Frequent Opportunistic Infection Research Articles

Protocol for the systematic review of the Pneumocystis jirovecii-associated pneumonia in non-HIV immunocompromised patients.

Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy. Despite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine. The protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review of literature published between January 2010 and July 2023, using the databases PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies. It is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research. Here, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients.

Clinical characteristics, diagnosis, treatment and outcomes of patients living with HIV and co-infected with tuberculosis and histoplasmosis: a 5-y retrospective case series.

In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6months of baseline evaluation, for a mortality rate of 57.1%. PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections.

P692 An IBD nurse-led educational programme on safety and efficacy of adjuvated recombinant zoster vaccine can improve vaccine uptake in IBD patients on immunosuppressive treatment

Abstract Background Herpes Zoster (HZ) represents one of the most frequent opportunistic infections in IBD patients under immunosoppressive treatment and can be prevented by vaccination. Adjuvated recombinant zoster vaccine (RZV) is the first HZ vaccine approved for immunocompromised persons. IBD patients are less likely to receive appropriate vaccinations compared to the general population. IBD nurses operate as the primary point of contact for patients and this unique position provides a suitable opportunity to positively impact patient care and encourage vaccination. We aimed to improve RZV vaccination rates by a nurse-led education intervention within an on-site RZV vaccination programme. Methods IBD patients on immunosuppressive therapies were actively recruited by phone contact, mail and during outpatient clinic or infusion centre attendance. Prior immunization to VZV was collected from medical records. Patients were randomly assigned to receive either standard explanation on the importance of HZ vaccination by the IBD attending physician (group P) or additional education by an IBD nurse (group N). Patients in group N were referred to an IBD nurse for an individual 15 minutes nurse–patient interview. During the interview, disease activity and current treatment, previous immunization to VZV and history of HZ were reviewed; the importance, benefits and safety of HZ vaccination with RZV were discussed with the patient. Patients were then referred to dedicated on-site vaccination clinics where vaccine administration was provided by the IBD nurses running the infusion centre. Reasons for vaccine refusal was also recorded. Results From February to April 2022, 164 (80%) out of 205 eligible patients were enrolled (median age 48.5 years, 54.1% male; 48.7% UC, 51.3% CD); 65 patients (39.6%) were randomized to group P and 99 patients (60.4%) to group N. Six months after randomization, 112 (68.2%) had received at least 1 RZV vaccine dose whereas vaccination was completed in 110 patients (67%). Vaccination rate was significantly higher in the nurse-led education intervention group compared to standard clinical care (group N 75.7% vs group P 56.9%,p<0.05). Most common reasons for vaccine hesitancy were concerns about side effects (40.9%), fear of vaccine aggravating the disease (14.7%), considering themselves not at risk (13.3%) and objection to the administration of vaccine (10.1%). Conclusion Vaccination recommendations should be responsibility of the IBD patient care team and efforts should be made to reduce vaccine hesitancy. We showed that a simple nurse-led educational intervention on vaccine safety and efficacy was able to improve RVZ vaccination rates in IBD patients on immunosuppressive treatment.

CMV and HIV Coinfection in Women from a Region in Eastern Europe.

(1) Background: Human cytomegalovirus (CMV) infection is one of the most frequent opportunistic infections in immunosuppressed patients. Romania has one of the highest incidences of patients living with human immunodeficiency virus (HIV) which determines an immunosuppressive state. The aim of this study was to establish the prevalence of CMV infection among women living with HIV in Southeastern Romania and also to evaluate and correlate antiretroviral therapy (ART) with CD4 level and CMV disease evolution. (2) Methods: Seventy women living with HIV from Southeastern Romania were screened for CMV infection using antigen quantification. Of these, 50 were included in the study. First, the patients filled out a questionnaire regarding social conditions and other associated diseases. Then, we explored the statistical correlations between the data and HIV status, CD4+ cell counts, viral load, and antiretroviral therapy (ART). (3) Results: Median age of the patients was 33 years. Twenty-nine cases were diagnosed with HIV after sexual life beginning and 21 before. Most of the patients had a CD4 level over 200 cells/µL. ART duration in the CD4 under 200 cells/µL group was a bit longer than that in the CD4 over 200 cells/µL group. Forty-one patients had undetectable viremia. CD4 average value in the lot of patients with undetectable viremia was 704.71 cells/µL and in the lot with detectable viremia was 452.44 cells/µL. Viremia values correlated negatively with CD4 level. A positive correlation between IgG CMV values and ART therapy length was identified. A negative significant correlation between values of IgG CMV and values of CD4 was identified. CD4 value correlated negatively with IgG CMV values and with CMV avidity. (4) Conclusions: IgG CMV values had a weak positive correlation with ART therapy length, and a negative statistically significant correlation with values of CD4. CMV avidity has a negative correlation with CD4 value.

