Opportunistic Infections Research Articles

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review.

Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.

Updated insights into adverse events associated with mepolizumab: a disproportionality analysis from the FDA adverse event reporting system database

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is used to treat severe eosinophilic asthma and other eosinophilia-related conditions. Given its growing use, there is a pressing need for the latest data to improve the understanding and management of its adverse events (AEs). This study aimed to investigate the safety of mepolizumab by analyzing the pharmacovigilance database of the US Food and Drug Administration.MethodsThe AE signals associated with mepolizumab from 2015 to 2024 were analyzed and the correlations using reporting ratios (RORs) quantified. Subgroup analyses were conducted to understand AEs in individuals ≤ 18 years of age. We also used time-to-onset (TTO) analysis to examine AE occurrence patterns.ResultsIn total, 82,478 AE reports linked to mepolizumab therapy were included. Our analysis, involving 24,156 patients, revealed a predominance of female patients, with the highest incidence of AEs occurring in those aged 18–65 years. Disproportionality analyses revealed significant signals across various system organ classifications (SOCs), most prominently respiratory, thoracic, and mediastinal disorders (ROR = 5.12, 95% confidence intervals [CI] 5.03–5.21), infections and infestations (ROR = 1.86, 95% CI 1.81–1.90), and immune system disorders (ROR = 1.14, 95% CI 1.08–1.21). The highest ROR was found for asthma crisis (ROR = 104.90, 95% CI 95.31–115.44) at the preferred term (PT) level, and the other notables were coronavirus infection (ROR = 7.33, 95% CI 6.05–8.88) and coronavirus disease 2019 (COVID-19) (ROR = 1.34, 95% CI 1.23–1.47). A subgroup analysis of patients ≤ 18 years old identified four significant SOC signals, with the highest ROR in respiratory, thoracic, and mediastinal disorders (ROR = 5.28, 95% CI 4.17–6.68). PT analysis revealed significant AEs, such as wheezing, bronchospasm, and chest discomfort. TTO analysis revealed that 18.5% of AEs occurred within the first 30 days of treatment. The Weibull shape parameter indicated an “early failure-type” pattern for mepolizumab-associated AEs, underscoring the need for vigilant monitoring during the initial stages of therapy.ConclusionOur study highlights the importance of post-market surveillance for monitoring the safety of mepolizumab, which revealed significant AE signals, particularly for respiratory diseases, infections, and immune system complications. The association with opportunistic infections, including COVID-19, highlights the need for vigilant surveillance and further research.

Evaluation of Multi-antibiotic Resistance Index (MAR) and Molecular Characterization of Pseudomonas aeruginosa Isolated in Pathological Products from Chad

Pseudomonas aeruginosa is a bacterium present in several ecological niches causing opportunistic infections in humans. In developing countries like Chad, this bacteria is responsible for various human pathologies. High-priority pathogens, such as Salmonella and Shigella, represent a particularly heavy burden in low- and middle-income countries, as do Pseudomonas aeruginosa and Staphylococcus aureus, which pose serious problems in health centers. The objective of this study was to evaluate the multi-antibiotic resistance index and to carry out a molecular characterization of Pseudomonas aeruginosa isolated in pathological products from Chad using by rep-PCR (GTG)5. Antibiotic resistance phenotypes were obtained by interpreting the results of our previous study on antimicrobial resistance of Pseudomonas aeruginosa isolated from human infections in N'Djamena, Chad. In this study, two phenotypes were obtained that is XDR and MDR. Thus, 24/36 of strains came from urine and 29/36 strains were MDR. The multi-antibiotic resistance (MAR) indexes varied from 0.33 to 0.86. The rep-PCR allowed good discrimination of Pseudomonas aeruginosa strains in this study. These isolates were grouped based on characteristic bands appearing in their genetic fingerprint profiles. In this study, Pseudomonas aeruginosa strains isolated from urinary tract infections and pus were classified as XDR and MDR type strains.

