Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Opportunistic Infections among newly diagnosed HIV patients in the largest tertiary facility in Ghana.

Background: Opportunistic infections (OIs) among newly diagnosed HIV patients are a marker for inadequateness of HIV awareness and testing. Despite global efforts at creating awareness for early detection, late HIV diagnosis and its associated OIs still exist. This study sought to determine the prevalence and patterns of OIs and associated factors among newly diagnosed HIV patients in Ghana. Methods: A retrospective study using data extraction was conducted among 423 newly diagnosed HIV patients aged ≥18 years at the Korle-Bu Teaching Hospital from July 1st 2018 to December 2019. Multivariate logistic regression was adopted to assess factors associated to OIs. Analysis was performed using SPSS version 16, and p-value < 0.05 was deemed significant. Results: The mean age of patients with a new HIV diagnosis was 40.15 ± 11.47 years. Male versus female sex differential was 30.3% and 69.7%, respectively. The prevalence of OIs among newly diagnosed HIV patients was 33.1% (95% CI = 34.6-44.1). About 70% (120/166) of patients with OIs were classified into WHO clinical stage III and IV. The most common OIs were candidiasis (oro-pharyhngeal-esophageal) (36.9%), and cerebral toxoplasmosis (19.9%). The odds of an OI at the time of HIV diagnosis among females was 51% lower than in males (aOR = 0.49, 95% CI = 0.28-0.86). Being employed increased the odds of OIs by 2.5 compared to the unemployed (aOR = 2.5; 95% CI = 1.11-5.61). Participants classified as World Health Organization (WHO) HIV clinical stage III and IV were 15.88 (95% CI = 9.41-26.79) times more likely to experience OIs. Conclusion: One in three patients newly diagnosed with HIV presented with an opportunistic infection, with men more likely to experience such infections. Significant attention should be given to improving case-finding strategies, especially among men.

HIV and skin infections.

HIV infection alters the skin microbiome and predisposes to a wide range of cutaneous infections, from atypical presentations of common skin infections to severe disseminated infections involving the skin that are AIDS-defining illnesses. Bacterial infection of the skin, most commonly caused by Staphylococcus aureus, occurs frequently and can result in bacteremia. Nontuberculous mycobacterial infections that are usually localized to the skin may disseminate, and guidance on the treatment of these infections is limited. Herpes simplex can be severe, and less common presentations such as herpetic sycosis and herpes vegetans have been reported. Severe herpes zoster, including disseminated infection, requires intravenous antiviral treatment. Viral warts can be particularly difficult to treat, and in atypical or treatment-resistant cases a biopsy should be considered. Superficial candidosis occurs very commonly in people living with HIV, and antifungal resistance is an increasing problem in non-albicans Candida species. Systemic infections carry a poor prognosis. In tropical settings the endemic mycoses including histoplasmosis are a problem for people living with HIV, and opportunistic infections can affect those with advanced HIV in all parts of the world. Most cutaneous infections can develop or worsen as a result of immune reconstitution in the weeks to months after starting antiretroviral therapy. Direct microscopic examination of clinical material can facilitate rapid diagnosis and treatment initiation, although culture is important to provide microbiological confirmation and guide treatment.

Recurrent Cryptococcal Meningitis in a Late Presenter of HIV: A Rare Case Report and Review of Literature.

BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of opportunistic infections such as cryptococcal meningitis (CM). Relapse of CM is associated with increased morbidity and mortality. The aim of the present case presentation is to report the clinical progress relapse of CM in a man who was a late presenter PLHIV, 1 year after ART initiation with increased CD4 cell count, undetectable viral load, and excellent compliance after disruption of secondary antifungal prophylaxis. CASE REPORT One year after initial diagnosis of HIV and CM, the patient had no neurological or other symptoms, and viral suppression and increased CD4 cell count were achieved. After the completion of 12 months of secondary prophylaxis with fluconazole, an episode of partial seizure with secondary generalization occurred, followed by a short-term memory loss. Magnetic resonance imaging (MRI) indicated a focal lesion in right frontal-parietal brain region. Lumbar puncture was conducted and Cryptococcus neoformans non-resistant to fluconazole was isolated. He received antiepileptic treatment, induction antifungal treatment with liposomal amphotericin and fluconazole, consolidation treatment with fluconazole, and secondary prophylaxis with fluconazole, as in the first episode of CM. One year after the relapse, antiepileptic treatment and secondary prophylaxis with fluconazole continues and no new episode has been reported. The diagnosis of immune reconstitution inflammatory syndrome (IRIS)-related relapse of CM cannot be excluded. CONCLUSIONS Further studies are needed for the evaluation of parameters such as duration of secondary prophylaxis and treatment options for induction and consolidation therapy to reduce the relapse rate of CM.

