Background Previous research has demonstrated the clinical significance of alanine aminotransferase (ALT) flares; however, studies have mostly been in Asian countries or populations, and it remains unclear whether ALT flares during treatment are associated with hepatitis B surface antigen (HBsAg) loss and long-term adverse clinical outcomes. Objectives To evaluate the association between ALT flares and virologic outcomes (HBsAg and hepatitis B e antigen [HBeAg] loss) as well as adverse clinical outcomes among patients with chronic hepatitis B in the United States, according to treatment status. Design Retrospective study using the Optum de-identified electronic health record dataset (2012–2019). Methods Marginal structural models estimated the associations between ALT flares and outcomes, accounting for time-varying confounding; adjusted odds ratios and 95% confidence intervals were reported. A Cox proportional hazards regression model was used to assess risk factors for flares. Results 14,328 patients were included in the untreated cohort; of these, 2298 (16.0%) initiated and 1541 (10.7%) subsequently discontinued treatment. At least one ALT flare was experienced by 364 patients (2.5%) in the untreated cohort, 84 (3.7%) in the treatment initiation cohort, and 22 (1.4%) in the discontinuation cohort. Risk factors for ALT flares in the untreated group included male sex, history of flares, metabolic syndrome, liver fibrosis, compensated cirrhosis (CC), and hepatic decompensation. Risk factors after treatment initiation included younger age, White race, history of flares, and evidence of liver damage (liver fibrosis, CC, or hepatic decompensation). Flares in the untreated group were associated with spontaneous HBsAg loss and with an increased risk of hepatic decompensation, hospitalization, and death. Flares after treatment initiation were associated with HBsAg and HBeAg loss but not with adverse clinical outcomes investigated. Conclusion ALT flares in untreated patients were associated with virologic and adverse clinical outcomes; no association with adverse clinical outcomes was observed in patients who initiated treatment.
Background Two-drug antiretroviral regimens are increasingly explored to simplify HIV-1 treatment while maintaining durable viral suppression. Doravirine combined with Islatravir (DOR/ISL) represents a novel non-integrase strand transfer inhibitor (non-INSTI) regimen. However, comprehensive synthesized evidence remains limited. Objectives To systematically evaluate the efficacy and safety of fixed-dose Doravirine (100 mg) plus Islatravir (0.25 or 0.75 mg) for HIV-1 treatment in adults. Design Systematic Review and Meta-Analysis. Data Sources and Methods Comprehensive searches of PubMed, Embase, Scopus, Cochrane CENTRAL, ICTRP, and ClinicalTrials.gov were performed to identify RCTs evaluating Doravirine/Islatravir for HIV-1 treatment. The primary outcome was viral suppression (HIV-1 RNA <50 copies/mL) at 48 weeks. Secondary outcomes included immunological and safety endpoints. Results Seven RCTs (N = 3,589) were included. In primary analyses restricted to the approved 0.25 mg dose (four RCTs, N = 1,639), DOR/0.25 mg ISL achieved non-inferior viral suppression compared to standard ART at 48 weeks (RR = 1.01, 95% CI: 0.97-1.04, p = 0.63), with consistent efficacy across virologically suppressed and treatment-naïve cohorts. DOR/0.25 mg ISL showed no significant differences versus controls in CD4+ cell count (MD = -6.35 cells/µL, p = 0.51) or total lymphocyte count changes (MD = -0.02 x 10 9 /L, p = 0.54). Statistically significant declines in CD4+ and lymphocyte counts were strictly restricted to the discontinued 0.75 mg dose. Overall adverse events and treatment discontinuations due to adverse events were comparable between groups. Conclusion DOR/ISL provides non-inferior virologic efficacy compared with standard antiretroviral therapy with a favorable safety profile. The 0.25 mg Islatravir dose maintains antiviral efficacy while avoiding the immunologic declines observed with 0.75 mg dose, supporting its suitability as a simplified two-drug regimen. Registration This review protocol was prospectively registered with PROSPERO ( CRD420261321479 ).