Fungi Associated with Olive Tree (cv. ‘Nocellara del Belice’) Decay in Trapani Province (Sicily, Italy)

Recently, in several locations in the province of Trapani (Sicily, Italy), olive growers have reported cases of decaying olive trees of cv. ‘Nocellara del Belice’, showing symptoms of defoliation, branch drying, xylem browning, and reduced production. Internal symptoms include white and brown wood rot, starting from the base of the trunk. These alterations have been observed in trees irrigated using a pipe system at the trunk with spray sprinklers. To identify the causal agents of decay, some trees were eradicated and dissected, and woody samples were processed to isolate and identify the associated fungal micro-organisms. The most common colonies were identified using morphological (macro- and microscopical observation) and molecular (PCR amplification of the rDNA-ITS region) analyses. Nine fungal taxa were identified, of which four were associated with this decay syndrome (Coriolopsis gallica, Fomitiporia mediterranea, Kirschsteiniothelia sp., and Pleurostoma richardsiae), three were considered ubiquitous and opportunistic fungi (Alternaria spp., Aspergillus amstelodami, and Trichoderma sp.), and the other two were mycelia sterilia. Artificial inoculation satisfied Koch’s postulates, confirming the pathogenicity of the aforementioned fungi, even though the infections in the fields seem to be related to the irrigation system. This hypothesis would seem to be confirmed by the progression of decay over time in the trees subjected to the irrigation system described but not reported in olive groves differently managed. It is therefore considered appropriate to conduct further and more in-depth investigations aimed at studying the correlation between the irrigation system, presence of fungal agents, and manifestation of the syndrome. A further ongoing investigation is aimed at the use of biostimulants (Agrusaver, Savory Sun, VA LLC) on symptomatic trees, with the aim of both improving the vegetative performance of the host and limiting the symptoms detected in the field.

Scots Pines With Tolerance to Melampsora pinitorqua and Diplodia sapinea Show Distinct Metabolic Profiles.

Diplodia sapinea causes Diplodia tip blight (DTB) and is recognised as an opportunistic necrotrophic pathogen affecting conifers. While DTB is associated with abiotic stress, the impact of biotic stress in the host on D. sapinea's lifestyle shift is unknown. Observed co-occurrences of D. sapinea and Melampsora pinitorqua, causing pine twisting rust on Scots pine (Pinus sylvestris), instigated an investigation into their interaction with and influence on the defence mechanisms of the host. We hypothesised that M. pinitorqua infections predispose the trees to D. sapinea by stressing the host and altering the shoot metabolites. Pines in a plantation were sampled over time to study pathogen biomass and host metabolites. Symptoms of both pathogens were consistent over years, and the preceding season's symptoms affected the metabolic profiles pre-infection and M. pinitorqua's proliferation. Symptoms of M. pinitorqua altered shoot metabolites more than fungal biomass, with co-symptomatic trees exhibiting elevated M. pinitorqua biomass. Specific phenolic compounds had a strong positive association with the shoot symptom × D. sapinea interaction. D. sapinea's biomass presymptoms was independent of previous disease symptoms and infection by M. pinitorqua. Some trees showed disease tolerance, with delayed rust infections and minimal DTB symptoms. Further investigations on this trait are needed.

Newly diagnosed advanced HIV infection in an older female in Poland

This paper presents the diagnostic and therapeutic challenges encountered in an older woman with advanced HIV infection. Upon admission, the patient exhibited severe symptoms of interstitial pneumonia and cachexia. During hospitalization, the patient was diagnosed with SARS-CoV-2 infection and a wide spectrum of opportunistic pulmonary infections, including Pneumocystis jiroveci, Candida krusei, and Staphylococcus haemolyticus. Another major diagnostic challenge posed the patient’s prolonged fever, which persisted despite comprehensive treatment. This report underscores the importance of considering new HIV infections in older patients presenting complex clinical pictures, its significant mortality risk in older individuals, and the need for timely initiation and adjustment of antiretroviral therapy.

African dust: Occurrence, health consequences, and impacts on Texas

The drylands of North Africa (Sahara and Sahel) are the world’s largest sources of airborne dust. Clouds of African dust aerosols have been long known to be blown westwards across the Atlantic, and by the 1990s were recognized to be transported across and over Texas. African dust incursions in Texas typically happen several times per year in late spring and summer, manifesting as hazy skies overhead and increased ground-level concentrations of PM2.5 (particulate matter fine enough to be inhaled into the human lower respiratory tract). African dust exposure has many reported human health effects in Europe and the Caribbean, including increased all-cause mortality and increased respiratory and cardiovascular disease morbidity and mortality. In Texas, African dust’s greatest impacts occur in the Houston metropolitan area where it has been quantitatively shown to increase ambient aerosol concentrations. The potential of African dust increasing concentrations of inhalable particulate matter beyond regulatory limits is of concern. A sequence of investigations filtering particles from the air, measuring their concentrations, and subjecting them to elemental analysis documented far-transported African dust’s role in air quality in Houston and Galveston. African dust’s contributions to air pollution have been separated from those of local soils and industrial emissions, and Saharan-Sahelian dust has been indicated to sometimes constitute the majority of PM2.5 mass in Houston. While studies show the presence of inhalable metals and microorganisms including opportunistic pathogens during Saharan air incursions in Houston, the human health effects of African dust in Texas remain yet unspecified and merit further investigation. Keywords: aerosols; Africa, Northern; air pollution; dust; particulate matter; public health; Texas

Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, has demonstrated induction of clinical remission at week 12 with maintenance through week 104 in patients with moderately-to-severely active ulcerative colitis (UC). Results are presented from the LUCENT-3 open-label extension study through week 152. Of 868 LUCENT clinical trial program mirikizumab-treated induction patients, 544 were responders of whom 365 were rerandomized to mirikizumab maintenance. Of these, 324 completed week 52 and 316 entered extension treatment (286 week 52 responders; 179 week 52 remitters). Efficacy and safety outcomes are reported for mirikizumab-treated LUCENT-3 participants, including biologic-failed patients, with data for week 52 maintenance responders/remitters. Discontinuations or missing data were handled by nonresponder imputation, modified nonresponder imputation (mNRI), and observed cases. Using mNRI, 81.6% of week 52 responders demonstrated clinical response at week 152. Week 152 remission rates for week 52 responders included clinical (56.1%), corticosteroid-free (CSF; 54.5%), endoscopic (61.0%), histologic-endoscopic mucosal remission (HEMR; 52.6%), symptomatic (74.9%), and bowel urgency (BU; 58.6%). At week 152, 53.3% of week 52 responders achieved histologic-endoscopic mucosal improvement (HEMI) and 74.3% achieved BU clinically meaningful improvement (CMI). Among week 52 remitters, 85.4% showed a clinical response at week 152, with clinical (70.1%), CSF (68.9%), endoscopic (72.0%), HEMR (63.4%), symptomatic (81.4%), and BU (60.8%) remission. At week 152, among week 52 remitters, 64.0% of patients achieved HEMI and 75.6% achieved BU CMI. Stool frequency, rectal bleeding, BU, and abdominal pain score reductions from induction baseline to maintenance week 52 were sustained through week 152 for week 52 completers. Overall, in the safety population, 7.4% of patients reported severe adverse events (AEs); 5.3% discontinued treatment due to AEs. AEs of special interest included opportunistic infection (1.8%), hepatic disorders (3.2%), cerebrocardiovascular events (1.5%), and malignancy (0.3%). Patients with antidrug antibodies reduced over time from 23.6% in year 1 to 3.2% in year 3. Symptomatic, clinical, endoscopic, histologic, and quality-of-life outcomes support long-term sustained benefit of mirikizumab treatment up to 152 weeks in patients with UC, including biologic-failed patients, with no new safety concerns. ClinicalTrials.gov: NCT03518086; NCT03524092; NCT03519945.

Lock, stock, and Leuconostoc: an unusual presentation of a rare pathogen

Leuconostoc mesenteroides is a Gram-positive bacterium in the Lactobacillaceae family. This species is rarely encountered clinically and in the past was regarded as a contaminant when cultured. Recently it is being recognized as a pathogen responsible for opportunistic infections in immunocompromised patients. Compared to other Gram-positive cocci, Leuconostoc spp. carry intrinsic resistance to vancomycin. It is not common for clinical microbiology laboratories to isolate this organism and instead incorrectly report enterococcus and streptococcus organisms. Here, we present a case of bacteremia resulting in febrile illness and pneumonia in an 81-year-old woman with a history of rheumatoid arthritis and a notable lapse between immunomodulator therapy exposure. She was successfully treated when this organism was identified, and her antibiotic therapy was switched from vancomycin to ampicillin-sulbactam. This case highlights the importance of considering L. mesenteroides as a source of infection in patients predisposed to an immunocompromised state despite this organism’s being a rare pathogen. Keywords: Leuconostoc mesenteroides, rheumatoid arthritis, immunomodulators; vancomycin resistance

Synthetic Antimicrobial Peptides. V. Histidine-containing Antifungal Peptides with a “Linear” Type of Amphipathicity

A number of histidine-containing synthetic antifungal peptides with a “linear” type of amphipathicity (SAMP LTA) (F2Hx, H10F2, H10, where x = 7, 10, 13 and 16) have been synthesized and studied. Biological screening of such histidine-containing peptides for their antifungal and hemolytic activity was carried out. It has been shown that the presented histidine-containing SAMP LTAs are capable of effectively inhibiting the growth of opportunistic fungi Candida albicans and have low hemolytic activity in most cases not exceeding 10% even at their relatively high concentration of 400 μM in a medium containing erythrocytes. The antifungal activity of the studied peptides increases with increasing histidine residues in their composition, reaching the maximum value for the histidine-containing peptide F2H16 (MIC50 = 1.0 µM). It has been shown that as the chain length of peptides increases, their hemolytic toxicity also increases. In terms of therapeutic significance, the optimal peptides in the presented series of peptides were F2H10 and F2H13, which have higher selectivity than the short or longer peptides F2H7 or F2H16. The therapeutic index (TI) for these peptides was 233, 247, 79 and 60, respectively. It has been shown that histidine-containing derivatives of peptides with phenylalanine residues at the N-terminus of the peptide (F2H10) are less effective compared to similar peptides (H10F2) containing phenylalanine residues at the C-terminus. Among all the studied peptides, the most active was the H10 peptide (MIC50 = 0.7 µM), which does not contain phenylalanine residues, which in its antifungal activity is not only more effective than all other histidine-containing peptides, including the F2H16 peptide with 16 histidine residues, but also 4-5 times more effective than the antifungal peptide P113 (MIC50 = 3.4 µM), a short active fragment of natural histatin 5, well known in the literature. Due to its relatively low hemolytic and high antifungal activity, the presented histidine-containing SAMP LTAs have relatively high TI values, more than 60. Among all the studied peptides, peptides H10 and P113 have minimal, almost zero, hemolytic activity. However, due to its higher antifungal activity, the selectivity of peptide H10 (TI 1400) exceeds that of peptide P113 (TI 340) by more than 4 times. Thus, peptide H10, due to its high antifungal activity, low hemolytic toxicity and, accordingly, high therapeutic significance, can be used as a promising antifungal peptide drug.

Atypical presentation of PJP: hypercalcemia and kidney injury in an allogeneic stem cell transplant recipient

BackgroundPneumocystis jirovecii pneumonia (PJP) is an opportunistic infection that primarily affects immunocompromised individuals. Typical symptoms of PJP include the subacute onset of dyspnea, nonproductive cough, and low-grade fever. In hematology patients, particularly those who are allogeneic stem cell transplant recipients, the disease often presents with a more aggressive clinical course. While hypercalcemia has been documented as a manifestation of PJP in some solid organ transplant recipients, it has not been reported in hematology or stem cell transplant patients.Case presentationHere, we present a case of PJP in a 56-year-old male allogeneic stem cell transplant recipient, who developed hypercalcemia and renal failure during the late post-transplant period. The patient had a history of allogeneic stem cell transplantation due to acute myeloid leukemia. He presented with symptoms of fatigue and weakness. Laboratory tests revealed hypercalcemia (13.8 mg/dL) and elevated serum creatinine levels (2.3 mg/dL). The patient was hospitalized, and despite initial treatment with hydration and furosemide, the hypercalcemia persisted, leading to the administration of denosumab. During follow-up, hypoxia was detected, and a chest CT scan revealed mosaic attenuation and ground-glass opacities. Bronchoscopy was performed, and PCR testing confirmed the presence of Pneumocystis jirovecii. Other causes of hypercalcemia were ruled out, with PTH measured at 13.8 pg/mL (normal range 15–65 pg/mL), albumin at 3.71 g/dL, 1.25-dihydroxy vitamin D3 at 96 ng/dL (normal range 26–95 ng/dL), and 25-hydroxy vitamin D at 32.5 ng/mL (normal range 20–40 ng/mL). A PET-CT scan demonstrated no pathological FDG uptake, with the exception of findings suggestive of a pulmonary infection. Following treatment with trimethoprim-sulfamethoxazole and denosumab, the patient’s hypercalcemia and infection resolved.Conclusions Although rare, PJP can present with hypercalcemia and kidney injury in allogeneic stem cell transplant recipients. Early diagnosis and treatment can improve both PJP and hypercalcemia.