The 'pulmonary diseases spectrum' in HIV infected children.

Despite advances in diagnostic, therapeutic and preventive strategies for HIV, pulmonary diseases continue to be the major cause of morbidity and mortality in infants and children infected with HIV. With effective programs to prevent perinatal HIV-1 transmission to early diagnosis in infants, we have seen a substantial decline in paediatric HIV incidence. Early initiation of Highly Active Anti-Retroviral Therapy (HAART) in all HIV infected children coupled with consistent use of Pneumocystis prophylaxis in all HIV exposed/infected children under 5 years of age has considerably reduced associated infections overall and respiratory infections in particular. In developing countries already burdened with poverty, malnutrition, suboptimal immunization coverage and limited access to health care and treatment, acute and chronic HIV-associated respiratory disease remain a major cause for concern. Prevention of severe respiratory infections in advanced HIV disease among children consists mostly of rapid and optimal HAART initiation & continuation, preventing severe TB disease with BCG and TB preventive treatment, preventing Pneumocystis jirovecii pneumonia with cotrimoxazole prophylaxis and administering age-appropriate vaccinations and catch-up vaccines as per National Immunization schedule.

Coexistence of Cryptococcal Fungemia and Pneumocystis jirovecii Pneumonia in an HIV-Infected Patient: A Case Report.

INTRODUCTION: Opportunistic infections caused by bacteria and fungi are common in human immunodeficiency virus (HIV)-infected patients. Cryptococcus neoformans and Pneumocystis jirovecii are the most common opportunistic infections in immunosuppressed individuals, but their coexistence is rare. To our knowledge, this is the first case presented in Turkey involving the coexistence of C.neoformans fungemia and P.jirovecii pneumonia. CASE PRESENTATION: A 26-year-old male patient presented with a cachectic appearance, cough, sputum, weakness, shortness of breath, and a weight loss of 15 kg in the last three months. It was learned that the patient was diagnosed with HIV three years ago, did not go to follow-ups, and did not use the treatments. CD4 cell count was 7/mm3 (3.4%), CD8 cell count was 100 (54%) mm3, and HIV viral load was 5670 copies/mL. In thorax computed tomography (CT), increases in opacity in diffuse ground glass density in both lungs and fibroatelectasis in lower lobes were observed. With the prediagnosis of P. jiroveci pneumonia, the HIV-infected patient was given trimethoprim-- sulfamethoxazole 15 mg/kg/day intravenously (i.v.). On the 4th day of the patient's hospitalization, mutiplex PCR-based rapid syndromic Biofire (Film Array) blood culture identification 2 (BCID2) test (Biomerieux, France) was applied for rapid identification from blood culture. C. neoformans was detected in the blood culture panel. The treatment that the patient was taking with the diagnosis of C. neoformans fungemia was started at a dose of liposomal amphotericin B 5 mg/kg/- day + fluconazole 800 mg/day. CONCLUSION: While the incidence of opportunistic infections has decreased with antiretroviral therapy (ART), it remains a problem in patients who are unaware of being infected with HIV or who fail ART or refuse treatment. High fungal burden, advanced age, low CD4+ cell count, and being underweight are risk factors for mortality in HIV-positive patients. Our case was a cachectic patient with a CD4 count of 7 cells/mm3. Despite the early and effective treatment, the course was fatal.

Pulmonary Histoplasmosis in People Living with Human Immunodeficiency Virus in French Guiana: Clinical Epidemiology, Medical Imaging and Prognostic.

BACKGROUND: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care. METHODS: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded. RESULTS: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%. CONCLUSION: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Talaromyces marneffei and Cytomegalovirus Infections in an HIV-Infected Patient.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening syndrome led by a highly stimulated but invalid immune response, and Talaromyces marneffei (T. marneffei) is an opportunistic infection with high mortality commonly among acquired immunodeficiency syndrome (AIDS) patients. METHODS: Here is a rare case, in which secondary HLH is caused by dual infections of T. marneffei and cytomega-lovirus (CMV). A 15 year old man with a 20-day history of fatigue and intermittent fever (maximum 41.0℃) was admitted to the department of infectious diseases. Marked hepatosplenomegaly and pulmonary infection were detected by computed tomography. Examination of peripheral blood and bone marrow (BM) smears provided clues pointing toward T. marneffei infection, and indicated prominent hemophagocytosis. RESULTS: Cytomegalovirus (CMV) and T. marneffei infections were confirmed by CMV quantitative nucleic acid testing and culture of blood and bone marrow, respectively. A diagnosis of acquired HLH caused by dual infections of T. marneffei and CMV was established because 5 of the 8 HLH diagnostic criteria were met. CONCLUSIONS: The case highlights the contribution of the morphological examination on peripheral blood and bone marrow smears in the diagnosis, which sometimes are the only locations that HLH and T. marneffei can be diagnosed.

Clinical metagenomics-assisted diagnosis of relapsed HIV-associated cryptococcal meningitis.

To date, the identification of crypotococcal relapse remains clinically challenging as it often has similar manifestation with paradoxical immune reconstitution inflammatory syndrome. This study reports on the use of metagenomics assisted next generation sequencing to aid in diagnosing recurrent cryptococcal meningitis in an person living with HIV experiencing recurring symptoms, despite negative culture results for Cryptococcus neoformans in the cerebrospinal fluid. Although fungal culture was negative, when reads from metagenomic and metatranscriptomic sequencing performed on the Day 308 cerebrospinal fluid sample were mapped onto the genome from the Day 4 isolate, 589 specific reads were identified. NCBI BLAST search also revealed Cryptococcus-specific 18S/25S/28S ribosomal RNA, indicating a relapse of the disease.

Development of a case fatality prognostic score for HIV-associated histoplasmosis.

OBJECTIVES: The burden of histoplasmosis is as great as that of tuberculosis in Latin America and the attributable mortality is even higher. A better assessment of severity could help reduce mortality. METHODS: From the French Guiana HIV-histoplasmosis database, we attempted to identify factors associated with 30-day death after antifungal drug initiation and constructed a prognostic score. We evaluated its discrimination performance using several resampling methods. RESULTS: Of the 415 patients included, 56 (13.5%) died within 30 days of treatment. The fatality-associated factors were performance status ≥3, altered mental status, dyspnea, C-reactive protein ≥75 mg/l, hemoglobin <9 g/dl and/or a platelet <100000/ml, and an interstitial lung pattern on chest X-ray. We constructed a 12-point prognostic score. A threshold ≥5 classified patients as alive or dead at 30 days with a sensitivity of 84%, a specificity of 81%, a positive predicted value of 40%, and a negative predicted value of 97%. The area under the curve of the receiver operating characteristic curves from the different resamples were stable between 0.88 and 0.93. CONCLUSION: The histoplasmosis case fatality score, which is easy and inexpensive to perform, is a good tool for assessing severity and helping in the choice of induction therapy. An external validation remains necessary to generalize these results.

Impact of prior cryptococcal antigen screening on in-hospital mortality in cryptococcal meningitis or fungaemia among HIV-seropositive individuals in South Africa: a cross-sectional observational study.

OBJECTIVES: We investigated whether patients with cryptococcal meningitis (CM) or fungaemia detected through South Africa's laboratory cryptococcal antigen (CrAg) screening programme had better outcomes than those presenting directly to the hospital. METHODS: We compared 14-day in-hospital case-fatality ratios of HIV-seropositive individuals with CD4 counts below 100 cells/µL and laboratory-confirmed CM/fungaemia from 2017-2021, with or without evidence of a positive blood CrAg test within 14 days prior to diagnosis. We evaluated whether the impact of prior CrAg screening on mortality varied according to the study period (pre-COVID-19: before March 2020 vs. COVID-19: after March 2020). RESULTS: Overall, 24.5% (830/3390) of patients had a prior positive CrAg test within 14 days of diagnosis. CrAg-screened patients were less likely to have an altered mental status at baseline than non-CrAg-screened patients (38.1% [296/776] vs. 42.6% [1010/2372], p = 0.03), and had a lower crude 14-day case-fatality ratio (24.7% [205/830] vs. 28.3% [724/2560]; OR, 0.83 [95% CI, 0.69-0.99]; p = 0.045). Previous CrAg screening was associated with a greater reduction in the crude 14-day mortality during the COVID-19 period (OR, 0.64 [0.47-0.87]; p = 0.005) compared with before (OR, 0.95 [0.76-1.19]; p = 0.68). After adjustment, previous CrAg screening within 14 days was associated with increased survival only during the COVID-19 period (adjusted OR, 0.70 [0.51-0.96]; p = 0.03). DISCUSSION: Previous CrAg screening was associated with a survival benefit in patients hospitalized with CM/fungaemia during the COVID-19 period, with fewer patients having an altered mental status at baseline, suggesting that these patients may have been diagnosed with cryptococcosis earlier.

Talaromyces marneffei infection and complicate manifestation of respiratory system in HIV-negative children.