Interventional pulmonary procedures and their outcomes in patients with STAT3 hyper IgE syndrome

BackgroundSTAT3 hyperimmunoglobulin E syndrome (STAT3-HIES) also referred to as autosomal dominant HIES (AD-HIES) is an inborn error of immunity characterized by the classic triad of eczema, frequent opportunistic infections, and elevated serum IgE levels. As a consequence of lung sequels due to repeated infections and impaired tissue healing, patients may require interventional pulmonary procedures.MethodFour patients with dominant-negative STAT3 mutations who had received interventional pulmonary procedures were enrolled. The demographic, clinical, and molecular characteristics were gathered through a medical record search. All reported STAT3-HIES patients in the literature requiring pulmonary procedures as part of their treatment were reviewed.ResultRecurrent episodes of pneumonia and lung abscess were the most prevalent symptoms. The most common non-immunological features were scoliosis, failure to thrive, and dental problems such as primary teeth retention and disseminated decays. Bronchiectasis, lung abscess, pneumatocele, and cavitary lesion were the most prevalent finding on high-resolution computed tomography at the earliest recording. All patients underwent pulmonary surgery and two of them experienced complications.ConclusionPatients with STAT3-HIES have marked pulmonary infection susceptibility which may necessitate thoracic surgeries. Since surgical procedures involve a high risk of complication, surgical options are recommended to be utilized only in cases of drug resistance or emergencies.

Long-term Outcomes of Patients With HIV and Pneumocystis jirovecii Pneumonia in the Antiretroviral Therapy Era.

Pneumocystis jirovecii pneumonia (PCP) is one of the most frequent opportunistic infections in people with HIV (PWH). However, there are limited data on long-term outcomes of PCP in the antiretroviral therapy (ART) era. We conducted a secondary analysis of 2 prospective studies on 307 PWH, 81 with prior PCP, with a median follow-up of 96 weeks. Laboratory data were measured at protocol-defined intervals. We reviewed clinically indicated chest computerized tomography imaging in 63 patients with prior PCP at a median of 58 weeks after PCP diagnosis and pulmonary function tests (PFTs) of patients with (n = 10) and without (n = 14) prior PCP at a median of 18 weeks after ART initiation. After 96 weeks of ART, PWH with prior PCP showed no significant differences in laboratory measurements, including CD4 count, when compared with those without prior PCP. Survival rates following ART initiation were similar. However, PWH with prior PCP had increased evidence of restrictive lung pathology and diffusion impairment in PFTs. Furthermore, on chest imaging, 13% of patients had bronchiectasis and 11% had subpleural cysts. Treatment with corticosteroids was associated with an increased incidence of cytomegalovirus disease (odds ratio, 2.62; P = .014). PCP remains an important opportunistic infection in the ART era. While it did not negatively affect CD4 reconstitution, it could pose an increased risk for incident cytomegalovirus disease with corticosteroid treatment and may cause residual pulmonary sequelae. These findings suggest that PCP and its treatment may contribute to long-term morbidity in PWH, even in the ART era.

Opportunistic Infections Among Human Immunodeficiency Virus (HIV) Infected Patients in Turkey: A Systematic Review.

This study aimed to identify opportunistic infections among human immunodeficiency virus (HIV) infected patients in Turkey. Therefore, we conducted a systematic literature review of the studies published up to October 1, 2022, in the Pubmed, Web of Science (WoS), and ULAKBİM TR Dizin databases. We searched for medical subject headings (MeSH) terms of (HIV) OR (AIDS) OR (human immunodeficiency virus) AND (opportunistic infections) AND (Turkey). Fifty-five studies in Pubmed, 68 in WoS, and 212 in ULAKBİM TR Dizin were listed with these keywords. After removing duplicated studies, we included 22 original articles, two poster presentations, one short communication, one letter to the editor, and 17 case reports/series. Out of 1582 patients, we defined 788 patients (49.8%) as late presenters. In addition, we detected tuberculosis (286, 5.5%), candidal infections (207, 4%), and Pneumocystis jirovecii pneumonia (PCP) (113, 2.1%) as the most frequent opportunistic infections. According to our analysis, late presentation is a major problem in our country, and more screening and sensitization campaigns should be carried out to ensure early diagnosis and earlier care of patients.

#5296 CYTOMEGALOVIRUS INFECTION AFTER COVID-19 IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Kidney transplant recipients (KTR) have adverse COVID-19 outcomes due to the immunosuppressed status and multiple comorbidities. Cytomegalovirus (CMV) is one of the most frequent opportunistic infections after kidney transplantation. However, data concerning its reactivation after COVID-19 is scarce. Herein, we present a single-center cohort of KRT presenting with CMV infection after COVID-19 and its clinical outcomes. Method Single-center cross-sectional study including 22 KTR with CMV viraemia detected by quantitative polymerase chain reaction up to 6 months after COVID-19, between 2020 and 2022. Demographic and clinical data were collected from the electronic records. Results A total of 22 KTR (13 male) were included with a mean age of 55.5±15.5 years and a median Charlson score of 4 (IQR 3-6). Median time after transplantation was 65 months (IQR 12.5-174.5; 3 KTR with <6 months) and only one patient had been submitted to living-donor transplantation. Eight patients received induction therapy with antithymocyte globulin (ATG). At transplantation time, CMV serologic status had been: 50% D+/R+, 13.6% D+/R- and 4.5% D-/R+. CMV infection prior to COVID-19 had been documented in 6 patients. Concerning COVID-19, severe or critical disease had been reported in 8 patients. Specific therapy had been used in 4 patients: 2 with remdesivir/baricitinib, one with remdesivir and one with molnupiravir. Moreover, immunosuppressive therapy had been adjusted in 11 patients, namely by withdrawing the antimetabolite and increasing steroids (7 patients). Median maximum steroid dose (expressed as equivalents of prednisone dose) had been 40 mg (IQR 20-40) and mean cumulative steroid dose had been 416±317 mg. CMV disease was documented in 8 patients (4 with gastrointestinal involvement) and the mean time of diagnosis after COVID-19 was 10±6 weeks. Maintenance immunosuppression included tacrolimus, antimetabolite and steroid in 12 patients; 6 patients had supratherapeutic levels of tacrolimus at CMV infection diagnosis. Median initial viraemia was 770 copies/mL (IQR 288-4106). Valganciclovir was used in 14 patients (one was already taking it as prophylaxis), ganciclovir in 4 patients and CMV enriched human intravenous immunoglobulin was used in one patient. Nine patients required hospitalization and 2 were transferred to an intensive care unit; one of these 2 patients died. Induction therapy with ATG, CMV serologic status at transplantation time, previous CMV infection, COVID-19 severity or supratherapeutic immunosuppressive drug levels were not associated with CMV infection severity or hospitalization. However, higher maximum steroid dose during COVID-19 was associated with CMV disease (p = 0.038), higher viraemia at diagnosis (p = 0.032) and hospitalization (p = 0.018). Conclusion CMV infection is a common and clinically relevant complication in KTR. Altered immunologic status after COVID-19 may predispose to this infection. In addition, immunosuppressive therapy adjustments, namely the increase in steroid dosing may be very relevant to favor reactivation of CMV. Larger studies are warranted, but careful monitoring could help identifying risk patients earlier and prophylaxis may be considered when increased corticosteroids are prescribed.

Losartan Plays a Fungistatic and Fungicidal Activity Against Candida albicans Biofilms: Drug Repurposing for Localized Candidosis.

