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Understanding the drivers of infection risk helps us to detect the most at-risk species in a community and identify species whose intrinsic characteristics could act as potential reservoirs of pathogens. This knowledge is crucial if we are to predict the emergence and evolution of infectious diseases. To date, most studies have only focused on infections caused by a single parasite, leaving out co-infections. Yet, co-infections are of paramount importance in understanding the ecology and evolution of host-parasite interactions due to the wide range of effects they can have on host fitness and on the evolutionary trajectories of parasites. Here, we used a multinomial Bayesian phylogenetic modelling framework to explore the extent to which bird ecology and phylogeny impact the probability of being infected by one genus (hereafter single infection) or by multiple genera (hereafter co-infection) of haemosporidian parasites. We show that while nesting and migration behaviours influenced both the probability of being single- and co-infected, species position along the slow-fast life-history continuum and geographic range size were only pertinent in explaining variation in co-infection risk. We also found evidence for a phylogenetic conservatism regarding both single- and co-infections, indicating that phylogenetically related bird species tend to have similar infection patterns. This phylogenetic signal was four times stronger for co-infections than for single infections, suggesting that co-infections may act as a stronger selective pressure than single infections. Overall, our study underscores the combined influence of hosts' evolutionary history and attributes in determining infection risk in avian host communities. These results also suggest that co-infection risk might be under stronger deterministic control than single infection risk, potentially paving the way toward a better understanding of the emergence and evolution of infectious diseases.

International audience; The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 continues to have a major impact on healthcare and social systems throughout the world. As the clinical and epidemiological features of COVID-19 have many parallels with influenza, it is important to ensure optimal management of both respiratory diseases as we anticipate their continued co-circulation. In particular, there is a need to ensure that effective surveillance and diagnostic capacities are in place to monitor these and other respiratory viruses, as this will underpin decisions on the appropriate clinical management of the respective diseases. As such, we propose a series of key recommendations for stakeholders, public health authorities, primary care physicians and surveillance bodies that will help mitigate the combined risks of concurrent influenza epidemics and the COVID-19 pandemic. We advocate the judicious use of influenza vaccines and antivirals, particularly among groups at high risk of complications, with healthcare workers also considered a priority for vaccination. It is likely that the increased use of emerging technologies such as telemedicine and contact tracing will permanently change our approach to managing infectious disease. The use of these technologies, alongside existing pharmaceutical strategies, will ensure that we achieve a holistic approach to the global public health measures needed to deal with the combined threat of influenza and COVID-19. Ensuring that this approach is optimal will be key as we move from a reactive pandemic response towards preparing for the long-term management of the remarkable clinical burden associated with these respiratory pathogens.

Schistosomiasis is a parasitic infection highly prevalent in Central Africa where it is co-endemic with many other parasitic infections, including soil-transmitted helminths (STHs). For its optimal control, there is a need of descriptive epidemiological data for each endemic region. The objective of the present study was to determine the epidemiological situation around schistosomiasis in Lambaréné, Gabon. A cross-sectional study was conducted among schoolchildren. One urine sample per day was collected on three consecutive days for the diagnosis of schistosomiasis using a urine filtration technique. One stool sample was collected for the detection of Schistosoma spp. and STH spp. eggs using the Kato-Katz technique, and for larvae, using the coproculture technique. A total of 614 schoolchildren were included in the analysis. The overall prevalence of schistosomiasis and STH infections was 26% (159/614) and 15% (70/473), respectively. Human-freshwater contact was the main risk factor for schistosomiasis in the area (relative risk (RR) = 2.96 [2.20-4.00], P < 0.001). Hematuria (RR = 5.53 [4.30-7.10], P < 0.001) and proteinuria (RR = 2.12 [1.63-2.75], P < 0.001) as well as infection with Trichuris trichiura (RR = 1.86 [1.33-2.61], P = 0.002) and Ascaris lumbricoides (RR = 1.96 [1.19-3.21], P = 0.039) were associated with an increased risk of schistosomiasis. Trichuris trichiura was the highest prevalent STH species in the area. Our study reports a moderate prevalence for schistosomiasis with human-water contact as the main risk factor, whereas the prevalence of STH infections appears to be low. Our results stress the need for the implementation of WHO recommendations for schistosomiasis control.

Epidemiology; HIV/HCV coinfection; Spain Epidemiologia; Coinfecció pel VIH/VHC; Espanya Epidemiologia; Coinfección por el VIH/VHC; España Objectives We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015–2018. Methods The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population. This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.

