Abstract Introduction Valacyclovir is the only treatment option during pregnancy which has been demonstrated to be effective within a randomized clinical trial for prevention of transplacental cytomegalovirus (CMV) transmission. However, the use of high dose intravenous hyperimmunoglobulin (HIG) could reduce the rate of vertical transmission according to some observational studies. Cases presentation We report three peculiar cases in which high dose HIG was administered in substitution to or in addition to valacyclovir to reduce the risk of transplacental transmission of CMV. Two were immunocompromised pregnant women—one with recurrent CMV reactivations due to solid organ transplant-related immunosuppression and one with primary CMV infection and lack of IgG production due to anti-CD20 treatment for multiple sclerosis—in which HIG was co-administered with valacyclovir. The third case involved an immunocompetent pregnant woman to whom HIG was administered in substitution to valacyclovir due to severe gastrointestinal side effects related to the latter medication. In all cases, the treatment was well tolerated and the newborns tested negative for CMV at birth. Conclusion Together, these cases give an interesting perspective on the possible role of HIG in selected immunocompromised pregnant women with primary and non-primary CMV infection in addition to valacyclovir, and in immunocompetent pregnant women unable to tolerate valacyclovir or in whom the drug is contraindicated.
Despite advancements in antiretroviral therapy (ART) in Tanzania, adherence remains a challenge, especially among young people living with HIV (YPLHIV) aged 10–24 years. This study, conducted in the Shinyanga region of Tanzania, explored the factors affecting access and adherence to ART among YPLHIV. Access to ART refers to the ability to reach, enroll, and receive HIV care and education; adherence refers to proper use of medications as prescribed. The research employed focus group discussions and in-depth interviews with YPLHIV and their caregivers. Data were transcribed and thematically analyzed using Atlas.ti software. The qualitative data analysis revealed clear categories of barriers and facilitators. Barriers to ART access and adherence included forgetfulness, lack of privacy, family instability, poverty, reflected in lack of food or water. Perceived stigma and discrimination from family, school or community members played a significant role, alongside low participation in adherence support activities. Factors facilitating ART access and adherence included disclosure of HIV status and access to social or emotional support from the family members, peers, teachers, health workers, and community members. These factors may increase knowledge about the risks of treatment failure and drug resistance, help reduce their perceived stigma and discrimination and support treatment continuity. Interventions by health workers, family members, peers, teachers—at individual and social levels—as well as by government and local health authorities—at the policy level—are needed to address the above barriers and facilitators to ART access and adherence among YPLHIV enrolled in HIV care. A pesar de los avances en la terapia antirretroviral (TAR) en Tanzania, la adherencia sigue siendo un desafío, especialmente entre los jóvenes que viven con VIH (JVVHIV) de entre 10 y 24 años. Este estudio, realizado en la región de Shinyanga en Tanzania, exploró los factores que afectan el acceso y la adherencia a la TAR entre los JVVHIV. El acceso a la TAR se refiere a la capacidad de llegar, inscribirse y recibir atención y educación sobre el VIH; la adherencia se refiere al uso adecuado de los medicamentos según lo prescrito. La investigación empleó discusiones en grupos focales y entrevistas en profundidad con los JVVHIV y sus cuidadores. Los datos fueron transcritos y analizados temáticamente utilizando el software Atlas.ti. El análisis cualitativo reveló categorías claras de barreras y facilitadores. Las barreras al acceso y la adherencia a la TAR incluyeron el olvido, la falta de privacidad, la inestabilidad familiar y la pobreza, reflejada en la falta de alimentos o agua. La percepción de estigma y discriminación por parte de familiares, compañeros de escuela o miembros de la comunidad desempeñó un papel significativo, junto con una baja participación en actividades de apoyo a la adherencia. Los factores que facilitan el acceso y la adherencia a la TAR incluyeron la divulgación del estado serológico y el acceso a apoyo social o emocional por parte de familiares, compañeros, maestros, trabajadores de la salud y miembros de la comunidad. Estos factores pueden aumentar el conocimiento sobre los riesgos de fracaso del tratamiento y resistencia a los medicamentos, ayudar a reducir la percepción de estigma y discriminación y apoyar la continuidad del tratamiento. Se necesitan intervenciones por parte de los trabajadores de la salud, familiares, compañeros, maestros—a nivel individual y social—así como por parte del gobierno y las autoridades sanitarias locales—a nivel de políticas—para abordar las barreras y facilitadores mencionados en el acceso y adherencia a la TAR entre los JVVHIV inscritos en cuidados por VIH.
Migrant Living with HIV (MLWH) are facing many barriers. Proposing targeted interventions requires a better understanding of the local epidemiology, but data are scarce. This population often comprises vulnerable groups such as men who have Sex with men and transgender individuals. This single-center cohort study aims to estimate the achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 goals and the 8-year loss-to-follow-up (LTFU) incidence rate in a cohort of MLWH under treatment at the Infectious and Tropical Diseases Unit of the “Careggi University Hospital”, Florence, Italy. We enrolled MLWH taken in care from 01/01/2014 to 31/12/2022. The end of the study was the end of follow-up (30/04/2023) or the date of LTFU (unreachable, relocated to another center, or dead). We enrolled 201 migrants with a median age of 33 [IQR 27–43]. One-hundred-and-six (52.7
Introduction:Scabies is a neglected disease that cause outbreaks in facilities such as hospitals and prisons. In Europe, treatment with 2 doses of ivermectin 200 mcg/kg, 7 days apart, is authorised and recommended especially in population mass treatment. We describe the management of a mass pre-emptive therapy of primary contacts of a confirmed case of classic scabies among health care workers. Patients and Methods:Hospital personnel were evaluated, and at-risk contacts were treated with oral ivermectin 200 mcg/kg single dose if asymptomatic. Hospital staff were called after 7, 30, and 60 days after the first visit to assess presence of adverse drug reactions (ADRs) or symptoms compatible with scabies. Results:Among 27 patients evaluated, 19/27 (70.4%) received single dose ivermectin for scabies pre-emptive therapy. A total of 11/13 patients were nurses, and 8/14 were healthcare assistants. A total of 87 tablets of ivermectin were administered, with a total cost of 423.69 euros. Two people reported ADRs at 7 days; one and two patients reported possible ADRs at 30 and 60 days, respectively. The efficacy in preventing scabies was 100%. Discussion and conclusions:To our knowledge, this is the first Italian experience in which a single dose of ivermectin has been implemented for mass pre-emptive therapy in asymptomatic primary contacts of classical scabies, showing excellent efficacy of the drug even when used as a single dose.
ObjectiveTo 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 DesignThis 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.ResultsSince 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.ConclusionsThe 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.
Cystic fibrosis (CF)-related central (CNS) and peripheral nervous system (PNS) disorders have not yet been fully described. We report the first case of post-infective neuromuscular hyperexcitability syndrome in a 23-year-old male patient with CF and pulmonary exacerbation. CNS radiological investigations were unremarkable and no autoantibodies were detected. The patient fully recovered after infectious state control and multidisciplinary assessment and no recurrence was observed at follow-up. In view of the rarity of this condition, an additional effort is advisable to collect data and define the optimal management strategy in patients with CF.
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.