Candidosis is one of the most frequent opportunistic infections and exhibits variable clinical presentations, including oral localized forms. Drugs affecting the renin-angiotensin system targets inhibit secreted aspartic proteases from Candida albicans. The objective of the study was to evaluate whether losartan has antimicrobial action against C. albicans biofilms. Biofilms were treated with losartan or aliskiren (for comparison) for 24 h. Metabolic activity of viable cells and growth inhibition of C. albicans biofilms were assessed using XTT [2,3-Bis(2-Methoxy-4-Nitro-5-Sulfophenyl)-5-[(Phenyl-Amino)Carbonyl]-2H-Tetrazolium Hydroxide] and colony-forming unit assays, respectively. In addition, the cytotoxicity of the drugs on human cells was evaluated using the AlamarBlue assay. Both drugs decreased fungal viability at all concentrations. In addition, all concentrations of losartan inhibited the growth of C. albicans biofilm, ranging from 47% to 88.5%, whereas aliskiren showed inhibition from 1 to 10 mg/mL, which ranged from 16% to 97.6%. Furthermore, at certain concentrations, these drugs maintained the viability of human cells. Losartan and aliskiren have fungistatic and fungicidal action against C. albicans biofilms and are compatible with human cells. Therefore, these antihypertensive drugs can be repurposed to interfere with the metabolism and development of Candida biofilms, which are widely associated with clinical forms of candidosis, including oral localized forms such as denture stomatitis.

Clinical Course, Nosocomial, and Opportunistic Infections Among Kidney Transplant Recipients with COVID-19: A Retrospective Single Center Study

We report the results of an observational study, analyzing the clinical course of kidney transplant patients hospitalized for COVID-19 and comparing it with a control to determine if outcomes, nosocomial, and opportunistic infections were different between groups. An observational, retrospective, case-control, single-center study, including a group of kidney transplant adults diagnosed with COVID-19, from March 2020 to April 2022. Transplant patients hospitalized for COVID-19 comprised the cases. The control group consisted of non-transplanted adults, without immunosuppressive treatment, hospitalized for COVID-19, and matched by age, sex, and month at diagnosis of COVID-19. Study variables were collected, including demographic/clinical, epidemiologic, clinical/biological at diagnosis, evolutive, and outcome variables. Fifty-eight kidney transplant recipients were included. Thirty required hospital admission. Ninety controls were included. Transplant recipients had a higher frequency of intensive care unit (ICU) admission, ventilatory support, and death. The relative risk for death was 2.45. When adjusted by baseline estimated glomerular filtration rate (eGFR) and comorbidity, only the risk for opportunistic infection remained high. Variables independently associated with death were dyslipidemia, eGFR at admission, MULBSTA score, and ventilatory support. Pneumonia by Klebsiella oxytoca was the most frequent nosocomial infection. Pulmonary aspergillosis was the most frequent opportunistic infection overall. Pneumocystosis and cytomegalovirus colitis were more frequent among transplant patients. The relative risk for opportunistic infection in this group was 1.88. Baseline eGFR, serum interleukin 6 level, and coinfection were independently associated with it. Evolutive course of COVID-19 requiring hospitalization in renal transplant recipients was primarily determined by comorbidity and baseline kidney function. At equal comorbidity and renal function, there were no differences in mortality, ICU admission, nosocomial infection, and hospital stay. However, the risk for opportunistic infection remained high.

Evaluation of the PneumoGenius® PCR assay for the diagnosis of Pneumocystis pneumonia and the detection of Pneumocystis dihydropteroate synthase mutations in respiratory samples.

Pneumocystis pneumonia (PCP) is the most frequent fungal opportunistic infection defining AIDS in HIV-infected patients, and is of growing importance in HIV-negative patients. In this latter category of patients, the diagnosis mainly relies on real-time polymerase chain reaction (qPCR) detection of Pneumocystis jirovecii (Pj) on respiratory samples. The PneumoGenius® kit (PathoNostics) allows the simultaneous detection of Pj mitochondrial large subunit (mtLSU) and dihydropteroate synthase (DHPS) polymorphisms, which could be of interest to anticipate therapeutic failure. This study aimed at evaluating its clinical performance on 251 respiratory specimens (239 patients), (i) for P. jirovecii detection in clinical samples, and (ii) for DHPS polymorphisms detection in circulating strains. Patients were classified according to modified European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, as having proven PCP (n=62), probable PCP (n=87), Pneumocystis colonization (n=37), and no PCP (n=53). Compared with in-house qPCR, the sensitivity of PneumoGenius® assay for P. jirovecii detection reached 91.9% (182/198), the specificity was excellent (100%, 53/53) and the global concordance was 93.6% (235/253). A total of four diagnoses of proven/probable PCP were missed by the PneumoGenius® assay, reaching a 97.5% sensitivity (157/161) in this sub-group. The 12 other 'false-negative' results were obtained in patients diagnosed as colonized using the in-house PCR. DHPS genotyping was successful for 147/182 samples with PneumoGenius® and revealed dhps mutation in 8 samples, which were all confirmed by sequencing. In conclusion, PneumoGenius® assay missed the detection of low-burden PCP. This lower sensitivity for PCP diagnosis can be balanced by a higher specificity (P. jirovecii colonization less frequently detected) and the efficient detection of DHPS hot spot mutations.