We evaluated the rates of viral respiratory co-infections among SARS-CoV-2-infected children. Twelve percent of SARS-CoV-2-infected children had viral co-infection with one or more common respiratory viruses. This was significantly more frequent than among their SARS-CoV-2-infected adult household contacts (0%; p=0.028). Compared to the same period the previous year, common respiratory viruses were less frequently detected (12% vs 73%, pConclusion: Despite partial lockdown with school and daycare closure, and consequently similar exposure to common viruses between children and adults, SARS-CoV-2-infected children had more frequent viral respiratory co-infections than their SARS-CoV-2-infected adult household contacts. Circulation of common respiratory viruses was less frequent during the SARS-CoV-2 outbreak when compared to the same period last year, showing the impact of partial lockdown on the circulation of common viruses. What is Known:• Viral respiratory co-infections are frequent in children.• SARS-CoV-2 can be identified alongside other respiratory viruses, but data comparing children and adults are lacking. What is New:• Children infected with SARS-CoV-2 are more likely to have viral respiratory co-infections than their SARS-CoV-2-infected adult household contacts, which is surprising in the context of partial lockdown with schools and daycare closed.• When compared to data collected during the same period last year, our study also showed that partial lockdown reduced circulation of common respiratory viruses.

BACKGROUND: The impact of SARS-CoV-2 in regions endemic for both Dengue and Chikungunya is still not fully understood. Considering that symptoms/clinical features displayed during Dengue, Chikungunya and SARS-CoV-2 acute infections are similar, undiagnosed cases of SARS-CoV-2 in co-endemic areas may be more prevalent than expected. This study was conducted to assess the prevalence of covert cases of SARS-CoV-2 among samples from patients with clinical symptoms compatible with either Dengue or Chikungunya viral infection in the state of Espírito Santo, Brazil. METHODS: Presence of immunoglobulin G (IgG) antibody specific to SARS-CoV-2 nucleoprotein was detected using a chemiluminescent microparticle immunoassay in samples from 7,370 patients, without previous history of COVID-19 diagnosis, suspected of having either Dengue (n = 1,700) or Chikungunya (n = 7,349) from December 1st, 2019 to June 30th, 2020. FINDINGS: Covert cases of SARS-CoV-2 were detected in 210 (2.85%) out of the 7,370 serum samples tested. The earliest undiagnosed missed case of COVID-19 dated back to a sample collected on December 18, 2019, also positive for Dengue Virus. Cross-reactivity with either Dengue virus or other common coronaviruses were not observed. INTERPRETATION: Our findings demonstrate that concomitant Dengue or Chikungunya outbreaks may difficult the diagnosis of SARS-CoV-2 infections. To our knowledge, this is the first study to demonstrate, with a robust sample size (n = 7,370) and using highly specific and sensitive chemiluminescent microparticle immunoassay method, that covert SARS-CoV-2 infections are more frequent than previously expected in Dengue and Chikungunya hyperendemic regions. Moreover, our results suggest that SAR-CoV-2 cases were occurring prior to February, 2020, and that these undiagnosed missed cases may have contributed to the fast expansion of SARS-CoV-2 outbreak in Brazil. Data presented here demonstrate that in arboviral endemic regions, SARS-CoV-2 infection must be always considered, regardless of the existence of a previous positive diagnosis for Dengue or Chikungunya. publishersversion published

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of, Guidelines on LTBI for low TB incidence countries – essential element of the @WHO #EndTB strategy and TB elimination http://ow.ly/RW8xn

