Molluscum contagiosum in the setting of Fingolimod: The experience at one institution.

Fingolimod treatment has been associated with opportunistic infections, most notably PML and cryptococcal meningitis. There are rare reports of other infections like molluscum contagiosum which are typically associated with impaired cellular immunity as seen in AIDS. Upon review of our multiple sclerosis patient database, we identified eight patients undergoing fingolimod treatment who developed molluscum contagiosum infections. We suspect that this association is a class effect and may also be observed with other S1P receptor modulators. While molluscum contagiosum infection is not life-threatening, it can be extremely distressing for patients, and resolution may require discontinuation of fingolimod.

Respiratory Complications in Children and Adolescents with Human Immunodeficiency Virus.

Respiratory complications comprise a large proportion of the burden of mortality and morbidity in children with human immunodeficiency virus (HIV). HIV-associated lower respiratory tract infection (LRTI) has declined in incidence with early diagnosis and use of antiretroviral therapy (ART) but is widespread in areas with limited access to ART. HIV-exposed uninfected infants have a higher risk of LRTI early in life than unexposed infants. Pulmonary tuberculosis (PTB) presenting as acute or chronic disease is common in highly TB endemic areas. Chronic lung disease is common; preceding LRTI, PTB or late initiation of ART are risk factors.

Pneumocystis pneumonia, a COVID-19 mimic, reminds us of the importance of HIV testing in COVID-19.

While clinical environments are highly focused on COVID-19, reports of missed or delayed treatment for conditions that imitate COVID-19, such as pneumonia caused by the fungus Pneumocystis jirovecii, are emerging. Given the uncertain spectrum of COVID-19 presentations and variable sensitivity of laboratory tests for SARS-CoV-2, there is a risk that, without a high index of suspicion, alternative aetiologies may be overlooked while pursuing a diagnosis of COVID-19. The British HIV Association has been calling for the inclusion of HIV testing in all patients admitted to hospital with suspected COVID-19. In this article we reflect on the importance of including HIV testing to prevent avoidable morbidity and mortality in our patients.

Landmark clinical observations and immunopathogenesis pathways linked to HIV and Cryptococcus fatal central nervous system co-infection.

Cryptococcal meningitis remains one of the leading causes of death among HIV-infected adults in the fourth decade of HIV era in sub-Saharan Africa, contributing to 10%-20% of global HIV-related deaths. Despite widespread use and early induction of ART among HIV-infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease. Cryptococcus species that causes fatal infection follows systemic spread from initial environmental acquired infection in lungs to antigenaemia and fungaemia in circulation prior to establishment of often fatal disease, cryptococcal meningitis in the CNS. Cryptococcus person-to-person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV-cryptococcal meningitis, seizures are common among a third of the patients, altered mental status is frequent, anaemia is prevalent with ensuing brain hypoxia and at autopsy, brain fibrosis and infarction are evident. In addition, fungal burden is 3-to-4-fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD-1/PD-L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple Cryptococcus species cause disease in this setting, observations are mostly generalised to cryptococcal infection/meningitis or regional dominant species (C neoformans or gattii complex) that may limit our understanding of interspecies differences in infection, progression, treatment or recovery outcome. Together, these factors and underlying mechanisms are hypotheses generating for research to find targets to prevent infection or adequate therapy to prevent persistent high mortality with current optimal therapy.

Care of Critically Ill Patients with Human Immunodeficiency Virus.

Care of patients with human immunodeficiency virus (HIV) infection in the intensive care unit (ICU) has changed dramatically since the infection was first recognized in the United States in 1981. The purpose of this review is to describe the current important aspects of care of patients with HIV infection in the ICU, with a primary focus on the United States and developed countries. The epidemiology and initial approach to diagnosis and treatment of HIV (including the newest antiretroviral guidelines), common syndromes and their management in the ICU, and typical comorbidities and opportunistic infections of patients with HIV infection are discussed.

Disease of the Year 2019: Ocular Toxoplasmosis in HIV-infected Patients.

Ocular toxoplasmosis (OT) may be an initial manifestation of acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected patients. OT has different clinical manifestations and can mimic other intraocular infections. Clinical findings may show single or multifocal retinochoroidal lesions or panuveitis. Atypical presentations are associated with extensive uni- or bilateral areas of retinal necrosis. OT lesions not associated with preexisting retinochoroidal scars are usually due to acquired rather than congenital infection. When CD4+ T cell counts are <100 c/uL, vitritis is frequently mild. Isolated anterior uveitis has been reported in single cases. Positive immunoglobulin M (IgM) antibodies are rare but their presence can support the diagnosis. As atypical presentations of OT are common, anterior chamber puncture for multiplex polymerase chain reaction amplification of infectious DNA should be considered, as early diagnosis and treatment can prevent massive tissue destruction and preserve vision. This review provides an overview of OT in HIV-infected patients.

The immunopathogenesis of tuberculous pericarditis.

Tuberculous pericarditis is a severe form of extrapulmonary tuberculosis and is the commonest cause of pericardial effusion in high incidence settings. Mortality ranges between 8 and 34%, and it is the leading cause of pericardial constriction in Africa and Asia. Current understanding of the disease is based on models derived from studies performed in the 1940-50s. This review summarises recent advances in the histology, microbiology and immunology of tuberculous pericarditis, with special focus on the effect of Human Immunodeficiency Virus (HIV) and the determinants of constriction.

Unpacking the dynamics of double stigma: how the HIV-TB co-epidemic alters TB stigma and its management among healthcare workers.

BACKGROUND: HIV and tuberculosis (TB) are intricably interlinked in South Africa. The social aspects of this co-epidemic remain relatively unexplored. More specifically, no research has quantitatively explored the double stigma associated with HIV and TB in this context, and more specifically the impact of the co-epidemic on [1] the stigmatisation of TB and [2] the TB stigma mangement strategy of covering (i.e. the use of TB as a cover for having HIV). The current study aims to address this research gap by disentangling the complex mechanisms related to HIV-TB stigma. METHODS: Using Structural Equation Modelling (SEM), data of 882 health care workers (HCWs) in the Free State province, South Africa, are analysed to investigate the link between the stigmatization of HIV and TB and the stigma management by those affected. The current study focuses on health care workers (HCWs), as both TB and HIV have a severe impact on this professional group. RESULTS: The results demonstrate that the perceived link between the epidemics is significantly associated with double HIV-TB stigmatization. Furthermore, the link between the illnesses and the double stigma are driving the stigmatization of TB. Finally, the link between HIV and TB as well as the stigmatization of both diseases by colleagues are associated with an increased use of covering as a stigma management strategy. CONCLUSIONS: This is the first quantitative study disentagling the mediating role of double stigma in the context of the co-epidemic as well as the impact of the co-epidemic on the social connotations of TB. The results stress the need for an integrated approach in the fight against HIV and TB recognizing the intertwined nature of the co-epidemic, not only in medical-clinical terms, but also in its social consequences. TRIAL REGISTRATION: South African National Clinical Trials Register, registration ID: DOH-27-1115-5204. Prospectively registered on 26 August 2015.

Interactions between immune response to fungal infection and microRNAs: The pioneer tuners.

Due to their physiological and biological characteristics, numerous fungi are potentially emerging pathogens. Active dynamicity of fungal pathogens causes life-threatening infections annually impose high costs to the health systems. Although immune responses play crucial roles in controlling the fate of fungal infections, immunocompromised patients are at high risk with high mortality. Tuning the immune response against fungal infections might be an effective strategy for controlling and reducing the pathological damages. MicroRNAs (miRNAs) are known as the master regulators of immune response. These single-stranded tuners (18-23 bp non-coding RNAs) are endogenously expressed by all metazoan eukaryotes and have emerged as the master gene expression controllers of at least 30% human genes. In this review article, following the review of biology and physiology (biogenesis and mechanism of actions) of miRNAs and immune response against fungal infections, the interactions between them were scrutinised. In conclusion, miRNAs might be considered as one of the potential goals in immunotherapy for fungal infections. Undoubtedly, advanced studies in this field, further identifying of miRNA roles in governing the immune response, pave the way for inclusion of miRNA-related immunotherapeutic in the treatment of life-threatening fungal infections.

Aortic Graft Infection With Mycobacterium Avium Complex.

Aortic graft infections are uncommon complications after endovascular aortic surgery. In the majority of cases, gram-positive and then gram-negative organisms are the causative agents leading to this condition. Atypical organisms are traditionally not responsible for graft infection unless the patient is immunocompromised. We are reporting a case of culture-confirmed mycobacterium avium complex infection of an aortic graft in a well-controlled patient with HIV who had an undetected viral load and a CD4 count of 324 while on highly active antiretroviral therapy.

Critically Ill Patients With HIV: 40 Years Later.

The development of combination antiretroviral therapies (cARTs) in the mid-1990s has dramatically modified the clinical presentation of critically ill, HIV-infected patients. Most cART-treated patients aging with controlled HIV replication are currently admitted to the ICU for non-AIDS-related events, mostly bacterial pneumonia and exacerbation of comorbidities, variably affected by chronic HIV infection (COPD, cardiovascular diseases, or solid neoplasms). Today, Pneumocystis jirovecii pneumonia, cerebral toxoplasmosis, TB, and other severe opportunistic infections only occur in patients with unknown viral status, limited access to cART, viral resistance, or compliance issues. Acute respiratory failure, neurological disorders, and sepsis remain the main conditions that lead HIV-infected patients to the ICU, although admissions for liver diseases or acute kidney injury are increasing. Case fatality dropped substantially over the past decades, reaching figures of HIV-uninfected critically ill patients with similar demographic characteristics, comorbidities, and level of organ dysfunctions. Several other facets of critical care management have evolved in this population, including diagnostic procedures, cART management at the acute phase of critical illness, and ethical considerations. The goal of this narrative review was to depict the current evidence and emerging challenges for the management of critically ill, HIV-infected patients, almost 40 years following the onset of the AIDS epidemic.

Eficácia antimicrobiana da terapia fotodinâmica no tratamento da candidíase oral em pessoas vivendo com HIV/Aids / Antimicrobial efficacy of photodynamic therapy on the treatment of oral candidiasis in people living with HIV/Aids / Eficacia antimicrobiana de la terapia fotodinámica en el tratamiento de la candidiasis bucal en personas viviendo con VIH/Sida

Objetivo: avaliar a eficácia antimicrobiana da terapia fotodinâmica no tratamento da candidíase oral em pessoas vivendo com HIV/aids. Método: estudo experimental, qualitativo e descritivo com 18 pessoas vivendo com HIV/aids que manifestavam a candidíase oral, maiores de 18 anos, que estavam em tratamento no Hospital Universitário Gaffrée e Guinle. Este grupo subdividiu-se em um grupo controle, composto por sete pessoas, que recebeu tratamento com a terapia fotodinâmica e antifúngicos, e um grupo experimental, com 11, que recebeu apenas a terapia fotodinâmica. A evolução do tratamento de cada participante foi acompanhada por registros fotográficos em duas consultas, inicial e final. Esta pesquisa foi aprovada pelo Comitê de Ética em Pesquisa do hospital, parecer número 2.431.107. Resultados: a maioria dos participantes apresentou melhora clínica, ainda que discreta, e em apenas um houve piora clínica. Conclusão: a terapia fotodinâmica antimicrobiana pode ser eficaz no tratamento da candidíase oral em pessoas vivendo com HIV/Aids

Objective: evaluate the antimicrobial efficacy of photodynamic therapy in the treatment of oral candidiasis in people living with HIV/ aids. Method: experimental, qualitative and descriptive study with 18 people living with HIV/aids who presented oral candidiasis, over 18 years of age, who were being treated at the Gaffrée and Guinle University Hospital. This group was subdivided into a control group, composed of seven people, who received treatment with photodynamic and antifungal therapy, and an experimental group, with 11, who received only the photodynamic therapy. The evolution of the treatment of each participant was followed by photographic registers in two appointments, initial and final. This research was approved by the Research Ethics Committee from the hospital, dictum number 2.431.107. Results: most of the participants showed clinical improvement, albeit discrete, and in only one there was clinical worsening. Conclusion: antimicrobial photodynamic therapy may be effective in the treatment of oral candidiasis in people living with HIV/Aids

