Pyogenic spondylodiscitis in HIV-positive patients under antiretroviral therapy: A case series.

Background: The incidence of pyogenic spondylodiscitis has been increasing in countries of Europe and North America, probably due to an increasing number of persons with risk factors for this infection. It is unclear whether HIV infection in the era of antiretroviral therapy (ART) increases the risk for spondylodiscitis. Method: We present 7 cases of pyogenic spondylodiscitis of the cervical, thoracic, and lumbar spine in six individuals living with HIV under ART with suppressed viral load. Results: All patients presented with severe non-radicular pain and elevated inflammatory markers. Diagnosis was confirmed by magnetic resonance imaging (MRI) scan and isolation of the pathogen. Staphylococcus aureus was the causative pathogen in five patients. One patient suffered from an infection with Klebsiella pneumoniae followed by a mixed infection with Cutibacterium acnes and Bacillus circulans 18 months later. All patients needed surgical intervention, and the mean duration of antibiotic treatment was 17 weeks (range 12-26). Five patients recovered fully, including two persons who also suffered from endocarditis. One patient died from multi-organ failure. Conclusion: Spondylodiscitis may be seen more frequently in persons living with HIV as they grow older and suffer from comorbidities which put them at risk for this infection. HIV physicians should be aware of the infection and its risk factors.

All-cause hospitalisation among people living with HIV according to gender, mode of HIV acquisition, ethnicity, and geographical origin in Europe and North America: findings from the ART-CC cohort collaboration.

BACKGROUND: Understanding demographic disparities in hospitalisation is crucial for the identification of vulnerable populations, interventions, and resource planning. METHODS: Data were from the Antiretroviral Therapy Cohort Collaboration (ART-CC) on people living with HIV in Europe and North America, followed up between January, 2007 and December, 2020. We investigated differences in all-cause hospitalisation according to gender and mode of HIV acquisition, ethnicity, and combined geographical origin and ethnicity, in people living with HIV on modern combination antiretroviral therapy (cART). Analyses were performed separately for European and North American cohorts. Hospitalisation rates were assessed using negative binomial multilevel regression, adjusted for age, time since cART intitiaion, and calendar year. FINDINGS: Among 23 594 people living with HIV in Europe and 9612 in North America, hospitalisation rates per 100 person-years were 16·2 (95% CI 16·0-16·4) and 13·1 (12·8-13·5). Compared with gay, bisexual, and other men who have sex with men, rates were higher for heterosexual men and women, and much higher for men and women who acquired HIV through injection drug use (adjusted incidence rate ratios ranged from 1·2 to 2·5 in Europe and from 1·2 to 3·3 in North America). In both regions, individuals with geographical origin other than the region of study generally had lower hospitalisation rates compared with those with geographical origin of the study country. In North America, Indigenous people and Black or African American individuals had higher rates than White individuals (adjusted incidence rate ratios 1·9 and 1·2), whereas Asian and Hispanic people living with HIV had somewhat lower rates. In Europe there was a lower rate in Asian individuals compared with White individuals. INTERPRETATION: Substantial disparities exist in all-cause hospitalisation between demographic groups of people living with HIV in the current cART era in high-income settings, highlighting the need for targeted support. FUNDING: Royal Free Charity and the National Institute on Alcohol Abuse and Alcoholism.

High seroprotection rates and geometric mean titre increases after repeated annual influenza vaccinations in a cohort of HIV-infected adults in Austria.

INTRODUCTION: Vaccination against seasonal influenza is recommended for all HIV-infected persons. Few data have been reported on the effect of repeated annual vaccination in this population. METHODS: We measured haemagglutination inhibition antibody responses and investigated seroprotection rates in 344 HIV-infected adults before and 12 weeks after influenza vaccination with a trivalent subunit vaccine. RESULTS: 68.3% of patients were male, the median age was 45 years. 83.7% had a viral load < 50 copies/mL. The median CD4 count was 604/µL. 304 patients (88.4%) had received influenza vaccinations in previous years. Seroprotection rates for A/H1N1 and B were over 90% in all age groups before vaccination and close to 100% after vaccination. For A/H3N2, seroprotection rates were lowest in individuals below 30 years both before and after vaccination (22.2% and 50.0%) and higher in older age groups (48.4% and 83.9% in people over 60 years). GMT fold increases were not significantly different across the age groups (3.0 to 4.2, p = 0.425). Previous influenza vaccinations were associated with higher seroprotection rates before and after vaccination (62.2% and 84.2% in patients with 8 or more previous vaccinations vs. 15.0% and 57.5% without previous vaccinations, respectively). Individuals with detectable viral load, elevated immune activation (urine neopterin ≥ 250 µmol/mol creatinine), and higher CD4 nadir (≥200 cells/µL) showed a trend towards inferior immune responses to vaccination, whereas gender and CD4 count did not have an effect. CONCLUSION: The lower seroprotection rates observed in younger individuals may be explained by the higher proportion of patients without HIV treatment and with fewer previous encounters with influenza strains. Good seroprotection rates can be achieved in elderly HIV-infected patients and after repeated annual vaccinations.

