos casos.

Transverse vaginal septum is a disorder that would arise from a failure in the fusion and/or channeling of the urogenital sinus and the müllerian ducts with low frequency but with a significant impact on the health of patients. The treatment is surgical and it will depend on the location and thickness of the septum. Sometimes, it described a female sex-limited autosomal recessive transmission but few cases of family association have been reported. We present the cases of two sisters who had this rare entity 5 years apart and were diagnosed by the presentation of an intense hypogastric abdominal pain at the age of 11 and 12 years when they had a Tanner stage III pubertal development and primary amenorrhea.

El tabique vaginal transverso es una anomalía que se originaría por un fracaso en la fusión y/o canalización del seno urogenital y de los conductos müllerianos con baja frecuencia, pero con un importante impacto en la salud de las pacientes que lo presentan. El tratamiento es quirúrgico y la vía de abordaje depende de la localización y del espesor del tabique. En ocasiones, se ha relacionado con una herencia que podría ser recesiva asociada al sexo, pero se han documentado pocos casos de asociación familiar. Se exponen los casos de dos hermanas que presentaron esta rara entidad con 5 años de diferencia y que se diagnosticaron por la aparición de dolor abdominal hipogástrico intenso a la edad de 11 y 12 años, cuando presentaban un desarrollo puberal estadio III de Tanner y amenorrea primaria.

Effectiveness of the WC/rBS oral cholera vaccine in the prevention of traveler's diarrhea: a prospective cohort study.

OBJECTIVE: Traveler's diarrhea (TD) is the most frequent disease among people from industrialized countries who travel to less developed ones, especially sub-Saharan Africa, Southern Asia and South America. The most common bacteria causing TD is enterotoxigenic Escherichia coli (ETEC). The WC/rBS cholera vaccine (Dukoral) has been shown to induce cross-protection against ETEC by means of the B subunit of the cholera toxin. The aim of the study was to evaluate the effectiveness of the WC/rBS cholera vaccine in preventing TD. METHODS: Between May 1 and September 30 (2007), people seeking pre-travel advice in ten Spanish international vaccination centers were included in a prospective cohort study of travelers to cholera risk countries. The incidence rates of TD were adjusted for variables whose frequencies were statistically different (entry point 0.10) between the vaccinated and non-vaccinated cohorts. FINDINGS: The vaccinated cohort (n = 544 travelers) included people vaccinated with the WC/rBS cholera vaccine, and the non-vaccinated cohort (n = 530 travelers) by people not vaccinated. The cumulative incidence rate of TD was 1.69 in vaccinated and 2.14 in non-vaccinated subjects. The adjusted relative risk of TD in vaccinated travelers was 0.72 (95% CI: 0.58-0.88) and the adjusted vaccination effectiveness was 28% (95% CI: 12-42). CONCLUSIONS: The WC/rBS cholera vaccine prevents TD in 2 out of 7 travelers (preventive fraction: 28%). The number needed to vaccinate (NNV) to prevent 1 case of TD is 10.

Tabique vaginal transverso diagnosticado en dos hermanas: Reporte de dos casos / Transverse vaginal septum diagnosed in sisters: Cases report

El tabique vaginal transverso es una anomalía que se originaría por un fracaso en la fusión y/o canalización del seno urogenital y de los conductos müllerianos con baja frecuencia, pero con un importante impacto en la salud de las pacientes que lo presentan. El tratamiento es quirúrgico y la vía de abordaje depende de la localización y del espesor del tabique. En ocasiones, se ha relacionado con una herencia que podría ser recesiva asociada al sexo, pero se han documentado pocos casos de asociación familiar. Se exponen los casos de dos hermanas que presentaron esta rara entidad con 5 años de diferencia y que se diagnosticaron por la aparición de dolor abdominal hipogástrico intenso a la edad de 11 y 12 años, cuando presentaban un desarrollo puberal estadio III de Tanner y amenorrea primaria.

Transverse vaginal septum is a disorder that would arise from a failure in the fusion and/or channeling of the urogenital sinus and the müllerian ducts with low frequency but with a significant impact on the health of patients. The treatment is surgical and it will depend on the location and thickness of the septum. Sometimes, it described a female sex-limited autosomal recessive transmission but few cases of family association have been reported. We present the cases of two sisters who had this rare entity 5 years apart and were diagnosed by the presentation of an intense hypogastric abdominal pain at the age of 11 and 12 years when they had a Tanner stage III pubertal development and primary amenorrhea.

Vaccination strategies to combat an infectious globe: oral cholera vaccines.

Cholera is a substantial health burden in many countries in Africa and Asia, where it is endemic. It is as well responsible for ongoing epidemics in sub-Saharan Africa which are becoming greater in terms of frequency, extension, and duration. Given the availability of two oral cholera vaccines and the new data on their efficacy, field effectiveness, feasibility, and acceptance in cholera-affected populations and in travelers, these vaccines should be used in endemic areas, in travelers for these areas and should be considered in areas at risk for outbreaks. The two vaccines currently available in worldwide are: (1) The killed oral vaccine (Dukoral, licensed by SBL-Sweden to Crucell-Holland) is recommended since 1999 by WHO and consists of a mixture of four preparations of heat or formalin killed whole cell Vibrio cholera O1 (Inaba and Ogaba serotypes, and classical and El Tor biotypes) that are then added with purified recombinant cholera toxin (CT) B subunit. Because CT cross-reacts with Escherichia coli LT the vaccine also provides short-term protection against ETEC (enterotoxigenic E. coli) which is of added benefit for travelers. It is available in more than 60 countries. (2) A bivalent O1 and O139 whole cell oral vaccine without CT B subunit (Shanchol) has been lately developed in Vietnam (licensed by VaBiotech-Viet Nam to Shantha Biotechnics-India. It is available in India and Indonesia. A structured search of papers in PubMed and reports on cholera vaccines by WHO and CDC, as well as critical reading and synthesis of the information was accomplished. Inclusion criteria were defined according to reports quality and relevance.