Respiratory infections represent the leading cause of lung damage in CF patients. A strong correlation has been shown between the flora colonizing the upper (UAW) and lower airways (LAW). We analyzed UAW and LAW to evaluate the role of bacterial infections of paranasal sinuses in the development of subsequent lung infections. Paired samples of UAW and LAW were screened performing microbiological analyses. UAW specimens were collected by nasal lavage. LAW specimens were collected as throat swab or sputum. Between December 2020 and March 2022, 109 adult patients in total were enrolled, including 83 (76.1%) not chronically colonized by Pseudomonas aeruginosa (PA) (Group A: 62.7% male; median age 29y; range 18-58), and 26 (23.9%) transplanted subjects (Group B: 61.5% male; median age 39y; range 19-60). Overall, 187 paired samples of UAW and LAW were screened, 141 for Group A, and 46 for Group B. The most prevalent bacterium in group A was Staphylococcus aureus (SA) in both UAW (41.1%) and LAW (69.5%) cultures (p<.05), followed by Enterobacteriaceae (UAW 17.7%, LAW 14.2%), Achromobacter xylosoxidans (UAW 3.5%, LAW 7.8%), methicillin-resistant SA (UAW 4.3%, LAW 3.5%), and PA (UAW 1.4%, LAW 6.4%; p<.05). Compared to group A, group B exhibited a higher prevalence of PA (UAW 36.1%, LAW 52.8%), a lower presence of SA (UAW 41.7%, LAW 44.4%) with lower bacterial diversity. The two groups of patients showed different airways microbiota. Upper airways could play a role as reservoir in the initial phases of lung disease and progression towards chronicity. In transplant patients the high PA prevalence in UAW could infect the allografts, conditioning the organ rejection. This work was supported by the Tuscany Region
Background: Cystic Fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene that make the CFTR protein dysfunctional, making secretions sticky. CF people can have a variety of symptoms, including infertility. In 2020, a triple combination therapy of elexacaftor/tezacaftor plus ivacaftor (ETI) was approved by EMA, capable of correcting the malfunction of the CFTR protein. The improvement in clinical conditions and life expectancy leads to an increase in the number of pregnancies. The effects of this drug on the mother and newborn are not yet fully known.
Cystic Fibrosis Transmembrane Conductance Regulator-Related Disorders (CFTR-RD) is a disease characterized by different organ involvement including disseminated bronchiestasis. Anatomical damage, altered mucociliary clearance and respiratory colonization may occur in CFTR-RD. Although this disorder may have common microbiological features with cystic fibrosis (CF) and non-CF bronchiectasis (nCFb), little is known about the respiratory microbiological profile of CFTR-RD.
The use of specific inhibitory drugs of intracellular signalling pathways (such as Bruton-Kinase inhibitors) for the treatment of Waldenström's macroglobulinaemia (WM) is a recognised risk factor for Aspergillus spp. infections. The overlapping clinical manifestations of the two diseases may require the involvement of different medical specialities. We describe the clinical course of a patient with pulmonary and encephalic aspergillosis, with concomitant orbital infiltration, which represented a difficult diagnosis: the case required a multidisciplinary approach to define the ocular lesions and an in-depth study of the literature.
Valacyclovir is currently the only pharmacological intervention demonstrated to reduce the risk of vertical CMV congenital infection within a randomized clinical trial in case of primary infection during pregnancy. So far, no data are available on the prognosis of children with congenital CMV infection diagnosed at birth after a negative amniocentesis whose mother were treated with valacyclovir during pregnancy, therefore it is essential to carry out a rigorous neurocognitive follow-up in these children in order to investigate the potential clinical consequence.
Molecular approach is widely used for the early diagnosis of difficult infections. Microbiological status of transplanted CF patients has been assessed by means of specific panels for lung pathogens.
Objectives: Upper airways (UAW) may represent an initial site of infection and reservoir for subsequent reinfection by CF respiratory pathogens. This study investigated lung microbiological status in patients with stable disease and in a lung transplant patients group and compared different nasal lavage (NL) sampling performances. Methods: Between December 2020 and November 2022, 202 patients were enrolled: 175 not chronically colonized by P. aeruginosa (PA) (group A: median age 18.6, range 3–58) and 27 lung transplanted subjects (group B: median age 38.3, range 15–60). For each patient one or more episodes were considered. LAW specimens (349) were sampled as sputum or throat swab and UAW specimens (370) were collected by NL with two methods, Mainz or Ryno-set, using randomization. Results: In group A, the prevalent bacterium was S. aureus (SA) in UAW (54.5%) and LAW(76.2%) cultures (p < 0.05), followed by