non-HIV Patients Research Articles

2311. Long-term prognosis and risk factors for overall mortality in patients with progressive multifocal leukoencephalopathy

Abstract Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by reactivation of JC virus, almost in patients with immunosuppressive conditions. PML is a fatal infection with a reported 3-month mortality rate of 30–50% and a 2-month mortality rate of up to 90% in the non-human immunodeficiency virus (HIV) population. Despite high mortality, studies on PML are still lacking due to its low prevalence and incidence. Therefore, this study aimed to figure out long-term prognosis of PML and prognostic factors for mortality through a long observation period. Methods We retrospectively reviewed 68 PML patients with admitted to two tertiary hospitals in South Korea from 1999 to 2021. A total of 47 PML patients were finally enrolled after exclusion. The primary endpoint was long-term overall mortality. For survival analysis, Kaplan-Meier curve and Cox proportional hazards model were used. Each patient was followed up until death or until the end of the study period, whichever came first. Results The median follow-up duration was 20 (interquartile range [IQR], 3–79) months. The median age was 46 years, 27 (57.4%) were diagnosed with HIV, 19 (40.4%) were using immunosuppressive drugs. The median last follow-up modified Rankin Scale (mRS) was higher in non-HIV PML patients group (5 [IQR, 4–6] vs 4 [IQR, 2–5], p=0.020). The median survival duration was 184 (IQR 74–1,566) days in the non-HIV group and 1,564 (IQR 254–3,444) days in the HIV group. The overall mortality rate of PML patients was significantly higher in non-HIV group (80.0% vs 40.7%, p=0.007), also confirmed by the Kaplan-Meier curve and log-rank test (p=0.007). Initial mRS (HR 1.685, 95% CI: 1.028–2.762, p=0.038), HIV patients with highly active antiretroviral therapy (HAART) (HR 0.374, 95% CI: 0.172–0.815, p=0.013) had a significant effect on overall mortality. Conclusion With the widespread adoption of HAART, the survival duration of HIV patients with PML has been extended, but the mortality rate is still high. Also, the prognosis for PML in non-HIV patients is still frustrated. Initial mRS is a significant risk factor for long-term overall mortality in PML patients. Early detection of PML and early initiation of HAART in HIV patients may improve the patient's prognosis. Disclosures All Authors: No reported disclosures.

1453. Clinical Manifestation and Risk Factors Associated with Mortality of Cytomegalovirus Infection in Immunocompetent Patients in King Chulalongkorn Memorial Hospital, Bangkok, Thailand: a 3-year experience

Abstract Background Cytomegalovirus (CMV) infection usually occurs in organ transplant or HIV-infected patients. Recently, we found CMV infection was increased in non-transplant and non-HIV infected patients. Our study aimed to determine the epidemiology, clinical manifestation, clinical outcome, and risk factors associated mortality of CMV infection in this population. Methods The retrospective study was conducted in King Chulalongkorn Memorial Hospital. Patients aged above 18 years with diagnosis of CMV infection from January 2017 to September 2019 were collected and identified by ICD-10 code. Patients with HIV infection, solid organ transplant and hematopoietic stem cell transplant were excluded. Results A total of 51 patients, including 28 males (54.9%) were identified. The median age was 61 years (range 48-73 years). 46 patients (90.2%) had underlying disease which were 19 cases (37.3%) of autoimmune disease, 13 cases (25.5%) of hematologic disease (mostly hematologic malignancy), 4 cases (7.8%) of chronic kidney disease, and 10 cases (21.6%) of others. CMV viremia was found in 31.4%. Regarding CMV end-organ disease, there were 20 cases of gastrointestinal tract CMV infection, 10 cases were CMV retinitis, 5 cases were CMV pneumonitis and 1 case was CMV hepatitis and CMV transverse myelitis. The all-cause mortality was 25.5% and significantly in age over 70-year-old (p=0.037). The end-organ disease and CMV viral load were not different in survived and death group (p=0.445 and p=0.838, respectively). Factors associated with mortality of CMV infection Conclusion CMV infection was an emerging problem in non-transplant and non-HIV infected adult patients, especially in age over 70-year-old in our Institute. The study showed infections predominated in rheumatologic and hematologic malignant patients who were received chemotherapy or immunosuppressive agent. Viremia and gastrointestinal tract were organs that mainly involved. CMV infection will become an important complication in the era of treatment with immuno-chemotherapy. Clinician should be aware of this potentially life-threatening infection. Disclosures All Authors: No reported disclosures.

