Therapeutic Advances in Infectious Disease最新文献

Common variable immunodeficiency (CVID) is the most common humoral immune deficiency in adults, characterized by recurrent sinopulmonary bacterial infections. Invasive fungal infections are rarely associated with CVID. Late-onset combined immunodeficiency (LOCID) is a recently recognized variant of CVID with low CD4 counts and immunoglobulins deficiency. The current study reveals the first documented case of invasive pulmonary aspergillosis (Aspergillus terreus) in a patient with LOCID. A 52-year-old female with a recurrent history of sinopulmonary infections presented with acute onset fever and shortness of breath. Blood culture and bronchoalveolar lavage culture grew A. terreus. Further evaluation revealed low immunoglobulins (IgG, IgM and IgA). Moreover, she also had low CD4 counts (<200 cells/µL). The patient was successfully treated with voriconazole and immunoglobulin therapy. Finally, the study discusses LOCID as a potential risk factor for invasive fungal infections, which can be easily overlooked and cause poor outcomes.

[This corrects the article DOI: 10.1177/20499361241256290.].

Chronic pulmonary aspergillosis (CPA) is a challenging respiratory infection caused by the environmental fungus Aspergillus. CPA has a poor prognosis, with reported 1-year mortality rates ranging from 7% to 32% and 5-year mortality rates ranging from 38% to 52%. A comprehensive understanding of the pathogen, pathophysiology, risk factors, diagnosis, surgery, hemoptysis treatment, pharmacological therapy, and prognosis is essential to manage CPA effectively. In particular, Aspergillus drug resistance and cryptic species pose significant challenges. CPA lacks tissue invasion and has specific features such as aspergilloma. The most critical risk factor for the development of CPA is pulmonary cavitation. Diagnostic approaches vary by CPA subtype, with computed tomography (CT) imaging and Aspergillus IgG antibodies being key. Treatment strategies include surgery, hemoptysis management, and antifungal therapy. Surgery is the curative option. However, reported postoperative mortality rates range from 0% to 5% and complications range from 11% to 63%. Simple aspergilloma generally has a low postoperative mortality rate, making surgery the first choice. Hemoptysis, observed in 50% of CPA patients, is a significant symptom and can be life-threatening. Bronchial artery embolization achieves hemostasis in 64% to 100% of cases, but 50% experience recurrent hemoptysis. The efficacy of antifungal therapy for CPA varies, with itraconazole reported to be 43-76%, voriconazole 32-80%, posaconazole 44-61%, isavuconazole 82.7%, echinocandins 42-77%, and liposomal amphotericin B 52-73%. Combinatorial treatments such as bronchoscopic triazole administration, inhalation, or direct injection of amphotericin B at the site of infection also show efficacy. A treatment duration of more than 6 months is recommended, with better efficacy reported for periods of more than 1 year. In anticipation of improvements in CPA management, ongoing advances in basic and clinical research are expected to contribute to the future of CPA management.

Background: Identifying secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) presents challenges due to the ECMO circuit's influence on traditional signs of infection.

Objectives: This study evaluates procalcitonin as a diagnostic marker for secondary infections in patients receiving ECMO with influenza or COVID-19 infection.

Design: Single-center retrospective cohort study.

Methods: All adult patients receiving veno-venous ECMO with underlying influenza or COVID-19 from November 2017 to October 2021 were included. Patient demographics, time receiving ECMO, culture data, and procalcitonin levels were examined. The first procalcitonin within 3 days of infection was compared to negative workups that were collected at least 10 days from the last positive culture. Furthermore, we compared procalcitonin levels by the type of pathogen and site of infection.

Results: In this study, 84 patients with influenza or COVID-19 who received ECMO were included. A total of 276 procalcitonin labs were ordered in this cohort, with 33/92 (36%) of the secondary infections having an associated procalcitonin value. When comparing procalcitonin levels, there was no significant difference between the infection and negative workup groups [1 ng/mL (interquartile ranges, IQR: 0.4-1.2) versus 1.3 (0.5-4.3), p = 0.19]. Using 0.5 ng/mL as the cut-off, the sensitivity of procalcitonin was 67% and the specificity was 30%. In our cohort, the positive predictive value of procalcitonin was 14.5% and the negative predictive value was 84%. There was no difference in procalcitonin by type of organism or site of infection. Procalcitonin levels did not routinely decline even after an infection was identified.