Enterobacteriaceae (UAW 11.9%, LAW 7.3%), PA (UAW3.3%, LAW 7.3%; p < 0.05) and other clinical relevant Gram-negative bacteria such as A. xylosoxidans, S. maltophilia, H. influenzae and members of B. cepacia complex (UAW 4.6%, LAW 13.9%). Compared to group A, group B exhibited loss of bacterial diversity and the two most prevalent pathogens were SA (UAW 34.4%, LAW 46.6%) and PA (UAW 44.3%, LAW 51.1%). In both groups, Ryno-set NL showed fewer PA isolations (group A 1.3%, group B 39.5%) compared to the samples collected with Mainz technique (group A 8.6%, group B 50%). Differences in microbiological outcome of the two nasal lavage sampling methods were not statistically significant. Conclusion: Group A was colonized by a higher variety of pathogens, suggesting that UAW could play a role as reservoir in the initial phases of lung disease. Transplant patients showed a reduced bacterial diversity; these isolates from sinuses could infect the allograft. The two methods of UAW lavage had similar performances. Funding: This work was supported by Tuscany Region K37, K35
aligning with prior publications. 8,9Conversely, Manesh et al. 10 found that crushed posaconazole DR tablets given per feeding tube at a dose of 300 mg daily produced therapeutic levels after 2 weeks of therapy in 19 of 19 patients receiving treatment for rhino-orbito-cerebral mucormycosis. 10any factors can impact drug levels of crushed posaconazole DR tablets, spanning from the obvious patient factors (i.e.absorption) to terminal tube placement (e.g.J-tube versus G-tube) or the more nuanced factors (preparation and administration technique).The literature supporting this practice is evolving, but still limited.It is currently unknown how different manufacturers' DR matrices may impact serum concentrations if crushed, or how crushed DR tablets would compare in a head-to-head comparison against the oral suspension.Our experience adds to the growing body of evidence suggesting that crushing and administering posaconazole DR tablets via enteral feeding tubes is safe and often results in therapeutic levels.Importantly, doses may likely need to be up-or down-titrated when switching to or from the formulation of crushed posaconazole DR tablets, respectively.Clinicians should consider this route of administration, when necessary, in conjunction with careful dose titration and frequent TDM.
More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0
Background: Syndrome-specific diagnostic panels have potential to provide quick etiological information about lower respiratory tract infections.Lower respiratory samples collected from people with cystic fibrosis (PwCF) who have undergone lung transplantation were evaluated with the newly developed BioFire FilmArray Pneumonia Panel Plus (Biomérieux), testing for 27 bacteria and viruses that cause pneumonia and other lower respiratory tract infections and for seven genetic markers of antibiotic resistance.This molecular approach could improve quick diagnosis of lung infections, including viruses and some unculturable microorganisms, in critically ill PwCF such as those who have undergone lung transplantation.Methods: Forty-one tract samples collected from 26 PwCF who have undergone lung transplantation in clinical stable conditions (median age 39, range 18-60) were analyzed using standard microbiological methods and the multiplex polymerase chain reaction (PCR) assay.Results: Results obtained with the panel displayed 75.6% agreement with standard methods.In 10 (24.4%) cases, there was a discrepancy between the two approaches.In four samples, bacterial pathogens (2 Staphylococcus aureus, 1 Streptococcus pneumoniae, 1 Serratia marcescens) were not isolated using conventional cultural techniques.Occurrence of bacterial variant with poor growth, selected by the CF environment, could explain this.Isolation problems due to concomitant growth of other bacteria should also be considered.In six samples, the multiplex PCR assay missed relevant bacteria: 4 Pseudomonas aeruginosa, 1 Enterobacter cloacae, 1 S. marcescens.This discrepancy could be explained by bacterial load; the number of colony-forming units per milliliter, evaluated with a semi-quantitative analysis included in the conventional approach, was about 10 3 for P. aeruginosa, E. cloacae, and S. marcescens in these five samples, whereas the panel is not set to reveal numbers of bacterial deoxyribonucleic acid below 10 4 copies per milliliter.Conclusions: This molecular approach could support clinical decisionmaking with markedly faster turn-around time than standard methods, which is perhaps the most important advantage, as well as better detection of viruses, atypical bacterial pathogens, and markers of antibiotic resistance.Nevertheless, this method has relevant limitations, including that it does not detect low levels of bacterial cells.Detection of low bacterial load is clinically relevant for PwCF who have undergone lung transplantation and in the early phases of P. aeruginosa lung infection.This is extremely significant also for other clinical settings.