Immediate treatment of acute HIV in a tertiary healthcare center: bridging gaps in communication using smartphones.

OBJECTIVES: Early initiation of antiretroviral therapy (ART) during acute HIV infection is associated with favourable clinical and epidemiological outcomes. Barriers to prompt treatment initiation limit the benefits of universal access to ART in Mexico. We sought to create an algorithm for the immediate detection and treatment of patients with acute HIV infection. METHODS: A nationwide cohort of patients with acute HIV infection was created in 2015. In order to identify cases and treat them promptly at our centre, an interdisciplinary group coordinated through an instant-messaging tool using smart phones was established. When a probable case was detected, a discussion was initiated to confirm the diagnosis and facilitate the administrative processes to initiate ART as soon as possible. We compared time to ART initiation with that in a comparison group of patients with chronic HIV infection enrolled during the same period (May 2015 to February 2017) through routine care, using survival analysis estimators and log-rank tests. RESULTS: We recruited 29 patients with acute HIV infection. The median time to ART initiation was 2 days in these patients, in contrast to 21 days for patients with chronic infection. There were no significant differences in the percentages of patients engaged in care, on treatment or virologically suppressed at 1 year of follow-up. CONCLUSIONS: Implementing immediate ART initiation programmes is feasible in Mexico, in spite of the substantial administrative barriers that exist in the country. More extensive replication of this model in other centres and in patients with chronic infection is warranted to evaluate its effect on the continuum of care.

Opsoclonus-myoclonus-ataxia syndrome associated with central nervous system HIV-1 escape phenomenon. / Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.

INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMA) syndrome is a rare neurological disorder characterized by involuntary conjugate saccadic eye movements, myoclonus, and ataxia. Few reports exist on patients with HIV and OMA. CASE REPORT: A 41-year-old man diagnosed with HIV-1 infection in 1997 coursed with multiple anti-retroviral schemes as a consequence of poor adherence. In 2008 he presented an HIV-1 viral load of 100,000 copies/mL and a CD4+ T cell count of 10 cells/mm3. In 2013 our patient arrived with an 11-month history of progressive opsoclonus and ataxia. He had undetectable plasma HIV-1 RNA load and CD4+ of 606 cells/mm3. No opportunistic infections were found. Cerebrospinal fluid analysis showed mildly elevated protein concentration and HIV-1 viral load of 534 copies/mL. Cerebrospinal fluid co-receptor tropism test showed selective CCR5 usage. A brain magnetic resonance imaging showed hippocampal atrophy and T2-weighted hyperintensities. Our patient exhibited a dramatic recovery and cerebrospinal fluid HIV clearance after adjustment of anti-retroviral treatment based on genotyping resistance and tropism analyses. CONCLUSIONS: In patients with HIV presenting cengral nervous system dysfunction without opportunistic infections, cerebro-spinal fluid and plasma HIV-1 viral load, resistance and tropism tests should be performed to assess a potential viral escape and to design the appropriate anti-retroviral therapy in an individual patient basis.

TITLE: Síndrome opsoclono-mioclono-ataxia asociado a fenómeno de escape viral por virus de la inmunodeficiencia humana en el sistema nervioso central.Introducción. El síndrome opsoclono-mioclono-ataxia (OMA) es un trastorno neurológico infrecuente caracterizado por movimientos oculares conjugados sacádicos involuntarios, mioclonías y ataxia. Existen pocos casos en la bibliografía de pacientes con virus de la inmunodeficiencia humana (VIH) y OMA. Caso clínico. Varón de 41 años y diagnóstico de infección por el VIH-1 desde 1997, que cursó con múltiples esquemas antirretrovirales debido a una pobre adhesión al tratamiento. En 2008 presentó una carga viral de 100.000 copias/mL y una cuenta linfocitaria CD4+ de 10 células/mm3. En 2013 sufrió un cuadro progresivo de 11 meses de evolución caracterizado por opsoclonía y ataxia. En ese momento, su carga viral era indetectable, y la cuenta de CD4+, de 606 células/mm3. Se descartaron infecciones oportunistas. El examen del líquido cefalorraquídeo demostró hiperproteinorraquia leve y una carga viral de 534 copias/mL. El examen del tropismo de correceptor en el líquido cefalorraquídeo demostró un uso selectivo de CCR5. La resonancia magnética cerebral objetivó atrofia hipocámpica e hiperintensidades en las secuencias ponderadas en T2. El paciente mostró una recuperación clínica franca y un aclaramiento de la carga viral en el líquido cefalorraquídeo tras el ajuste de antirretrovirales basado en la resistencia de genotipo y el análisis de tropismo. Conclusiones. En pacientes con infección por el VIH y disfunción del sistema nervioso central sin infecciones oportunistas, debería llevarse a cabo una determinación de la carga viral en el plasma y el líquido cefalorraquídeo para descartar un potencial fenómeno de escape viral, así como exámenes de resistencia y tropismo para diseñar el tratamiento antirretroviral adecuado.