Conclusion: While procalcitonin is a proposed potential diagnostic marker for secondary infections in patients receiving ECMO, this single-center study demonstrated low sensitivity and specificity of procalcitonin in identifying secondary infections. Furthermore, there was no association of procalcitonin levels with etiology of infection when one was present. Procalcitonin should be used cautiously in identifying infections in veno-venous ECMO.

Background: Recently recognized by the World Health Organization as a neglected tropical disease, Noma, an acute and destructive gangrenous disease affecting the gums and facial structures within the oral cavity, has a high mortality rate if untreated.

Objectives: To investigate the prevalence and impact of Noma among internally displaced populations in Northeastern Nigeria.

Design: A retrospective study.

Methods: This retrospective study investigates the prevalence and impact of Noma among internally displaced populations in Northeastern Nigeria. Noma is endemic in Northern Nigeria, Africa, and its occurrence has been linked to extreme poverty, malnutrition, poor hygiene, and inadequate healthcare - conditions exacerbated by the ongoing Boko Haram conflict.

Results: The retrospective descriptive cross-sectional analysis of 17 cases reveals a median age of 8 years, with most of the patients being children who suffer significant social stigmas, such as difficulties in speaking, eating, and social integration, including reduced school attendance and marital prospects.

Conclusion: The study highlights the urgent need for comprehensive research into the etiology of Noma and its socio-economic impact. It emphasizes the necessity for early and effective intervention strategies, particularly in conflict-stricken areas with limited healthcare access.

Background: Aspergillus, a widespread fungus in the natural environment, poses a significant threat to human health by entering the human body via the airways and causing a disease called aspergillosis. This study comprehensively analyzed data on aspergillosis in published articles from mainland China to investigate the prevalence of Aspergillus, and risk factors, mortality rate, and underlying condition associated with aspergillosis.

Methods: Published articles were retrieved from Google Scholar, PubMed, and Science Direct online search engines. In the 101 analyzed studies, 3558 Aspergillus isolates were meticulously collected and classified. GraphPad Prism 8 was used to statistically examine the epidemiology and clinical characteristics of aspergillosis.

Results: Aspergillus fumigatus was prominently reported (n = 2679, 75.14%), followed by A. flavus (n = 437, 12.25%), A. niger (n = 219, 6.14%), and A. terreus (n = 119, 3.33%). Of a total of 9810 patients, 7513 probable cases accounted for the highest number, followed by confirmed cases (n = 1956) and possible cases (n = 341). In patients, cough emerged as the most common complaint (n = 1819, 18.54%), followed by asthma (n = 1029, 10.48%) and fever (1024, 10.44%). Of total studies, invasive pulmonary aspergillosis (IPA) was reported in 47 (45.53%) studies, exhibiting an increased prevalence in Beijing (n = 12, 25.53%), Guangdong (n = 7, 14.89%), and Shanghai (n = 6, 12.76%). Chronic pulmonary aspergillosis (CPA) was reported in 14 (13.86%) studies. Among the total of 14 studies, the occurrence of CPA was 5 (35.71%) in Beijing and 3 (21.42%) in Shanghai. Allergic bronchopulmonary aspergillosis (ABPA), was reported at a lower frequency (n = 8, 7.92%), Guangdong recorded a relatively high number (n = 3, 37.5%), followed by Beijing (n = 2, 25.0%), and Shanghai (n = 1, 12.5%). Percentage of death reported: IPA had the highest rate (n = 447, 68.87%), followed by CPA (n = 181, 27.88%) and ABPA (n = 14, 2.15%). Among the aspergillosis patients, 6220 had underlying conditions, including chronic lung disease (n = 3765, 60.53%), previous tuberculosis (n = 416, 6.68%), and organ transplant or organ failure (n = 648, 10.41%). Aspergillosis was also found in patients using corticosteroid therapy (n = 622, 10.0%).

Conclusion: This review sheds light on the prevalence patterns of Aspergillus species, risk factors of aspergillosis, and gaps in surveillance that could be helpful for the control and treatment of aspergillosis and guide the researchers in future studies.

Registration: This systematic review was prospectively registered on PROSPERO: Registration ID CRD42023476870.

Background: Syphilis is a serious global public health challenge. Despite prior progress in syphilis control, incidence has been increasing in recent years. Syphilis is a common coinfection among people living with HIV (PLHIV). In Panama, few data describe syphilis prevalence among PLHIV. We describe syphilis antibody and high-titer (⩾1:8) active syphilis prevalence and associated factors among individuals who attended an antiretroviral clinic.

Methods: A cross-sectional study was undertaken during February-March 2022 and September-October 2022 for adults (⩾18 year) assigned male and female at birth, respectively. Participants provided peripheral blood samples and self-administered a questionnaire. Samples were screened using immunochromatography; antibody-positive samples were tested using rapid plasma regain to 1:512 dilutions. Logistic regression was used to identify factors associated with syphilis antibody and high-titer active syphilis.

Results: In all, 378 participants gave blood samples; 377 individuals participated in the questionnaire (216 self-reported male sex [males], 158 female [females], and three intersex individuals). Median age was 36 years (interquartile range: 28-45 years). Overall, syphilis antibody prevalence was 32.3% (122/378) (males, 50.7% [108/2013]; females, 5.7% [9/158]; intersex individuals, 100.0% (3/3)], p < 0.01. High-titer active syphilis was found among 24.6% (n = 30) of samples with positive antibody test (males 27.8% [n = 30], females 0.0% [0/9], intersex individuals 0.0% [0/3]). Antibody positivity was associated in the multivariable model with males (50.7%, AOR = 24.6, 95%CI: 1.57-384.53). High-titer active syphilis was associated with younger participant age (18-30 years, 13.2%, OR = 4.82, 95%CI: 1.17-19.83); 31-40 years, 7.8%, OR = 4.24, 95%CI: 1.04-17.21 versus 3.2% >40 years), homosexual identity (16.0% OR = 34.2, 95%CI: 4.50-259.27 versus 0.6% among heterosexual identity); in the multivariable model, associated with sexual identity (bisexual 19.1%, AOR = 10.89, 95%CI: 1.00-119.06) compared to heterosexual identity (0.6%) and weakly associated with concurrency (⩾1 ongoing sexual relationships, 15.9%, AOR = 3.09, 95%CI: 0.94-10.14).

Conclusion: This study found very high prevalence of syphilis antibodies and high-titer syphilis among PLHIV in Panama. Those most affected are males, younger in age, those who practice concurrent sexual relationships, and those who reported homosexual and bisexual identity. Targeted interventions should include repetitive testing and treatment, especially among individuals who may be at increased infection risk.

Background: Despite the increased frequency of oropharyngeal candidiasis among people living with human immunodeficiency virus (HIV), its management is no longer effective due to empirical treatment and emergence of antifungal resistance (AFR). This study sought to investigate the prevalence of oropharyngeal candidiasis and assess the antifungal susceptibility profile of oropharyngeal Candida species isolated from people living with human immunodeficiency virus. Additionally, we evaluated the correlation between oropharyngeal candidiasis and CD4 T cell as well as viral load counts.

Methods: A descriptive cross-sectional study was carried out from April to October 2023 in which 384 people living with HIV underwent clinical examination for oral lesions. Oropharyngeal swabs were collected and cultured on Sabouraud Dextrose agar to isolate Candida species which were identified using the matrix assisted laser desorption ionization time of flight mass spectrometry. Additionally, the antifungal susceptibility profile of Candida isolates to six antifungal drugs was determined using VITEK® (Marcy-l'Étoile, France) compact system. Data on viral load were retrieved from records, and CD4 T cell count test was performed using Becton Dickinson Biosciences fluorescent antibody cell sorter presto.