Low level of antifungal resistance in Candida species recovered from Iranian HIV-associated oral infection.

Oral candidiasis (OC) is the most frequent opportunistic fungal infection, which is a predictive indicator of immunosuppression and disease progression among people living with HIV/AIDS (PLWHA). In the present study, 109 Candida isolates were collected from 94 PLWHA afflicted with oral Candida infection (OCI) following highly active antiretroviral therapy (HAART). The susceptibility profiles of Candidaspp. to six antifungal agents were evaluated using CLSI broth microdilution. The prevalence of OCI was 34.06%. The susceptibility profile of Candidaspp. revealed 100% sensitivity to caspofungin, while 6.4%, 5.4%, 24.5%, and 2.8% of Candida isolates showed resistance or nonwild-type MICs to fluconazole, itraconazole, posaconazole, and amphotericin B, respectively. Notably, 15.9% of patients and 3.7% of isolates showed mixed Candida infections and multidrug resistance, respectively. The low-level resistance to antifungal agents observed in the present study may be explained by the fact that none of the participants had prior and prolonged exposure to these antifungals. However, more focus should be placed on the mechanisms of reduced susceptibility and low-level resistance in Candida species since they can serve as stepping stones to developing clinical resistance. Alongside this, it seems a must to understand the local epidemiology of Candida spp. and their susceptibility pattern.

Late Onset Combined Immune Deficiency (LOCID) Revealed by a Haemolytic Anaemia in a Child: A Case Report

Variable Common Immune Deficiency (VCID) is a very heterogeneous condition both clinically and immunologically. It is a group of molecular abnormalities responsible for a defect in antibody production leading to hypogammaglobulinemia often associated with autoimmune and/or lymphoproliferative manifestations. Late Onset Combined Immune Deficiency (LOCID) is a type of Variable Common Immune Deficiency (VCID) defined by a defect in antibody production (IgG and IgA ± IgM type), profound CD4 T-cell lymphopenia and frequent opportunistic infections. LOCID has been considered as a distinct entity from VCID due to its particular clinical and immunological profile.

A study of opportunistic infections in people living with HIV

Background: Human immunodeficiency virus (HIV) virus, causative agent in acquired immunodeficiency syndrome, is fast becoming a major threat in the Indian subcontinent, with an estimated 3.7 million persons being infected with HIV. HIV infection is complicated by various opportunistic infections (OIs) such as tuberculosis (TB), candidiasis, herpes zoster, Pneumocystis jirvoceii, and cytomegalovirus (CMV). This study carried out to know the clinical profile of HIV patients with OIs. Aims and Objectives: The aim of the study was (i) to assess the pattern of OIs in HIV infected patients visiting ART Centre of Sir T Hospital; (ii) to estimate the proportions of various OIs among HIV infected patients; and (iii) to assess the frequency distribution of OIs with different CD4 counts categories. Materials and Methods: A case series study was carried out at a tertiary care hospital in Bhavnagar, Gujarat, India. A hospital based case series study was conducted after taking permission from ethical committee among 400 HIV patients with OIs Government Medical College and Sir T General Hospital, Bhavnagar during January 2021–September 2021. Data were collected to gather information on clinical profile. The statistical tests used were descriptive statistics and independent t-test. Results: Among 400 patients, 26% were females and 74% males. High proportions of patients were observed in 30–39 years of age group and heterosexual route was the most common mode of transmission. TB (51.25%) is the most frequent OI followed by candidiasis (49%), pneumocystis (8.75%) and others. The mean CD4 cell count in TB was 206.78 cells/mm3 and in candidiasis 205.73 cells/mm3. Low values were observed in promyelocytic leukemia 45 cells/mm3, CMV 90 cells/mm3 and in toxoplasmosis 80.5 cells/mm3. Conclusions: Respiratory system was the most common system involved by OIs and most of patients with OIs had CD4 T cell count below 200 cells/mm3, whereas there were no patients in the study with counts above 500 cells/mm3.