HIV-1 Langerhans' cell tropism associated with heterosexual transmission of HIV.

Heterosexual transmission by vaginal intercourse accounts for most transmission of human immunodeficiency virus-type 1 (HIV-1) in Africa and Asia but is less important in the HIV-1 epidemics of the United States and Western Europe. Epithelial Langerhans' cells (LCs) represent a possible source of initial cell contact for vaginal infection. Fifteen primary isolates of HIV-1 from U.S. homosexuals and 18 HIV-1 isolates from Thailand heterosexuals were evaluated for growth in LCs of U.S. origin. All the viruses from the Thai heterosexuals, which were subtype E, grew more efficiently in the LCs than any of the viruses from the U.S. homosexuals, which are subtype B. These results suggest that LC tropism is associated with the efficiency of heterosexual transmission of HIV.

Effects of two new steroids and cyproterone on some biomarkers of oxidative stress and serotonergic system on rat prostate and brain.

The purpose of this study was to evaluate the effect of cyproterone acetate (CPA, A) compared with new synthetic steroids 3alpha-acetoxy-5,6-epoxy-16-pregnen-20-one (B) and 17alpha-hydroxy-16beta-methyl-1,4,6-pregnatriene-3,20-dione (C) in rat prostate and brain. Groups of animals were treated either with A, B or C (4 mg kg(-1) day(-1)) by the intraperitoneal route for 5 days. Levels of reduced glutathione (GSH), 5-hydroxy-indole acetic acid (5-HIAA), lipid peroxidation (as thiobarbituric acid reactive substances, TBARS) and the activities of Na(+), K(+)- and total ATPases were assayed in prostate and brain for each group of animals including a control group. No appreciable changes were shown in Na(+), K(+)-ATPase and total ATPases and TBARS on prostate and brain of rats that received A, B and C steroids. However, the levels of GSH and 5-HIAA decreased significantly (P < 0.05) in both tissues for the steroids assayed. It is concluded that CPA and the homologues B and C steroids induce changes in the levels of GSH and serotonin in rat prostate and brain.

Degradation of immobilized azo dyes by Klebsiella sp. UAP-b5 isolated from maize bioadsorbent.

The degradation of two immobilized dyes by Klebsiella sp. UAP-b5 was studied. In batch experiments, the azo dyestuffs Basic Blue 41 and Reactive Black 5 were immobilized onto corn cobs by adsorption, and the adsorption process was characterized by a pseudo-second-order kinetic equation. Klebsiella sp. UAP-b5 was previously isolated from the corn waste and shown to decolorize these dyes in liquid systems. Here, we demonstrate anaerobic decolorization and reductive biodegradation of these dyes by means of spectrophotometry, HPLC, and IR spectroscopy of the solid waste and desorption solutions. We also demonstrate adsorption of compounds that resemble known degradation products.

Loci Identification of a N-acyl Homoserine Lactone Type Quorum Sensing System and a New LysR-type Transcriptional Regulator Associated with Antimicrobial Activity and Swarming in Burkholderia Gladioli UAPS07070.

A random transposition mutant library of B. gladioli UAPS07070 was analyzed for searching mutants with impaired microbial antagonism. Three derivates showed diminished antimicrobial activity against a sensitive strain. The mutated loci showed high similarity to the quorum sensing genes of the AHL-synthase and its regulator. Another mutant was affected in a gene coding for a LysrR-type transcriptional regulator. The production of toxoflavin, the most well known antimicrobial-molecule and a major virulence factor of plant-pathogenic B. glumae and B. gladioli was explored. The absence of a yellowish pigment related to toxoflavin and the undetectable transcription of toxA in the mutants indicated the participation of the QS system and of the LysR-type transcriptional regulator in the regulation of toxoflavin. Additionally, those genes were found to be related to the swarming phenotype. Lettuce inoculated with the AHL synthase and the lysR mutants showed less severe symptoms. We present evidence of the participation of both, the quorum sensing and for the first time, of a LysR-type transcriptional regulator in antibiosis and swarming phenotype in a strain of B. gladioli.

Extracellular HIV-1 Nef protein modulates lytic activity and proliferation of human CD8+ T lymphocytes.