CLINICAL, PARACLINICAL FEATURES OF PATIENTS WITH CYTOMEGALOVIRUS DISEASE AT THE NATIONAL HOSPITAL FOR TROPICAL DISEASES 2020 - 2022

Objectives: To describe the clinical and paraclinical characteristics of patients with CMV disease at the National Hospital for Tropical Diseases.Subjects and methods: Retrospective combined with a prospective cohort study on 58 patients diagnosed with CMV disease treated at the National Hospital of Tropical Diseases in 2 years from January 2020 to June 2022.Results: In a total of 58 patients with CMV disease, 56.9% of patients were male and the mean age was 45.57 ± 15.7 years. HIV (55.17%), history of prolonged corticoid therapy (20.7%), diabetes (10.34%), alcoholism (3.45%), transplantation (1.72%) were major comorbidities. Common clinical symptoms were:fever (74.13%), low visual acuity (37.93%), weight loss (31.03%), productive cough (31.03%), headache(27.59%), lymphadenopathy (24.14%), dry cough (22.41%). 43.1% had monocytosis status, most patientshad normal white blood cell (WBC) count, and slightly increased inflammation markers (ESR, CRP, PCT).The interquartile range of T-CD4 was48 (11.75 - 215), and 60% of patients had T-CD4 countless than 100cells/µL. There was no difference between two groups of HIV and non-HIV patients in sex ratio. The HIVgroup had higher mean age than non-HIV. Low visual acuity, lymphadenopathy, and weight loss were more frequent in the HIV group, and liver damage was only seen in the non-HIV group.Conclusion: The study showed that the clinical and paraclinical signs of CMV disease are diverse, nonspecific and need to be considered for screening in patients with suspected symptoms with a history of HIV, prolonged corticoid, diabetes, alcoholism, or transplantation.

1032. Janus Kinase Inhibition for Refractory Post-infectious Inflammatory Response in Previously Healthy Patients with Cryptococcal Meningoencephalitis

Abstract Background Post-infectious inflammatory response syndrome(PIIRS) is a previously reported complication of non-HIV cryptococcal meningitis (CM) involving a pathological T cell-mediated neuroinflammatory response once the fungus has been cleared. Although corticosteroids have been successfully used as therapy, side effects preclude prolonged use. Additionally, alternative targeted agents may be required as adjunctive therapy in steroid-refractory PIIRS. We report the clinical course in 3 patients in whom Janus kinase (JAK) inhibitor use led to favorable outcomes when used along with corticosteroids. Methods Medical records of three previously healthy CM-PIIRS patients admitted to the NIH between January 2021 to December 2021 were used to prepare this report. All were transferred from another facility due to worsening neurological status. Neurological exam and radiological findings were compared at baseline and one month after ruxolitinib initiation. CSF parameters including cellular markers of T-cell inflammation (HLA-DR+ CD4+ and HLA-DR+ CD8 cells and monocytes) and soluble CSF cytokines, including IL-6 and sCD25, were also included in the comparison. Results One patient was on 1mg/kg oral prednisone for 8 months with no improvement in symptoms despite VP shunt placement. The other two had also been on moderate-dose oral steroids for approximately 6 weeks for a recent diagnosis of PIIRS. All three were started on ruxolitinib (5-10 mg PO BID) as an adjunct to prednisone with a significant improvement in their neurological status, CSF inflammatory markers, and radiological findings. CSF fungal cultures remained negative with no occurrence of adverse events 3 months after ruxolitinib initiation. Therapy with ruxolitinib allowed continued corticosteroid taper without clinical flairs of disease in each patient. Conclusion The selective JAK1/2 inhibitor, ruxolitinib, was safe in a small group of HIV-negative patients with CM. This agent may offer promise in conjunction with corticosteroids in the treatment of non-HIV CM patients with refractory PIIRS who are at risk for adverse side effects related to prolonged steroid use. Further study will be required to determine efficacy, tolerability and ability to reduce corticosteroid use. Disclosures All Authors: No reported disclosures.

CMV Retinitis with Panretinal Occlusive Vasculitis

ABSTRACT Purpose To report the clinical features of cytomegalovirus (CMV) retinitis with panretinal occlusive vasculitis. Methods Retrospective case series. Results Four eyes in 3 non-HIV patients (male: female = 3:0) were included. Previous medical history included diabetes mellitus (n = 2), age-related macular degeneration (n = 1), and Multiple myeloma under chemotherapy (n = 1). All patients were treated with oral valganciclovir and intravitreal ganciclovir. Slow resolution of retinitis related retinal opacification was noted in all 4 eyes. Two eyes had anti-viral agents discontinued despite the persistent retinitis related opacification and the lesions slowly resolved in the following months. The final decimal visual acuity was equal to or worse than 0.02 in 3 of the 4 eyes. Conclusion In eyes of CMV retinitis with panretinal occlusive vasculitis, rapid resolution of retinitis lesions is an unreliable sign evaluating the therapeutic efficacy of anti-viral agents. Besides, despite treatment of anti-viral agents, deteriorating vascular occlusion may further endanger macular function.

Dysregulation of iron metabolism modulators in virologically suppressed HIV-infected patients.

Iron metabolism plays an essential role in cellular functions. Since virologically suppressed chronic HIV-infected subjects under effective antiretroviral treatment (ART) exhibit a persistent immune dysfunction that leads to comorbidities, iron homeostasis may be relevant in this context. We aimed to explore iron metabolism in virologically suppressed chronic HIV infected subjects under a successful ART. In this retrospective study, traditional iron metabolism biomarkers (total iron, ferritin, transferrin, and transferrin saturation index), as well as soluble transferrin receptor (sTfR), hepcidin, and inflammatory markers were determined in virologically suppressed chronic HIV-infected subjects under at least 2 years of ART (HIV) who also had >350 CD4-T-cells/mm3 (N=92) from Spain. As controls, we collected non-HIV age-matched healthy donors (Young, N=25) and elderly subjects (>65 years old; Elderly; N=25). Additionally, an external group of non-HIV patients with ferritin<50 ng/mL diagnosed with absolute iron deficiency (Ferropenic group; N=84) was included. Comparisons between groups were performed using Kruskal-Wallis or Mann-Whitney U-tests, while associations between variables were explored by Spearman's rho correlation coefficient. We selected samples from HIV-infected subjects (aged 42[34-47], 95% males), young age-matched (aged 40[30-58], 60% males), and elderly controls (aged 82[78-88], 100% males). Compared to both healthy (Young and Elderly) groups, HIV exhibited decreased iron, transferrin saturation, and sTfR, and increased ferritin, but similar hepcidin levels. Notably, associations between sTfR and iron (Young, r=-0.587, p=0.002; Elderly, r=-0.496, p=0.012) or transferrin saturation index (Young, r=-0.581, p=0.002; Elderly, r=-0.489, p=0.013) were negative in both controls while positive in HIV (r=0.464, p<0.0001 and r=0.421, p<0.0001, respectively). Moreover, the expected negative correlation between hepcidin and sTfR, observed in controls (Young, r=-0.533, p=0.006; Elderly, r=-0.473, p=0.017), was absent in HIV (r=0.082; p=0.438). Interestingly, the HIV inflammatory profile differed from the Elderly one, who despite their inflammaging-related profile, succeed in maintaining these associations. Furthermore, subjects from the ferropenic group (aged 42[32-51], 5% males), showing significantly lower levels of hepcidin and higher sTfR, as expected, reflected similar correlations as those Young and Elderly, in contrast to HIV. Virologically suppressed chronic HIV-infected patients under successful ART exhibit altered levels of iron metabolism modulators suggesting a complex functional iron deficiency.

Clinical, Imaging, and Prognostic Differences of Neurosyphilis in HIV and Non-HIV Individuals

Background Neurosyphilis remains an important health issue, particularly in populations at risk like men who have sex with men. Our aim was determining differences in the clinical presentation and neuroimaging findings in HIV-positive and non-HIV neurosyphilis patients. Methods This is a retrospective study that included 30 patients who were classified either as non-HIV (n = 16) or HIV positive (n = 14) during the period 1997–2017 at the Instituto Nacional de Neurología y Neurocirugía. Results The main clinical signs in non-HIV patients were dementia (56%, P = 0.02), dementia plus neuro-ophthalmic alterations (50%, P = 0.01), delirious ideas (62.5%, P = 0.03), and judgment errors (44%, P = 0.02). In contrast, neuro-ophthalmic alterations were predominant in HIV-positive patients (85.7%, P = 0.02) along with pachymeningitis (57.1%, P = 0.021) and optic neuritis (57.1%, P = 0.023), as determined by neuroimaging. No significant differences in the cytochemical characteristics of cerebrospinal fluid were observed. Conclusions Dementia was predominant in non-HIV subjects, whereas neuro-ophthalmic lesions were observed earlier and more frequently in HIV-positive patients. Our results highlight the importance of visual signs in HIV-positive patients as an early manifestation of neurosyphilis, and the relevant role of the cerebrospinal fluid Venereal Disease Research Laboratory test in the evaluation of patients with dementia.

Antifungal susceptibility and molecular characteristics of Cryptococcus spp. based on whole-genome sequencing in Zhejiang Province, China.

Cryptococcus spp. is a complex species that often causes cryptococcosis, which is one of the most common opportunistic infections in adults living with HIV and has very high morbidity and mortality rates. This study aimed to investigate the antifungal susceptibility profiles and epidemiological characteristics of the Cryptococcus neoformans species complex (CNSC) and the Cryptococcus gattii species complex (CGSC) in Zhejiang Province, China. A total of 177 CNSC and 3 CGSC isolates were collected, and antifungal susceptibility was tested by FUNGUS 3 and verified with an E-test. Moreover, multiple classification methods and genomic analyses were performed. The majority of the isolates (96.11%) were C. neoformans (formerly C. neoformans var. grubii) (ST5-VNI-A-α). Our study highlights that most of the patients with cryptococcosis were non-HIV patients in China, and nearly half of them did not have underlying diseases that led to immune insufficiency. Most of the Cryptococcus spp. isolates in this study were sensitive to common antifungal drugs. Two 5-flucytosine (5-FC)-resistant strains were identified, and FUR1 mutation was detected in the 5-FC-resistant isolates. Typing based on whole-genome sequencing (WGS) showed better discrimination than that achieved with multilocus sequence typing (MLST) and indicated a clear population structure. A phylogenetic analysis based on WGS included more genomic information than traditional classification methods.

