Motile microfilaria captured by fluorescent microscopy and the unmasking of eosinophilia following treatment.

A 24-year-old patient from Cameroon presented to our hospital because of a foreign structure in her left eye. To our knowledge, for the first time, fluorescent microscopy revealed motile microfilariae, and the diagnosis of loiasis was established. Despite substantial microfilaremia, eosinophilia only unmasked after the initiation of antiparasitic therapy.

Sexually transmitted diseases in people living with HIV after implementation of cost coverage of HIV pre-exposure prophylaxis by statutory health insurance in Germany.

OBJECTIVES: After pre-exposure prophylaxis (PrEP) was introduced, rates of sexually transmitted infections (STIs) increased among PrEP users. However, data on STI trends in people living with HIV since then are limited. Since September 2019, PrEP has been covered by statutory German health insurance (SHI) in vulnerable groups. This study aimed to determine whether this coverage of PrEP costs affected STI rates in people living with HIV (specifically, men who have sex with men). METHODS: All patients of the HIVCENTER Frankfurt diagnosed with at least one STI within the observation period were retrospectively enrolled in the study. STIs included infection with Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. The observation period covered 1 year before and 1 year after the coverage of PrEP costs by German SHI. Data were collected from outpatient clinic records. RESULTS: In total, 143 patients were enrolled in the study. The observation period was September 2018 to August 2019 for group 1 (n = 73) and September 2019 to August 2020 for group 2 (n = 70). The most frequent STIs were syphilis and infections due to chlamydia, gonococci, and trichomonads, in descending order. Infections with T. pallidum occurred more often in group 2 than in group 1 (60.0% vs. 50.7%; p = 0.253) as did chlamydia (37.1% vs. 28.8%; p = 0.286). CONCLUSIONS: A tendency for an increased ratio of STIs in people living with HIV was observed after the introduction of PrEP coverage by German SHI. STIs should be discussed intensively with people living with HIV, since the communities of PrEP users and people living with HIV overlap, and changes in risk behaviour might influence both groups.

HIV-1 Infection of Long-Lived Hematopoietic Precursors In Vitro and In Vivo.

Latent reservoirs in human-immunodeficiency-virus-1 (HIV-1)-infected individuals represent a major obstacle in finding a cure for HIV-1. Hematopoietic stem and progenitor cells (HSPCs) have been described as potential HIV-1 targets, but their roles as HIV-1 reservoirs remain controversial. Here we provide additional evidence for the susceptibility of several distinct HSPC subpopulations to HIV-1 infection in vitro and in vivo. In vitro infection experiments of HSPCs were performed with different HIV-1 Env-pseudotyped lentiviral particles and with replication-competent HIV-1. Low-level infection/transduction of HSPCs, including hematopoietic stem cells (HSCs) and multipotent progenitors (MPP), was observed, preferentially via CXCR4, but also via CCR5-mediated entry. Multi-lineage colony formation in methylcellulose assays and repetitive replating of transduced cells provided functional proof of susceptibility of primitive HSPCs to HIV-1 infection. Further, the access to bone marrow samples from HIV-positive individuals facilitated the detection of HIV-1 gag cDNA copies in CD34+ cells from eight (out of eleven) individuals, with at least six of them infected with CCR5-tropic HIV-1 strains. In summary, our data confirm that primitive HSPC subpopulations are susceptible to CXCR4- and CCR5-mediated HIV-1 infection in vitro and in vivo, which qualifies these cells to contribute to the HIV-1 reservoir in patients.

Evaluation of Platelet Activation by HIV Protease Inhibitors - The HIV-PLA II Study.

BACKGROUND: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previous HIV-PLA I-study lead to the assumption that platelet activation could play a substantial role in increasing CVE risks. METHODS: The open label, monocentric HIV-PLA II-study investigated HIV-1-infected, therapy-naïve adults (n=45) starting with cART, consisting either of boosted PI (atazanavir, n= 6, darunavir, n=11), NNRTI (efavirenz, n=14) or integrase inhibitor (raltegravir, n=14), each plus tenofovir/emtricitabine co-medication. Main exclusion criteria were tobacco smoking, the intake of NSAIDs or abacavir or past CVE. Platelet adhesive molecule p-selectin (CD62P) and FITC anti-human Integrin α-IIb/Integrin ß-3 (CD41/CD61) antibody (PAC-1) binding, monocyte CD11b/monocyte-associated CD41 expression and the endogenous thrombin potential (ETP) were assessed ex vivo-in vitro at baseline, weeks 4, 12 and 24. Therapy regimens were blinded to the investigators for laboratory and statistical analyses. RESULTS: CD11b and ETP showed no significant changes or differences between all study groups. In contrast, the mean + SD mean fluorescence units (MFI) of CD62P and PAC-1 increased significantly in patients taking PI, indicating an enhanced potential for thrombocyte activation and aggregation. CONCLUSION: CD62P expression, detecting the ɑ-platelet degranulation of pro-inflammatory and pro-thrombotic factors and adhesive proteins, and PAC-1 expression, representing a marker for conformation changes of the GIIb/IIIa receptor, increased significantly in patients taking HIV protease inhibitors. The findings of this study revealed a yet unknown pathway of platelet activation, possibly contributing to the increased risk for CVE under HIV protease inhibitor containing cART. CLINICAL TRIAL REGISTRATION NO: DRKS00000288.

Disseminated disease due to non-tuberculous mycobacteria in HIV positive patients: A retrospective case control study.

INTRODUCTION: Disseminated infection due to non-tuberculous mycobacteria has been a major factor of mortality and comorbidity in HIV patients. Until 2018, U.S. American guidelines have recommended antimycobacterial prophylaxis in patients with low CD4 cell counts, a practice that has not been adopted in Europe. This study aimed at examining the impact of disseminated NTM disease on clinical outcome in German HIV patients with a severe immunodeficiency. MATERIALS AND METHODS: In this retrospective case control study, HIV patients with disseminated NTM disease were identified by retrospective chart review and matched by their CD4 cell counts to HIV patients without NTM infection in a 1:1 alocation. Primary endpoints were mortality and time to first rehospitalisation. In addition, other opportunistic diseases, as well as antimycobacterial and antiretroviral treatments were examined. RESULTS: Between 2006 and 2016, we identified 37 HIV patients with disseminated NTM disease. Most of them were suffering from infections due to M. avium complex (n = 31, 77.5%). Time to event analysis showed a non-significant trend to higher mortality in patients with disseminated NTM disease (p = 0.24). Rehospitalisation took place significantly earlier in patients with disseminated NTM infections (median 40.5 days vs. 109 days, p<0.0001). CONCLUSION: In this retrospective case control study, we could demonstrate that mortality is not significantly higher in HIV patients with disseminated NTM disease in the ART era, but that they require specialised medical attention in the first months following discharge.

Risk factors for IRIS in HIV-associated Pneumocystis-pneumonia following ART initiation.

BACKGROUND: HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care. METHODS: An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 - June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions. RESULTS: IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p = 0.009), intensive care treatment (66.7vs. 30.6%; OR = 4.54; p = 0.018), and longer median hospitalization (48 days vs. 23; p < 0.001). A high HIV-RNA level (> 6Log10/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p = 0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0 vs. 1446.5; p = 0.023). CONCLUSION: Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of > 6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.

Myocardial Fibrosis and Inflammation by CMR Predict Cardiovascular Outcome in People Living With HIV.

OBJECTIVES: The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART). BACKGROUND: PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood. METHODS: This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization). RESULTS: A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/m2 [49 to 77 g/m2] vs. 57 g/m2 [49 to 64 g/m2]), and N-terminal pro-B-type natriuretic peptide (109 pg/l [25 to 337 pg/l] vs. 48 pg/l [23 to 82 pg/l]) (all p < 0.05). In multivariable analyses, native T1 was independently predictive of adverse events (chi-square test, 15.9; p < 0.001; native T1 [10 ms] hazard ratio [95% confidence interval]: 1.20 [1.08 to 1.33]; p = 0.001), followed by a model that also included LV mass (chi-square test, 17.1; p < 0.001). Traditional cardiovascular risk scores were not predictive of the adverse events. CONCLUSIONS: Our findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).