Diarrheal disease is the second most frequent cause of mortality in children younger than 5 years worldwide, causing more than half a million deaths each year. Our knowledge of the epidemiology of potentially pathogenic agents found in children suffering from diarrhea in sub-Saharan African countries is still patchy, and thereby hinders implementation of effective preventative interventions. The lack of cheap, easy-to-use diagnostic tools leads to mostly symptomatic and empirical case management. An observational study with a total of 241 participants was conducted from February 2017 to August 2018 among children younger than 5 years with diarrhea in Lambaréné, Gabon. Clinical and demographic data were recorded, and a stool sample was collected. The samples were examined using a commercial rapid immunoassay to detect Rotavirus/adenovirus, conventional bacterial culture for Salmonella spp., and multiplex real-time PCR for Cryptosporidium spp., Giardia lamblia, Cyclospora cayetanensis, enterotoxigenic Escherichia coli (ETEC), and enteroinvasive Escherichia coli (EIEC)/Shigella. At least one infectious agent was present in 121 of 241 (50%) samples. The most frequently isolated pathogens were EIEC/Shigella and ETEC (54/179; 30.2% and 44/179; 24.6%, respectively), followed by G. lamblia (33/241; 13.7%), Cryptosporidium spp. (31/241; 12.9%), and Rotavirus (23/241; 9.5%). Coinfection with multiple pathogens was observed in 33% (40/121) of the positive cases with EIEC/Shigella, ETEC, and Cryptosporidium spp. most frequently identified. Our results provide new insight into the possible causes of diarrheal disease in the Moyen-Ogooué region of Gabon and motivate further research on possible modes of infection and targeted preventive measures.

Background Although the incidence of dengue across Africa is high, severe dengue is reported infrequently. We describe the clinical features and the outcome of dengue according to raceduring an outbreak in Dar es Salaam, Tanzania that occurred in both native and expatriate populations. Methods Adults with confirmed dengue (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) were included between December 2013 and July 2014 in outpatient clinics. Seven-day outcome was assessed by a visit or a call. Association between black race and clinical presentation, including warning signs, was assessed by logistic regression adjusted for age, malaria coinfection, secondary dengue and duration of symptoms at inclusion. The independent association between demographic and comorbidities characteristics of the patients and severe dengue was evaluated by multivariate logistic regression that included potential confounders. Results After exclusion of 3 patients of mixed race, 431 patients with dengue (serotype 2, genotype Cosmopolitan) were included: 241 of black and 190 of non-black race. Black patients were younger (median age 30 versus 41 years; p

Background Men who have sex with men (MSM) and male-to-female transgender women (transwomen) are disproportionately at risk of syphilis infection in Peru. Methods From 2013 to 2014, MSM and transwomen seeking human immunodeficiency virus (HIV) or sexually transmitted infection (STI) testing and/or treatment were recruited into a 2-year observational cohort study to determine predictors of recently acquired syphilis infection (defined as a rapid plasma reagin [RPR] titer ≥1:16 and a reactive treponemal antibody test) in Lima, Peru. At baseline, interviewers collected sociodemographic, behavioral, and medical characteristics from participants. All cohort participants were tested for syphilis, HIV, Chlamydia trachomatis (CT), and Neisseria gonorrhoeae (NG) infection. Using cross-sectional analyses, bivariate and multivariate models were used to determine factors associated with recently acquired syphilis infection and calculate adjusted prevalence ratios. Results We recruited 401 participants, 312 MSM and 89 transwomen, with median ages of 29.0 and 32.5 years old (interquartile ranges: 23.3, 37.4 and 27.2, 39.5, respectively). The prevalence of recently acquired syphilis infection at baseline was 16.8% for MSM and 6.7% for transwomen. Among MSM and transwomen, 30.1 and 33.7% were infected with HIV, 18.6 and 24.7% were infected with CT, and 14.2 and 19.1% were infected with NG, respectively. Co-infection rates among MSM with recently acquired syphilis infection included: 44.2% with HIV, 40.4% with CT (32.7% with anal CT and 7.7% with pharyngeal CT), and 19.2% with NG (11.5% with anal NG and 7.7% with pharyngeal NG). Co-infection rates among transwomen with recently acquired syphilis infection included: 66.7% with HIV, 0% with CT, and 16.7% with anal NG. In multivariate analysis among the entire cohort, recently acquired syphilis infection was independently associated with younger age (adjusted prevalence ratio [aPR] = 0.96, 95% confidence interval [CI] = 0.93–0.99), receptive role during anal sex (aPR = 2.56, 95% CI = 1.05–6.25), prior HIV diagnosis (aPR = 1.70, 95% CI = 1.11–2.61), anal CT or NG infection (aPR = 1.69, 95% CI = 1.09–2.60), and prior syphilis diagnosis (aPR = 3.53, 95% CI = 2.20–5.68). Conclusions We recruited a cohort of MSM and transwomen who had a high prevalence of recently acquired syphilis infection in Lima, Peru. Recently acquired syphilis infection was associated with socio-demographic characteristics, sexual risk, and sexually transmitted co-infections.

Background: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Item does not contain fulltext AIM: To retrospectively investigate the epidemiology of cryptococcosis in Ljubljana, Slovenia. METHODOLOGY: Forty-six sequentially obtained isolates from 19 patients were subjected to amplified fragment length polymorphism (AFLP) genotyping, microsatellite typing, mating- and serotype PCRs and antifungal susceptibility testing. RESULTS: Majority of the isolates were Cryptococcus deneoformans (n = 29/46; 63%) followed by Cryptococcus neoformans (n = 16/46; 34.8%) and their interspecies hybrid (n = 1/46; 2.2%). Mating-type alpha was predominant, two mating-type a C. deneoformans isolates and one mating-type a/alpha isolate were observed. Several mixed infections were found by microsatellite typing; one patient had a persisting C. deneoformans infection for > 2.5 years. For C. deneoformans, the in vitro antifungal MIC90 and susceptibility ranges were for amphotericin B 0.25 microg/ml (0.031-0.25 microg/ml), 5-fluorocytosine 0.25 microg/ml (0.063-4 microg/ml), fluconazole 8 microg/ml (0.5-16 microg/ml), voriconazole 0.063 microg/ml (0.008-0.125 microg/ml), posaconazole 0.063 microg/ml (0.008-0.063 microg/ml) and itraconazole 0.063 microg/ml (0.031-0.125 microg/ml). For C. neoformans, these values were for amphotericin B 0.25 microg/ml (0.063-0.5 microg/ml), 5-fluorocytosine 1 microg/ml (0.063-1 microg/ml), fluconazole 16 microg/ml (0.5-64 microg/ml), voriconazole 0.125 microg/ml (0.008-0.25 microg/ml), posaconazole 0.063 microg/ml (0.008-0.063 microg/ml) and itraconazole 0.063 microg/ml (0.031-0.125 microg/ml). CONCLUSIONS: Majority of the cases were caused by C. deneoformans; mating-type alpha was predominant. Several mixed infections were identified by AFLP genotyping and microsatellite typing. Despite antifungal therapy, a cryptococcal isolate could persist for years. Voriconazole, itraconazole and posaconazole were the most potent antifungal drugs.

Clinical experience suggests that a high proportion of orthopaedic infections occur in persons with diabetes.We reviewed several databases of adult patients hospitalized for orthopaedic infections at Geneva University Hospitals from 2004 to 2014 and retrieved 2740 episodes of infection.Overall, diabetes was noted in the medical record for 659 (24%) of these cases. The patients with, compared with those without, diabetes had more than five times more foot infections (274/659 [42%] vs 155/2081 [7%]; p0.01) and a significantly higher serum C-reactive protein level at admission (median 96 vs 70 mg/L; p0.01). Diabetic patients were older (median 67 vs 52 years; p0.01), more often male (471 [71%] vs 1398 [67%]; p = 0.04), and had more frequent polymicrobial infections (219 [37%] vs 353 [19%]; p0.01), including more gram-negative non-fermenting rods (90 [15%] vs 168 [9%]; p0.01). Excluding foot infections from these analyses did not change the statistically significant differences. Diabetes was present in 17% of all infected orthopaedic patients without foot involvement. In Geneva canton, the overall prevalence of diabetes is estimated at 5.1%, while we have found that the prevalence is 13% in our hospitalized adults.Diabetes is present in 24% of all adult patients hospitalized for surgery for an orthopaedic infection, a prevalence that is several times higher than for the general population and twice as high as that for the population of hospitalized patients. Compared with non-diabetics, patients with diabetes have significantly more infections that are polymicrobial, including gram-negative non-fermenting rods.