A case of human Dirofilaria repens infection, causing an asymptomatic subcutaneous nodule.

We present a case of subcutaneous dirofilariasis, a vector-borne zoonotic disease, in a young woman from Austria. The diagnosis was confirmed by ultrasound and histology of the excised subcutaneous nodule. The parasite species was identified as Dirofilaria repens by polymerase chain reaction. We expect to see more cases of human dirofilariasis also due to climate change and associated increase of the spectrum of suitable mosquito vectors.

Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study - 2012 - 2015.

BACKGROUND: It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. METHODS: Individuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. RESULTS: Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. CONCLUSION: The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

Anal Ureaplasma spp. positivity among HIV positive men who have sex with men may be associated with high-risk-type HPV infections.

OBJECTIVE: HIV positive individuals, particularly men having sex with men (MSM), are at increased risk of sexually transmitted infections (STIs) at genital and extra-genital sites. Data on anorectal Ureaplasma infections are lacking. The aim of our study was to characterize anal Ureaplasma positivity among a cohort of HIV positive MSM and evaluate possible association with papillomavirus infection at the same site. METHODS: Anal swab samples, collected as part of routine screening for Chlamydia trachomatis and Neisseria gonorrhea, were additionally tested for HPV genotypes as well as for Ureaplasma and Mycoplasma using nucleic acid amplification method. RESULTS: Out of a total of 222 study participants, 195 (89%, 95% CI (84.9-93.2)) were positive for HPV, approximately three quarter being high-risk genotypes. Forty three individuals (19.4%, 95% CI (14.4-24.3)) harbored Ureaplasma spp. Infection with high-risk HPV types was significantly associated with co-presence of Ureaplasma with an odds ratio (95% confidence-interval) of 2.59 (1.03-6.54), P = 0.04. CONCLUSION: Besides a high predominance of HPV infection, asymptomatic HIV positive MSM had a high prevalence of anal Ureaplasma positivity. Concomitant infections with high-risk HPV genotypes were common and statistically significant. The role of this co-existence as a potential risk factor for anal carcinogenesis needs further elucidation.

[Guidelines for vaccination of immunocompromised individuals]. / Impfungen bei Immundefekten/Immunsuppression - Expertenstatement und Empfehlungen.

Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

Serological evidence for Parapoxvirus infection in chamois from the Tyrol regions of Austria and Italy.

Orf-virus (ORFV) is a parapoxvirus that infects small ruminants worldwide causing sporadic zoonotic infections, mainly transmitted by direct contact with sheep and goats. Following an ORFV case in a hunter of Alpine chamois (Rupicapra rupicapra), who did not report previous contact to domestic animals, a serological survey in Western Austria was conducted to assess the seroprevalence of ORFV in this species. In addition, this study also tested blood/tissue samples of chamois from different areas of the adjacent province of Bolzano/Northern Italy for antibodies against ORFV using immunofluorescence and ELISA. The observed seropositivity rates in the chamois tested on the Austrian and Italian side of the Alps were 23.5% and 9.5%, respectively, with a combined 95% confidence interval ranging from 0.0678 to 0.238. Although the prevalence was significantly lower than the one observed in Austrian sheep flocks, this study provided the first evidence that parapoxviruses have spilled over into chamois populations to a significant degree in the Tyrol regions of Austria and Italy.

[Pitfalls in diagnosis and treatment of cutaneous larva migrans: three unusual cases from a dermatology clinic]. / Das kutane Larva migrans Syndrom: Schwierigkeiten bei Diagnose und Behandlung anhand von drei Fallbeispielen.

Cutaneous larva migrans (CLM, creeping eruption) is a skin disease commonly seen in travelers returning from the tropics. The lesions are caused by intradermal migration of animal hookworm larvae which cannot mature in humans. While the typical serpiginous skin lesions are easily diagnosed and treated with albendazole or ivermectin, unusual presentations can be misdiagnosed and cause prolonged morbidity. We present 3 cases of CLM, which were difficult to diagnose and/or treat.Case 1 is a 34-year old Caucasian male who presented with itchy papular lesions on the soles of both feet and was initially treated for plantar psoriasis.Case 2 is a 54-year old Caucasian male who suffered from extensive follicular larva migrans on the buttocks for several months and was only cured after repeated courses of albendazole and ivermectin.Case 3 is a 29-year old Caucasian male with pruritic inflammatory papules on the trunk. Despite extensive diagnostic procedures including skin biopsies and tissue cultures the correct diagnosis was only made later during the course of the illness. After treatment for CLM with albendazole (800 mg/d for 3 days) and after resolution of perifocal edema and inflammation the typical serpiginous tracks became more obvious. They responded rapidly to anthelminthic treatment.These cases highlight the importance of careful history taking and work-up in individuals presenting with atypical skin lesions. In case of exposure to CLM empiric anthelminthic treatment might be considered.