The effect of extracellular HIV Nef (exNef) protein on the induction of lytic activity and proliferation of CD8+T lymphocytes from 18 donors was studied. At 10 ng/ml, exNef-induced a 2- to 8-fold enhancement of basal lytic activity in cells from all donors in an allogeneic induction assay, whereas it was ineffective at 100ng/ml. The extent of enhancement was inversely correlated with the basal level of lytic activity without exNef. Only in combination with PHA did both exNef concentrations stimulate proliferation, and in a manner inversely related to the effect of PHA alone. Thus, concentrations of exNef commonly found in sera of HIV-infected patients were found to modulate the induction of lytic activity and proliferation of CD8+ T lymphocytes in vitro, to an extent strongly dependent on the quite variable responsiveness of each donor. These findings point to Nef as a potential agent for modulating CD8+ T cell function in pathogenesis and therapy.

Interstitial cells of Cajal in patients with chagasic megacolon originating from a region of old endemicity.

UNLABELLED: Megacolon is the second most frequent and most important digestive manifestation of Chagas' disease. It is characterized by motor disorders and dilatation of the distal segments of the colon. Several theories have been presented to explain the physiopathology of chagasic megacolon, e.g. the plexus theory. OBJECTIVE: In the present study the distribution of interstitial cells of Cajal (ICC) was evaluated in colon biopsies from chronic chagasic patients originating from a region of old endemicity for Trypanosoma cruzi and for comparison in subjects with other colon disorders. The chagasic patients had been submitted to colectomy for the investigation of other possible mechanisms underlying the physiopathogenesis of megacolons. DESIGN STUDY: Twenty-two colon biopsies (15 from chagasic patients and 7 from nonchagasic patients) were examined. ICC were identified by immunohistochemistry by using the anti-CD117 antibody. The number of ICC was determined in longitudinal and circular muscle layers and in the myenteric plexus, and the results were analyzed by the Kruskal-Wallis and Student t-tests. RESULTS: A reduced number of ICC was observed in all layers and in the myenteric plexus of patients with chagasic megacolon (P<0.05). CONCLUSIONS: We conclude that the physiopathological manifestations observed in the large bowel of chagasic patients originate from alterations that occur in the ICC, which play an important role in the control of gut motility.

Genetic variation within human immunodeficiency viruses generates rapid changes in tropism, virulence, and transmission.

The human immunodeficiency viruses (HIV-1) undergo high rates of variation. Only a few point mutations in the envelope gene are required to switch the tropism of HIV-1 from a growth preference for monocytes to lymphocytes or to acquire lytic properties for rapid killing of infected T4 lymphocytes. Since heterosexual transmission efficiency is high for HIV-1's that are most prevalent in Africa or Asia, but low for HIV-1 B, which dominates in the US and western Europe, we asked whether African and Asian viruses had a particular tropism for cells of the reproductive tract. Langerhans' cells (LC), showed only minimal susceptibility to infection with HIV-1B from the US, but substantially greater sensitivity for infections by HIV-1 E and HIV-1 C, subtypes that predominate in Asia and Africa.

Human T-lymphotropic virus type I (HTLV-I)-specific antibodies and cell-free RNA in crevicular fluid-rich saliva from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy.

Despite the likely role of mucosae in human T cell leukemia virus type I (HTLV-I) transmission, little is known about the mucosal immune response to HTLV-I. The present study evaluated the antibody response to HTLV-I in oral mucosa and the value of crevicular fluid rich saliva (CFRS) for diagnosing HTLV-I infection. CFRS and sera from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), asymptomatic carriers, and HTLV-I seronegative individuals from Tumaco, Colombia, were analyzed for HTLV-I specific IgG, IgA, and secretory IgA (sIgA). Detection of IgG in CFRS by enzyme-linked immunosorbent assay correlated with its presence in sera for TSP/HAM patients and asymptomatic carriers. IgA and sIgA were more frequently detected in CFRS and sera from TSP/HAM patients than in those from asymptomatic carriers. An HTLV-I pol fragment could be amplified from CFRS by reverse transcriptase-PCR in 3 TSP/HAM patients and one asymptomatic carrier, all of whom had an IgA response in CFRS but not in sera. The more frequent detection of IgA and sIgA in sera and CFRS of TSP/HAM patients suggests increased viral replication. Further, the association of viral RNA in CFRS with a local IgA response may signify rounds of viral replication in the oral cavity.

Second recorded case of human infection by Echinococcus oligarthrus.