Tuberculosis (TB) treatment in patients with acute intermittent porphyria (AIP) is challenging because several first-line antituberculous drugs can precipitate porphyric crises, and evidence to guide management is limited. We describe a 26-year-old woman with peritoneal TB who developed acute abdominal pain, hyponatraemia, seizures, and neuropsychiatric manifestations within 24 hours of standard isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E) therapy. AIP was confirmed by elevated urinary porphobilinogen levels, and the patient required hemin for the acute crises. Antituberculous therapy was modified to a rifampicin-free regimen including moxifloxacin, linezolid, and ethambutol; isoniazid was cautiously reintroduced once the patient had stabilised. Recurrent porphyric crises and treatment-related toxicity ultimately led to therapy discontinuation after 167 doses. The patient achieved substantial neurological recovery without TB relapse after one year of follow-up. This case illustrates the need to balance TB control with porphyria safety, and to consider acute hepatic porphyria when patients develop unexplained abdominal pain, hyponatraemia, or neurological symptoms after starting antituberculous therapy. Rifampicin and isoniazid carry the highest porphyrinogenic risk, whereas moxifloxacin, ethambutol, and linezolid appear to be safer alternatives. Given limited evidence and the absence of standardised protocols for this rare coexistence, we offer a pragmatic framework to support shared decision-making in tuberculosis and porphyria.
Background Human toxocariasis is among the most common helminthic zoonoses worldwide, and larvae traverse the lungs during visceral migration. Respiratory morbidity among diagnosed patients remains poorly characterised, in contrast to the much larger seroepidemiological literature linking Toxocara seropositivity to asthma. Objectives To map the reported occurrence and clinical spectrum of respiratory disease in confirmed or probable human toxocariasis, and to identify evidence gaps. Eligibility criteria Case reports, case series, cross-sectional studies, cohorts and trials reporting a respiratory outcome in confirmed or probable toxocariasis. Seroepidemiological association studies, non-Toxocara larva migrans and reports lacking patient-level respiratory data were excluded. Sources of evidence MEDLINE (via PubMed) and the Web of Science Core Collection, from database inception to 13 June 2026. Charting methods Two reviewers independently screened and charted data, with disagreements resolved by a third. Findings are presented descriptively, without critical appraisal or meta-analysis. Results Sixty-five studies reporting 989 patients were included, published 1980 to 2026. Case reports predominated (46/65; 70.8%) and only 1/65 (1.5%) originated from sub-Saharan Africa. Any respiratory symptom was documented in 32/46 case reports (69.6%). Across 12 studies of other designs (593 patients), study-level prevalence ranged from 0.0% to 80.7%, and from 0.0% to 66.7% excluding one cohort reporting a non-disaggregable pooled figure. Imaging was reported in 53/65 studies (81.5%), most often nodules (22/53; 41.5%), interstitial infiltrates (16/53; 30.2%) and ground-glass opacity (14/53; 26.4%). Peripheral eosinophilia was present in 58/65 (89.2%) and explicitly absent in 2/65 (3.1%); lung function was reported in 2/65 (3.1%). Conclusion Respiratory findings were reported in a substantial share of published cases, spanning imaging abnormalities to eosinophilic lung disease; eosinophilia was frequent but not universal. Because the evidence comprises largely case reports from a respiratory-focused search, these proportions describe what has been reported rather than true frequency. Prospective studies in endemic, resource-limited settings are needed.
Background Rabies is a major global public health problem, with case fatality rate approaching 100% once clinical symptoms appear, causing severe neurological complications and significant social and economic burdens. Ethiopia bears a high burden of rabies, with the disease remaining endemic and contributing to considerable vaccine-preventable deaths, largely due to low community awareness, inadequate preventive practices, and limited access to timely post-exposure prophylaxis. Although studies have examined community knowledge, attitudes, and preventive practices regarding rabies in Ethiopia; however, the reported findings vary across studies. Objectives This review was conducted to estimate the pooled prevalence and identify associated factors of community knowledge, attitudes, and preventive practices related to rabies prevention in Ethiopia. Design Systematic review and meta-analysis. Data Sources and Methods A comprehensive and systematic literature search was conducted in PubMed/MEDLINE, EMBASE, ScienceDirect, Semantic Scholar, Google Scholar, the Cochrane Library, and the National Institute for Health and Care Excellence (NICE), together with relevant grey literature to identify studies reporting on community knowledge, attitudes, and preventive practices regarding rabies in Ethiopia. Data on prevalence estimates and associated determinants were extracted using Microsoft Excel and subsequently analyzed using Stata version 17.0. A random-effects model was applied to estimate the pooled prevalence, and subgroup analyses were performed to explore potential sources of heterogeneity among the included studies. Publication bias was assessed through visual inspection of funnel plots and Egger’s regression test. The methodological quality of the included studies was evaluated using the Joanna Briggs Institute (JBI) critical appraisal checklist. Results A total of 27 studies involving 11,964 participants were included in the final analysis. The pooled estimates of good knowledge, favorable attitudes, and good preventive practices toward rabies were 60.36%, 58.56%, and 54.62%, respectively. Individuals living in urban areas, formal education and previous exposure to rabies were positively associated with good knowledge of rabies prevention. Conclusions Community awareness, attitudes, and preventive behaviors toward rabies in Ethiopia remain suboptimal, with disparities among rural populations and individuals with lower educational status. The findings highlight the need for focused education intervention, improved availability of vaccination and post-exposure services, and enhanced collaboration through the One Health approach. Future efforts should focus on scaling up community awareness and preventive behaviors to support rabies control. Registration Not registered.
Background Extensively drug-resistant (XDR) typhoid fever is a major public health concern in Pakistan, with limited treatment options and rising morbidity. There is a limited amount of evidence available on the role of the environmental factors that may impact the severity of the disease in adults. Objectives To evaluate clinical outcomes, antimicrobial resistance patterns, and environmental factors associated with disease severity among adults with XDR typhoid fever in Northern Punjab, Pakistan. Design Prospective observational study. Methods A prospective observational study was conducted from January 2024 to January 2025 at a tertiary care hospital in Northern Punjab. The enrollment occurred among adult patients (18- 60 years) with blood culture-confirmed XDR Salmonella enterica serovar Typhi infection using consecutive sampling. Clinical characteristics, susceptibility to antimicrobials, and environmental exposure were recorded. Severity of the disease was defined based on clinically significant complications and adverse outcomes. The chi-square test and Fisher exact test were used to analyze the associations, followed by multivariable logistic regression analysis to adjust for potential confounders. Results Among 110 patients, meropenem (98.2%) and azithromycin (96.4%) showed the highest antimicrobial susceptibility. Contaminated drinking water, poor sanitation, street food and season of diagnosis were also significantly associated with severe disease (p<0.05). Conclusion XDR typhoid fever in Northern Punjab was characterized by extensive antimicrobial resistance, while poor sanitation, contaminated drinking water, street food consumption, and season of diagnosis were significantly associated with severe disease. There is an immediate need to strengthen water, sanitation, antibiotic stewardship, and vaccination strategies. Registration Not applicable.
Background Visceral leishmaniasis (VL) remains a significant public health concern in East Africa, with an estimated 30,000 cases reported annually. Ethiopia is among the most affected countries in the region, with the southern part of the country bearing a substantial share of the disease burden. Despite the high endemicity of VL in these areas, evidence regarding the factors contributing to disease occurrence among at-risk populations remains limited. Objectives This study aims to identify the determinants of visceral leishmaniasis among patients admitted to selected public hospitals in Guji and Borena Zones, Southern Oromia, Ethiopia, in 2022. Design A facility-based unmatched case-control study was conducted from April 15 to June 15, 2022. Methods The study was conducted among randomly selected 335 (67 cases and 268 controls) patients in Nagele Borena and Yabelo General Hospitals of Guji and Borena Zones from April 15 to June 15/2022. A pretested and structured face-to-face interviewer administered questionnaire and chart review were used to collect the data. Data was entered into Epi Data version 4.6.0 and exported to SPSS version 25.0 for analysis. Bi-variable and multi variable binary logistic regression model were used to identify the determinants of VL. Adjusted odds ratio with 95% Confidence level and p-value of <0.05 were used to declare statistically significant associations. Result A total of 335 study participants comprising 67 cases and 268 controls were included, with an overall response rate of 100%. In this study, presence of a dog in the household (AOR=7.2; 95%CI:3.6-18.1), presence of acacia trees around the home (AOR = 8.3; 95% CI: 4.2–17.1), presence of domestic animals in the household (AOR = 6.8; 95% CI: 2.3–16.7), no formal education (AOR = 3.6; 95% CI: 1.1–12.2), and termite hill around the home (AOR = 3.2; 95% CI: 2.02–9.3) were significantly associated with VL. Conclusion and recommendation Our study identified several determinants of VL, that no formal education, presence of dog in the household, termite hill around the home, presence of domestic animals in the household and acacia trees around the home. Therefore, strengthening community awareness and promoting environmental risk-reduction strategies, including minimizing exposure to domestic animals, termite hills, and acacia trees in close proximity to households, may help reduce the risk of visceral leishmaniasis in the study area.
Human norovirus (HuNoV) is a leading cause of acute viral gastroenteritis worldwide and represents a major unmet challenge in antiviral drug and vaccine development. HuNoV is a non-enveloped, positive-sense RNA virus characterized by extensive genetic diversity and rapid evolution, which contribute to recurrent outbreaks in the absence of effective licensed therapeutics. Despite substantial progress in understanding HuNoV molecular biology, effective antiviral strategies remain limited, in part due to historical limitations in experimental model systems and the virus’s ability to evade host antiviral responses. Recent advances in HuNoV in vitro culture systems, particularly human intestinal enteroids, and inhibitor screening platforms have improved the identification of antiviral candidates, while parallel efforts in vaccine development have yielded immunogenicity data in preclinical and early-stage clinical studies. However, significant challenges persist, including antigenic diversity, strain-specific immunity, and limited correlates of protection. This review provides a critical analysis of the molecular mechanisms governing HuNoV infection, immune evasion, and replication, with a focused emphasis on key antiviral targets, inhibitory strategies, and therapeutic development. Moreover, this review outlines key limitations and future directions for the development of effective therapeutic and preventive measures against HuNoV infection.
Diabetes mellitus is among the strongest independent risk factors for severe influenza, hospitalization, and influenza-associated acute respiratory distress syndrome (ARDS). The mechanistic basis of this association, and its clinical implications for immunomodulatory therapy, has been examined extensively in basic immunology and virology but is rarely synthesized for the practicing intensivist. This narrative review synthesizes the mechanistic basis by which diabetes predisposes to severe influenza and to translate the established pathogen-driven versus host-driven lung injury framework into a bedside-relevant heuristic for immunomodulatory decision-making. PubMed/MEDLINE and the Cochrane Library were searched from inception through April 2026, integrating evidence across innate and adaptive immunology, viral pathogenesis, and clinical trial data. The review was guided by the SANRA framework. Diabetes plausibly impairs early antiviral containment through disruption of type I interferon signaling, alveolar macrophage function, neutrophil-mediated barrier defense, and CD8 + T-cell responses, predominantly demonstrated in vitro and in murine models with supportive observational human data. The resulting prolonged viral replication, superimposed on baseline endothelial vulnerability, may contribute to rapid, severe lung injury. The framework applies most directly to type 2 diabetes; mechanistic differences between type 1 and type 2, and between acute glucose-driven and chronic structural mechanisms, are addressed. Available observational and meta-analytic evidence consistently associates corticosteroids with worse outcomes in influenza pneumonia. Selective adjunctive strategies, most notably mTOR inhibition with sirolimus and combination clarithromycin–naproxen–oseltamivir, show early hypothesis-generating signals but require confirmatory trials. This synthesis is intended as hypothesis-generating, not definitive.
Melioidosis is a serious infectious disease caused by Burkholderia pseudomallei , a bacterium endemic to tropical regions, including Taiwan. The disease can involve multiple organs; however, cardiac involvement, particularly cardiac tamponade, is rare. To date, only four cases of melioidosis presenting with cardiac tamponade have been reported in the literature. Here, we report an extremely rare case of melioidosis complicated by pericardial effusion and cardiac tamponade, which was successfully treated with pericardiocentesis and appropriate antimicrobial therapy.
Background:Immunocompromised patients have a risk of severe COVID-19. Objectives:To describe the outcomes of ensitrelvir in hospitalized immunocompromised patients with COVID-19, with remdesivir as a reference. Design:Single-center retrospective cohort study. Methods:We analyzed patients with moderate/severe immunodeficiency who received ensitrelvir or remdesivir as initial therapy. The primary outcome was 28-day all-cause mortality; secondary outcomes were time to discharge and viral clearance. Exploratory analyses used inverse probability of treatment weighting (IPTW) based on propensity scores and Cox proportional-hazards models. Results:Among 56 patients (22 ensitrelvir; 34 remdesivir), 28-day mortality was 4.5% versus 8.8%, respectively. Time to discharge and viral clearance were similar. IPTW-adjusted 28-day mortality was 4.2% with ensitrelvir and 10.7% with remdesivir (hazard ratio 0.39; 95% CI 0.04-3.64). Conclusion:In this small, single-center exploratory cohort, ensitrelvir was associated with low mortality, although comparison with remdesivir should be interpreted cautiously given treatment selection, treatment switching, and limited sample size.
Background:Pneumocystis jirovecii pneumonia (PJP) in non-HIV immunocompromised adults carries 30%-60% mortality. Adjunctive corticosteroids are standard in HIV-PJP but remain contested in non-HIV PJP. Objectives:To determine whether adjunctive corticosteroids reduce mortality and invasive mechanical ventilation (IMV) in non-HIV PJP, and whether effect estimates differ between randomized and observational study designs. Design:Systematic review and meta-analysis. Data sources and methods:Six databases and two trial registers were searched from inception to February 7, 2026. Randomized and observational studies comparing adjunctive corticosteroids versus no corticosteroids or placebo in non-HIV adults with PJP were eligible. Random-effects meta-analyses (restricted maximum likelihood) of two co-primary outcomes included subgroup, sensitivity, E-value, and Grading of Recommendations Assessment analyses. Results:Twenty-eight studies were included (one randomized controlled trial (RCT), 27 observational; ∼ 5300 patients): 22 contributed corticosteroid-versus-no-corticosteroid comparisons and six contributed dose-comparison data only. Evidence was discordant by design (interaction p = 0 . 006 ): the RCT showed lower IMV (hazard ratio (HR) 0.36, 95% CI 0.14-0.90) and lower 90-day mortality (HR 0.59, 0.37-0.93); regression-adjusted observational studies suggested harm (odds ratio (OR) 1.56, 1.10-2.22); propensity-based estimates were null-compatible. Pre-specified mortality pools were non-significant short-term (OR 1.22, 0.88-1.70) and intermediate-term (OR 1.39, 0.85-2.29). Secondary infections ( k = 4 ): OR 1.04 (0.63-1.72); RCT 0.59 (0.32-1.06). E-values for RCT effects (3.44 IMV; 2.24 mortality) exceeded the 1.81 E-value of the adjusted observational mortality pool. Certainty was very low for pooled mortality and moderate for RCT outcomes. Conclusion:Reliable inference rests on the single RCT rather than the pooled observational estimate, which is discordant by design and most consistent with confounding by indication. In the RCT, corticosteroids did not significantly reduce 28-day mortality but lowered IMV and 90-day mortality and sped respiratory recovery, without clear excess secondary infections (low certainty). Corticosteroids may be considered for severe respiratory failure using the PIC (ClinicalTrials.gov NCT02944045) protocol; adequately powered confirmatory trials are needed. Trial registration: PROSPERO CRD420261304396.
Background: In 2016, Uganda adopted the WHO HIV drug resistance (HIVDR) monitoring strategy to track treatment outcomes following the introduction of a dolutegravir (DTG) based regimen as first line among people living with HIV (PLHIV). However, despite widespread transition to DTG-based regimens, evidence on acquired DTG resistance and its determinants remains limited. Objectives: To determine the prevalence of acquired DTG resistance among PLHIV with virologic failure and identify associated factors in North-Eastern Uganda. Design: We conducted a retrospective cross-sectional study from 24 accredited antiretroviral therapy health facilities in North-Eastern Uganda by 28th February 2025. Methods: The study included eligible PLHIV on DTG-based regimens with at least 2 viral loads >1000 copies/mL and a documented HIV genotypic resistance testing result between April 2022 and July 2024. Clinical data were extracted from the national drug resistance dashboard and verified against facility electronic medical records. Logistic regression via generalised estimating equations (GEE) was used to identify factors associated with DTG resistance. A p -value < 0.05 was considered statistically significant. Results: Of 225 participants, the median age was 19 years (interquartile range: 15–39), and 55.1% ( n = 124) were male. The prevalence of high-level to intermediate DTG resistance was 18.7% ( n = 42), with 14.2% ( n = 32) having high-level resistance to DTG and 4.4% ( n = 10) intermediate resistance. Most participants were unemployed (60.0%, n = 135) and had not disclosed their HIV status (74.2%, n = 167). DTG resistance was associated with presence of nucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs) (adjusted odds ratio (aOR); 12.14, 95% confidence interval (CI): 4.14–35.65, p < 0.001), poor adherence (aOR; 6.19, 95% CI: 2.54–15.11, p = 0.001), DTG use ⩾ 3 years (aOR; 9.19, 95% CI: 1.60–52.74, p = 0.013), and alcohol/substance abuse (aOR; 3.94, 95% CI: 1.74–8.91, p = 0.001). Conclusion: Nearly one in five PLHIV with virologic failure exhibited DTG resistance, predominantly high-level. Key associated factors included poor adherence, being on DTG for ⩾3 years, alcohol/substance abuse, and the presence of relevant NRTI DRM. Strengthening family and peer support, integrating substance abuse screening and management in HIV care, and improving adherence may help reduce the risk of DTG resistance. These findings highlight the urgent need for enhanced HIVDR monitoring and tailored interventions to sustain progress toward HIV epidemic control by 2030.
Magnusiomyces clavatus, formerly Saprochaete clavata or Geotrichum clavatum, is an ascomycetous yeast found in the environment as well as the gastrointestinal and respiratory tracts of humans. It has been described as an emerging, albeit rare, cause of invasive fungal disease affecting immunocompromised patients. Intrinsic resistance to fluconazole and echinocandins has been theorized; however, little else is known regarding optimal treatment regimens for this opportunistic pathogen. To our knowledge, only 13 infectious cases have been described in pediatric patients, all of which utilized a combination of antifungals including liposomal amphotericin B (LAmB) and voriconazole with or without flucytosine (5-FC). Here we report a case of a 4-year-old, 12.3 kg, female patient who immigrated from Ukraine and was admitted to our institution for an allogeneic umbilical cord blood transplant in the setting of bone marrow failure secondary to Fanconi anemia. On day +6 after cell transplantation, the patient developed febrile neutropenia found to be because of invasive M. clavatus fungemia on day +7. The patient was empirically treated with LAmB, micafungin, and posaconazole (POS), the latter of which failed to reach therapeutic levels. Ultimately, our patient defervesced and cleared blood cultures after transitioning LAmB to 5-FC, followed by definitive treatment with isavuconazole (ISA) monotherapy. To our knowledge, this is the first case of pediatric M. clavatus ultimately treated with 5-FC plus POS followed by ISA alone.
Background: General-purpose large language model (LLM)–based systems are increasingly accessible to clinicians and are being explored for applications in clinical microbiology and infectious diseases (ID). However, rapid adoption has outpaced the development of specialty-specific guidance, raising concerns related to safety, reliability, accountability, and antimicrobial stewardship. Objectives: The project aims to develop consensus-based statements, endorsed by Study Group for Artificial Intelligence and Digitalisation of the European Society of Clinical Microbiology and Infectious Diseases (ESGAID), that describe principles, opportunities, and limitations in the interactions of clinical microbiologists and ID specialists with general-purpose LLM-based systems. Secondary objectives are to quantify expert agreement and identify areas of uncertainty and disagreement. Design: The project follows a structured expert consensus design using the RAND/UCLA Appropriateness Method. Methods and analysis: A multidisciplinary panel of 15 experts will be selected through ESGAID using predefined criteria to ensure balanced expertise across clinical microbiology, infectious diseases, ethics, legal aspects, and patient safety. Ten draft statements, each supported by a structured literature review, will be developed by project coordinators. Statements will be evaluated through iterative rounds of anonymous rating on a 1–9 scale, combined with moderated remote discussions. Median scores will classify statements as supported, uncertain, or unsupported. Consensus will be defined as ⩾70% agreement with <15% disagreement during final anonymous voting. Discussion: This protocol provides a transparent and reproducible framework to generate interim, specialty-specific statements on principles, opportunities, and limitations in the interactions of clinical microbiologists and ID specialists with general-purpose LLM-based systems. By combining structured evidence review with expert judgment, the resulting statements aim to delineate guidance on principles for interacting with these systems, highlight the nature of both existing risks and excessive skepticism, and identify research priorities in a rapidly evolving technological and regulatory landscape.
Magnusiomyces clavatus , formerly Saprochaete clavata or Geotrichum clavatum , is an ascomycetous yeast found in the environment as well as the gastrointestinal and respiratory tracts of humans. It has been described as an emerging, albeit rare, cause of invasive fungal disease affecting immunocompromised patients. Intrinsic resistance to fluconazole and echinocandins has been theorized; however, little else is known regarding optimal treatment regimens for this opportunistic pathogen. To our knowledge, only 13 infectious cases have been described in pediatric patients, all of which utilized a combination of antifungals including liposomal amphotericin B (LAmB) and voriconazole with or without flucytosine (5-FC). Here we report a case of a 4-year-old, 12.3 kg, female patient who immigrated from Ukraine and was admitted to our institution for an allogeneic umbilical cord blood transplant in the setting of bone marrow failure secondary to Fanconi anemia. On day +6 after cell transplantation, the patient developed febrile neutropenia found to be because of invasive M. clavatus fungemia on day +7. The patient was empirically treated with LAmB, micafungin, and posaconazole (POS), the latter of which failed to reach therapeutic levels. Ultimately, our patient defervesced and cleared blood cultures after transitioning LAmB to 5-FC, followed by definitive treatment with isavuconazole (ISA) monotherapy. To our knowledge, this is the first case of pediatric M. clavatus ultimately treated with 5-FC plus POS followed by ISA alone.
We present the case of a 9-year-old girl from the Peruvian Andean Region (Ancash), diagnosed with fascioliasis, who was also suffering from severe malnutrition. Initially, she was referred for treatment of skin necrosis caused by cutaneous visceral loxoscelism, but during hospitalisation she developed persistent vomiting and pancreatitis. Magnetic resonance cholangiography showed dilation of the intrahepatic and common bile ducts. Endoscopic retrograde cholangiopancreatography identified an adult Fasciola spp. specimen. She also expelled adult worms of Ascaris lumbricoides during vomiting. Delivery of triclabendazole was initiated via a nasogastric tube initially and subsequently via the rectal route, although absorption was limited due to persistent oral intolerance. The patient later developed upper gastrointestinal bleeding and sepsis of abdominal origin and died. During this period, the patient remained on broad-spectrum antibiotic therapy, although sepsis was attributed to persistent biliary obstruction. Fascioliasis and ascariasis should remain in the differential diagnosis for pancreatitis and cholestasis in paediatric patients from endemic areas. Oral triclabendazole is the treatment of choice for fascioliasis, but surgical management should be considered in cases of persistent biliary obstruction or treatment failure, usually seen in complicated chronic infections.
Background:Viral hepatitis is a major cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma, with significant morbidity and mortality. Individuals with sickle cell disease (SCD) are at increased risk of hepatitis C virus (HCV) infection due to frequent transfusions. Despite the high burden of HCV in Uganda, recent data on HCV seroprevalence among individuals with SCD are limited. Objective:To determine HCV seroprevalence and describe characteristics among patients with SCD receiving care at Mulago National Referral Hospital (MNRH), Kampala, Uganda. Design:Hospital-based cross-sectional study. Methods:Individuals with SCD attending the MNRH outpatient SCD clinic in Kampala, Uganda, were recruited between July and September 2025. Sociodemographic, clinical, and behavioral data were collected using a structured questionnaire. Anthropometric measurements were taken using standardized scales. HCV, hepatitis B surface antigen (HBsAg), and HIV rapid tests were performed. Data were analyzed using the SAS statistical package version 9.4. Results:There were 119 participants with SCD enrolled, with a mean age of 13.1 years, and 55.5% (n = 66) were male. Most participants had a SCD diagnosis for 6 years or longer. HCV seroprevalence was 12.6% (n = 15). All HCV-seropositive participants were less than 18 years, with nearly two-thirds of those aged 9-17 years (66.7%, n = 10). Nearly all HCV-seropositive participants had a history of blood transfusion (n = 14, 93.3%), with 53.3% (n = 8) reporting three or more transfusions. Only one participant (0.84%) tested positive for HIV, and none tested positive for HBsAg. Conclusion:This study revealed a high seroprevalence of HCV among individuals with SCD in Uganda. Strengthening routine HCV screening, linkage to care, and infection prevention, including within blood transfusion services, is needed. Larger studies incorporating HCV RNA testing are recommended to assess the true burden of active infection and risk factors among patients with SCD to inform targeted prevention, screening, and treatment strategies.