ORF virus infection in a hunter in Western Austria, presumably transmitted by game.

A variety of animals host parapoxviruses. Orf virus is prevalent in sheep and goats in the Tyrol region of Austria and Northern Italy. Zoonotic infections in humans mostly occur after occupational exposure. We report here a case of a hunter with a typical Orf lesion (contagious ecthyma) on the finger, with no history of direct contact with domestic animals. Three weeks previously he had been hunting chamois (Rupicapra rupicapra) and cut his finger while handling a carcass. Parapoxvirus infection was confirmed by electron microscopy and PCR, and the species was identified by DNA sequencing. The sequence was highly homologous with prevalent sheep Orf virus and rather distant from parapoxviruses found in red deer in Northern Italy. As this case indicated that the infection was acquired via game, we performed spot testing in the suspected area and detected several seropositive animals. This is a strong indication that Orf virus has been introduced into chamois in Western Austria. This probably occurred via roaming domestic sheep sharing the high alpine areas during the summer months.

Cannabinoids lead to enhanced virulence of the smallpox vaccine (vaccinia) virus.

Indian hemp is used since thousands of years as herbal drug. We found that a single dose of cannabis resin was equally active as Δ9-tetrahydrocannabinol (THC) enhancing severity and duration of symptoms in vaccinia virus infected mice. Cowpox virus did not cause symptomatic disease, but some reduction of specific antibody production was observed in drug treated animals. In vitro cannabis was superior to THC alone at inhibiting mitogen stimulated proliferation of human and mouse spleen cells and peripheral blood mononuclear cells. Also resin sub-fractions other than THC, cannabidiol and cannabinol, recovered also from cigarette smoke, were found inhibitory, suggesting additional involvement of constituents other than psychoactive THC. The immunoregulatory effects must be differentiated from apoptotic effects on spleen cells and lymphocytic mouse cell lines, which were observed with resin and THC but not with cannabidiol or cannabinol. A significant contribution of cytotoxic effects seems unlikely as drug treated lymphocytes were still capable of producing cytokines after T-cell receptor-specific stimulation. Considering a recent case of unusually severe cowpox virus infection in a young drug taker these data confirm a risk of "soft drugs" for acquiring poxvirus infection or enhancing side effects of the smallpox vaccine and perhaps also other live vaccines.

Diazepam leads to enhanced severity of orthopoxvirus infection and immune suppression.

Benzodiazepines are drugs widely used as tranquilizers and in various other indications. We treated Balb/c mice with diazepam and infected them with cowpox (CPXV) and vaccinia virus (VACV). Disease index, weight loss and the antibody response were determined. Additionally the influence of different benzodiazepines on the mitogen response of human peripheral blood lymphocytes and spleen cells was tested. Diazepam led to earlier disease onset, prolonged duration of symptoms, higher weight loss and overall disease index in VACV infected mice. CPXV infected mice developed poxviral skin lesions only after drug administration and a significant decrease in the specific antibody response was also observed. Diazepam and alprazolam also inhibited the proliferative response of human lymphocytes/spleen cells in vitro but did not show noteworthy apoptotic effects. It is surprising that even a single dose of diazepam has a profound influence on the immune system, sufficient to facilitate symptomatic infectious disease. These data provide first evidence that commonly used drugs like Valium may augment severity of rare poxvirus infections such as CPXV or monkeypox. As VACV is still used as life vaccine against smallpox there is also a risk of enhanced side effects or possible interference with the success of vaccination.

Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy.

OBJECTIVE: Higher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). METHODS: Plasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12 months of effective antiretroviral therapy (ART). Results were compared with CD4+ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin. RESULTS: Before ART, phe/tyr was mean+/-S.D.: 0.99+/-0.57 micromol/micromol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs=0.434, and rs=0.392; both p<0.001) and less strongly with HIV-RNA levels (rs=0.173) and CD4+ counts (rs=-0.182, both p<0.05). After ART, phe/tyr dropped to 0.72+/-0.16 (=-27%; U=5.21, p=0.01) which was due to an average decline of -14% of phe concentrations from 73.1+/-34.0 micromol/L at baseline to 62.9+/-17.8 micromol/L after ART (U=2.51, p=0.01) and a concomitant increase of tyr concentrations (+13%, U=2.46, p=0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART. CONCLUSIONS: Increased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients.