Development and Clinical Evaluation of a Rapid Diagnostic Test for Yellow Fever Non-Structural Protein 1.

A rapid diagnostic test (RDT) kit was developed to detect non-structural protein 1 (NS1) of yellow fever virus (YFV) using monoclonal antibody. NS1 protein was purified from the cultured YFV and used to immunize mice. Monoclonal antibody to NS1 was selected and conjugated with colloidal gold to produce the YFV NS1 RDT kit. The YFV RDTs were evaluated for sensitivity and specificity using positive and negative samples of monkeys from Brazil and negative human blood samples from Korea. Among monoclonal antibodies, clones 3A11 and 3B7 proved most sensitive, and used for YFV RDT kit. Diagnostic accuracy of YFV RDT was fairly high; Sensitivity was 0.0% and specificity was 100% against Dengue viruses type 2 and 3, Zika, Chikungunya and Mayaro viruses. This YFV RDT kit could be employed as a test of choice for point-of-care diagnosis and large scale surveys of YFV infection under clinical or field conditions in endemic areas and on the globe.

Drug metabolism and transport gene polymorphisms and efavirenz adverse effects in Brazilian HIV-positive individuals.

Objectives: There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. Methods: We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. Results: There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. Conclusions: In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.

First report of persistent dengue-1-associated autoimmune neurological disturbance: neuromyelitis optica spectrum disorder.

Dengue virus (DENV) causes immune-mediated diseases. Neurological involvement represents a severe condition that is rarely observed in DENV-1 infection. Neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) are idiopathic immune-mediated demyelinating syndromes of the central nervous system. We report a 17-year-old female with oligosymptomatic DENV-1 viremia, diagnosed as NMOSD. Magnetic resonance imaging showed spinal cord and brainstem lesions. Antibody for aquaporin 4 was negative. DENV-1 RNA infection was detected by serial RT-PCR and confirmed by phylogenetic analysis in serum. Although there are some reports of NMO post-dengue infection, there are not any published accounts of NMOSD with coexistent and persistent DENV-1 infection.

Cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis in people with HIV.

OBJECTIVES: The study aimed to assess and compare cerebrospinal fluid (CSF)-CXCL13 levels in People with HIV (PWH) with suspected neurosyphilis (NS), those with syphilis but without NS, and patients without treponema infection. Additionally, it aimed to evaluate changes in CSF-CXCL13 concentrations before and after antibiotic treatment. DESIGN: This was a prospective cohort study involving 93 PWH suspected of NS. All participants underwent lumbar puncture, with CSF-CXCL13 levels measured at baseline and during follow-up in patients diagnosed with NS. METHODS: CSF-CXCL13 levels were quantified using ELISA. The Mann-Whitney U test was used to analyze differences between groups, while the Wilcoxon test assessed within subject changes. ROC curve analysis determined the diagnostic efficacy of CSF-CXCL13 for NS. RESULTS: Significantly higher CSF-CXCL13 levels were observed in patients with NS compared to those with syphilis without NS and non-syphilis patients. Posttreatment, a decline in CSF-CXCL13 levels was noted in all NS cases. A CSF-CXCL13 threshold exceeding 60.0 pg/ml, in conjunction with reactive CSF-FTA-ABS, yielded a sensitivity of 88.9% and a specificity of 97.6% for NS diagnosis. CONCLUSIONS: CSF-CXCL13 emerges as a valuable adjunctive biomarker for detecting NS in PWH, especially in cases with nonreactive CSF-VDRL. Monitoring CSF-CXCL13 levels also appears effective in evaluating therapeutic response in PWH undergoing NS treatment.

Correction: Hemostasis in elderly patients with human immunodeficiency virus (HIV) infection-Cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0227763.].

Secondary syphilis presenting as Syphilide psoriasiforme: lessons from the older syphilology literature.

It is essential for health care providers to be familiared with the full spectrum of clinical presentations of syphilis. We present herein a case of syphilide psoriasiforme, an uncommon but well recognized clinical presentation of secondary syphilis. A 46-year-old HIV-infected female patient was referred to our attention with a presumptive diagnosis of palmoplantar psoriasis. On examination, there were exuberant pinkish-red papules and plaques covered with a thick silvery scale in the palms, flexor surfaces of the wrists, and the medial longitudinal arches of the feet. Serological and histopathological analyses uncovered the diagnosis of syphilis. Clinical remission was obtained after treatment. A detailed review of the literature on syphilide psoriasiforme, including descriptions from older syphilology textsis provided. The present case report emphasizes the need for clinicians to have a heightened awareness of the varied and unusual clinical phenotypes of syphilis.

Hemostasis in elderly patients with human immunodeficiency virus (HIV) infection-Cross-sectional study.

INTRODUCTION: Aging and chronic HIV infection are clinical conditions that share the states of inflammation and hypercoagulability. The life expectancy of the world population has increased in the last decades, bringing as complications the occurrence of diseases that undergoing metabolic, bone, cardiological, vascular and neurological alterations. HIV-infected patients experience these changes early and are living longer due to the success of antiretroviral therapy. The objectives of this study was to evaluate some changes in the plasma hemostatic profile of 115 HIV-reactive elderly individuals over 60 years old in the chronic phase of infection, and compare with 88 healthy uninfected elderly individuals. Plasma determinations of D-dimers, Fibrinogen, von Willebrand Factor, Antithrombin, Prothrombin Time, Activated Partial Thromboplastin Time, and platelet count were performed. In the HIV-reactive group, these variables were analyzed according to viral load, protease inhibitor use and CD4+ T lymphocyte values. After adjusted values for age and sex, the results showed higher levels of Antithrombin (103%; 88%, p = 0.0001) and Prothrombin Time activities (92.4%; 88.2%, p = 0.019) in the HIV group compared to the control group. We observed higher values of Fibrinogen in protease inhibitor users in both the male (p = 0.043) and female (p = 0.004) groups, and in the female HIV group with detected viral load (p = 0.015). The male HIV group with a CD4+ count> 400 cells / mm3 presented higher von Willebrand Factor values (p = 0.036). D-Dimers had higher values in the older age groups (p = 0.003; p = 0.042, respectively). CONCLUSION: Our results suggest that the elderly with chronic HIV infection with few comorbidities had a better hemostatic profile than negative control group, reflecting the success of treatment. Protease inhibitor use and age punctually altered this profile.

A case of Bartonella neuroretinitis with macular star diagnosed by clinical, epidemiological, serological, and molecular data: resolution after initiation of antimicrobial therapy.

The differential diagnosis of optic neuritis is broad and varied. We report the case of a 24-year-old Brazilian man who presented with five-week history of fever, malaise, myalgia, severe fatigue, tender right preauricular lymphadenopathy, and acute vision blurring associated with right optic disc swelling and exudates in a macular star pattern. His illness developed soon after an infestation of fleas broke out among his cats. Diagnosis of ocular bartonellosis was confirmed by serological and molecular analyses targeting amplification of Bartonella spp. htrA gene. Signs and symptoms only improved after initiation of antimicrobial therapy.

Palate ulcer, uvular destruction and nasal septal perforation caused by Sporothrix brasiliensis in an HIV-infected patient.

Sporotrichosis is a human and animal disease caused by dimorphic pathogenic species of the genus Sporothrix. We report a dramatic presentation of Sporothrix brasiliensis infection, with destruction of the nasal septum, soft palate, and uvula of an HIV-infected woman. She was successfully treated with amphotericin B deoxycholate followed by itraconazole. Sporotrichosis remains a neglected opportunistic infection in patients with AIDS and awareness of this potentially fatal infection is of utmost importance.

Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report

Introduction: Previous retrospective studies have demonstrated that the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis and, additionally, in the monitoring of therapeutic efficacy. Objective: To describe three cases of patients with neurosyphilis (NS) treated at Hospital Universitário Gaffrée e Guinle, in Rio de Janeiro, Brazil, with suspected active syphilis with neurological symptoms. Case report: Three patients from Rio de Janeiro, Brazil, were investigated for symptomatic NS. The concentration of CSF-CXCL13 was prospectively performed by enzyme-linked immunosorbent assay (ELISA) in all participants at baseline and in follow-up visits at 3 months after therapy. CSF-CXCL13 concentrations were significantly higher in all three patients with established NS. The CSF-CXCL13 concentrations decreased after 3 months of therapy compared to baseline in all cases reported. The added high concentration of CSF-CXCL13 plus CSF-TPHA reactivity above 1:40 titer agreed with the diagnosis of NS in 100% of the cases. Conclusion: In this case series, we present three cases of NS diagnosed using CXCL13 in CSF as a complementary test. These case series suggest that the clinical use of CSF-CXCL13 is useful as a supplementary biomarker for NS and for monitoring the effectiveness of NS therapy, especially in patients with nonreactive CSF-VDRL, excluding other neurologic diseases

A sad portrait of congenital syphilis in the State of Rio de Janeiro. Case report with Polymerase Chain Reaction (PCR) of scrapings from skin lesions and placenta fragment positive for Treponema pallidum

Introduction: Congenital syphilis is a serious public health problem that causes high rates of intrauterine morbidity and mortality, revealing flaws and weaknesses in the health system. Objective: to report a case of congenital syphilis in a university hospital in the Center-South Region of the State of Rio de Janeiro, Brazil. Case report: A pregnant woman, aged between 19 and 23 years old, carrying a Pregnant Woman's Handbook with a record of seven prenatal consultations and a note of the serological reaction for positive syphilis, but without any treatment, hospitalized at the University Hospital of Vassouras (RJ), in labor, gave birth to a newborn (NB) with a clinical picture and serological test of congenital syphilis. The NB required care in an intensive care unit and was discharged 28 days after birth. Scraping of skin lesions of the NB and placenta was performed for analysis by molecular biology (PCR in house) and genetic material of Treponema pallidum was detected. Conclusion: Congenital syphilis is a serious outcome of syphilis during pregnancy, consuming high financial resources and significant emotional distress for the mother, father, the whole family, as well as for the health teams. Our case report was the first that we are aware of in Brazil with a diagnosis by PCR for positive Treponema pallidum of skin scraping and placental fragment. It also showed poor quality prenatal care, a common factor in most cases of CS in our reality

Chlamydia trachomatis asymptomatic urethritis recurrence among males living with HIV-1.

A prevalence of 3.47% of asymptomatic Chlamydia trachomatis urethritis has been previously reported among males living with HIV infection in Brazil. This study aims to assess the recurrence of C. trachomatis urethritis three years later in the same cohort of patients and analyze associated risk factors. A total of 115 male patients diagnosed with HIV infection, with no symptoms of urethritis and observed since May of 2015 in followup visits were enrolled. They had urine samplers tested by PCR for C. trachomatis and N. gonorrhoeae between February and March 2018. Results: Three of the four patients who had asymptomatic C. trachomatis urethritis three years before were recurrently positive for C. trachomatis urethritis. Two new patients were diagnosed as positives, accounting for a total asymptomatic C. trachomatis urethritis prevalence of 4.34%. The prevalence during the whole study was 5.21%. The relative risk for a new urethritis episode among those previously diagnosed with urethritis is RR=41.62 (95% CI: 9.42-183.84), p < 0.01. Patients who presented asymptomatic urethritis anytime and who were recurrently positive for C. trachomatis had a lower mean age (p<0.01). Married individuals were protected regarding asymptomatic urethritis [p<0.01, OR = 0.04 (0.005-0.4)] and had lower risk to develop recurrence [p<0.01, RR = 0.86 (0.74-0.99)]. Illicit drugs users had risk associated to asymptomatic urethritis [p=0.02, OR= 5.9 (1.03-34)] and higher risk to develop recurrence [p<0.01, RR=1.1 (1-1.22)]. Conclusion: The recurrence of asymptomatic C. trachomatis urethritis after treatment among males living with HIV infection in Brazil can be considered high and should not be neglected.

Prevalence of asymptomatic urethritis by Chlamydia trachomatis and Neisseria gonorrhoeae and associated risk factors among males living with HIV-1.

OBJECTIVES: The increase in HIV transmissibility in non-ulcerative sexually transmitted infection is already well-established. It is estimated that symptomatic carriers of N. gonorrhoeae and C. trachomatis have a relative risk of 4.8-fold and 3.6-fold, respectively, for the sexual acquisition of HIV. This type of evaluation for asymptomatic urethritis is necessary to reinforce strategies to combat HIV transmission. This study aims to assess the prevalence of patients with asymptomatic urethritis among men diagnosed with HIV-1 and determine the risk factors associated with this infection. METHODS: We enrolled a total of 115 male patients aged 18 years or older who have been diagnosed with HIV infection and have no symptoms of urethritis or other sexually transmitted infections and who have been evaluated between May and August 2015 in a follow-up visit at the Immunology Outpatient Clinic of a Brazilian University Hospital. RESULTS: Four asymptomatic patients were positive for C. trachomatis and were considered asymptomatic carriers of urethritis. Prevalence was 3.47%. Patients who were positive for C. trachomatis urethritis had a lower mean age (p = 0.015). CONCLUSION: The presence of asymptomatic sexually transmitted infection is a challenge in clinical practice. We recommend that, in outpatient practice, the habit of inquiring on previous sexual behavior to obtain more information about risks and associations with asymptomatic sexually transmitted infection, a routine physical examination and complementary tests to detect STI pathogens should be performed to discard these conditions. The development of rapid tests for this purpose should also be encouraged.

Dengue infection in the nervous system: lessons learned for Zika and Chikungunya.

Dengue, Zika and Chikungunya are emerging arboviruses and important causes of acute febrile disease in tropical areas. Although dengue does not represent a new condition, a geographic expansion over time has occurred with the appearance of severe neurological complications. Neglect has allowed the propagation of the vector (Aedes spp), which is also responsible for the transmission of other infections such as Zika and Chikungunya throughout the world. The increased number of infected individuals has contributed to the rise of neurological manifestations including encephalitis, myelitis, meningitis, Guillain-Barré syndrome and congenital malformations such as microcephaly. In this narrative review, we characterize the impact of the geographic expansion of the vector on the appearance of neurological complications, and highlight the lack of highly accurate laboratory tests for nervous system infections. This represents a challenge for public health in the world, considering the high number of travelers and people living in endemic areas.

Lymphocyte CD4+ cell count, strength improvements, heart rate and body composition of HIV-positive patients during a 3-month strength training program.

BACKGROUND: There is a lack of information regarding the positive effects of different types of physical training on HIV-positive patient immune function, body composition and physical fitness. The goal of this study was two-fold: 1) to determine the effects of a three-month progressive strength training program on lymphocyte CD4+ cell counts in HIV-positive patients; and 2) to measure strength improvements, body composition and cardiovascular alterations in HIV-positive patients after a strength training program. METHODS: Sixteen HIV-positive male subjects participated in a strength-training program. CD4+ cell count, heart rate body composition and strength measurements were acquired at rest two days before and two days after the program. RESULTS: The average CD4+ cell count was increased (%=23%, P=0.0005), and all strength tests also showed improvement (%=95%, P=0,0001). Patient resting heart rate decreased (%=9%, P=0.0042), as did the skinfold sum (%=16%, P=0.002). Limb circumference sum and body weight did not change. CONCLUSIONS: Considering that a decrease in CD4+ cell count, muscle mass and overall physical fitness are expected results of HIV infection, the strength training protocol described here is an effective and safe way to improve immune function, body composition and cardiovascular fitness in HIV-positive patients. The results provided an important evidence for the effectiveness of a 3-month progressive resistance exercise training program at increasing immune function and physical fitness, strongly recommending its inclusion in the standardized treatment plan of HIV-positive patients.