Objetivo: evaluar la eficacia antimicrobiana de la terapia fotodinámica en el tratamiento de la candidiasis bucal en personas que viven con VIH/sida. Método: estudio experimental, cualitativo y descriptivo con 18 personas viviendo con VIH/sida que manifestaban la candidiasis bucal, mayores de 18 años, que estaban en tratamiento en el Hospital Universitario Gaffrée y Guinle. Este grupo se subdividió en grupo control, compuesto por siete personas, que recibió tratamiento con la terapia fotodinámica y antifúngicos, y un grupo experimental, con 11, que recibió sólo la terapia fotodinámica. La evolución del tratamiento de cada participante fue acompañada por registros fotográficos en dos consultas, inicial y final. La investigación fue aprobada por el Comité de Ética en Investigación del lugar, dictamen número 2.431.107. Resultados: la mayoría de los participantes presentó mejoría clínica, aunque discreta, y en apenas uno hubo empeoramiento clínico. Conclusión: la terapia fotodinámica antimicrobiana puede ser eficaz en el tratamiento de la candidiasis bucal en personas que viven con el VIH/Sida

Skin nodules in a young patient with HIV/AIDS.

AIDS-related Kaposi sarcoma (KS) is a malignancy seen in patients with HIV/AIDS that results from unrestrained human herpesvirus 8 infection. It can have an atypical presentation and an aggressive clinical course in patients with uncontrolled HIV infection. We present an interesting case of AIDS-related KS with an atypical initial presentation with skin nodules and debilitating lymphoedema. Patient was successfully managed with supportive measures, antiretroviral therapy and systemic chemotherapy.

Clinical features of Kaposi's sarcoma: experience from a Taiwanese medical center.

BACKGROUND: Most of the previous reports regarding the clinical features of Kaposi's sarcoma (KS) have been performed in Western and African countries. The clinical characteristics of KS have not been well defined in Han Chinese or Taiwanese patients. In this study, we analyzed the clinical features of KS patients in a Taiwanese medical center. METHODS: Medical records from Kaohsiung Medical University Hospital over the past 20 years (1996-2016) were comprehensively reviewed. RESULTS: There were 55 patients with KS (50 males and 5 females), including 37 patients (67%) with classic disease, 17 patients (31%) with AIDS-associated disease, and one patient (2%) with immunosuppressive medication-related disease. The average age was 58.7 years (range 20-87 years), and the average age was younger for AIDS patients (33.8 years) compared with non-AIDS patients (69.8 years). Among patients with classic KS, lesions were mostly localized to the lower extremities, whereas AIDS-associated KS patients were more likely to develop disseminated skin lesions, skin lesions on atypical sites (head and neck, trunk), and extracutaneous involvement (particularly oral cavity). The most common underlying diseases were diabetes mellitus (20% of patients) and hepatitis B (15% patients), and 38% of KS patients were smokers. Patients with AIDS-associated KS usually responded well to chemotherapy, whereas only 32% of patients with non-AIDS-associated KS showed complete response to radiotherapy. CONCLUSIONS: The findings of the current study will serve as important references for clinicians in the diagnosis of KS and may form the basis for the implementation of KS clinical practice guidelines in Taiwan.

A Model to Predict In-Hospital Mortality in HIV/AIDS Patients with Pneumocystis Pneumonia in China: The Clinical Practice in Real World.

We aimed to develop and validate a predictive model to evaluate in-hospital mortality risk in HIV/AIDS patients with PCP in China. 1001 HIV/AIDS patients with PCP admitted in the Beijing Ditan hospital from August 2009 to January 2018 were included in this study. Multivariate Cox proportional hazard model was used to identify independent risk factors of death, and a predictive model was devised based on risk factors. The overall in-hospital mortality was 17.3%. The patients were randomly assigned into derivation cohort (801cases) and validation cohort (200 cases) in 8:2 ratio, respectively, in which in derivation cohort we found that 7 predictors, including LDH >350U/L, HR>130 times/min, room air PaO2 <70mmHg, later admission to ICU, Anemia (HGB≤90g/L), CD4<50cells/ul, and development of a pneumothorax, were associated with poor prognosis in HIV/AIDS patients with PCP and were included in the predictive model. The model had excellent discrimination with AUC of 0.904 and 0.921 in derivation and validation cohort, respectively. The predicted scores were divided into two groups to assess the in-hospital mortality risk: low-risk group (0-11 points with mortality with 2.15-12.77%) and high-risk group (12-21 points with mortality with 38.78%-81.63%). The cumulative mortality rate also indicated significant difference between two groups with Kaplan-Meier curve (p<0.001). A predictive model to evaluate mortality in HIV/AIDS patients with PCP was constructed based on routine laboratory and clinical parameters, which may be a simple tool for physicians to assess the prognosis in HIV/AIDS patients with PCP in China.

Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.

Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.

AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.