The influence of HLA/HIV genetics on the occurrence of elite controllers and a need for therapeutics geotargeting view.

The interaction of HIV-1, human leukocyte antigen (HLA), and elite controllers (EC) compose a still intricate triad. Elite controllers maintain a very low viral load and a normal CD4 count, even without antiretrovirals. There is a lot of diversity in HIV subtypes and HLA alleles. The most common subtype in each country varies depending on its localization and epidemiological history. As we know EC appears to maintain an effective CD8 response against HIV. In this phenomenon, some alleles of HLAs are associated with a slow progression of HIV infection, others with a rapid progression. This relationship also depends on the virus subtype. Epitopes of Gag protein-restricted by HLA-B*57 generated a considerable immune response in EC. However, some mutations allow HIV to escape the CD8 response, while others do not. HLA protective alleles, like HLA-B*27, HLA-B*57 and HLA-B*58:01, that are common in Caucasians infected with HIV-1 Clade B, do not show the same protection in sub-Saharan Africans infected by HIV-1 Clade C. Endogenous pathway of antigen processing and presentation is used to present intracellular synthesized cellular peptides as well as viral protein fragments via the MHC class I molecule to the cytotoxic T-lymphocytes (CTLs). Some epitopes are immunodominant, which means that they drive the immune reaction to some virus. Mutation on an anchor residue of epitope necessary for binding on MHC class I is used by HIV to escape the immune system. Mutations inside or flanking an epitope may lead to T cell lack of recognition and CTL escape. Studying how immunodominance at epitopes drives the EC in a geographically dependent way with genetics and immunological elements orchestrating it may help future research on vaccines or immunotherapy for HIV.

The influence of HLA/HIV genetics on the occurrence of elite controllers and a need for therapeutics geotargeting view

The interaction of HIV-1, human leukocyte antigen (HLA), and elite controllers (EC) compose a still intricate triad. Elite controllers maintain a very low viral load and a normal CD4 count, even without antiretrovirals. There is a lot of diversity in HIV subtypes and HLA alleles. The most common subtype in each country varies depending on its localization and epidemiological history. As we know EC appears to maintain an effective CD8 response against HIV. In this phenomenon, some alleles of HLAs are associated with a slow progression of HIV infection, others with a rapid progression. This relationship also depends on the virus subtype. Epitopes of Gag protein-restricted by HLA-B*57 generated a considerable immune response in EC. However, some mutations allow HIV to escape the CD8 response, while others do not. HLA protective alleles, like HLA-B*27, HLA-B*57 and HLA-B*58:01, that are common in Caucasians infected with HIV-1 Clade B, do not show the same protection in sub-Saharan Africans infected by HIV-1 Clade C. Endogenous pathway of antigen processing and presentation is used to present intracellular synthesized cellular peptides as well as viral protein fragments via the MHC class I molecule to the cytotoxic T-lymphocytes (CTLs). Some epitopes are immunodominant, which means that they drive the immune reaction to some virus. Mutation on an anchor residue of epitope necessary for binding on MHC class I is used by HIV to escape the immune system. Mutations inside or flanking an epitope may lead to T cell lack of recognition and CTL escape. Studying how immunodominance at epitopes drives the EC in a geographically dependent way with genetics and immunological elements orchestrating it may help future research on vaccines or immunotherapy for HIV. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

Spondylodiscitis investigation and therapeutic protocol: neurosurgery service results / Protocolo investigativo e terapêutico de espondilodiscite: resultados de um serviço de neurocirurgia / Investigación de espondilodiscitis y protocolo terapéutico: resultados del servicio de neurocirugía

ABSTRACT Objective: Spondylodiscitis is still a frequent pathology among neurosurgical services, and its correct treatment involves infectious, neurological and orthopedic goals. The authors describe the protocol and report the diagnostic and therapeutic results after its implementation. Methods: A prospective prognostic study (Level I) including patients with primary spondylodiscitis treated in the Neurosurgical Service of Cristo Redentor Hospital from January 2014 to March 2018. Demographic, spine, infectious and treatment-related variables were analyzed. The numerical variables are presented as mean and standard deviation or median and interquartile range (according to their parametricity), and are compared by the student's t-Test or Mann-Whitney U Test, respectively. Results: Thirty seven patients were included. The sexes were evenly distributed, with predominantly Caucasians, and a mean age of 56.89 ±15.33. Hypertension and type 2 diabetes were the most frequent comorbidities. Vertebral lumbar level was the most involved segment. Pathogens were identified in 34 cases (91%), with Staphylococcus aureus being the most prevalent, followed by Koch Bacilli. Inflammatory markers are higher in pyogenic infections at hospital admission, but lower at hospital discharge when compared to tuberculous discitis (p<0.01). Mean hospital stay was higher in the pyogenic group. Conclusion: The protocol described has a high diagnostic level of the pathogen, with cure of infection and satisfactory neurologic outcome in all cases. Level of Evidence I, Diagnostic Studies - Investigating a Diagnostic Test.

RESUMO Objetivo: Espondilodiscite é uma patologia frequente nas enfermarias neurocirúrgicas, cujo tratamento adequado envolve questões infecciosas, neurológicas e ortopédicas. Os autores descrevem um protocolo reportando resultados diagnósticos e terapêuticos após sua implementação. Método: Estudo prognóstico prospectivo (Nível I) incluindo pacientes com espondilodiscite primária tratados de janeiro 2014 a março de 2018. Variáveis relacionadas a dados demográficos, vertebrais, infecciosos e terapêuticos foram analisados. Variáveis numéricas serão apresentadas como média e desvio padrão ou mediana e intervalo interquartil (conforme sua parametricidade) e analisadas com Teste T-Student ou Teste Mann-Whittney, respectivamente. Resultados: 37 pacientes foram incluídos, cuja média de idade foi 56.89 ±15.33. Hipertensão arterial e Diabetes foram as comorbidades mais prevalentes. O segmento lombar foi o mais acometido. Houve identificação do patógeno em 34 casos (91%), sendo o Staphylococcus aureus o mais frequente, seguido pelo Bacilo de Koch. Os marcadores inflamatórios foram maiores no grupo de discite piogênica no momento da admissão hospitalar, mas com valores inferiores aos da discite tuberculosa na alta hospitalar (p<0.01). A média de internação hospitalar foi maior no grupo piogênico. Conclusão: O protocolo descrito tem elevada taxa de identificação do patógeno com critérios de cura infecciosa e desfecho neurológico satisfatório em todos os casos descritos. Nível de Evidência I, Estudos diagnósticos - Investigação de um exame para diagnóstico.

RESUMEN Objetivo: La espondilodiscitis sigue siendo una patología frecuente en los servicios de neurocirugía y su tratamiento correcto incluye objetivos infecciosos, neurológicos y ortopédicos. Los autores describen un protocolo e informan los resultados diagnósticos y terapéuticos después de su implementación. Métodos: Estudio pronóstico prospectivo (Nivel I) que incluyó pacientes con espondilodiscitis primaria tratados en el Servicio de Neurocirugía del Hospital Cristo Redentor desde enero de 2014 hasta marzo de 2018. Se analizaron variables demográficas, vertebrales, infecciosas y relacionadas con el tratamiento. Las variables numéricas se presentan como promedio y la desviación estándar o mediana y rango intercuartil (según su parametricidad) y se comparan mediante la prueba t de Student o la prueba U de Mann-Whitney, respectivamente. Resultados: Se incluyeron 37 pacientes. Los sexos se distribuyeron uniformemente, con predominancia de caucásicos y una edad promedio de 56,89 ± 15,33. La hipertensión y la diabetes tipo 2 fueron las comorbilidades más frecuentes. El nivel lumbar fue el segmento más afectado. Se identificaron patógenos en 34 casos (91%), siendo el Staphylococcus aureus el más frecuente, seguido por el bacilo de Koch. Los marcadores inflamatorios fueron más en las infecciones piógenas en el hospital, pero más bajos en el alta hospitalaria en comparación con la discitis tuberculosa (p < 0,01). La estancia hospitalaria promedio fue mayor en el grupo piógeno. Conclusiones: El protocolo descrito tiene un alto nivel de diagnósticos del patógeno, con curación de la infección y resultados neurológicos satisfactorios en todos los casos. Nivel de Evidencia I, Estudios de diagnósticos - Investigación de un examen para diagnóstico.

Cell Index in the Diagnosis of External Ventricular Drain-Related Infections.

BACKGROUND: The use of an external ventricular drain is required for the treatment of many diseases, such as traumatic brain injury and subarachnoid hemorrhage (SAH). Meningitis and ventriculitis are frequent complications arising from the use of external ventricular drain therapy. This study aimed to determine the sensitivity, specificity, and cutoff point for cell index (CI) in patients with traumatic brain injury, SAH, and hemorrhagic stroke. METHODS: Our study population consisted of patients with different underlying diseases and few culture-positive cerebrospinal fluid samples. The diagnosis of infection was based on Centers of Disease Control and Prevention criteria. RESULTS: Overall CI analysis showed an area under the curve (AUC) of 0.982. The cutoff of 2.9 for overall CI provided a sensitivity of 95% and a specificity of 92.9%. In patients with SAH, the AUC was 1.0 for a CI of 2.8; furthermore, sensitivity and specificity were 100%. The relative variation of the CI was also assessed. This analysis revealed an AUC of 0.882, and a 4.33-fold increase was found be indicative of infection (P = 0.002), findings similar to those in the literature. In addition, a heatmap analysis demonstrated that the CI is unlikely to return to normal in patients with meningitis, even after treatment. CONCLUSIONS: Therefore, CI is valuable for the diagnosis of infection, but was inadequate for monitoring treatment. We hope to use the new cutoff point proposed by this study in our institution to improve patient clinical outcome.

External Ventricular Drain-Related Infection in Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: We aimed to analyze infection rates in patients with spontaneous intracranial hemorrhage who underwent surgical external ventricular drain (EVD) placement. METHODS: This prospective study included 94 consecutive patients who required an EVD for spontaneous intracranial hemorrhage at the Neurosurgery Department of Hospital Cristo Redentor, Porto Alegre, Rio Grande do Sul, Brazil. RESULTS: The mean duration of EVD use was 7 days. Overall sample mortality was 45%, and overall infection rate was 36%. Patients who had an EVD in place >10 days had higher odds of infection than patients who had an EVD in place ≤10 days (odds ratio = 3.1, 95% confidence interval, 1.1-8.7). Culture positivity rate was 5.3%. CONCLUSIONS: Our findings suggest that EVD infection is a very common complication, occurring in 36.2% of cases. We adopted ventriculitis as the standard diagnosis, as advocated by the U.S. Centers for Disease Control and Prevention. Considering the high lethality associated with intracranial hemorrhage, use of a more aggressive treatment protocol for this patient population might improve morbidity and mortality rates.

Distribution of filamentous fungi causing invasive fungal disease at the Haematological Unit, Hospital de Clínicas de Porto Alegre, Brazil.

Very limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7%), followed by Zygomycetes (13.8%). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced.

Distribution of filamentous fungi causing invasive fungal disease at the haematological unit, Hospital de Clínicas de Porto Alegre, Brazil

Very limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7 percent), followed by Zygomycetes (13.8 percent). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced.