Disseminated nocardiosis and anti-GM-CSF antibodies.

Infections that are unusually severe or caused by opportunistic pathogens are a hallmark of primary immunodeficiency (PID). Anti-cytokine autoantibodies (ACA) are an emerging cause of acquired immunodeficiency mimicking PID. Nocardia spp. are Gram-positive bacteria generally inducing disseminated infections in immunocompromised patients, but seldom also occurring in apparently immunocompetent hosts. Anti-GM-CSF autoantibodies are associated with autoimmune pulmonary alveolar proteinosis (PAP). In those patients, an increased incidence of disseminated nocardiosis and cryptococcosis has been observed. It is unclear whether the PAP or the autoantibodies predispose to the infection. We report an apparently immunocompetent woman presenting with disseminated nocardiosis without any evidence of PAP. Clinical data and radiological images were retrospectively collected. Lymphocyte populations were analyzed by flow cytometry. Anti-GM-CSF autoantibodies were measured by ELISA. A 55-year-old otherwise healthy woman presented with cerebral and pulmonary abscesses. Personal and familial history of infections or autoimmunity were negative. After extensive examinations, a final diagnosis of disseminated nocardiosis was made. Immunologic investigations including neutrophilic function and IFN-γ/IL-12 circuitry failed to identify a PID. Whole-exome sequencing did not find pathogenic variants associated with immunodeficiency. Serum anti-GM-CSF autoantibodies were positive. There were no clinical or instrumental signs of PAP. Trimethoprim-sulfamethoxazole and imipenem were administered, with progressive improvement and recovery of the infectious complication. We identified anti-GM-CSF autoantibodies as the cause of disseminated nocardiosis in a previously healthy and apparently immunocompetent adult. This case emphasizes the importance of including ACA in the differential diagnosis of PID, especially in previously healthy adults. Importantly, anti-GM-CSF autoantibodies can present with disseminated nocardiosis without PAP.

Toscana virus (TOSV) meningitis with atypical characteristics: Report of two cases.

Toscana virus (TOSV) is an emerging cause of central nervous system (CNS) infections, especially in endemic countries during summer. Cerebrospinal fluid (CSF) is usually clear, with < 500 leukocytes/mm3, normal glucose (> 60 % serum glucose) and normal (< 45 mg/dL) to slightly increased protein levels. Here we present two cases of TOSV meningitis with misleading CSF characteristics observed at Santa Maria Annunziata Hospital (Bagno a Ripoli, Florence, Italy). Case 1 presented with signs and symptoms of meningitis. CSF was opalescent on macroscopic examination, with 1192 cells/mm3, hypoglycorrhachia (30 % serum glucose) and hyperproteinorachia (228.0 mg/dL). TOSV meningitis was confirmed with serology. Case 2 presented with headache, vomiting and mild neck stiffness. CSF was slightly turbid, with 1092 cells/mm3, normal glucose (61 % serum glucose) and slightly increased protein (77.0 mg/dL) levels. TOSV meningitis was confirmed with serology and molecular test on CSF. We performed a literature review including cases of TOSV neuroinvasive infections in which CSF characteristics were reported. Pleocytosis > 500 cells/mm3 was reported in 12/62 (19.4 %) patients, hypoglycorrhachia in 3/62 (4.8 %) patients, mild hyperproteinorachia (45 - 75 mg/dL) in 7/62 (11.3 %) patients and severe hyperproteinorachia (> 75 mg/dL) in 40/62 (64.5 %) patients. TOSV should be considered in the differential diagnosis of CNS infections in endemic areas during the warm season even when CSF examination shows atypical results.

When it rains, it pours: Early treatment with tecovirimat of cardiac complications associated with monkeypox infection in a person with HIV and previously undiagnosed Lyme disease. A case report.

Cardiac involvement, such as myocarditis and pericarditis, can be a severe complication of monkeypox virus (mpox) infection and could be related to other co-infections with cardiac involvement. Tecovirimat is an antiviral specifically designed to inhibit smallpox infection diffusion and approved by the FDA for other Orthopoxvirus infections; its efficacy in mpox-infected patients is not well established. We present the case of a cardiac complication during mpox infection in a previously undiagnosed Lyme disease in a 42-year-old man living with HIV. Two days after the typical maculopapular rash, the patient reported a rise in body temperature up to 39 °C, chest pain without irradiation, and shortness of breath. We found an increase in troponin level, a slight reduction in ejection fraction, and grade 2 AV block (Mobitz 1 and 2) with frequent sinus pauses (the longest of 10.1 s). Given the suspicion of myopericarditis with cardiac conduction system involvement, the patient was admitted to the Intermediate Care Unit for continuous monitoring and further evaluation. Treatment included Ibuprofen 600 mg every 12 hours (bid) and colchicine 1 mg once daily for anti-inflammatory purposes. Concomitantly, treatment with tecovirimat was started at 600 mg bid for a total of 14 days. Cardiac MRI with gadolinium showed mild interstitial edema and pericardial enhancement. However, despite the clinical and laboratory resolution of the acute phase, bradycardia with episodes of AV block persisted at follow-up, suggesting the possibility of an additional etiology. Thus, the patient was investigated for Lyme disease because high-degree AV block is the most common presentation of Lyme carditis. Serological results evidenced a previous Borrelia burgdorferi senso latu. We decided to start treatment with doxycycline 100 mg every 12h, even pending the uncertainty of the role of a previous Lyme disease in determining the cardiac rhythm disturbances. At the evaluation on day 44, the patient was systemically well, and after cardiologist consultation, pace-maker implantation was not deemed indicated. This case underscores the importance of considering alternative causes of carditis when the clinical picture remains unclear or persists after the acute phase.

Prevention, diagnosis and pharmacological treatment of infections in pregnancy: The mobile app GAIA! for healthcare providers and patients.

OBJECTIVE: To develop and assess the GAIA! app, designed to assist pregnant women and healthcare professionals in managing infectious diseases during pregnancy, and to bridge the information gap between health professionals and expectant mothers. STUDY DESIGN: This collaborative initiative in Italy involved partnerships with the University of Florence, Careggi University Hospital, and other institutions. The app, built on the Ionic framework, is available on both Apple and Google App Stores. It offers two distinct modes: "healthcare providers" and "patients." Content for the app was derived from extensive literature reviews and clinical guidelines. RESULTS: Since its August 2022 launch, the GAIA! app has garnered over 2,500 downloads, indicating its effectiveness and acceptance within the community. The app differentiates itself from others, such as the Sanford Guide, by focusing specifically on the needs of pregnant women. It ensures cross-platform compatibility, a user-friendly interface, and offline functionality. CONCLUSIONS: The GAIA! app has successfully addressed a niche in infectious disease management for pregnant women, gaining significant traction within the community. While it has seen substantial success, challenges like continuous updates and potential language expansion remain. Future endeavors will address these challenges and further evaluate the app's impact on maternal and child health.

Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

Facilitators and barriers in HIV testing and continuum of care among migrant transgender women who are sex workers residing in Florence, Italy.

Background: An increased risk of contracting HIV infection, suboptimal adherence, and a loss to follow-up have been observed in migrants, particularly if those individuals are transgender or sex workers. A clear picture of the HIV epidemic among migrants is complex due to the lack of specific national data. Aims: We developed a qualitative study that describes the barriers and facilitators (cultural, social, and personal) in HIV testing and the continuum of care for a group of migrant transgender women who are sex workers. Methods: A semi-structured interview was conducted with a group of migrant transgender women who are sex workers living with HIV or with unknown HIV serostatus residing in the Florentine metropolitan area. Results: We included 12 participants: 3 had unknown HIV serostatus and 9 were living with HIV in follow-up at the Clinic of Infectious and Tropical Diseases, Careggi University hospiral, Florence, Italy. Among barriers, the perceived stigma due to their identity as migrants and transgender people, the language lack of ability and the legal position in the host country played a significant role. Moreover, the interviewees claimed having no alternative to sex work: for those individuals, changing their lifestyle condition is perceived as difficult or impossible due to social prejudices. Conversely, the interviewees considered support services, such as cultural mediators/interpreters and street units, as facilitators to HIV testing, access to care, and continuum of care. Having regular and accessible ART and the availability of a more consistent health care system, represent reasons for HIV-positive migrants living with HIV to move to Italy. Conclusions: Knowledge of this population's personal experience regarding the barriers and factors that facilitate access to the HIV care system is essential for planning public health interventions capable of responding to the real needs of patients.

Oral microbiota signatures associated with viremia and CD4 recovery in treatment-naïve HIV-1-infected patients.

PURPOSE: Few reports focused on the role of oral microbiome diversity in HIV infection. We characterized the microbiota-immunity axis in a cohort of treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy (ART) focusing on the oral microbiome (OM) and immunological responsivity. METHODS: The sequencing of 16S rRNA V3-V4 hypervariable region was performed on salivary samples of 15 healthy control (HC) and 12 HIV + patients before starting ART and after reaching virological suppression. Then, we correlated the OM composition with serum cytokines and the Short Chain Fatty acids (SCFAs). RESULTS: The comparison between HIV patients and HC oral microbiota showed differences in the bacterial α-diversity and richness. We documented a negative correlation between oral Prevotella and intestinal valeric acid at before starting ART and a positive correlation between oral Veillonella and gut acetic acid after reaching virological suppression. Finally, an increase in the phylum Proteobacteria was observed comparing saliva samples of immunological responders (IRs) patients against immunological non-responders (INRs). CONCLUSIONS: For the first time, we described an increase in the oral pro-inflammatory Proteobacteria phylum in INRs compared to IRs. We provided more evidence that saliva could be a non-invasive and less expensive approach for research involving the oral cavity microbiome in HIV patients.

Impact of rapid-antiretroviral therapy in a cohort of treatment-naïve migrants living with HIV in a high income setting.

BACKGROUND: We evaluated the effect of rapid ART (RA) compared to delayed ART (DA) on viral load suppression (viral load <50 cp/mL) and loss to follow-up (LTFU) in a cohort of migrants living with HIV (MLWHs) in Italy. METHODS: Data were retrospectively gathered from MLWHs who began care at the Infectious and Tropical Diseases Unit of the Careggi University Hospital from January 2014 to December 2022. RA was defined as antiretrovirals prescribed within 7 days of HIV diagnosis. The study ended on April 30, 2023, or upon patient LTFU. Chi-square and non-parametric tests assessed differences in categorical and continuous variables, respectively. Kaplan-Meyer survival analysis was performed to estimate the probability of loss to follow-up. Cox regression analysis was performed to evaluate factors associated with a loss to follow-up. RESULTS: 87 MLWHs were enrolled: 20 (23%) on RA and 67 (77%) on DA. In the RA group there were more PLWH with a previous AIDS event (p < .001) however, there was no significant difference in the LTFU rates between the groups (aHR 0.6, 95%CI 0.1-3.1; p = .560; Logrank = 0.2823). Being an out-of-status MLWH was the only predictor of LTFU. By 6 months, virological suppression was achieved in 61.2% (n = 41) in DA and 70.0% in the RA group (n = 14) (Logrank p = .6747). CONCLUSIONS: RA did not significantly affect LTFU rates or the achievement of viral load suppression. The study suggests that further research is needed to assess the impact of RA in high income settings.

Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients.

OBJECTIVE: Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity. METHODS: In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients. RESULTS: Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients' ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination. CONCLUSION: These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.

Antibodies Induced by Smallpox Vaccination after at Least 45 Years Cross-React with and In Vitro Neutralize Mpox Virus: A Role for Polyclonal B Cell Activation?

AIMS: To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory. METHODS: Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry. RESULTS: None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals. CONCLUSIONS: ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.

Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales: results from a prospective, multinational case-control-control matched cohorts study (EURECA).

OBJECTIVES: To assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. METHODS: A prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. RESULTS: The cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3-20.0), (HR, 2.57; 95% CI, 1.55-4.26; p < 0.001), and 15.4% (95% CI, 10.5-20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57-5.77; p < 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99-3.50; p 0.06) and 3.65 (95% CI, 2.29-5.82; p < 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78-2.67; p 0.24). DISCUSSION: CRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality.

Latent Tuberculosis Infection and COVID-19: Analysis of a Cohort of Patients from Careggi University Hospital (Florence, Italy).

Data regarding the relationship between coronavirus disease (COVID-19) and active or latent tuberculosis (TB) are discordant. We conducted a retrospective study examining the impact of latent tuberculosis infection (LTBI) on the clinical progression of COVID-19 patients. We selected 213 patients admitted with COVID-19 in a tertiary-level Italian hospital (February-December 2020), who underwent a QuantiFERON-TB test (QFT) and/or chest radiological exam. The population was divided into three groups: (i) QFT negative and without radiological TB sequelae (Neg); (ii) QFT positive and without radiological TB sequelae (Pos); (iii) radiological TB sequelae regardless of QFT result (Seq). In-hospital mortality and oro-tracheal intubation (OTI) showed significantly higher results in the Seq group (Seq 50% vs. Pos 13.3% vs. Neg 9.3%, p < 0.001; Seq 16.7% vs. Pos 6.7% vs. Neg 4.9%, p = 0.045). Considering the Pos and Seq groups' patients as the population with defined LTBI, in-hospital mortality (20/51, 39.2%) and OTI risk (7/51, 13.7%) were statistically higher with respect to patients without LTBI (in-hospital mortality: 15/162, 9.3%, p < 0.001; OTI risk: 8/162, 4.9%, p = 0.023), respectively. Multivariate analysis showed that radiological sequelae and the Charlson Comorbidity Index (CCI) were significantly associated with higher mortality rate; despite the higher CCI of Seq population, we cannot exclude the correlation between COVID-19 in-hospital mortality and the presence of radiological TB sequelae.

Low risk of serological cross-reactivity between dengue and COVID-19

In the near future, the overlap of Coronavirus disease 2019 (COVID-19) and dengue epidemics is a concrete threat in tropical regions. Co-epidemics of COVID-19 and dengue could be an overwhelming challenge for health systems in low- and middle-income countries. In this work, we investigated potential serological cross-reactions between COVID-19 and dengue patients. Among 32 COVID-19 positive sera, no positive Dengue virus (DENV) IgG/IgM results were observed. On the other hand, one false-positive result was observed among 44 DENV-positive sera tested for COVID-19 antibodies with each of the two rapid tests used. Further data on accuracy of COVID-19 diagnostic test are urgently warranted.

Anticuerpos contra Trichinella spiralis en la población rural de la provincia Cordillera, Bolivia / Seroprevalence of antibodies to Trichinella spiralis among rural residents of Cordillera province, Bolivia

Se realizó un estudio seroepidemiológico para determinar la prevalencia de anticuerpos contra Trichinella spiralis en el área rural de la provincia Cordillera del Departamento de Santa Cruz en Bolivia. Se examinaron 234 muestras de suero mediante el ensayo de inmunoabsorción enzimática (ELISA) y se detectaron los anticuerpos en siete muestras (3 por cien). Los resultados documentan por primera vez la presencia de infestación humana por Trichinella en Bolivia y sugieren la necesidad de fortalecer la vigilancia sanitaria de la triquinosis en los mataderos municipales, impedir la faena clandestina de animales y, sobre todo, lograr que los productores y pobladores tomen conciencia de los peligros de esta zoonosis

A seroepidemiological study was conducted to determine the prevalence of antibodies to Trichinella spiralis among rural residents of Cordillera province, Santa Cruz Department, Bolivia. Using the enzyme-linked immunosorbent assay (ELISA), 234 serum samples were examined, and antibodies were detected in seven of the samples (3%). The results document for the first time the presence of human infestation with Trichinella in Bolivia and suggest the need to strengthen trichinelosis surveillance in the municipal slaughterhouses, to prevent the clandestine slaughter of animals, and particularly to ensure that residents and meat producers in the area become aware of the dangers of this zoonosis