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2.
BMC Infect Dis ; 20(1): 410, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532212

RESUMO

BACKGROUND: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts< 100 cells/µL, followed by pre-emptive antifungal therapy among CrAg positive (CrAg+) persons, to prevent cryptococcal meningitis related deaths. This strategy may also be considered for those persons with a CD4+ T cell count of < 200 cells/uL according the WHO guidelines. However, there is sparse evidence in the literature supporting CrAg screening and pre-emptive antifungal therapy in those HIV-infected persons with this CD4+ T cell counts< 200 cells/µL. METHOD: We conducted a meta-analysis using data extracted from randomized controlled studies (RCTs) and cohort studies found in a search of Pubmed, Web of Science, the Cochrane Library and the EMBASE/MEDLINE database. RESULTS: The pooled prevalence of CrAg positivity in HIV-infected persons with CD4+ T cell counts< 200 cells/µL was 5% (95%CI: 2-7). The incidence of CM in CrAg+ persons was 3% (95%CI: 1-6). Among those CrAg+ persons who did not receive pre-emptive treatment, or those who received placebo, the incidence of CM was 5% (95%CI: 2-9), whereas the incidence of CM among those who received pre-emptive antifungal therapy was 3% (95%CI: 1-6), which is a statistically significant reduction in incidence of 40% (RR: 7.64, 95%CI: 2.96-19.73, p < 0.00001). As for persons with CD4+ T cell counts between 101 ~ 200 cells/µL, the risk ratio for the incidence of CM among those receiving placebo or no intervention was 1.15, compared to those receiving antifungal treatment (95%CI: 0.16-8.13). CONCLUSIONS: In our meta-analysis the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4 <  200 cells/µL. However, more specific observational data in persons with CD4+ T cell counts between 101 ~ 200 cells/µL are required in order to emphasize specific benefit of CrAg screening and pre-emptive antifungal treating in CrAg+ persons with CD4+ T cell counts < 200 cells/µL.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antifúngicos/uso terapêutico , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/prevenção & controle , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antígenos de Fungos/sangue , Contagem de Linfócito CD4 , Cryptococcus/imunologia , Cryptococcus/isolamento & purificação , Humanos , Incidência , Programas de Rastreamento , Meningite Criptocócica/imunologia , Meningite Criptocócica/microbiologia , Prevalência
3.
BMC Infect Dis ; 20(1): 65, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964363

RESUMO

BACKGROUND: The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce. METHODS: Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV-1 co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells and PBMC using hemozoin crystals. Samples were analyzed using enzyme immunoassays and quantitative PCR. RESULTS: (i) IL-27 was markedly up-regulated in malaria patients compared with controls and HIV-infected patients without malaria, showing no relation to HIV co-infection. (ii) IL-27 was correlated with P. falciparum parasitemia and von Willebrand factor as a marker of endothelial activation, but not with disease severity. (iii) In vitro, IL-27 modulated the hemozoin-mediated cytokine response in endothelial cells and PBMC with enhancing effects on IL-6 and attenuating effects on IL-8. CONCLUSION: Our findings show that IL-27 is regulated during falciparum malaria, mediating both inflammatory and anti-inflammatory effects, potentially playing an immune-regulatory role during falciparum malaria.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Coinfecção/imunologia , HIV-1 , Interleucinas/sangue , Interleucinas/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Coinfecção/sangue , Estudos Transversais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Hemeproteínas/farmacologia , Humanos , Interleucinas/genética , Interleucinas/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Malária Falciparum/sangue , Masculino , Pessoa de Meia-Idade , Moçambique , Parasitemia/imunologia , Estudos Prospectivos , Adulto Jovem
4.
Virology ; 539: 18-25, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31629226

RESUMO

KSHV-associated inflammatory cytokine syndrome (KICS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). KICS is associated with high-level, systemic replication of KSHV. This study characterized the clinical and virologic features of a KICS patient over time. Additionally, it compared the cytokine profiles of the KICS case to Kaposi's sarcoma (KS) (n = 11) and non-KS (n = 6) cases. This KICS case presented with elevated levels of KSHV and IL-10, as expected. Surprisingly, this case did not have elevated levels of IL-6 or human immunodeficiency virus 1 (HIV-1). Nevertheless, treatment with anti-IL6 receptor antibody (tocilizumab) reduced KSHV viral load and IL-10. The KSHV genome sequence showed no significant changes over time, except in ORF24. Phylogenetic analysis established this isolate as belonging to KSHV clade A and closely related to other US isolates. These findings suggest IL-10 as potential biomarker and therapy target for KICS.


Assuntos
Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/fisiologia , Interleucina-10/sangue , Replicação Viral/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Biomarcadores/sangue , Síndrome da Liberação de Citocina , DNA Viral/sangue , DNA Viral/genética , Genoma Viral/genética , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/tratamento farmacológico , Herpesvirus Humano 8/classificação , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/isolamento & purificação , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Filogenia , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Carga Viral
5.
Mycoses ; 63(1): 4-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31597205

RESUMO

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.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , MicroRNAs , Micoses , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Animais , Aspergilose/imunologia , Aspergilose/metabolismo , Candidíase/imunologia , Candidíase/metabolismo , Coinfecção/imunologia , Coinfecção/metabolismo , Coinfecção/microbiologia , Criptococose/imunologia , Criptococose/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunoterapia , MicroRNAs/biossíntese , MicroRNAs/imunologia , MicroRNAs/metabolismo , MicroRNAs/uso terapêutico , Micoses/imunologia , Micoses/terapia , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/metabolismo , Transdução de Sinais/genética
6.
Physiol Rev ; 100(2): 603-632, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600121

RESUMO

Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Asma/imunologia , Infecções por HIV/imunologia , HIV/imunologia , Hipertensão Pulmonar/imunologia , Neoplasias Pulmonares/imunologia , Pulmão/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Infecções Respiratórias/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Animais , Fármacos Anti-HIV/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/virologia , Modelos Animais de Doenças , HIV/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/virologia , Hospedeiro Imunocomprometido , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/virologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/virologia , Prognóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/virologia , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Fatores de Risco
7.
Vasc Endovascular Surg ; 54(2): 191-194, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31578128

RESUMO

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.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Prótese Vascular/efeitos adversos , Infecções por HIV/tratamento farmacológico , Complexo Mycobacterium avium/patogenicidade , Infecção por Mycobacterium avium-intracellulare/microbiologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Adulto , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Implante de Prótese Vascular/instrumentação , Remoção de Dispositivo , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/imunologia , Infecção por Mycobacterium avium-intracellulare/terapia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/imunologia , Infecções Relacionadas à Prótese/terapia , Resultado do Tratamento
8.
J Infect Chemother ; 26(2): 279-281, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31543435

RESUMO

We report an AIDS patient with a high HIV RNA copy number in the plasma who was successfully treated for prolonged Mycobacterium avium bacteremia and other complications. An HIV-infected patient with high fever, anemia, high alkaline phosphatase, cystic lung lesions, hepatitis B virus infection and Kaposi's sarcoma was referred to our hospital. PCR of the blood revealed Mycobacterium avium bacteremia and the time to blood culture positivity was 8 days. The HIV-1 RNA copy number in the plasma was more than ten million copies/ml and the CD4-positive T cell count was 21 cells/µL. Although the high fever resolved five days after therapy for Mycobacterium avium was started, the fever recurred just before starting anti-retroviral therapy (ART) including dolutegravir. The patient experienced repeated but self-limiting bouts of severe inflammation. Mycobacteremia was intermittently detected up to 79 days, suggesting that the recurrent episodes of inflammation were due to the intermittent dissemination of mycobacteria, and that persistent treatment is needed. Five months after the beginning of ART, the HIV-1 RNA copy number in the plasma was still 28,000 copies/ml. An HIV drug-resistance test revealed sensitivity to all anti-retroviral drugs. Eleven months after the initiation of ART, the HIV RNA copy number in the plasma decreased to 45 copies/mL and the CD4-positive T cell count recovered to 205 cells/µL. Our case also suggests that dolutegravir can be effective in cases with prolonged high levels of HIV RNA. Our findings emphasize that prompt diagnosis and persistent therapy for mycobacterial infection are important for successful treatment.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Bacteriemia/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , RNA Viral/sangue , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Síndrome de Imunodeficiência Adquirida/complicações , Síndrome de Imunodeficiência Adquirida/imunologia , Adulto , Antibacterianos/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Bacteriemia/complicações , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/complicações , Retinite por Citomegalovirus/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Inflamação/complicações , Masculino , Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/complicações , Oxazinas , Piperazinas , Piridonas , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/tratamento farmacológico , Resultado do Tratamento
9.
Afr Health Sci ; 20(1): 219-226, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33402910