Reasons for Choice of Antiretroviral Regimens in HIV Patients Presenting Late for Initial Treatment in Europe.

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count <200/µL and/or an AIDS-defining disease (late presenters, LPs), is still a challenge, even for HIV specialists. At present, there is little information on the decision process and selection criteria that physicians must take into account when choosing the presumably optimal initial ART for LPs. This study analyzes reasons for the individual choice of first-line ART in HIV LPs. We conducted a prospective multi-center study to analyze the decision-making process of physicians treating naive HIV patients presenting with a CD4 cell count <200/µL and/or an AIDS-defining condition. Two European HIV treatment centers based in Frankfurt (Germany) and A Coruna (Spain) participated in the study. Physicians documented the reasons that led to their decision for a specific first-line ART regimen. A questionnaire was designed for the study. Decisions of the participating physicians were evaluated. A total of 52 treatment decisions were analyzed. Evaluation of the choice of antiretroviral treatment demonstrated that for the overall group of physicians, simplicity of the regimen was the most important selection criterion in 34.6% of cases. The presence of comorbidities was given as the decisive selection criterion in 26.9%, followed by experience with the chosen drugs in 21.2% of cases. In the group of physicians choosing an integrase strand transfer inhibitor (INSTI)-based regimen for first-line ART, the same selection criteria were identified as in the overall group; 33.3% of clinicians selected an INSTI-based regimen because of its simplicity. The presence of comorbidities was the second most frequent decisive criterion (31.0%), followed by personal experience with the prescribed ART (23.8%). In the protease inhibitor group, simplicity was also the most common selection criterion with 40%. Results of clinical trials were stated as the most important criterion for the selection of ART in 38% of all cases, followed by the expected adherence of the patient (22%). Among the physicians who used a non-nucleoside reverse transcriptase inhibitor-based regimen, patients' desire to have children was the most frequent criterion for selection of ART (60%). An ongoing pregnancy was the second most frequent selection criterion, followed by ART's simplicity (8%). For patients treated with a single-tablet regimen, simplicity of ART was comprehensibly the most important decisive criterion (54.5%). Experience with the chosen drugs was the decisive selection criterion in 24.2%, followed by comorbidities in 18.2% of cases. Physicians' selection of individual ART in patients presenting late for first-line treatment seems to be predominantly dependent on patient-centered factors such as adherence issues as well as the clinical experience of physicians with the prescribed drugs.

Influence of tenofovir exposure in utero on primary dentition.

Tenofovir disoxoproxil fumarate (TDF) is recommended for antiretroviral treatment for pregnant women living with HIV. As a comparative method to study bone density, we investigated the influence of in utero tenofovir exposure on the prevalence and distribution of developmental defects of enamel (DDE) in the primary dentition, as the mineralization process in teeth is higher and more complex and thus more vulnerable. HIV-exposed children with in utero exposition to tenofovir were included in this prospective observational single-center study. Dental status and enamel defects were assessed by an experienced dentist following a standardized protocol. Further information was collected using a standardized questionnaire, available in German and English. The prevalence of developmental defects in children with intrauterine tenofovir exposure was compared with literature data from a recent study of 377 healthy children in Germany and literature data from a study of 1221 healthy African children. Thirty-one children (mean age 2.1 ± 0.3 years; 41.9% female) were included. Median tenofovir exposure in utero was 28 weeks (mean ± 10.52 SD). Prevalence of developmental defects in the primary dentition in tenofovir-exposed children was similar compared to data of unexposed children (16.1% vs. 5.3%, p = 0.051 (compared to German cohort); 16.1% vs. 33.3%, p = 0.068 (compared to African cohort)).Conclusion: HIV-uninfected infants with in utero exposure to TDF showed no significant differences in the prevalence of DDE in comparison to cross-sectional data of HIV- and TDF-unexposed children; thus, the in utero exposure to TDF did not negatively influence the prevalence or distribution of DDE. What is Known: • There are no data available on the prevalence of developmental defects of enamel (DDE) in the primary dentition in intrauterine HIV- and tenofovir-exposed children. • Conclusions can be drawn from intrauterine milk tooth development to bone development and mineralization. What is New: • Prevalence of developmental defects in the primary dentition in tenofovir-exposed children was similar compared to data of unexposed children. • Preterm birth and hospitalization did not show a significant association on the prevalence of developmental defects in the primary dentition.

Species distribution and clinical features of infection and colonisation with non-tuberculous mycobacteria in a tertiary care centre, central Germany, 2006-2016.

PURPOSE: NTM are ubiquitous bacteria that can cause colonisation and infection in immunocompetent and compromised hosts. The aim of this study was to elucidate the epidemiology of infection or colonisation with NTM for the metropolitan region of Frankfurt, Germany. METHODS: All patients from whom NTM were isolated within the period from 2006 to 2016 were included in this retrospective analysis. Patient data were retrieved using the local patient data management system. Different groups were formed according to clinical manifestations, underlying diseases and mycobacterial species. They were compared in regard to mortality, duration of infection/colonisation and their geographical origins. RESULTS: A total of 297 patients with a median of 28 new patients each year were included. Most patients suffered from lung infection or colonisation (72.7%, n = 216), followed by disseminated mycobacteriosis (12.5%, n = 37). The majority were HIV-positive, suffering from malignoma or cystic fibrosis (29.3%, n = 87, 16.2%, n = 48, and 13.8%, n = 41, respectively). 17.2% of patients showed no predisposing condition (n = 51). Mycobacterium avium complex (MAC) species were most frequently isolated (40.7%, n = 121). Infection/colonisation was longest in CF patients (median of 1094 days). The mortality was highest in malignoma patients (52.4%), while CF patients had the lowest overall mortality rate (5.3%). But mortality analysis showed non-significant results within different mycobacterial species and clinical manifestations. CONCLUSION: NTM remain rare but underestimated pathogens in lung and disseminated disease. MAC were the species most frequently isolated. Depending on species and underlying predispositions, the duration of infection/colonisation can be unexpectedly long.

Clinical characteristics in a sentinel case as well as in a cluster of tularemia patients associated with grape harvest.

BACKGROUND: Tularemia is caused by Francisella tularensis and can occasionally establish foodborne transmission. METHODS: Patients were identified by active case detection through contact with the treating physicians and consent for publication was obtained. Clinical data were accumulated through a review of the patient charts. Serology, culture, and PCR methods were performed for confirmation of the diagnosis. CASE CLUSTER: A 46-year-old patient was hospitalised in the University Hospital Frankfurt (a tertiary care hospital) for pharyngitis and cervical lymphadenitis with abscess. A diagnosis of tularemia was made serologically, but treatment with ciprofloxacin initially failed. F. tularensis was detected in pus from the lymph node using a specific real-time PCR. The use of RD1 PCR led to the identification of the subspecies holarctica. Antibiotic therapy with high-dose ciprofloxacin and gentamicin was administered and was subsequently changed to ciprofloxacin and rifampicin. During a must-tasting, five other individuals became infected with tularemia by ingestion of contaminated must. All patients required treatment durations of more than 14 days. CONCLUSIONS: Mechanically harvested agricultural products, such as wine must, can be a source of infection, probably due to contamination with animal carcasses. The clinical course of tularemia can be complicated and prolonged and requires differentiated antibiotic treatment.

New Lineage of Lassa Virus, Togo, 2016.

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

Favipiravir and Ribavirin Treatment of Epidemiologically Linked Cases of Lassa Fever.

Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.

Complete Genome Sequence of an Ebola Virus Isolate Imported from Sierra Leone to Germany Determined by Circle Sequencing.

We report here a complete genome sequence of Ebola virus Makona from a nonfatal patient sample that originated in Sierra Leone during the last Ebola virus outbreak in West Africa (species Zaire ebolavirus) using a highly accurate circle sequencing (Cir-seq) method.

Genome Sequence of Lassa Virus Isolated from the First Domestically Acquired Case in Germany.

Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus endemic in West Africa, for which no approved vaccines or specific treatment options exist. Here, we report the genome sequence of LASV isolated from the first case of acquired Lassa fever disease outside of Africa.

Impact of Stereotactic Biopsy in HIV Patients.

OBJECTIVE: During their disease a significant number of human immunodeficiency virus (HIV)-infected patients develop neurologic symptoms due to intracerebral pathologies. Entities commonly found are toxoplasmosis, lymphomas, or progressive multifocal leukoencephalopathy. In some patients, diagnosis is not feasible with imaging alone, requiring biopsy. The objective of this study was to evaluate the impact of stereotactic biopsy in HIV patients on adjustment of therapy. METHODS: Between January 2004 and May 2015 at our clinic, 26 HIV-infected patients underwent stereotactic biopsy. Thin-layer magnetic resonance images were obtained and fused with computed tomography scans, taken with the stereotactic frame (Leksell) mounted. Biopsy material was evaluated pathologically and microbiologically. RESULTS: Histologic analysis revealed B-cell lymphoma in 6 patients (23.1%) and progressive multifocal leukoencephalopathy in 2 patients (7.7%). Abscess and toxoplasmosis were found in 3 patients each (11.5% and 11.5%), and encephalitis occurred in 4 patients (15.4%). In 2 patients each (7.7%), vasculitis, metastasis, and glioblastoma were diagnosed. Further findings comprised non-Hodgkin lymphoma and Burkitt lymphoma in 1 patient each. After biopsy, treatment was significantly changed in 18 (69.2%) patients (P < 0.01). Antibiotic therapy was adjusted in 6 patients (23.1%), and chemotherapy in 3 patients (16.7%). Other changes included antibiotic/antiviral therapy to chemotherapy in 3 patients (16.7%), chemotherapy to radiation, cortisone to chemotherapy, and aciclovir to cortisone in 1 patient each. One patient with glioblastoma underwent resection, and another patient received radiation. One patient underwent palliative care. CONCLUSION: Stereotactic biopsy in HIV-infected patients results in significant changes of therapy in more than two thirds of the patients.

Rapid regression of Kaposi's sarcoma of the hard palate under therapy with boosted elvitegravir-containing fixdose antiretroviral combination therapy.

INTRODUCTION: Kaposi's sarcoma (KS) is a rare vascular tumor that may occur in a severe, rapidly progressive form, namely in HIV/AIDS patients. HIV-associated KS mainly affects the skin and mucous membranes. CASE PRESENTATION: We report about an HIV-positive patient who presented with an exophytic growing tumor in the region of the hard palate and severe problems regarding his dental status. Histological examination revealed evidence of AIDS-related KS. Antiretroviral therapy initiation with elvitegravir/cobicistat/emtricitabine(FTC)/tenofovirdisoproxilfumarat (E/c/F/T-fix dose combination) resulted in rapid complete remission of the KS within 2 months. CONCLUSION: In this case of a treatment-naive HIV-infected patient with coexisting KS, antiretroviral therapy with E/c/FTC/TDF was very well suited to achieve rapid complete remission of KS.

Management of Microbiological Samples in a Confirmed Case of Ebola Virus Disease: Constraints and Limitations.

In light of the recent Ebola virus outbreak, it has to be realized that besides medical treatment, precise algorithms for the management of complicating microbial infections are mandatory for Ebola virus disease (EVD) patients. While the necessity of such diagnostics is apparent, practical details are much less clear. Our approach, established during the treatment of an EVD patient at the University Hospital in Frankfurt am Main, Germany, provides a roadmap for reliable and safe on-site microbiological testing.