Clinical Research in Africa: Collaborative Project between Senegal and France to Improve the Diagnosis and Therapeutic Management of Adult Lymphoma Patients

Background: Little is known about Non-Hodgkin Lymphoma (NHL) in Africa except for the high incidence of Burkitt lymphoma in children and the high association with HIV in Eastern Africa but not Western Africa. Difficulties including low access to health care, use of cytopuncture instead of nodal biopsy, cost of drugs and absence of supportive care lead to poor prognosis for NHL patients (pts) (overall response rate (ORR) <30%) (Diop et al., Bull Soc Patho Exo 2004). Meaningful lymphoma research cannot be conducted without accurate diagnosis (Naresh et al., Br J Hematol 2011). The Senegal Government has built a national anti-cancer program, focusing on prevention and improvement of diagnosis and treatment. A prospective single arm non-randomized phase 2 clinical trial was thus designed for adult pts with newly diagnosed diffuse large B-cell lymphoma (DLBCL) at Dakar (Senegal) University Hospital (DUH), in collaboration with Nancy (France) University Hospital (NUH). Methods: Histological results of suspected lymphoma in pts likely to be included in this trial are reported here. Only non-HIV adult patients were enrolled. A first histological study was performed in the pathology department of DUH. This included biopsies that were submitted to apposition before embedding. Hematoxylin and eosin staining was performed as well as immunohistochemistry (IHC). The panel used allowed to examine the expression of the following antigens: CD20, CD79a, CD3, CD5, CD23, cyclin D1, CD30, Bcl2, CD10 and Ki67. Biopsies were reviewed via an international telepathology platform using the i-Path software and retrospectively, in NUH Pathology department, by sending paraffin-embedded blocks on site. Findings: Between July 2018 and May 2022, 70 pts admitted with a clinical presentation suggestive of NHL were evaluated with a surgical biopsy, 31 of whom being confirmed with a diagnosis of DLBCL or equivalent as T-cell/histiocyte-rich large B cell LBCL, and thus eligible for the therapeutic trial. Median age of the 70 pts was 42 years old (18-70) and 32% were female. Other hematological diagnoses were Hodgkin lymphoma, small B-cell lymphoma, T-cell lymphoma, unclassed lymphoma and histiocytosis. There was no Burkitt lymphoma. Non-hematological diagnoses were achieved for 14 pts: lipoma, tuberculosis, reactive adenitis or metastasis of solid neoplasia. In nearly half of all cases, diagnosis was obtained without IHC, notably due to non-hematological diagnoses. In nearly half of all cases, the diagnosis was obtained without IHC. When IHC was used, CD20 and CD3 were mainly used to establish the diagnosis. The median time to obtain pathology results was 31 days. Thirty-one cases were diagnosed with the help of I-Path. Currently, 17 biopsies have been reviewed at NUH with diagnosis concordance in 71% of cases. The 5 inconsistent diagnoses were 2 NHL ultimately classified as adenocarcinoma, 1 reactive adenitis being in fact DLBCL and 2 T-cell/histiocyte-rich LBCL diagnosed as respectively DLBCL and small B-cell lymphoma. Interpretation: This is a large cohort of consecutive surgical biopsies performed in Senegal for lymphoma suspicion, showing the distribution of lymphoma in Western Africa and more interestingly, demonstrating that an accurate diagnosis is possible locally. The current hindrances in lymphoma diagnosis include basing treatment decisions on fine needle aspiration cytology in a large proportion of cases, poor quality histology or complete lack of IHC in cases where biopsies are performed, limited number of hematopathologists and lack of discussion between hematopathologists. In this study, systematic surgical biopsy, homogenous IHC staining procedures, electronic interaction between hematopathologists and retrospective review of biopsies have contributed to a huge improvement of the quality of diagnosis.

Development and validation of tools for predicting the risk of death and ICU admission of non-HIV-infected patients with Pneumocystis jirovecii pneumonia.

The mortality rate of non-HIV-infected Pneumocystis jirovecii pneumonia (PCP) is high. This research aimed to develop and validate two clinical tools for predicting the risk of death and intensive care unit (ICU) admission in non-HIV-infected patients with PCP to reduce mortality. A retrospective study was conducted at Peking Union Medical College Hospital between 2012 and 2021. All proven and probable non-HIV-infected patients with PCP were included. The least absolute shrinkage and selection operator method and multivariable logistic regression analysis were used to select the high-risk prognostic parameters. In the validation, the receiver operating characteristic curve and concordance index were used to quantify the discrimination performance. Calibration curves were constructed to assess the predictive consistency compared with the actual observations. A likelihood ratio test was used to compare the tool and CURB-65 score. In total, 508 patients were enrolled in the study. The tool for predicting death included eight factors: age, chronic lung disease, respiratory rate, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), cytomegalovirus infection, shock, and invasive mechanical ventilation. The tool for predicting ICU admission composed of the following factors: respiratory rate, dyspnea, lung moist rales, LDH, BUN, C-reactive protein/albumin ratio, and pleural effusion. In external validation, the two clinical models performed well, showing good AUCs (0.915 and 0.880) and fit calibration plots. Compared with the CURB-65 score, our tool was more informative and had a higher predictive ability (AUC: 0.880 vs. 0.557) for predicting the risk of ICU admission. In conclusion, we developed and validated tools to predict death and ICU admission risks of non-HIV patients with PCP. Based on the information from the tools, clinicians can tailor appropriate therapy plans and use appropriate monitoring levels for high-risk patients, eventually reducing the mortality of those with PCP.

Clinical Characteristics and Treatment Outcomes of HIV+ and HIV- Tuberculosis Patients Followed and Treated at the Regional Hospital of Oyem, Northern Gabon: A Two-Year Retrospective Study

Background: The objective of this study was to analyse the clinical characteristics of HIV+ and HIV- tuberculosis patients followed and treated at the Oyem Regional Hospital Centre (ORHC).&#x0D; Materials and Methods: During this study conducted between January 2019 and December 2021, data collection was based on the exploitation of medical records and registers of results from the medical analysis laboratory of the regional hospital of Oyem, in which there were personal data (gender and age) of the patients, the status of HIV infection, clinical characteristics (pulmonary or extra pulmonary TB), and finally, the therapeutic outcomes of the patients after anti-tuberculosis and antiretroviral treatment. Binomial test following the Normal distribution was used to find an association between the percentages of extrapulmonary TB and TB+/HIV+ co-infection.&#x0D; Results: In this study, 128 confirmed TB cases were selected. While 54 (42.19%) were co-infected with TB+/HIV+, 74 patients (57.81%) were monoinfected with TB+/HIV+. Among all these patients, 93 (72.66%) were reported to have extra pulmonary TB and 35 (27.34%) had pulmonary TB. A normal binomial test showed that TB+/HIV+ co-infection was significantly associated with extrapulmonary TB (p=0.04). Patients were put on anti-tuberculosis treatment according to the manufacturers' indications. Despite a total of 15 deaths (8.93%) in both mono- and co-infected patients, there was a favourable outcome, with 35 patients (27.34%) declared cured. With 8 deaths, mortality was higher in the co-infected than in the non-HIV infected TB patients who recorded 7 deaths.&#x0D; Conclusion: By indicating a relatively high prevalence of HIV infection in TB patients, this study showed that TB+/HIV+ co-infection was associated with extra pulmonary TB, the severe form of the disease, and increased mortality in patients, hence the need to strengthen joint activities to control this co-infection.

The diagnostic value of metagenomic next-generation sequencing for identifying Pneumocystis jirovecii infection in non-HIV immunocompromised patients.

Pneumocystis jirovecii pneumonia (PJP) remains an important cause of morbidity and mortality in non-HIV immunocompromised patients especially in transplant recipients. But its diagnosis remains challenging due to the insuffificient performance of conventional methods for diagnosing Pneumocystis jirovecii(P. jirovecii) infection. Therefore, the auxiliary diagnostic function of metagenomics next-generation sequencing (mNGS) in clinical practice is worth of exploring. 34 non-HIV immunocompromised patients who were diagnosed as PJP by clinical manifestations, imaging findings, immune status of the host, and Methenamine silver staining were tested by mNGS from October 2018 to December 2020 in Sichuan Provincial People's Hospital. The clinical performances of mNGS for P. jirovecii infection diagnosis were also evaluated with genome reads abundance and comparing with other traditional diagnostic methods. We diagnosed a total of 34 non-HIV PJP patients by the clinical composite diagnosis. Our data shows that, compared with the clinical microbiological test, the detection rate of mNGS for P. jirovecii in non-HIV infected PJP patients is significantly higher than that of Methenamine silver staining and serum 1-3-β-D-glucan. mNGS can be used as an auxiliary diagnostic tool to help diagnosis. The number of reads mapped to the genome of P. jirovecii and the duration of patients from onset to sampling collection were statistically significant between the two groups (Reads>100 and Reads ≤ 100) (8days vs. 23days, p=0.020). In addition, univariate analysis showed that C-reactive protein (15.8mg/L vs.79.56mg/L, p=0.016), lactate dehydrogenase (696U/l vs. 494U/l, p=0.030) and procalcitonin (0.09ng/ml vs. 0.59ng/ml, p=0.028) was also statistically significant between the two groups. An effective detection rate was achieved in PJP patients using mNGS testing of bronchoalveolar lavage fluid (BALF) or blood. The study also confirmed that the abundance of reads of P. jirovecii is related to the interval between the onset and sample collection. And the inflammation status during simultaneous mNGS detection might determine the abundance of pathogens. Hence, we conclude that the mNGS strategy could benefit disease diagnosis as well as treatment when complicated clinical infections appeared.

Ocular Findings of Cryptococcal Meningitis in Previously Healthy Adults.

Patients with cryptococcal meningitis (CM) often have ocular manifestations; although data are describing these findings in nonimmunosuppressed, previously healthy individuals are scarce. A retrospective chart review was performed for previously healthy patients with CM who underwent a complete ophthalmological examination within a 5-year period at the National Institutes of Health. Demographics, CSF parameters, findings on initial ophthalmological examination, and MRI abnormalities were analyzed. Forty-four patients within a median of 12 weeks after CM diagnosis were included in our study; 27 patients (61%) reported abnormal vision on presentation. Seventy-one percent of patients were not shunted at the time of their initial eye examination. The most common ocular abnormalities were visual field defects in 21 (66%), decreased visual acuity in 14 (38%), and papilledema in 8 (26%) patients. Intraocular pressure was within normal range in all patients. Cranial nerve defects were identified in 5 patients and optic neuropathy in 2 patients. Patients who had hydrocephalus or did not receive a ventriculoperitoneal shunt were not noted to have worse ocular abnormalities. The most common ocular findings in our cohort of nontransplant, non-HIV cryptococcal meningitis patients were visual field defects, decreased visual acuity, and papilledema. Our results emphasize the need for a comprehensive eye examination in patients with CM who may not always report a change in vision on presentation.

Temporal Trend and Clinical Outcomes in HIV and Non-HIV Patients following Liposuction: A Propensity-Matched Analysis.

Because of the availability of highly active antiretroviral therapy, individuals infected with human immunodeficiency virus (HIV) are enjoying greater longevity with chronic conditions including abnormal adipose distribution. However, prior data on postoperative outcomes of liposuction in HIV-positive patients were limited by small sample size. Therefore, the authors aimed to compare differences in temporary trend, clinical characteristics, and outcomes between patients with and without HIV who underwent liposuction. The National Inpatient Sample database from 2010 to 2017 was queried to identify patients who underwent liposuction. Univariate, multivariate logistic regression and 1:4 propensity score-matched analyses were used to assess the primary outcomes (i.e., in-hospital mortality and postoperative outcomes) and secondary outcomes (i.e., discharge disposition, prolonged length of stay, and total cost). Overall, 19,936 patients who underwent liposuction were identified, among whom 61 patients (0.31%) were infected with HIV. Patients with HIV were more likely to be male, insured by Medicare, and had more comorbidities and lower income. Unadjusted length of stay was longer among patients with HIV (OR, 1.81; 95% CI, 1.09 to 2.99; P = 0.020); nevertheless, multivariable models and propensity score-matched analysis demonstrated that patients with HIV were no more likely to have complications than the general population. This was also the case for length of stay and total costs. The authors' findings indicated that patients with HIV who underwent liposuction did not experience an increased risk of major complication or mortality. Liposuction could be safely considered as a surgical treatment for HIV-positive patients with local fat deposition. Risk, II.

P171 Pneumocystis Jirovecii Pneumonia in non-HIV immunosuppressed patients: Acase series

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveIncreased usage of immunosuppressive medications and lack of guidance about when to initiate primary Pneumocystis Jirovecii Pneumonia (PCP) prophylaxis has led to a rising incidence of PCP in non-HIV immunosuppressed patients. The objective of this case series is to review clinical challenges in diagnosis and management of these patients.Patients, methods, and resultsThis is a retrospective case series of all 6 cases which were seen at Jupiter Hospital from January 2020 to October 2021 (Table 1).ConclusionThe presence of the above-mentioned predisposing factors should raise the suspicion of PCP. Non-invasive investigations like serum LDH, BDG, PET CT scan/HRCT scan of chest can help in the diagnosis. This can be confirmed by BAL PCR, which is both, more sensitive and specific than immunofluorescence microscopy. Trimethoprim- sulfamethoxazole (TMP- SMX), the standard treatment, cannot be used in some circumstances and alternate treatment may have to be used.Guidance about prophylaxis, antimicrobial therapy for PCP, and adjuvant steroid therapy in non-HIV patients is unavailable, which is an unmet clinical need.

P248 Fungal meningitis in an immunocompetent individual

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveFungal meningitis is commonly seen in individuals who are immunocompromised. It's a significant cause of morbidity and mortality in people living with HIV worldwide. Among HIV-infected patients of Manipur, it is the most common cause of meningitis and Cryptococcus neoformans is the only species identified so far both in HIV infected population and non-HIV patients in Manipur. The aim of this paper is to highlight the detection of C. gattii meningitis in the high HIV prevalence state of India.MethodA 53-year-old male, mechanic by profession residing in a village in Thoubal district of Manipur attended Medicine OPD with complaints of intractable headache, aggravated by sound and light, generalized weakness, hiccups, vomiting, and decreased appetite for 2 weeks. There was no history of altered sensorium. He is a known case of hypertension and was recently diagnosed with T2DM, not on medication.ResultsAn MRI brain (Fig.1) showed a tiny sub-centric lesion in the bilateral centrum semiovale. Cerebrospinal fluid examination by India Ink preparation revealed capsulated budding yeast cells suggestive of Cryptococcus sps. Cryptococcal antigen testing (CryptoPS, Biosynex) was positive with a high titer. Culture on SDA and BSA showed growth of Cryptococcus sps. For phenotypic identification and antifungal susceptibility testing, the isolate was processed in VITEK 2(Biomerieux) system which identified it as C. gatti (94% probability). The isolate was sensitive to amphotericin B (mic: 0.5 μg/ml) and flucytosine (mic: 2 μg/ml). He tested negative for HIV on two occasions and his CD4 + count was 888 cell/mm3. Blood sugar was 225 mg/dl, with urine glucose leakage in traces. Blood and urine were collected for fungal culture which showed no growth. The patient was put on liposomal amphotericin B 200 mg daily. After 1 week, patient's condition was not deteriorating, although the improvement was minimal. The isolate was sent to the National Culture Collection of Pathogenic Fungi, PGIMER, Chandigarh, and it was confirmed as Cryptococcus gattii by MALDI-TOF assay.ConclusionDetection of C. gattii in an immunocompetent patient in Manipur state, with a high prevalence of HIV is alarming because cryptococcal meningitis is the commonest form of meningitis in this population. In future, whenever Cryptococcus sps is isolated, it will be pertinent to keep in mind the possibility of other species of Cryptococcus to be the causative pathogen. We emphasize the importance and need for surveillance to detect its environmental niche.

S2.2c Talaromycosis in HIV-negative patients: challenges and counter-measures

S2.2 Histoplasmosis and talaromycosis, September 21, 2022, 3:00 PM - 4:30 PM Talaromycosis is an infection caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). It is endemic in tropical countries of Asia and Southeast Asia and has recently been recognized far beyond the traditional endemic areas. Talaromycosis was thought to be exclusively associated with HIV infection. However, an increasing number of T. marneffei infections have been reported in non-HIV-infected patients. Although the incidence of talaromycosis in non-HIV-infected patients is ˂ 10%, the atypical presentation of this disease can lead to misdiagnosis, inappropriate treatment, and poor outcomes, in addition to tremendous burden and suffering for patients and their families. Screening for immunodeficiencies in patients with talaromycosis is crucial in clinically suspicious cases. Our cohort studies identified three major immunodeficiencies in non-HIV patients with talaromycosis: (1) 85.9% anti-interferon-γ autoantibodies, (2) primary immunodeficiency disorders, and (3) tumors. In disseminated talaromycosis, most patients present with fever, anemia, weight loss, respiratory symptoms, hepatosplenomegaly, lymphadenopathy, and osteolytic destruction and are often misdiagnosed as tuberculosis and other diseases. Localized talaromycosis, on the other hand, is usually manifested by ulcers or masses in the mouth, throat, and external genitalia. Although antigen screening is an effective approach for diagnosing talaromycosis in patients with advanced HIV disease, pathogen-based detection is still limited by atypical clinical presentation. Direct microscopic examination, mycological culture, and histopathology are the standard traditional diagnostic methods used to isolate T. marneffei from clinical specimens, however, due to time-consuming, it might lead to delay diagnosis. Metagenomic next-generation sequencing (mNGS) technology has shown promising results as a rapid, convenient method for detecting T. marneffei from various types of specimens, leading to correct diagnosis and appropriate treatment. Based on our current retrospective study, mNGS has been shown to be equivalent and possibly superior to conventional fungal culture in terms of speed and specificity in the diagnosis of talaromycosis. In terms of final clinical diagnosis, mNGS showed a high sensitivity of 97.22% compared with conventional culture (61.11%). Correction of underlying immunodeficiencies and early use of antifungal agents are important treatment strategies for talaromycosis. Currently, there is no optimal therapeutic regimen for the treatment of talaromycosis in this specific group of patients. Amphotericin B is the first line to initial antifungal treatment, other antifungal agents such as voriconazole have shown good efficacy against talaromycosis. We investigated the efficacy of voriconazole in the treatment of talaromycosis using population pharmacokinetics. C-reactive protein (CRP) was found to significantly affect voriconazole plasma concentrations. Optimization of initial dosing based on CRP levels may be useful to guide voriconazole dosing in clinical practice. The mortality rate in non-HIV talaromycosis is higher than in the HIV population, which may be due to the nonspecific and complex clinical manifestations. Failure to initiate antifungal treatment in a timely manner often results in poor prognosis and even death. The course of treatment is protracted, unclear, and depends on the immune status of the patient. Diagnosis and treatment of talaromycosis remain a challenge. Optimization of diagnostic tools and treatment regimens to ensure early detection and prompt antifungal treatment should be considered.

P144 The uncommon meets the common: Invasive Aspergillosis and tuberculosis co-infection in non-neutropenic patients— arare association

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground and ObjectiveInvasive aspergillosis (IA) is known to occur in immunocompromised patients including neutropenic patients. But, recently increasing cases have been reported in patients with non-classical risk factors and non-neutropenic patients like diabetes mellitus, chronic lung disease, HIV infection, critically ill patients, etc. According to ISHAM these non-classical risk factors should be included in EORTC/MSG host criteria for diagnosis of invasive aspergillosis.India has a high tuberculosis (TB) burden, and this is always considered as the first differential for any patient with fever, cough, hemoptysis, and weight loss. Post-tubercular chronic pulmonary aspergillosis common reported condition. However, co-infection of active TB and invasive aspergillosis is less reported. This co-infection could be one of the contributors of high morbidity and mortality in cases with tuberculosis.We hereby present a series of five cases of TB concomitant with invasive aspergillosis in non-neutropenic patients.MethodsThis is a prospective observational study, all patients admitted with molecular diagnosis (GeneXpert) of tuberculosis and with at least one non-classical risk factor for invasive aspergillosis were subjected to further evaluation. Diagnosis of invasive aspergillosis was considered in patients who had at least one clinical and one mycological EORTC criteria. Galactomannan level in different samples was measured via PlateliaTM ELISA. The efficacy of different antifungals and outcomes were analyzed.ResultsTotal 57 patients with TB underwent for evaluation of invasive aspergillosis. Among them, five patients were diagnosed to have concomitant TB and invasive aspergillosis, of which three cases of CNS TB and CNS aspergillosis and two had concomitant pulmonary infections. The average age was 31 ± 12 years with a female preponderance (4/5). Two patients were HIV positive, while among non-HIV patients, one had CD4 cytopenia (CD4-171). One patient had no known predisposing factor. Radiologically, most common pulmonary lesions were patchy consolidation with centrilobular nodules with tree in bud appearance, while CNS lesions showed multiple ring-enhancing lesions. All the patients had CBNAAT positive, two from BAL sample, 1 from CSF, and 1 from the lymph node. Rifampicin was sensitive in all, except one who had rifampicin resistance indeterminate. Of these patients, four were probable invasive aspergillosis satisfying the host, mycological and clinical factors as per the EORTC/MSGERC 2021 guidelines. The treatment of coinfection is challenging due to the interaction of rifampicin with voriconazole, which is the drug of choice for invasive aspergillosis. Here, 3 patients were treated with Inj amphotericin B, while the other 2 patients were started on voriconazole with rifampicin sparing regimen for TB. Of the 5 patients, 4 patients survived with excellent response to the treatment, with one fatality.ConclusionThe possibility of concurrent TB and invasive aspergillosis in non-neutropenic hosts should be considered to avoid devastating outcomes. The lack of clinical suspicion may result in misdiagnosis, and most importantly, the chronicity of the infection makes it indistinguishable from TB. Moreover, the co-administration of antifungal and anti-TB medications presents significant therapeutic challenges necessitating thorough evaluation and monitoring.

Too much of a good thing: Immune reconstitution inflammatory syndrome in a patient with Still's disease

Immune Reconstitution Inflammatory Syndrome (IRIS) is a potential complication when treating non HIV immunosuppressed patients with opportunistic infections. We present a case of a 49-year-old female with Adult-onset Still's disease on prednisone 40 mg daily who came to ED with right leg weakness and intractable headache for one week. She was diagnosed with Cryptococcus meningitis. Patient completed the induction phase of antifungal therapy and the steroids were tapered over four weeks. One month after discharge, a patient was brought in to ED, minimally responsive to verbal stimuli and had new left hemiparesis with persistent right leg weakness was noted on exam. An MRI of the brain was consistent with diffuse leptomeningeal enhancement compatible with meningoencephalitis. LP was notable for elevated opening pressure of 36cmH2O and CSF studies were negative for recurrence of cryptococcal infection. Given the timeline of patients presentation one month after discontinuation of steroids, and workup consistent with sterile meningitis, immune reconstitution inflammatory syndrome was identified as the likely diagnosis. The patient was started on 50 mg of Prednisone daily. Six weeks after presentation, the patient's mental status returned to baseline, left hemiparesis resolved, and right lower extremity strength significantly improved. Clinicians should have a high index of suspicion for CNS IRIS in patients presenting with new neurologic findings in the setting of rapid discontinuation of steroids due to infection. IRIS in HIV patients with cryptococcal meningitis is a well-established entity; the purpose of this case report is to bring attention to similar inflammatory syndrome in non-HIV patients with cryptococcal meningitis.

Exploring the Differences in Pneumocystis Pneumonia Infection Between HIV and Non-HIV Patients.

Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections worldwide that affects the lung. Pneumocystis leads to pneumonia, caused by Pneumocystis jirovecii, formerly known as Pneumocystis carinii. In recent decades, PCP has been a major health problem for human immunodeficiency virus (HIV) patients and is responsible for most of mortality and morbidity. However, the increasing number of immunosuppressive-related diseases has led to outbreaks in other patient populations, raising the concern for PCP as it becomes a major concern among those patients. These changes led to marked changes in the prevalence and mortality rates of PCP. Huge variations in those parameters among HIV and non-HIV patients have been seen also. Historically, the diagnosis was made by staining and direct visualization of the organism within the bronchoalveolar lavage (BAL) fluid. The diagnosis is now made by microscopic examination and a real-time polymerase chain reaction (PCR) of BAL. Serum (1,3)-β-D-glucan, which is a component of the Pneumocystis jirovecii cell wall that distinguishes it from other fungi, has become an important diagnostic tool. Early diagnosis and treatment play a vital role in the patient’s survival and in the infection outcome; hence, empirical PCP therapy should be started immediately when the infection is suspected without waiting for the results of the diagnostic test. Steroids play an important role in the treatment of HIV patients, especially patients who present with hypoxia and respiratory failure. Prophylaxis is very effective and should be given to all patients at high risk of PCP. Antiretroviral therapy (ART) should be started as soon as possible in newly diagnosed HIV-infected patients with PCP, and the immune status of immunocompromised patients with PCP should be improved by temporarily withholding immunosuppressive drugs or reducing their doses.