The paper reviews a previously published case of hydatid disease in the human heart of a Brazilian person who died of tetanus. Based on present knowledge about the distinguishing characteristics of Echinococcus granulosus, E. vogeli, and E. oligarthrus, it was recognized that the infection was due to E. oligarthrus, mainly based the morphologic features of the hooklets of the protoscolex. This is the second human infection due to E. oligarthrus and the first showing wall features of cysts. Therefore, some human infections of polycystic hydatid disease observed outside the range of the bush dog, the only definitive host of E. vogeli (Panama to Northern Argentina), may be due to E. oligarthrus rather than to E. vogeli.

Relationship between Trypanosoma cruzi and human chagasic megaesophagus: blood and tissue parasitism.

The persistence of Trypanosoma cruzi in tissue and blood of 52 patients in the digestive form of chronic Chagas disease was studied. These patients had chagasic megaesophagus and underwent corrective surgery. Parasitologic (xenodiagnosis, hemoculture, or both), histopathologic (hematoxylin and eosin, and peroxidase-anti-peroxidase staining), and molecular (polymerase chain reaction [PCR] followed by slot-blot hybridization) tests were used in the analysis. The presence of T. cruzi, its genomic fragments, or its antigens could be detected in 98% (51 of 52) of the patients. The parasite was randomly identified in 76.9% of esophageal tissues and in 90.4% by PCR and in 73.1% by parasitologic methods from the blood. Fifty percent (26 of 52) of tissue samples had inflammation, 80.8% of which was associated with the parasite. Trypanosoma cruzi was also identified unassociated with inflammatory alterations. Higher tissue parasitism and intense inflammatory processes were observed in esophageal tissue from patients with Grade IV megaesophagus. These data demonstrate that in the digestive form of Chagas' disease, particularly in cases of megaesophagus, T. cruzi is frequently found, both in blood and tissues and may contribute to the pathogenic mechanisms involved.

Histoplasma capsulatum isolated from Didelphis albiventris (Marsupialia: Didelphidae) in the State of Minas Gerais, Brazil.

We report the isolation of Histoplasma capsulatum from a culture of the viscera of Didelphis albiventris, one of the marsupial species found in Brazil. To our knowledge, this is the first report of the isolation of this fungus from this mammalian species. This finding confirms the ubiquitous presence of H. capsulatum in nature.

Nocardiasis in patients with HIV infection.

The frequency of Nocardia infection in HIV-infected patients has increased during the past few years from 0.3% in 1985 to 1.8% in 1989. Although it is not of great concern as an AIDS-associated infection, the nonspecific clinical presentation in these patients might be confused with other lung infections such as tuberculosis (TB). The mortality rate can be as high as 60%. The authors diagnosed three homosexual men with nocardiasis among 1060 HIV-infected patients (0.2%) in a tertiary care center in Mexico City from 1981 to 1997. The mean age was 32 years. The CD4 count was less than 260 cells/mm3 in all these individuals. The clinical presentations were subacute sinusitis, chronic localized abdominal abscess, and acute disseminated nocardiasis. The respective associated infections were none; TB and cytomegalovirus (CMV); and candidiasis, TB, CMV, Isospora belli, and disseminated Mycobacterium avium complex (MAC). Trimethoprim/sulfamethoxazole (TMP/SMX) was the treatment in all the cases; at the time of this writing, two patients were living and one had died during the acute episode. A literature search uncovered 130 cases of Nocardia infection in HIV patients since 1982. According to the published data and our results, nocardiasis should be suspected in those HIV-infected patients who (1) do not respond to appropriate antituberculous treatment; (2) are intravenous drug users; and (3) develop a characteristic pericardial infection. Finally, adequate surgical or percutaneous drainage of abscesses are extremely valuable for diagnosis and therapy.

[The evaluation of a new complement fixation microtechnic (Garcia & Sotelo, 1991) for the diagnosis of chronic Chagas disease with different antigenic preparations]. / Avaliação de uma nova microtécnica de fixação de complemento (Garcia & Sotelo, 1991) para o diagnóstico da doença de Chagas crônica com diferentes preparações antigênicas.

From this present data it has been evaluated a new complement fixation test, comparatively to indirect immunofluorescence to diagnose chronic Chagas' disease, utilizing one watery extract of epimastigotes of Trypanosoma cruzi and three other ethanolic extracts: one from epimastigotes, one from tripomastigotes and a third one of amastigotes obtained from cultures. Utilizing 236 serum samples indirect immunofluorescence test was performed: 109 positives (20 of them with positive parasitologic diagnostic) and 127 negatives (96 of healthy blood donors and 31 with other diseases). The results have showed that is possible a positive reaction in diluted samples up to 1:16. The best limits of reactivity found were the dilutions 1:4 for the ethanolic extract of amastigotes and 1:2 for the others antigens. The correlation index among the new complement fixation test and indirect immunofluorescence test showed that the ethanolic extract from epimastigotes was the best antigen to be utilized to diagnosis purposes. Its co-positivity index with indirect immunofluorescence was 0.92207 and the co-negative index was 0.90000. Concluding, the new complement fixation test showed itself as a fast, sensible, easily applicable semiquantitative microtechnique to the diagnosis of chronic Chagas' disease.