Results: The prevalence of oropharyngeal candidiasis was 7.6%. Oropharyngeal candidiasis was significantly associated with low CD4 T cell count and high viral load. A total of 35 isolates were obtained out of which Candida albicans comprised of 20 (57.1%) while C. tropicalis and C. glabrata comprised 4 (11.4%) each. C. parapsilosis, C. dubliniensis and C. krusei accounted for 2 (5.7%) each. Additionally, 7 (20%) isolates were resistant to fluconazole, 1 (2.9%) to flucytocine and 0.2 (5.7%) isolates were intermediate to caspofungin. However, specific specie isolates like C. albicans showed 20% (4/20), C. glabrata 50% (2/4) and C. krusei 50% (1/2) resistance to fluconazole. Additionally, C. krusei showed 50% resistance to flucytosine.

Conclusion: The prevalence of oropharyngeal candidiasis (OPC) among people living with HIV was low, and there was a significant association between OPC and CD4 T cell count as well as viral load. C. albicans was the most frequently isolated oropharyngeal Candida species. C. glabrata and C. krusei exhibited the highest AFR among the non-albicans Candida species. The highest resistance was demonstrated to fluconazole.

Background: Despite adoption of the 'test-and-treat' strategy, a high proportion of antiretroviral therapy (ART) naïve people living with HIV (PLHIV) enrol in care with, and die of advanced HIV disease (AHD) in Uganda. In this study, we aimed to determine the prevalence of AHD among ART naïve adults enrolling in care and associated factors at selected public health facilities in Kampala, Uganda.

Methods: From April to July 2022, we conducted a mixed-methods study at Kiswa Health Centre III, Kitebi Health Centre III, and Kawaala Health Centre IV. The study involved cross-sectional enrolment and evaluation of 581 participants, utilizing an interviewer-administered questionnaire and chart reviews. Modified Poisson regression was employed to identify factors associated with AHD, complemented by a qualitative component comprising fifteen in-depth interviews, with data analysed through thematic analysis.

Results: Overall, 35.1% (204/581) of the study participants had AHD. Being male [adjusted prevalence ratio (aPR): 1.4, 95% CI: 1.04-1.88] and aged 35-50 years (aPR: 1.81, 95% CI: 1.14-2.88) were associated with AHD. Participants with no personal health perception barriers had 37% lower odds of presenting to care with AHD (aPR: 0.63, 95% CI: 0.46-0.85). Qualitative findings indicated that individual factors, such as waiting until physical health deteriorated and initially opting for alternative therapies, took precedence in contributing to enrolment in care with AHD.

Conclusion: Over one in every three ART naïve adults presents to public health facilities in Uganda with AHD. Male gender, age 35-50 years, and personal health perception barriers emerged as significant factors associated with AHD; emphasizing the need for targeted interventions to address these disparities and enhance early detection and engagement in care. Routine HIV testing should be emphasized and incentivized especially for men and persons aged 35-50 years.

Background: Cognitive decline among people living with HIV (PLWH) is growing concern as world populations become increasing older including higher proportions of PLWH. It is vitally important to understand psychosocial predictors of age-related cognitive decline men who have sex with men (MSM) living with HIV.

Objectives: The current study seeks to examine psychosocial risk factors the contribute to the risk of age-related cognitive impairment as measured by Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score in a racially diverse sample of MSM living with HIV.

Design: The present analysis utilizes data from the baseline (n = 196) and 6-month follow-up (n = 135) time points of a longitudinal cohort study of PLWH.

Methods: Using a self-report survey, we examine the associations between psychosocial predictors (e.g. trauma, mental health, chronic pain, sleep disturbance, etc.) and risk of dementia using the CAIDE risk score. Analyses include linear and logistic regression.

Results: In adjusted model stress, chronic pain, Black racial identity, and having a sexual identity that is bisexual or another category are all positively associated with CAIDE scores. Childhood sexual abuse history was negatively associated with CAIDE scores indicating a protective effect. Sleep disorder has a positive association with CAIDE scores after adjusting for the baseline CAIDE scores.

Conclusion: These results indicate modifiable correlates of cognitive risk (stress and chronic pain). Interventions should seek to address these comorbid factors including the consideration of minority stress and stigma. Interventions should seek to reach Black and bisexual men living with HIV, including possible cultural tailoring to interventions and messaging. Lastly, future research should examine the impact of variation within childhood sexual abuse histories to better understand their association with cognitive impairment later in life. This may include considering the nature, severity, and potential treatment of trauma symptoms.