Leveraging a new data resource to define the response of C. neoformans to environmental signals: How host-like signals drive gene expression and capsule expansion in Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and during in vitro growth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of five signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-Seq in quadruplicate, yielding 881 RNA-Seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either CO2 or exogenous cyclic AMP (cAMP). Surprisingly, adding either of these pushes overall gene expression in the opposite direction from tissue culture media alone, even though both are required for capsule development. Another unexpected finding was that rich medium blocks capsule growth completely. Statistical analysis further revealed many genes whose expression is associated with capsule thickness; deletion of one of these significantly reduced capsule size. Beyond illuminating capsule induction, our massive, uniformly collected dataset will be a significant resource for the research community.

Alternative sulphur metabolism in the fungal pathogen Candida parapsilosis

Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28.

Electron-Beam-Killed Staphylococcus Vaccine Reduced Lameness in Broiler Chickens

Broiler chicken lameness caused by bacterial chondronecrosis with osteomyelitis (BCO) is presently amongst the most important economic and animal welfare issues faced by the poultry industry, and the estimated economic loss is around USD 150 million. BCO lameness is associated with multiple opportunistic bacterial pathogens inhabiting the respiratory and gastrointestinal tracts. In cases of immune deficiency resulting from stress, injury, or inflammation of the tissue, opportunistic pathogens, mainly Staphylococcus spp., can infiltrate the respiratory or gastrointestinal mucosa and migrate through the bloodstream to eventually colonize the growth plates of long bones, causing necrosis that leads to lameness. This is the first report of developing a Staphylococcus vaccine against BCO lameness disease in broiler chickens. Electron beam (eBeam) technology causes irreparable DNA damage, preventing bacterial multiplication, while keeping the epitopes of the cell membrane intact, helping the immune system generate a more effective response. Our results show a 50% reduction of lameness incidence in the eBeam-vaccinated chicken group compared to the control. Additionally, the eBeam-vaccinated chickens present higher titer of anti-Staphylococcus IgA, signifying the development of an efficient and more specific humoral immune response. Our data establish the eBeam-killed Staphylococcus vaccine as an effective approach to reducing the incidence of lameness in broiler chickens.

MANIFESTAÇÕES ORAIS DAS LEUCEMIAS EM PACIENTES PEDIÁTRICOS

Leukemias can be described as blood dyscrasias resulting from the disordered multiplication of hematopoietic tissue cells. The manifestations of the disease occur systemically and have a major impact on the oral cavity, with repercussions in response to the disease itself and to elective treatment, whether surgical, chemo- or radiotherapy. The objective of this study is to discuss the oral alterations of greatest clinical value in pediatric patients, discussing the role of the dentist in the diagnosis and treatment of these manifestations. The study was carried out from the perspective of an integrative bibliographic review, following the previously established inclusion and exclusion criteria. The results emphasize the correlation between oral health and the integrity of all systems, demonstrating that the most prevalent alterations are oral mucositis, gingival enlargement followed by spontaneous bleeding and petechiae, opportunistic infections, cavities, xerostomia and hyposalivation. It is therefore concluded that there is a need for the dentist to evaluate and monitor the treatment process of pediatric patients with leukemia who are the target of antineoplastic therapy.

Mucosal leishmaniasis of the lips and cheeks: a first concomitant presentation of visceral and mucosal leishmaniasis in a patient living with HIV/AIDS in Monastir, Tunisia

BackgroundVisceral Leishmaniasis (VL) is the most severe and fatal disease if left untreated. In people living with HIV/AIDS (PLHA), VL is considered an emerging opportunistic infection. The aim of this manuscript was to report a first case in Tunisia of a concomitant presentation of visceral and oral leishmaniasis in a patient LHA. A systematic review of the literature was performed according to PRISMA guidelines, as well.Case presentationThe patient, a 43-year-old heterosexual man, treated for HIV/AIDS was referred for macrocheilitis of the upper and lower lips. A noticeable nodular and painless swelling extending to the cheeks’ mucosa was noted. The patient's poor oral hygiene was evident due to the presence of multiple dental caries. Histological analysis of the biopsied lower lip sample revealed the presence of numerous Leishmania amastigotes. The diagnosis of VL was clinically confirmed by the presence of a mild splenomegaly and pancytopenia and biologically by the identification of the parasite using PCR Lei and the species L. infantum involved using RFLP-PCR and culture. The treatment consisted of an intravenous administration of liposomal Amphotericin B (Ambisome®, 40 mg/kg/weight) for a period of 6 weeks. A favorable outcome was noted after one year with the resolution of clinical symptoms and a negative Leishmania blood PCR test. After 2 years, the patient remained asymptomatic but showed a positive Leishmania blood PCR test. Dolutegravir® was introduced in the patient’s ART regimen.ConclusionsTo the best of our knowledge, this is the first case report in Tunisia of atypical VL diagnosed through an uncommon oral location in an HIV/AIDS co-infected patient . Since VL is a severe and potentially fatal disease, it is essential for dentists to perform a thorough clinical examination and adopt a multidisciplinary approach in order to ensure an early diagnosis and an effective treatment outcome.

Disseminated Cryptococcus over pancreas, lung, and brain: a case report

BackgroundCryptococcus is an opportunistic infection acquired through inhalation from the environment, primarily affecting individuals with compromised immune systems. It typically leads to pneumonia upon passing through lung tissue. The infection can disseminate to various organs via the bloodstream, resulting in meningitis or encephalitis in the central nervous system. Disseminated Cryptococcus has been reported to involve the skin, liver, eyes, lymph nodes, bone marrow, spleen, kidneys, and intestines, significantly increasing morbidity and mortality. However, pancreatic involvement in Cryptococcus is relatively rare, and a few case reports have highlighted severe organ damage and high mortality rates.Case presentationIn this case report, we present the case of a 36-year-old Asian man who presented with a 2-week history of headaches and blurred vision in his right eye. Brain magnetic resonance imaging revealed multiple brain masses, along with a mass in the lower left lung field and a tumor in the pancreatic tail, as detected by chest computed tomography. Endoscopic ultrasound-guided fine needle biopsy and computed tomography-guided lung biopsy confirmed the diagnosis of disseminated cryptococcal infection involving the pancreas, lung, and brain. The patient’s clinical condition improved following antifungal therapy. Additionally, we identified anti-granulocyte–macrophage colony-stimulating factor antibody as a risk factor for disseminated cryptococcal infection in this patient.ConclusionDisseminated cryptococcosis can be a potentially lethal condition, as highlighted by previous literature. However, early diagnosis using contrast-enhanced harmonic endoscopic ultrasound and endoscopic ultrasound-guided biopsies, as well as prompt treatment as demonstrated in our case, can improve outcomes and prevent mortality.

Profile Of Opportunistic Infections Among HIV Patients On ART Attending At Tertiary Health Care Center

Profile Of Opportunistic Infections Among HIV Patients On ART Attending At Tertiary Health Care Center

Normalized Interferon Signatures and Clinical Improvements by IFNAR1 Blocking Antibody (Anifrolumab) in Patients with Type I Interferonopathies

PurposeA causal role of type-I interferons (IFN-I) in autoinflammatory type-I interferonopathies such as SAVI (STING–associated vasculopathy with onset in infancy) and CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures) is suggested by elevated expression of IFN-I stimulated genes (ISGs). Hitherto, the lack of specific inhibitors of IFN-I signaling has prevented the verification of a causal role for IFN-I in these conditions. Commonly used inhibitors of the JAK/STAT pathway exert broad effects on multiple signaling pathways leading to more general immunosuppression beyond IFN-I signaling.MethodsHere we show in four patients with SAVI and one patient with CANDLE syndrome that blockade of the IFNAR1 receptor (Anifrolumab) exerts an additive effect over JAK-inhibitor alone. In two patients with SAVI, monotherapy with Anifrolumab is sufficient to retain a suppressed IFN-I signature and clinical improvement.ResultsAnifrolumab normalizes IFN-I signature genes and relieves symptoms beyond what is typically achieved by a JAK-inhibitor (Baricitinib) alone in patients with type-I interferonopathies. In two patients Anifrolumab was used successfully as monotherapy. Addition of Anifrolumab enabled steroid tapering and cessation with reduced overall immunosuppression and lower risks of opportunistic infections and improved metabolic states and growth which is highly beneficial in these young patients.ConclusionThese results verify a causal role of IFN-I signaling in type-I Interferonopathies SAVI and CANDLE and suggests Anifrolumab as an important new treatment option in autoinflammatory diseases with elevated IFN-I induced gene expression.Genia Kretzschmar, Laura Piñero Páez, and Ziyang Tan are shared-first authors.Sara Alehashemi, AnnaCarin Horne, and Petter Brodin are co-senior author.