Diagnostic, and therapeutic challenges In HIV+ patient, presented with left-sided Haemiparesis and MRI changes

Neurological features occur during the later stages of HIV infection. The most common manifestations are opportunistic infections like cerebral toxoplasmosis and progressive multifocal leukoencephalopathy, as well as malignant lymphomas like primary EBV associated CNS lymphoma. We present a case of a 21-yearold man, diagnosed as HIV+ in 2010. The patient receives HAART (kivexa/kaletra) from 13.08.2013 to date with poor adherence. The current complaints began two weeks ago with weakness in the lower extremities, gait disturbances and headache. The neurological examination at the admission time showed no meningeal signs, weakened tendon reflexes in left limbs, absent abdominal reflexes, central facial palsy on the left, positive Babinski sign. Upon admission to the hospital the patient presented with CD 4-34c/mm³, VL- 2180 c/ml. Cerebral spinal fluid viral load was <20 c/ml. The results of the serological and virological tests from cerebral spinal fluid were: PCR EBV (-); PCR CMV (-); IgM EBV (-); IgG CMV (-); T.gondii IgM (-); IgG(-); PCR for pathogenic free-living amoeba (-). MRI: space occupying lesion, interpreted as a lymphoma, MRI after 6 months: progression of the lesion. A biopsy of peripheral lymph node showed nonspecific finding. The patient was put on patogenetic treatment against cerebral edema, treatment against T. gondii infection (clindamycin, co-trimoxazole), and gancyclovir, meronem, fungolon, ART as well. The patient was without precise, laboratory confirmed diagnosis, but the general condition is better

Coinfection of the intestinal tract with Aeromonas hydrophila, Clostridium difficile and Rotavirus - a case report

Most cases of acute diarrhea in adults are of infectious etiology, likely viral and self-limited. Among those with severe diarrhea, however, bacterial causes are responsible for most cases.Apart from the standard stool cultures, to increase the positive yield a novel multiplex molecular test can be performed simultaneously. The authors present a patient with recurrent diarrhea and detection of Aeromonas hydrophila by culturing and Rotavirus and Clostridioides difficile by multiplex molecular test. They discuss and justify which is the most likely actionable pathogen. Good communication between the physicians and interpretation on the multiple positive results in the context of clinical picture and the test employed were important for a better management and favourable outcome of the patient

Non-neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6Chi inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection.ISSN:0014-2980ISSN:1521-414

Non‐neutralizing antibodies protect against chronic LCMV infection by promoting infection of inflammatory monocytes in mice

Antibodies play an important role in host defense against microorganisms. Besides direct microbicidal activities, antibodies can also provide indirect protection via crosstalk to constituents of the adaptive immune system. Similar to many human chronic viral infections, persistence of Lymphocytic choriomeningitis virus (LCMV) is associated with compromised T- and B-cell responses. The administration of virus-specific non-neutralizing antibodies (nnAbs) prior to LCMV infection protects against the establishment of chronic infection. Here, we show that LCMV-specific nnAbs bind preferentially Ly6Chi inflammatory monocytes (IMs), promote their infection in an Fc-receptor independent way, and support acquisition of APC properties. By constituting additional T-cell priming opportunities, IMs promote early activation of virus-specific CD8 T cells, eventually tipping the balance between T-cell exhaustion and effector cell differentiation, preventing establishment of viral persistence without causing lethal immunopathology. These results document a beneficial role of IMs in avoiding T-cell exhaustion and an Fc-receptor independent protective mechanism provided by LCMV-specific nnAbs against the establishment of chronic infection.ISSN:0014-2980ISSN:1521-414

Transmitted HIV Drug Resistance in Bulgaria Occurs in Clusters of Individuals from Different Transmission Groups and Various Subtypes (2012–2020)

Transmitted HIV drug resistance in Bulgaria was first reported in 2015 using data from 1988–2011. We determined the prevalence of surveillance drug resistance mutations (SDRMs) and HIV-1 genetic diversity in Bulgaria during 2012–2020 using polymerase sequences from 1053 of 2010 (52.4%) antiretroviral therapy (ART)-naive individuals. Sequences were analyzed for DRM using the WHO HIV SDRM list implemented in the calculated population resistance tool at Stanford University. Genetic diversity was inferred using automated subtyping tools and phylogenetics. Cluster detection and characterization was performed using MicrobeTrace. The overall rate of SDRMs was 5.7% (60/1053), with 2.2% having resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 1.8% to non-nucleoside reverse transcriptase inhibitors (NNRTIs), 2.1% to protease inhibitors (PIs), and 0.4% with dual-class SDRMs. We found high HIV-1 diversity, with the majority being subtype B (60.4%), followed by F1 (6.9%), CRF02_AG (5.2%), A1 (3.7%), CRF12_BF (0.8%), and other subtypes and recombinant forms (23%). Most (34/60, 56.7%) of the SDRMs were present in transmission clusters of different subtypes composed mostly of male-to-male sexual contact (MMSC), including a 14-member cluster of subtype B sequences from 12 MMSC and two males reporting heterosexual contact; 13 had the L90M PI mutation and one had the T215S NRTI SDRM. We found a low SDRM prevalence amid high HIV-1 diversity among ART-naive patients in Bulgaria during 2012–2020. The majority of SDRMs were found in transmission clusters containing MMSC, indicative of onward spread of SDRM in drug-naive individuals. Our study provides valuable information on the transmission dynamics of HIV drug resistance in the context of high genetic diversity in Bulgaria, for the development of enhanced prevention strategies to end the epidemic

Rapid T cell–based identification of human tumor tissue antigens by automated two-dimensional protein fractionation

Identifying the antigens that have the potential to trigger endogenous antitumor responses in an individual cancer patient is likely to enhance the efficacy of cancer immunotherapy, but current methodologies do not efficiently identify such antigens. This study describes what we believe to be a new method of comprehensively identifying candidate tissue antigens that spontaneously cause T cell responses in disease situations. We used the newly developed automated, two-dimensional chromatography system PF2D to fractionate the proteome of human tumor tissues and tested protein fractions for recognition by preexisting tumor-specific CD4+ Th cells and CTLs. Applying this method using mice transgenic for a TCR that recognizes an OVA peptide presented by MHC class I, we demonstrated efficient separation, processing, and cross-presentation to CD8+ T cells by DCs of OVA expressed by the OVA-transfected mouse lymphoma RMA-OVA. Applying this method to human tumor tissues, we identified MUC1 and EGFR as tumor-associated antigens selectively recognized by T cells in patients with head and neck cancer. Finally, in an exemplary patient with a malignant brain tumor, we detected CD4+ and CD8+ T cell responses against two novel antigens, transthyretin and calgranulin B/S100A9, which were expressed in tumor and endothelial cells. The immunogenicity of these antigens was confirmed in 4 of 10 other brain tumor patients. This fast and inexpensive method therefore appears suitable for identifying candidate T cell antigens in various disease situations, such as autoimmune and malignant diseases, without being restricted to expression by a certain cell type or HLA allele