Enfermedad de Castleman multicéntrica en pacientes HIV positivos. Reporte de dos casos y revisión de la literatura / Multicentric Astleman disease in HIV positive patients. Two cases. Report and literature review

La enfermedad de Castleman (EC) es un proceso linfoproliferativo poco frecuente que se caracteriza por hiperplasia de los ganglios linfáticos. Existen dos variedades histológicas bien diferenciadas la hialino-vascular y la plasmocelular, que a su vez pueden ser localizadas o multicéntricas. La forma hialino-vascular suele ser asintomática y localizada en mediastino mientras que la plasmocelular se presenta frecuentemente con signo-sintomatología sistémica y suele ser difusa o multicéntrica. En el contexto de la enfermedad debida al virus de la inmunodeficiencia humana (VIH), la EC se asocia en su patogenia a la infección por el herpes virus humano tipo-8 (HHV-8). La mayoría de los casos corresponden a la variante hialino-vascular (80/90%) en tanto un pequeño porcentaje (10/20%) son de la variante plasmocelular. En algunos pacientes, el patrón histopatológico puede ser mixto. Se describen dos casos de enfermedad de Castleman multicéntrica HHV8- positiva en pacientes con enfermedad HIV/SIDA.

Castleman's disease (CD), is a rare hematological condition of uncertain etiology, involves a massive proliferation of lymphoid tissues and typically presents as mediastinal masses. This is considered as a distinct type of lymphoproliferative disorder associated with inflammatory symptoms. In the context of human immunodeficiency virus (HIV) infection, CD is associated with human herpesvirus-8 (HHV8) infection. Most cases of CD represent either the hyaline vascular variant (80­90% of cases) or the plasma cell variant (10­20%); a small percentage present with a mixed histologic appearance. Two cases of Castleman's disease associated with HHV-8 and HIV/AIDS infection are described

Immunopathogenesis in HIV-associated pediatric tuberculosis.

Tuberculosis (TB) is an increasing global emergency in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients, in which host immunity is dysregulated and compromised. However, the pathogenesis and efficacy of therapeutic strategies in HIV-associated TB in developing infants are essentially lacking. Bacillus Calmette-Guerin vaccine, an attenuated live strain of Mycobacterium bovis, is not adequately effective, which confers partial protection against Mycobacterium tuberculosis (Mtb) in infants when administered at birth. However, pediatric HIV infection is most devastating in the disease progression of TB. It remains challenging whether early antiretroviral therapy (ART) could maintain immune development and function, and restore Mtb-specific immune function in HIV-associated TB in children. A better understanding of the immunopathogenesis in HIV-associated pediatric Mtb infection is essential to provide more effective interventions, reducing the risk of morbidity and mortality in HIV-associated Mtb infection in infants. IMPACT: Children living with HIV are more likely prone to opportunistic infection, predisposing high risk of TB diseases. HIV and Mtb coinfection in infants may synergistically accelerate disease progression. Early ART may probably induce immune reconstitution inflammatory syndrome and TB pathology in HIV/Mtb coinfected infants.

Osteomielitis por Klebsiella pneumoniae BLEE. Reporte de un caso y revisión de la literatura. / OSTEOMYELITIS DUE TO KLEBSIELLA PNEUMONIAE ESBL. REPORT OF A CASE AND LITERATURE REVIEW

Las betalactamasas de espectro extendido (BLEE) son enzimas producidas por bacilos gram negativos capaces de hidrolizar las cefalosporinas de amplio espectro y los monobactámicos. La mayoría pertenece a la familia de Enterobacteriae, tales como Klebsiella pneumoniae y Escherichia coli: Sin embargo, se asocian también con otras bacterias como Proteus, Serratia, Salmonella, Pseudomonas aeruginosa y Acinetobacter. Las enterobacterias productoras de carbapenemasas no sólo han sido aisladas en el ambiente hospitalario, sino que también provienen de la comunidad. Se presenta una paciente de sexo femenino con antecedentes de sida y osteomielitis secundaria a artritis séptica producida por una Klebsiella pneumoniae BLEE de la comunidad. Un tratamiento oportuno y eficaz puede evitar la opción quirúrgica, disminuyendo la morbimortalidad asociada con esta afección

Extended-spectrum beta-lactamases (ESBL) are enzymes produced by gram-negative rods capable of hydrolyzing broad-spectrum cephalosporins and monobactams. Most belong to the Enterobacteriae family, such as Klebsiella pneumoniae and Escherichia coli. However, they are also associated with other bacteria such as Proteus, Serratia, Salmonella, Pseudomonas aeruginosa and Acinetobacter. Carbapenemase-producing Enterobacteriaceae have not only been isolated from the hospital environment, but also from the community. We present a female patient with a history of AIDS and secondary osteomyelitis to septic arthritis caused by a community Klebsiella pneumoniae ESBL. It is concluded that a timely and effective treatment can avoids the surgical option, reducing the morbidity and mortality of this condition.

Cryptococcal antigen carriage among HIV infected children aged 6 months to 15 years at Laquintinie Hospital in Douala.

BACKGROUND: Up to 15% of deaths of people living with HIV is attributable to meningeal cryptococcosis, with nearly 75% occuring in sub-Saharan Africa. Although rare in children, it is a major cause of morbidity and mortality in people living with HIV. A strong association between cryptococcal antigenemia and the development of meningeal cryptococcosis has been shown in adults. Thus, in 2018, the World Health Organization published an updated version of its guidelines for the diagnosis, prevention and management of cryptococcal infection in adults, adolescents and the HIV-infected child. GOAL: To determine the prevalence of cryptococcal antigenemia and to identify its determinants in children infected with HIV. METHODS: An analytical cross-sectional study was carried out at the approved treatment center of Laquintinie hospital in Douala over a period of 4 months. Children were recruited consecutively after informed parental consent. Cryptococcal antigenemia and CD4 assay were performed using a Cryptops® immunochromatographic rapid diagnostic test and flow cytometry, respectively. The data collected included the socio-demographic, clinical and paraclinical variables of the children, as well as their antecedents. Data analysis was performed using Epiinfo software version 3.1 and SPSS 21.0. The significance threshold was set at 5%. RESULTS: A total of 147 children were enrolled. The mean age was 9.8 ± 4.09 years. The majority were on antiretroviral therapy (142, 96.60%). Only 13 (8.80%) were in severe immunosuppression. No child showed signs of meningeal cryptococcosis. The prevalence of cryptococcal antigenemia was 6.12%. Severe immunosuppression [OR: 10.03 (1.52-65.91), p = 0.016] and contact with pigeons [OR: 9.76 (1.14-83.65), p = 0.037] were independent factors significantly associated with the carriage of the cryptococcal antigen. CONCLUSION: We recommend screening for cryptococcal antigenemia and routine treatment with fluconazole of all HIV positive children with cryptococcal antigen whether symptomatic or not.

Impact of HIV-1 Infection and Antigen Class on T Follicular Helper Cell Responses to Pneumococcal Polysaccharide-Protein Conjugate Vaccine-13.

Pneumococcal infections are common and serious complications of HIV-1 disease. Prevention has been compromised by the limited magnitude and quality of Ab responses to T cell-independent type 2 pneumococcal capsular polysaccharides (PPS). The pneumococcal polysaccharide-protein conjugate vaccine-13 (PCV-13) contains PPS conjugated to the T cell-dependent protein (diphtheria toxoid [DT] [CRM197]). We investigated the differential response to PPS and DT by human Ab-secreting B cells (ASC) after immunization with PCV-13 in newly diagnosed healthy HIV+ and control adults. The numbers of PPS-specific IgG ASC increased significantly and similarly in HIV+ and controls. However, DT-specific IgG ASC increased in controls but not HIV+ subjects. To determine the cellular basis of these disparate responses to DT and PPS, we characterized the frequency and activation of T follicular helper (Tfh) cells, the predominant T cell subset providing B cell help. Expression of inducible T cell costimulator (ICOS), which sustains Tfh function and phenotype, increased significantly among controls, when compared with the HIV+ group. Increases in ICOS+ Tfh correlated with changes in T-dependent, DT-specific IgG ASC in controls but not in HIV+ In contrast, ICOS expression did not correlate with T cell-independent type 2 PPS-specific ASC in either group. Of note, upon optimized ex vivo stimulation, CD4 T cells from HIV+ subjects differentiated into Tfh cells and formed synapses with Raji B cells at frequencies similar to that of controls. In summary, PCV-13-induced increase in ICOS expression on Tfh was associated with responses to DT, which was compromised in recently diagnosed healthy HIV+ adults and can be restored ex vivo by providing effective Tfh-differentiating signals.

Functional and Activation Profiles of Mucosal-Associated Invariant T Cells in Patients With Tuberculosis and HIV in a High Endemic Setting.

Background: MAIT cells are non-classically restricted T lymphocytes that recognize and rapidly respond to microbial metabolites or cytokines and have the capacity to kill bacteria-infected cells. Circulating MAIT cell numbers generally decrease in patients with active TB and HIV infection, but findings regarding functional changes differ. Methods: We conducted a cross-sectional study on the effect of HIV, TB, and HIV-associated TB (HIV-TB) on MAIT cell frequencies, activation and functional profile in a high TB endemic setting in South Africa. Blood was collected from (i) healthy controls (HC, n = 26), 24 of whom had LTBI, (ii) individuals with active TB (aTB, n = 36), (iii) individuals with HIV infection (HIV, n = 50), 37 of whom had LTBI, and (iv) individuals with HIV-associated TB (HIV-TB, n = 26). All TB participants were newly diagnosed and sampled before treatment, additional samples were also collected from 18 participants in the aTB group after 10 weeks of TB treatment. Peripheral blood mononuclear cells (PBMC) stimulated with BCG-expressing GFP (BCG-GFP) and heat-killed (HK) Mycobacterium tuberculosis (M.tb) were analyzed using flow cytometry. MAIT cells were defined as CD3+ CD161+ Vα7.2+ T cells. Results: Circulating MAIT cell frequencies were depleted in individuals with HIV infection (p = 0.009). MAIT cells showed reduced CD107a expression in aTB (p = 0.006), and reduced IFNγ expression in aTB (p < 0.001) and in HIV-TB (p < 0.001) in response to BCG-GFP stimulation. This functional impairment was coupled with a significant increase in activation (defined by HLA-DR expression) in resting MAIT cells from HIV (p < 0.001), aTB (p = 0.019), and HIV-TB (p = 0.005) patients, and higher HLA-DR expression in MAIT cells expressing IFNγ in aTB (p = 0.009) and HIV-TB (p = 0.002) after stimulation with BCG-GFP and HK-M.tb. After 10 weeks of TB treatment, there was reversion in the observed functional impairment in total MAIT cells, with increases in CD107a (p = 0.020) and IFNγ (p = 0.010) expression. Conclusions: Frequencies and functional profile of MAIT cells in response to mycobacterial stimulation are significantly decreased in HIV infected persons, active TB and HIV-associated TB, with a concomitant increase in MAIT cell activation. These alterations may reduce the capacity of MAIT cells to play a protective role in the immune response to these two pathogens.

APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection.

Apolipoprotein L1 (APOL1), an innate immune factor against African trypanosoma brucei, inhibits HIV-1 in vitro. The impact of APOL1 G1-G2 variants on HIV-1-associated opportunistic infections (OIs) is unknown. Here, we report findings from a metaanalysis of four HIV/AIDS prospective cohorts (ALIVE, LSOCA, MACS, and WIHS) including 2066 African American participants. Using a global test combining all four cohorts, carriage of two APOL1 variant alleles is associated with a 50% reduction in odds of OI (combined OR 0.50, 95% CI 0.33-0.76). Subgroup analysis of OI etiological categories (viral, parasitic, fungal and Mycobacterial) suggests the possibility of specific protection from fungal infections (OR 0.54. 95% CI 0.32-0.93; PBonferroni corrected = 0.08). We observe an association of APOL1 variant alleles with host protection against OI in HIV-positive individuals. The study suggests a broader role of APOL1 variant alleles in innate immunity in vivo.

Determinant factors for the occurrence of tuberculosis after initiation of antiretroviral treatment among adult patients living with HIV at Dessie Referral Hospital, South Wollo, Northeast Ethiopia, 2020. A case-control study.

INTRODUCTION: Globally, tuberculosis takes the first rank for the ill-health of people living with HIV/AIDS. Despite the favorable outcome of antiretroviral therapy, the risk of tuberculosis remains higher among HIV patients. This obliges to identify factors for its occurrence and further prevention of drug-resistant tuberculosis. There is a contradiction between different studies and studies conducted in Ethiopia studied poorly the association between adherence to antiretroviral therapy and viral load with tuberculosis. Studies conducted in the study area were limited to cross-sectional study design. Therefore, this study claimed to identify factors determining the occurrence of tuberculosis after initiation of antiretroviral therapy. METHODS: This study was conducted at Dessie Referral Hospital by using a case-control study design on a sample of 565 with a control: case ratio of 3:1. Participants from controls were selected by systematic random sampling and from cases by consecutive random sampling. The data were collected by interviewing through structured questionnaires and from the medical record. The data were entered into Epi data version 3.1. In the multivariable analysis, variables with a P-value of ≤0.05 were anticipated as independent determinant factors. RESULT: Patients without separate kitchen (AOR: 3.547, 95% CI: 2.137, 5.888), having opportunistic infection (AOR: 3.728, 95% CI: 2.058, 6.753), CD4 count of <350 cells/mm3 (AOR: 3.383, 95% CI: 1.520, 7.528), baseline WHO stage III (AOR: 3.321, 95% CI: 1.688, 6.534) or IV (AOR: 2.900, 95% CI: 1.251, 6.722), don't taking IPT (AOR: 3.701, 95% CI: 2.228, 6.147) and those who were poorly adherent (AOR: 2.626, 95% CI: 1.272, 5.423) or moderately adherent (AOR: 3.455, 95% CI: 1.885, 6.335) to anti-retroviral therapy were more likely to develop tuberculosis after anti-retroviral therapy initiation. CONCLUSION: Poor housing conditions, having an opportunistic infection, low CD4 count, starting ART at the advanced HIV stage, don't take IPT, and being poorly adherent to antiretroviral therapy were associated with the occurrence of TB after initiation of ART. The institution should screen for TB as early as possible and strictly follow their drug adherence.

Intracranial Mass Lesions in Human Immunodeficiency Virus Patients in the Philippines: A Retrospective Cohort Study.

BACKGROUND: Central nervous system involvement is commonly seen in patients with human immunodeficiency virus (HIV) infection, with up to 2%-10% of patients presenting with intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population. METHODS: We performed a retrospective chart review of patients with HIV and evidence of intracranial mass lesions on cranial magnetic resonance imaging or computed tomography from 2007 to 2018. Demographic data, clinical features, etiology, surgical management, and outcomes were collected. RESULTS: The prevalence of intracranial mass lesions in our cohort was 2.2% (45/2032). Patients were predominantly male (98%), with a mean age at diagnosis of 28 years. The most common clinical manifestations were headache (75%), focal weakness (49%), and seizures (32%). The most common diagnoses were toxoplasmic encephalitis (51%) and tuberculosis (24%). Biopsy or excision was performed in 10% of cases, leading to a definitive diagnosis in 60% of these cases. A favorable outcome was observed in 58% of all patients at 46 months median follow-up, with adequate disease-specific treatment. CONCLUSIONS: The prevalence of intracranial mass lesions in Filipino patients with HIV is 2.2%. The most common etiology was toxoplasmic encephalitis followed by tuberculosis. These findings are substantially different from other findings reported in the literature and should be considered in formulating guidelines for the Filipino population.

Anti-Toxoplasmic Immunoglobulin G Quantitation Correlates with Immunovirological Parameters of HIV-Infected Cameroonians.

BACKGROUND: Toxoplasmosis is still a neglected common opportunistic infection in immunocompromised individuals, who are mainly people living with HIV (PLHIV) in whom reactivation of toxoplasmosis may occur with advanced HIV conditions in resource-limited settings (RLS). OBJECTIVE: The objective was to assess the correlation between anti-toxoplasmic immunoglobulin G (anti-Toxo IgG) concentration and the immuno-virological status of PLHIV. METHODS: A cross-sectional study was conducted in the year 2018 among 100 PLHIV aged ≥18 years in Yaounde-Cameroon. For each participant, anti-Toxo IgG, CD4-T lymphocytes, and plasma viral load (PVL) were measured using ELISA, flow cytometry, and real-time PCR, respectively. RESULTS: Overall, 56% of the participants were seropositive for anti-Toxo IgG, while 33% were negative and 11% were equivocal. All (n=19) those with PVL>1000 copies/mL were seropositive to anti-Toxo IgG versus 52.85% (37/70) with PVL<1000 copies/mL; p<0.0001. Interestingly, all (n=11) those with severe immunodeficiency (T-CD4<200 cells/µL) were positive to anti-Toxo IgG versus 57.69% (45/78) with T-CD4>200 cells/µL; p<0.0001. Most importantly, PVL and anti- Toxo IgG concentration were positively correlated (r = 0.54; p<0.0001), while T-CD4 and anti- Toxo IgG concentration were negatively correlated (r = - 0.70; p<0.0001). Adjusting age, gender, immune status, and virological profile in logistic regression shows that only immune status was independently associated with the serological status of toxoplasmosis (p=0.0004). CONCLUSION: In Cameroon, about half of PLHIV might be seropositive to anti-Toxo IgG, with decreasing immunity appearing as a risk of toxoplasmosis relapse. Thus, in the context of immunodeficiency, routine quantification of anti-Toxo IgG would alleviate the programmatic burden of this opportunistic infection in RLS with the generalized HIV epidemic.

Types and prevalence of HIV-related opportunistic infections/conditions among HIV-positive patients attending Kenyatta National Hospital in Nairobi, Kenya.

BACKGROUND: Although antiretroviral therapy (ART) has resulted in significant decrease in opportunistic infections (OIs), OIs continue to cause significant morbidity and mortality among HIV patients. OBJECTIVE: To determine the prevalence and types of HIV/AIDS-related OIs among patients attending Kenyatta National Hospital (KNH) in Nairobi, Kenya. METHODS: A cross-sectional study was conducted from May to August 2010 among patients ≥19 years. An interviewer-administered questionnaire was used to collect data on socio-demographic factors, HIV and OIs. CD4 data were extracted from clinical records. RESULTS: Most patients (72%) had lived with HIV for ≤ 5 years and 78.8% had an OI. The 3 most common OIs were TB (35%), Herpes Zoster (HZ; 15.4%) and oral thrush (OT; 8%). Years of HIV infection significantly predicted TB (p=0.01). Patients with CD4 ≤ 349 were almost twice as likely to have TB, than those with CD4 ≥500. Type of occupation predicted OT (p=0.04) with skilled workers less likely to have OT. Patients with primary/vocational/technical education were >3 times more likely to have HZ than those with tertiary education. CONCLUSION: Due to the complex management of HIV and its associated OIs, appropriate implementation of the recommended guidelines for care and prevention among patients at KNH is important.

HIV and the tuberculosis "set point": how HIV impairs alveolar macrophage responses to tuberculosis and sets the stage for progressive disease.

As HIV has fueled a global resurgence of tuberculosis over the last several decades, there is a growing awareness that HIV-mediated impairments in both innate and adaptive immunity contribute to the heightened risk of tuberculosis in people with HIV. Since early immune responses to Mycobacterium tuberculosis (Mtb) set the stage for subsequent control or progression to active tuberculosis disease, early host-pathogen interactions following Mtb infection can be thought of as establishing a mycobacterial "set point," which we define as the mycobacterial burden at the point of adaptive immune activation. This early immune response is impaired in the context of HIV coinfection, allowing for a higher mycobacterial set point and greater likelihood of progression to active disease with greater bacterial burden. Alveolar macrophages, as the first cells to encounter Mtb in the lungs, play a critical role in containing Mtb growth and establishing the mycobacterial set point. However, a number of key macrophage functions, ranging from pathogen recognition and uptake to phagocytosis and microbial killing, are blunted in HIV coinfection. To date, research evaluating the effects of HIV on the alveolar macrophage response to Mtb has been relatively limited, particularly with regard to the critical early events that help to dictate the mycobacterial set point. A greater understanding of alveolar macrophage functions impacted by HIV coinfection will improve our understanding of protective immunity to Mtb and may reveal novel pathways amenable to intervention to improve both early immune control of Mtb and clinical outcomes for the millions of people worldwide infected with HIV.

Anakinra in the treatment of protracted paradoxical inflammatory reactions in HIV-associated tuberculosis in the United Kingdom: a report of two cases.

Paradoxical reactions, including immune reconstitution inflammatory syndrome (IRIS), are common in patients co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Paradoxical reactions may confer substantial morbidity and mortality, especially in cases of central nervous system (CNS) TB, or through protracted usage of corticosteroids. No high-quality evidence is available to guide management in this scenario. Interleukin-1-mediated inflammation has been implicated in the pathophysiology of TB-IRIS. We describe two cases where anakinra (human recombinant interleukin-1 receptor antagonist) was used as steroid-sparing therapy for life-threatening protracted paradoxical inflammation in HIV-associated TB. In the first case of disseminated TB with lymphadenitis, protracted TB-IRIS led to amyloid A amyloidosis and nephrotic syndrome. In the second case of disseminated TB with cerebral tuberculomata, paradoxical inflammation caused unstable tuberculomata leading to profound neuro-disability. In both cases, paradoxical inflammation persisted for over a year. Protracted high-dose corticosteroid use led to adverse events yet failed to control inflammatory pathology. In both patients, anakinra successfully controlled paradoxical inflammation and facilitated withdrawal of corticosteroid therapy. Following anakinra therapy, nephrotic syndrome and neuro-disability resolved, respectively. Anakinra therapy for protracted paradoxical inflammation in HIV-associated TB may be a viable therapeutic option and warrants further research.

The prevalence of cryptococcal antigen (CrAg) and benefits of pre-emptive antifungal treatment among HIV-infected persons with CD4+ T-cell counts < 200 cells/µL: evidence based on a meta-analysis.

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.

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.

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.

Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria.

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.

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.

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.