In malaria patients admitted to the study hospital, the likelihood of a co-diagnosis decreased with an increasing parasite count. In malaria-endemic settings, parasite densities provide important information for patient management, in particular for antimicrobial medication., Background The epidemiology of pediatric febrile illness is shifting in sub-Saharan Africa, but malaria remains a major cause of childhood morbidity and mortality. The present study describes causes of febrile illness in hospitalized children in Ghana and aims to determine the burden of malaria coinfections and their association with parasite densities. Methods In a prospective study, children (aged ≥30 days and ≤15 years) with fever ≥38.0°C were recruited after admission to the pediatric ward of a primary hospital in Ghana. Malaria parasitemia was determined and blood, stool, urine, respiratory, and cerebrospinal fluid specimens were screened for parasitic, bacterial, and viral pathogens. Associations of Plasmodium densities with other pathogens were calculated. Results From November 2013 to April 2015, 1238 children were enrolled from 4169 admissions. A clinical/microbiological diagnosis could be made in 1109/1238 (90%) patients, with Plasmodium parasitemia (n = 728/1238 [59%]) being predominant. This was followed by lower respiratory tract infections/pneumonia (n = 411/1238 [34%]; among detected pathogens most frequently Streptococcus pneumoniae, n = 192/299 [64%]), urinary tract infections (n = 218/1238 [18%]; Escherichia coli, n = 21/32 [66%]), gastrointestinal infections (n = 210 [17%]; rotavirus, n = 32/97 [33%]), and invasive bloodstream infections (n = 62 [5%]; Salmonella species, n = 47 [76%]). In Plasmodium-infected children the frequency of lower respiratory tract, gastrointestinal, and bloodstream infections increased with decreasing parasite densities. Conclusions In a hospital setting, the likelihood of comorbidity with a nonmalarial disease is inversely correlated with increasing blood levels of malaria parasites. Hence, parasite densities provide important information as an indicator for the probability of coinfection, in particular to guide antimicrobial medication.

Background We assessed the prevalence of antibodies against hepatitis C virus (HCV-Abs) and active HCV infection in patients infected with human immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those of similar studies performed in 2002, 2009, and 2015. Methods The study was performed in 43 centers during October–November 2016. The sample was estimated for an accuracy of 2% and selected by proportional allocation and simple random sampling. During 2016, criteria for therapy based on direct-acting antiviral agents (DAA) were at least significant liver fibrosis, severe extrahepatic manifestations of HCV, and high risk of HCV transmissibility. Results The reference population and the sample size were 38904 and 1588 patients, respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%, 50.2%, 37.7%, and 34.6%, respectively (P trend Conclusions Our findings suggest that with universal access to DAA-based therapy and continued efforts in prevention and screening, it will be possible to eliminate active HCV among HIV-infected individuals in Spain in the short term. However, the burden of HCV-related cirrhosis will continue to be significant among HIV-infected individuals.

Background & Aims Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. We assessed the epidemiological characteristics of HDV infection in the nationwide Swiss HIV Cohort Study and evaluated its impact on clinical outcomes. Methods All HIV-infected patients with a positive hepatitis B surface antigen test were considered and tested for anti-HDV antibodies. HDV amplification and sequencing were performed in anti-HDV-positive patients. Demographic and clinical characteristics at initiation of antiretroviral therapy, as well as causes of death were compared between HDV-positive and HDV-negative individuals using descriptive statistics. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate the association between HDV infection and overall mortality, liver-related mortality as well as incidence of hepatocellular carcinoma (HCC). Results Of 818 patients with a positive hepatitis B surface antigen tests, 771 (94%) had a stored serum sample available and were included. The prevalence of HDV infection was 15.4% (119/771, 95% CI: 12.9–18.0) and the proportion of HDV-positive patients with HDV replication 62.9% (73/116). HDV-infected patients were more likely to be persons who inject drugs (60.6% vs. 9.1%) and to have a positive hepatitis C virus (HCV) serology (73.1% vs. 17.8%) compared to HDV-uninfected ones. HDV infection was strongly associated with overall death (adjusted hazard ratio 2.33, 95% CI 1.41–3.84), liver-related death (7.71, 3.13–18.97) and with the occurrence of HCC (9.30, 3.03–28.61). Results were similar when persons who inject drugs or HCV-coinfected patients were excluded from the analyses. Conclusions The prevalence of HDV in hepatitis B surface antigen-positive patients in the Swiss HIV Cohort Study (SHCS) is high and HDV infection is independently associated with mortality and liver-related events, including HCC. Lay summary Hepatitis delta virus (HDV) infection accelerates the progression of hepatitis B virus (HBV)-related liver disease. In a nationwide cohort of HIV-infected individuals in Switzerland, 15% of HBV-coinfected patients had antibodies to HDV infection, of which a majority had active HDV replication. HDV-infected individuals were 2.5 times more likely to die, eight times more likely to die from a liver-related cause and nine times more likely to develop liver cancer compared to HDV-uninfected ones. Our results emphasize the need for prevention programs (including HBV vaccination), the systematic screening of at risk populations as well as close monitoring, and underline the importance of developing new treatments for chronic HDV infection.

[Abstract] The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation. Instituto de Salud Carlos III; CPII14/00014 Instituto de Salud Carlos III; PI10/02166 Instituto de Salud Carlos III; PI13/02266 Instituto de Salud Carlos III; CM15/00233 Instituto de Salud Carlos III; FI14/00557

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

The prevalence of HCV coinfection in HIV-infected individuals in Spain has decreased significantly in the last decade. Patients with active HCV infection mainly have genotypes 1a and 4, and a high percentage have liver cirrhosis., Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.

Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.

In an active diarrhea surveillance study of children aged 12-24 months in Lima, Peru, norovirus was the most common pathogen identified. The percentage of mixed (bacterial and noroviral) infections was significantly higher among norovirus-positive samples (53%) than among norovirus-negative samples (12%). The combination of norovirus with the most common bacterial pathogens was associated with increased clinical severity over that of either single-pathogen norovirus or single-pathogen bacterial infections.

The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness for the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalised rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95%[95% CI:77.5-98.7]. Against G2P[4], the vaccine effectiveness was 85%[CI:63.7-93.8]. G4P[8]- and G3P[8]-specific vaccine effectiveness was 90%[CI:19.2-98.7] and 87%[CI:-5.2-98.4], respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (P

Background Results from cohort studies evaluating the severity of respiratory viral co-infections are conflicting. We conducted a systematic review and meta-analysis to assess the clinical severity of viral co-infections as compared to single viral respiratory infections. Methods We searched electronic databases and other sources for studies published up to January 28, 2013. We included observational studies on inpatients with respiratory illnesses comparing the clinical severity of viral co-infections to single viral infections as detected by molecular assays. The primary outcome reflecting clinical disease severity was length of hospital stay (LOS). A random-effects model was used to conduct the meta-analyses. Results Twenty-one studies involving 4,280 patients were included. The overall quality of evidence applying the GRADE approach ranged from moderate for oxygen requirements to low for all other outcomes. No significant differences in length of hospital stay (LOS) (mean difference (MD) −0.20 days, 95% CI −0.94, 0.53, p = 0.59), or mortality (RR 2.44, 95% CI 0.86, 6.91, p = 0.09) were documented in subjects with viral co-infections compared to those with a single viral infection. There was no evidence for differences in effects across age subgroups in post hoc analyses with the exception of the higher mortality in preschool children (RR 9.82, 95% CI 3.09, 31.20, p

BACKGROUND: High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). METHODS: We assessed the association between the genetic bottleneck of HIV at transmission and the prevalence and incidence of HCV coinfection in HIV-infected MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the transmission bottleneck, we used the fraction of ambiguous nucleotides detected by genotypic resistance tests sampled during early HIV infection. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously established threshold (0.5%). RESULTS: From the SHCS, we identified 671 MSM with available results of HCV serologic tests and with an HIV genotypic resistance test performed during early HIV infection. Of those, 161 (24.0%) exhibited a broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV transmission bottlenecks exhibited a 2-fold higher odds of having ever experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI}, 1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission bottlenecks. CONCLUSIONS: Our results indicate that the currently occurring sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV transmission bottlenecks. This is consistent with an important role of high-risk behavior and mucosal barrier impairment in the transmission of HCV among MSM.

Background Successful vaccination strategies against norovirus will require understanding the burden of disease and relevant genotypes in populations. However, few data are available from cohort studies of adults living in low- and middle-income countries (LMIC). Materials and Methods We conducted a nested case-control study within a Peruvian military cohort to characterize the burden of norovirus infection, predominant genotypes, and associated symptoms from 2004 through 2011. Randomly selected case and control stools were tested for norovirus, bacteria, and parasites. The odds ratio of the association between norovirus infection and diarrhea was estimated using multiple logistic regression and co-infection adjusted attributable fractions were calculated. Results Of the 3,818 cohort study participants, 624 developed diarrhea. Overall and norovirus-associated diarrhea incidence rates were 42.3 and 6.0 per 100 person-years, respectively. The most prevalent norovirus genogroup was GII (72.5%, 29/40), which was associated with diarrhea (AOR 3.4, 95% CI: 1.3–8.7, P = 0.012). The co-infection adjusted GII attributable fraction was 6.4%. Discussion Norovirus was a frequent cause of diarrhea in an adult population followed longitudinally in an LMIC setting. Vaccine strategies should consider targeting adults in endemic settings and special populations that could serve as community transmission sources.