Secondary Syphilis Presenting as Glossodynia, Plaques en Prairie Fauchée, and a Split Papule at the Oral Commissure: Case Report and Review.

Syphilis has been coined "the great imitator" due to its extreme heterogeneity of presentation and mimicry of other conditions. Therefore, it is essential that physicians be familiar with the full spectrum of its manifestations. Syphilis may also lead to oral lesions that, occasionally, are unaccompanied by concomitant tegumentary findings. Such patients will pose unique diagnostic challenges. We report the case of a 45-year-old HIV-infected male patient in whom secondary syphilis presented with burning mouth and dysgeusia that progressed to glossodynia and odynophagia. Examination revealed painful, shallow erosions on the posterior aspect of the tongue, in a pattern of plaques en prairie fauchée. A painful split papule (fausse perlèche or false angular cheilitis) was also present in the left commissure. There were no cutaneous lesions. The oral lesions were considered highly suggestive of secondary syphilis. A novel VDRL assay (which was previously negative) yielded a titer of 1/128. Complete clinical remission was rapidly achieved after initiation of penicillin therapy. A comprehensive review of the literature on oral manifestations of syphilis is offered.

Facial botryomycosis-like pyoderma in an HIV-infected patient: remission after initiation of darunavir and raltegravir.

Botryomycosis is an uncommon, chronic, suppurative, bacterial infection that primarily affects the skin and subcutaneous tissues. It has long been associated with defects of cellular immunity. We report a 28-year-old woman who presented with a chronic, ulcerated lesion with draining sinuses in the right malar region. Predisposing factors were HIV infection with poor immunological control, alcoholism, and a previous trauma to the right cheek. Several courses of antimicrobial therapy provided only partial and temporary remission. Complete clinical remission was only achieved 5 years later when a novel antiretroviral regimen composed of darunavir and raltegravir was initiated.

Disseminated dermatophytosis and acquired immunodeficiency syndrome: literature review and presentation of clinical experience / Dermatofitose disseminada e síndrome da imunodeficiência adquirida: revisão de literatura e apresentação de experiência clínica

Introduction: Dermatophytosis are very common fungal infections caused by the fungal species Microsporum, Epidermophyton or Trichophyton, which mostly affect the skin, the interdigital region, groin and scalp. Although they do not cause serious diseases, in patients with the human immunodeficiency virus the infection manifests itself and evolves exuberantly, usually with extensive and disseminated lesions. Objective: To review the literature on dermatophytosis in people living with human immunodeficiency virus and to present the experience in clinical care in a patient living with human immunodeficiency virus with extensive and disseminated dermatophytosis. Methods: A literature review on the topic was carried out in the PubMed/National Library of Medicine ­ USA databases, using the keywords dermatophytosis, or dermatophytosis associated with the words AIDS, human immunodeficiency virus or immunodeficiency, from 1988­2022. The clinical experience showed a patient living with human immunodeficiency virus developing AIDS and presenting with disseminated skin lesions. Samples of the lesion were collected by scraping, which were submitted to culture and there was growth of fungi of the Trichophyton sp genus. A biopsy of the lesion was also performed using the Grocott-Gomori's Methenamine Silver stain. Results: We found 1,014 articles, of which only 34 presented a direct correlation with our paper, and were used to discuss the main themes narrated in this article. We present clinical experience in the management of a patient with human immunodeficiency virus/AIDS and low adherence to antiretroviral treatment, showing extensive and disseminated erythematous-squamous lesions with a clinical diagnosis of tinea corporis, manifesting with a clinical picture usually not found in immunocompetent patients. The diagnosis was confirmed by laboratory tests with isolation of the Trichophyton sp fungus. The patient was treated with oral fluconazole, with complete remission of the clinical picture after two months. She was also thoroughly encouraged to use the prescribed antiretroviral medication correctly. Conclusion: Dermatophytosis in patients living with human immunodeficiency virus can present extensive and disseminated forms. The antifungal treatment is quite effective, with remission of the condition. Antiretroviral therapy is an important adjuvant for better recovery of the sickness.

Introdução: Dermatofitoses são infecções comuns, causadas pelas espécies fúngicas Microsporum, Epidermophyton ou Trichophyton, que acometem preferencialmente a pele da região interdigital, da virilha e do couro cabeludo. Apesar de não causar doenças graves, em pacientes portadores do vírus da imunodeficiência humana, a infecção se manifesta e evolui de forma exuberante, normalmente com lesões extensas e disseminadas. Objetivo: Fazer revisão de literatura sobre dermatofitose em pessoas vivendo com vírus da imunodeficiência humana e apresentar a experiência na atenção clínica em uma paciente vivendo com o vírus e dermatofitose extensa e disseminada. Métodos: A revisão de literatura sobre o tema baseou-se nos dados do Pubmed/National Library of Medicine, dos Estados Unidos, utilizando-se as palavras-chave dermatofitose, dermatofitose e AIDS, dermatofitose e vírus da imunodeficiência humana, e dermatofitose e imunodeficiência, de 1988­2022. Descreveu-se a experiência clínica na abordagem de uma paciente vivendo com vírus da imunodeficiência humana, a qual desenvolveu AIDS e apresentou lesões cutâneas disseminadas. Por raspado, foram coletadas amostras da lesão e submetidas à cultura, e constatou-se crescimento de fungos do gênero Trichophyton sp. Realizou-se também biópsia da lesão, corada pelo método da metenamina de prata de Grocott-Gomori. Resultados: Foram encontrados 1.014 artigos, dos quais apenas 34 apresentaram correlação direta com nosso trabalho, e foram utilizados para discorrer sobre os principais temas narrados neste artigo. Apresentou-se experiência clínica na abordagem de uma paciente com vírus da imunodeficiência humana/AIDS e baixa adesão ao tratamento antirretroviral, exibindo lacerações eritematoescamosas extensas e disseminadas, com diagnóstico clínico de Tinea corporis, manifestando-se com quadro clínico usualmente não encontrado em pacientes imunocompetentes. O diagnóstico foi confirmado por exames laboratoriais com isolamento do fungo Trichophyton sp. Tratada com fluconazol via oral, a paciente apresentou remissão parcial das infecções aos dois meses e completa aos seis meses. Também foi exaustivamente estimulada a usar corretamente a medicação antirretroviral prescrita. Conclusão: A dermatofitose em pacientes com vírus da imunodeficiência humana pode se apresentar de forma extensa e disseminada. O tratamento antifúngico é eficaz, com remissão do quadro. A terapia antirretroviral é importante adjuvante para melhor recuperação dos enfermos

Laryngeal paracoccidioidomycosis presenting as solitary true vocal fold disease.

Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by Paracoccidioides brasiliensis or P. lutzii. It is a neglected tropical infectious disease that poses a major public health burden in endemic areas of Latin America. Mucosae of the upper digestive and respiratory tracts are commonly involved and many patients have disease at multiple mucosal sites, with or without lung involvement. Mucosal PCM presenting as solitary true vocal fold disease is relatively rare. We present the case of a 67-year-old Brazilian forest guard who presented with a 6-month history of hoarseness and globus pharyngeus due to a solitary left true vocal fold infiltration and vegetation diagnosed as PCM. Silent pulmonary disease was also present. A laryngoscopy video is offered as supplemental material to this report. He completely remitted after surgical removal and amphotericin B deoxycholate treatment.