The hamster (Mesocricetus auratus) as experimental model in Chagas' disease: parasitological and histopathological studies in acute and chronic phases of Trypanosoma cruzi infection.

This research characterizes the acute and chronic phases of Chagas' disease in hamster through parasitological and histopathological studies. The acute phase was achieved with 44 young hamsters injected intraperitoneally with 100,000 blood trypomastigotes of Benedito and Y strains of T. cruzi. The chronic phase was induced in 46 hamsters injected intraperitoneally with 35,000 trypomastigotes of Vicentia, Benedito and Y strains. Animals were sacrificed at regular intervals of 24 hours of acute phase and from the 3rd to the 10th month of infection of chronic phase. In the acute phase, parasites were easily recovered from all animals and there was an inflammatory reaction characterized by mononuclear and polymorphous leukocyte infiltration of variable degree in the majority of tissues and organs, specially in the connective loose and fatty tissues, smooth muscle myocardium and skeletal muscle. In the chronic phase the lesions occurred in the same tissues and organs, but the inflammatory response was less severe and characterized by mononuclear infiltration mainly with focal or zonal fibrosis in the myocardium. In 50% of infected animals parasites were found in myocardium and recovered from pericardic, peritoneal and ascitic fluids in some animals. Signs of heart failure, sudden death and enlargement of bowel were observed regularly. We concluded that the hamster is an useful model for Chagas' disease studies.

[First evidence of Trypanosoma rangeli in the southeast of Brazil, an endemic region for Chagas' disease]. / Primeira evidência de Trypanosoma rangeli no sudeste do Brasil, região endêmica para doença de Chagas.

This short communication informs the discovery of Trypanosoma rangeli for the first time at Triângulo Mineiro region, South-east of Brazil, a highly endemic area of Chagas' disease and also the natural infection of Didelphis albiventris with the same trypanosome. Both the findings were demonstrated through blood smears, xenodiagnosis, microhematocrit technics and PCR. The last one was realized in faeces and hemolymph of Triatoma infestans utilizing as controls strains of T. rangeli from Colombia.

[Susceptibility of Triatoma infestans to various strains of Trypanosoma cruzi isolated from chagasic patients from the Triângulo Mineiro]. / Susceptibilidade do Triatoma infestans a diferentes cepas de Trypanosoma cruzi isoladas de pacientes chagásicos do Triângulo Mineiro.

This data evaluated the susceptibility of T. infestans to seven different strains of T. cruzi from chagasic patients of the Triângulo Mineiro, isolated and adapted in Swiss mice. A total of 200 bugs were fed in mice in acute phase injected with the different strains of T. cruzi and at each 30 days, during 5 months, their feces were obtained by abdominal compression or spontaneous dejection. The overall positivity of T. infestans infection with these different strains of T. cruzi was 62.08%. There was a high mortality rate (60%) during the examination period. We conclude that T. infestans has a low susceptibility to these strains. This could explain the low rate of positivity in the xenodiagnosis in chagasic chronic patients of the Triângulo Minerio.

[Cardiac neuronal depopulation in hamsters (Mesocricetus auratus) chronically infected with Trypanosoma cruzi]. / Despopulação neuronal cardíaca em hamsters (Mesocricetus auratus) cronicamente infectados com o Trypanosoma cruzi.

The aim of this study was to obtain an experimental animal model of destruction of cardiac neurons in order to investigate the behavior of the cardiac nervous system of hamsters chronically infected with Trypanosoma cruzi. We counted the neuronal cells of the cardiac autonomic nervous plexus in hamsters inoculated with 35,000 blood forms of three different T. cruzi strains and killed 5, 8 and 10 months after infection. We showed for the first time severe neuronal destruction in an experimental animal model with characteristics similar to those observed in human Chagas'disease.

Hepatocyte metaplasia in experimental chagasic pancreatitis: preliminary report.

Beginning the study of chronic pathologic changes in pancreas of hamsters experimentally infected with Trypanosoma cruzi Vic strain, hepatocyte metaplasia was observed in one animal from infected group. This is the first report of oncocytes in Chagas' disease, which could be due to aberrant regenerative response to pancreas inflammatory process.