RESUMO

Background: Parvovirus B19 (B19) has tropism for cells of the erythroid lineage, which may lead to transient inhibition of erythropoiesis. Several studies and case reports suggested that B19 infection may contribute significantly to severe chronic anemia in HIV infected persons. Objective: To detect parvovirus B19 DNA in treatment-naïve HIV patients. Methods: This was a case control retrospective study. One hundred nineteen anemic and 81 non-anemic treatment-naïve HIV infected patients participated in the study at the Lagos University Teaching Hospital, Lagos, Nigeria. Polymerase chain reaction was used to detect B19 DNA. Results: Out of 200 patients analysed, 13(6.5%) had parvovirus B19 DNA. Eight HIV patients with anemia had B19 DNA while five non-anemic HIV patients had B19 DNA. This suggests that the presence of B19 DNA in the blood of HIV positive individuals may contribute to anemia because the majority (61.5%) who were positive for B19 DNA had anemia as compared to the non-anemic control group (38.5%). Conclusion: This study shows that the presence of B19 DNA in anemic HIV infected patients is not associated with chronic anaemia in HIV infection because no significant association exist.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Anemia/virologia , Infecções por HIV/complicações , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Idoso , Anemia/epidemiologia , Anemia/imunologia , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Criança , DNA Viral/análise , Feminino , Infecções por HIV/epidemiologia , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Infecções por Parvoviridae/sangue , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/imunologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Adulto Jovem
10.
Rev Chilena Infectol ; 36(5): 663-666, 2019 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-31859809

RESUMO

Bacteremia is an atypical presentation of Campylobacter jejuni infection and it is more frequent in patients with advanced inmunodepression due to HIV or other sistemic diseases. Because of the highly active antiretroviral therapy, in the last decades the number of cases had declined. We report a case of a homeless woman with HIV in C3 stage who was diagnosed with the bacteremia during her hospitalization for pulmonary tuberculosis, and a brief review of C. jejuni bacteremia in HIV patients.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Bacteriemia/microbiologia , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/imunologia , Infecções por Campylobacter/tratamento farmacológico , Infecções por Campylobacter/imunologia , Feminino , Humanos , Tuberculose Pulmonar/tratamento farmacológico
11.
Artigo em Inglês | MEDLINE | ID: mdl-31859848

RESUMO

Mycobacterium haemophilum is a nontuberculous mycobacterium that causes localized or disseminated disease, mainly in immunocompromised hosts. We report the case of a 35-year-old HIV-infected woman who presented with several enlarging cutaneous lesions over the arms and legs. Histopathological examination revealed the diagnosis of a cutaneous mycobacterial disease. Mycobacterial analyses unveiled M. haemophilum infection. Six months after completion of a successful antimycobacterial treatment, she developed an immune reconstitution inflammatory syndrome (IRIS). This paradoxical relapse presented as tenderness, redness and swelling at the precise sites of the healed lesions and took place in the setting of significant recovery of the CD4 cell count (from 05 to 318 cells/mm 3 ). Microbiological analyses of these worsening lesions were negative, and they spontaneously remitted without the initiation of a novel antimycobacterial treatment cycle. M. haemophilum infection should always be considered as a cause of skin lesions in immunocompromised subjects. Physicians should be aware of the possibility of IRIS as a complication of successful antiretroviral therapy in HIV-infected patients with M. haemophilum infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antirretrovirais/efeitos adversos , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Infecções por Mycobacterium/microbiologia , Mycobacterium haemophilum/isolamento & purificação , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Adulto , Antirretrovirais/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune/imunologia , Síndrome Inflamatória da Reconstituição Imune/metabolismo , Hospedeiro Imunocomprometido , Masculino , Infecções por Mycobacterium/imunologia
13.
Rev. chil. infectol ; 36(5): 663-666, oct. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1058093

RESUMO

Resumen La bacteriemia es una presentación atípica de la infección por Campylobacter jejuni, y es más frecuente en pacientes con inmunodepresión avanzada debido al VIH u otras enfermedades sistémicas. Debido a la terapia anti-retroviral, en las últimas décadas el número de casos ha disminuido. Presentamos el caso de una mujer en situación de calle, con VIH en etapa C3, que cursó con una bacteriemia por C. jejuni durante su hospitalización por una tuberculosis pulmonar. Realizamos una breve revisión de bacteriemia por C. jejuni en pacientes con VIH.


Bacteremia is an atypical presentation of Campylobacter jejuni infection and it is more frequent in patients with advanced inmunodepression due to HIV or other sistemic diseases. Because of the highly active antiretroviral therapy, in the last decades the number of cases had declined. We report a case of a homeless woman with HIV in C3 stage who was diagnosed with the bacteremia during her hospitalization for pulmonary tuberculosis, and a brief review of C. jejuni bacteremia in HIV patients.


Assuntos
Humanos , Feminino , Adulto , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/isolamento & purificação , Bacteriemia/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Infecções por Campylobacter/imunologia , Infecções por Campylobacter/tratamento farmacológico , Bacteriemia/imunologia , Bacteriemia/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antibacterianos/uso terapêutico
15.
Mycopathologia ; 184(6): 735-745, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31473910

RESUMO

Knowledge about the clinical and laboratory characteristics and prognosis of Talaromyces marneffei infection in children is limited. A retrospective study was conducted on pediatric patients with disseminated T. marneffei infection in a clinical setting. Extracted data included demographic information (age and sex), clinical features, laboratory findings, treatment, and prognosis. Eleven HIV-negative children were enrolled. The male/female ratio was 8:3. The median age of onset was 17.5 months (3.5-84 months). The mortality rate in these children was 36.36% (4/11). Seven children had underlying diseases. All of the children had multiple immunoglobulin abnormalities and immune cell decline. Ten children received voriconazole treatment, and most of the children (7/10) had a complete response to therapy at primary and long-term follow-up assessment; only three children died of talaromycosis. One patient recovered from talaromycosis but died of leukemia. The child who received itraconazole treatment also showed clinical improvement. No adverse events associated with antifungal therapies were recorded during and after the treatment. Talaromycosis is an indicator disease for undiagnosed severe immunodeficiencies in children. Awareness of mycoses in children by pediatricians may prompt diagnosis and timely treatment. Voriconazole is an effective, well-tolerated therapeutic option for disseminated T. marneffei infection in non-HIV-infected children.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Micoses , Talaromyces , Voriconazol/uso terapêutico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , China , Feminino , HIV-1 , Humanos , Lactente , Itraconazol/efeitos adversos , Itraconazol/uso terapêutico , Masculino , Micoses/tratamento farmacológico , Micoses/imunologia , Micoses/microbiologia , Micoses/mortalidade , Estudos Retrospectivos , Talaromyces/efeitos dos fármacos , Talaromyces/patogenicidade , Voriconazol/efeitos adversos
17.
PLoS Med ; 16(7): e1002840, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31276515

RESUMO

BACKGROUND: In high-burden settings, case fatality rates are reported to be between 11% and 32% in hospitalized patients with HIV-associated tuberculosis, yet the underlying causes of mortality remain poorly characterized. Understanding causes of mortality could inform the development of novel management strategies to improve survival. We aimed to assess clinical and microbiologic determinants of mortality and to characterize the pathophysiological processes underlying death by evaluating host soluble inflammatory mediators and determined the relationship between these mediators and death as well as biomarkers of disseminated tuberculosis. METHODS AND FINDINGS: Adult patients with HIV hospitalized with a new diagnosis of HIV-associated tuberculosis were enrolled in Cape Town between 2014 and 2016. Detailed tuberculosis diagnostic testing was performed. Biomarkers of tuberculosis dissemination and host soluble inflammatory mediators at baseline were assessed. Of 682 enrolled participants, 576 with tuberculosis (487/576, 84.5% microbiologically confirmed) were included in analyses. The median age was 37 years (IQR = 31-43), 51.2% were female, and the patients had advanced HIV with a median cluster of differentiation 4 (CD4) count of 58 cells/L (IQR = 21-120) and a median HIV viral load of 5.1 log10 copies/mL (IQR = 3.3-5.7). Antituberculosis therapy was initiated in 566/576 (98.3%) and 487/576 (84.5%) started therapy within 48 hours of enrolment. Twelve-week mortality was 124/576 (21.5%), with 46/124 (37.1%) deaths occurring within 7 days of enrolment. Clinical and microbiologic determinants of mortality included disseminated tuberculosis (positive urine lipoarabinomannan [LAM], urine Xpert MTB/RIF, or tuberculosis blood culture in 79.6% of deaths versus 60.7% of survivors, p = 0.001), sepsis syndrome (high lactate in 50.8% of deaths versus 28.9% of survivors, p < 0.001), and rifampicin-resistant tuberculosis (16.9% of deaths versus 7.2% of survivors, p = 0.002). Using non-supervised two-way hierarchical cluster and principal components analyses, we describe an immune profile dominated by mediators of the innate immune system and chemotactic signaling (interleukin-1 receptor antagonist [IL-1Ra], IL-6, IL-8, macrophage inflammatory protein-1 beta [MIP-1ß]/C-C motif chemokine ligand 4 [CCL4], interferon gamma-induced protein-10 [IP-10]/C-X-C motif chemokine ligand 10 [CXCL10], MIP-1 alpha [MIP-1α]/CCL3), which segregated participants who died from those who survived. This immune profile was associated with mortality in a Cox proportional hazards model (adjusted hazard ratio [aHR] = 2.2, 95%CI = 1.9-2.7, p < 0.001) and with detection of biomarkers of disseminated tuberculosis. Clinicians attributing causes of death identified tuberculosis as a cause or one of the major causes of death in 89.5% of cases. We did not perform longitudinal sampling and did not have autopsy-confirmed causes of death. CONCLUSIONS: In this study, we did not identify a major contribution from coinfections to these deaths. Disseminated tuberculosis, sepsis syndrome, and rifampicin resistance were associated with mortality. An immune profile dominated by mediators of the innate immune system and chemotactic signaling was associated with both tuberculosis dissemination and mortality. These findings provide pathophysiologic insights into underlying causes of mortality and could be used to inform the development of novel treatment strategies and to develop methods to risk stratify patients to appropriately target novel interventions. Causal relationships cannot be established from this study.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Coinfecção , Infecções por HIV/mortalidade , Mortalidade Hospitalar , Tuberculose/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Biomarcadores/sangue , Causas de Morte , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno , Humanos , Hospedeiro Imunocomprometido , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Sepse/imunologia , Sepse/microbiologia , Sepse/mortalidade , África do Sul/epidemiologia , Fatores de Tempo , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/microbiologia
18.
Braz J Infect Dis ; 23(3): 151-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271732

RESUMO

BACKGROUND: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. METHODS: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. RESULTS: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. CONCLUSIONS: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Fármacos Anti-HIV/uso terapêutico , Antígenos de Bactérias/imunologia , Linfócitos T CD8-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Tuberculose/imunologia , Apresentação do Antígeno/imunologia , Antígenos de Bactérias/efeitos dos fármacos , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Imunofenotipagem , Transmissão Vertical de Doenças Infecciosas , Masculino , Estudos Prospectivos , Adulto Jovem
19.
Arq Neuropsiquiatr ; 77(5): 357-365, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31189001

RESUMO

OBJECTIVE: Infections caused by the human immunodeficiency virus (HIV) and by the larvae of Taenia solium (i.e., cysticercosis) are still widespread in many developing countries. Both pathologies modify host immune status and it is possible that HIV infection may modulate the frequency and pathogeny of cysticercosis of the central nervous system (i.e., neurocysticercosis [NCC]). To describe published cases of NCC among HIV-positive patients and to evaluate whether the characteristics of NCC, including frequency, symptoms, radiological appearance, and response to treatment differed between HIV-positive and HIV-negative patients. METHODS: Forty cases of NCC/HIV co-infected patients were identified in the literature. Clinical and radiological characteristics, as well as response to treatment, were compared with non-matching historical series of NCC patients without HIV infection. RESULTS: Most of these patients had seizures and multiple vesicular parasites located in parenchyma. Clinical and radiological characteristics were similar between HIV-positive and HIV-negative patients with NCC, as well as between immunocompromised and non-immunocompromised HIV-positive patients. CONCLUSION: Our review did not reveal clear interactions between HIV and NCC. This may be partially due to the small number of cases and reliance on published research. A systematic, multi-institutional effort aiming to report all the cases of this dual pathology is needed to confirm this finding and to clarify the possible relationship between both pathogens.


Assuntos
Coinfecção , Infecções por HIV/complicações , Neurocisticercose/etiologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Contagem de Linfócito CD4 , Coinfecção/imunologia , Coinfecção/terapia , Feminino , Infecções por HIV/imunologia , Infecções por HIV/terapia , Humanos , Imunocompetência , Masculino , Neurocisticercose/imunologia , Neurocisticercose/terapia , Resultado do Tratamento
20.
J Infect Chemother ; 25(12): 1060-1064, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31227383

RESUMO

Mycobacterium genavense (M. genavense) is one of the most fastidious, difficult to culture Mycobacterium species. Patients infected with human immunodeficiency virus (HIV) may develop immune reconstitution inflammatory syndrome (IRIS) due to disseminated M. genavense infection as well as disseminated M. avium and intracellulare complex infection. Consensus regarding treatment of IRIS due to disseminated mycobacterium infection has not yet been obtained, although systemic steroid therapy has been recommended in recent guidelines. Here we report the case of a 48-year-old Japanese man diagnosed with HIV and disseminated M. genavense infection. His initial CD4-positive T cell count was 3/µL, and his HIV1-RNA viral load was 13,000 copies/mL. He developed IRIS due to disseminated M. genavense infection after two weeks of receiving antiretroviral agents. The patient's serum alkaline phosphatase level, as a barometer of disseminated M. genavense infection in this case, was difficult to control with several anti-mycobacterial agents, although his fever was improved by non-steroidal anti-inflammatory drugs. About five weeks after the onset of IRIS, the patient developed acute left upper quadrant pain and was diagnosed with splenic infarction by contrast-enhanced computed tomography. After the splenic infarction, the patient's serum alkaline phosphatase level decreased without systemic steroid therapy or anticoagulant agents, and his left upper quadrant pain improved naturally within a few days. This case suggests that IRIS due to disseminated M. genavense infection can complicate splenic infarction in patients with HIV, and splenic infarction could improve the IRIS due to disseminated M. genavense infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Síndrome Inflamatória da Reconstituição Imune/microbiologia , Infecções por Mycobacterium não Tuberculosas/complicações , Mycobacterium/isolamento & purificação , Infarto do Baço/imunologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Síndrome Inflamatória da Reconstituição Imune/complicações , Síndrome Inflamatória da Reconstituição Imune/tratamento farmacológico , Síndrome Inflamatória da Reconstituição Imune/imunologia , Masculino , Pessoa de Meia-Idade , Mycobacterium/imunologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/imunologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Baço/irrigação sanguínea , Baço/diagnóstico por imagem , Infarto do Baço/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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