BACKGROUND: Respiratory symptoms are the earliest clinical manifestation of Talaromyces marneffei (TM) infection. In this study, we aimed to improve the early identification of TM infection in human immunodeficiency virus (HIV)-negative children with respiratory symptoms as the first manifestation, analyze the risk factors, and provide evidence for diagnosis and treatment. METHODS: We retrospectively analyzed six cases of HIV-negative children with respiratory system infection symptoms as the first presentation. RESULTS: All subjects (100%) had cough and hepatosplenomegaly, and five subjects (83.3%) had a fever; other symptoms and signs included lymph node enlargement, rash, rales, wheezing, hoarseness, hemoptysis, anemia, and thrush. Additionally, 66.7% of the cases had underlying diseases (three had malnutrition, one had severe combined immune deficiency [SCID]). The most common coinfecting pathogen was Pneumocystis jirovecii, which occurred in two cases (33.3%), followed by one case of Aspergillus sp. (16.6%). Furthermore, the value of ß-D-glucan detection (G test) increased in 50% of the cases, while the proportion of NK decreased in six cases (100%). Five children (83.3%) were confirmed to have the pathogenic genetic mutations. Three children (50%) were treated with amphotericin B, voriconazole, and itraconazole, respectively; three children (50%) were treated with voriconazole and itraconazole. All children were tested for itraconazole and voriconazole plasma concentrations throughout antifungal therapy. Two cases (33.3%) relapsed after drug withdrawal within 1 year, and the average duration of antifungal treatment for all children was 17.7 months. CONCLUSION: The first manifestation of TM infection in children is respiratory symptoms, which are nonspecific and easily misdiagnosed. When the effectiveness of anti-infection treatment is poor for recurrent respiratory tract infections, we must consider the condition with an opportunistic pathogen and attempt to identify the pathogen using various samples and detection methods to confirm the diagnosis. It is recommended the course for anti-TM disease be longer than one year for children with immune deficiency. Monitoring the blood concentration of antifungal drugs is important.

Rare Co-Infection of the Lungs with EBV and Pneumocystis Carinii in a Patient with Kidney Cancer: a Case Report.

BACKGROUND: Epstein-Barr virus (EBV) is the primary agent of infectious mononucleosis, lymphoma, and naso-pharyngeal carcinoma, but rarely involves the lungs. Pneumocystis carinii is commonly found in patients with HIV infection and is not pathogenic when the host is healthy, but opportunistic infections can occur when the body is immunocompromised, causing pneumocystis pneumonia (PCP). It is rare for both diseases to occur in the lungs of the same patient. METHODS: Next-generation sequencing (NGS), laboratory examination, chest CT scan, electronic bronchoscopy, and pathogenetic examination were used in this study. RESULTS: Laboratory tests showed (1-3)-ß-D-glucan of 889.47 pg/mL, negative human immunodeficiency virus (HIV) antibody, and negative Aspergillus immunological test. Chest CT showed multiple high-density shadows in both lungs, and EBV infection combined with Pneumocystis carinii pneumonia was confirmed by bronchoscopic biopsy and NGS examination. CONCLUSIONS: Elevated serum (1-3)-ß-D-glucan is not a specific index for infectious diseases. Bronchoscopy and the NGS has high specificity in pathogen detection of infectious diseases.

Cryptococcal lymphadenitis-First presentation in an HIV-positive patient.

Cryptococcal infection is a life-threatening, opportunistic infection in human immunodeficiency virus-infected individuals. The infection most commonly begins in the respiratory tract, with secondary involvement of the brain, skin, and lymph nodes. We report a rare case of isolated cervical cryptococcal lymphadenitis diagnosed on fine needle aspiration cytology, which was the initial presentation of secondary immunodeficiency in the patient. Periodic acid-Schiff stain, India ink preparation, and culture were done to confirm the diagnosis. He was diagnosed as HIV-positive on further investigation.

Spectrum and mortality of opportunistic infections among HIV/AIDS patients in southwestern China.

We describe the opportunistic infections (OIs) of HIV/AIDS to understand the spectrum, mortality, and frequency of multiple coinfected OIs among HIV/AIDS patients in southern China, where OIs are severe. We carried out a retrospective cohort study of hospitalized HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from Jan. 2011 to May. 2019. The chi-square test was used to analyze cross-infection; the Kaplan‒Meier analysis was used to compare mortality. A total of 12,612 HIV-infected patients were admitted to this cohort study. Among them, 8982 (71.2%) developed one or more OIs. The overall in-hospital mortality rate was 9.0%. Among the patients, 35.6% coinfected one OI, and 64.4% coinfected more than two OIs simultaneously. Almost half of the patients (60.6%) had CD4 + T-cell counts < 200 cells/µL. Pneumonia (39.8%), tuberculosis (35.3%), and candidiasis (28.8%) were the most common OIs. Coinfected cryptococcal meningitis and dermatitis are the most common combined OIs. The rate of anaemia (17.0%) was highest among those common HIV-associated complications. Multiple OIs are commonly found in hospitalized HIV/AIDS patients in southwestern China, which highlights the need for improved diagnosis and treatment.