Diagnosis and Treatment of Tuberculous Meningoencephalitis and Toxoplasma Encephalitis in Positive HIV Patient: Case Report

Background Tuberculous meningoencephalitis (TBME) and toxoplasma encephalitis (TE) are the most frequent cerebral opportunistic infections in positive HIV patients in developed countries. This study aims to determine a presumptive diagnosis of TBME and TE based only on clinical, CD4-count, and radiology features and to attend suitable early treatment for better patient outcomes. Case Description A 40-year-old presented to the emergency unit of dr. Mintohardjo Naval Hospital with decreased consciousness. History of positive HIV status, pulmonary tuberculosis for six months and anti-tubercular-treatment (ATT) drop-out. The GCS was E2M5V2, lung crackles, nuchal rigidity, positive Babinski reflex, and duplex hemiparesis. CD4-count: 4 cells/mm3. Multiple hypodense lesions, “finger-like-oedema”, featured on non-contrast head CT-scan. A lumbar puncture was not performed. Treatment of TBME included an ATT regimen, pyridoxine, cotrimoxazole, anti-oedema, and TE treatment included clindamycin and pyrimethamine. Based on the clinical and radiological diagnosis of TBME (nuchal rigidity, history of ATT drop-out, multiple hypodense lesions on CT-scan) and TE (altered mental status, duplex hemiparesis, CD4-count, “finger-like-oedema” projections on CT-scan), ATT and TE treatment were given for ten days. There were significant clinical improvements by GCS E4M6V3, negative nuchal rigidity after being treated early by ATT and TE treatment. Conclusions Presumptive Diagnosis of TBME and TE in HIV patients can be determined only based on clinical, CD4-count, and radiology examination. However, there are significant clinical improvements in giving ATT along with TE treatment immediately in positive HIV patients.

Opportunistic Infections and Associated Factors among HIV-Infected Adult Persons on Antiretroviral Therapy at Ruhengeri Referral Hospital, Rwanda: A cross-sectional study

Background 
 Human Immunodeficiency Virus (HIV) is among the highest health crises that humanity ever confronted and it causes progressive weakening of the immune system leading to opportunistic infections (OIs) or malignancies during the natural course of the disease.
 This study aimed at assessing the prevalence and factors associated with the occurrence of OIs among adult PLWHIV on antiretroviral therapy (ART) at Ruhengeri referral hospital.
 Methodology
 A cross-sectional study was performed by reviewing records of HIV-positive adult (≥ 15 years) on ART enrolled at Ruhengeri referral hospital from 1st January 2007 to 31st December 2017. Opportunistic infections were reported based on clinical diagnosis and the prevalence of OIs was determined.
 Results 
 The study reviewed records from 423 PLWHIV. Thirty-nine (9.2%) PLWHIV had been diagnosed with OIs; and frequent OIs were tuberculosis (20%), oral candidiasis, pneumonia and STI (15.6% each). The independent risk factors for developing OIs were being jobless (AOR = 5.03, 95% CI = 2.13, 32.99), spending more than five years on ART (AOR = 4.34, 95% CI = 1.12-16.78) and starting ART at WHO clinical stage III (AOR = 4.88, 95% CI = 1.65-16.78).
 Conclusion
 There is a need to strengthen the management of opportunistic infections despite the use of ART at Ruhengeri referral hospital.
 Rwanda J Med Health Sci 2022;5(3):323-331

National survey of prevention and management of CMV infection in pediatric kidney transplantation in comparison to clinical practice guidelines.

Cytomegalovirus (CMV) is one of the most frequent opportunistic infections in kidney transplant (KT) recipients and is a risk factor for patient and graft survival after KT. Center-to-center variation, optimal prevention and treatment strategies in pediatric KT are currently unknown. This survey aimed to assess current CMV prevention and treatment strategies used among French pediatric KT centers. A web-based survey was sent to all 13 French pediatric kidney transplantation centers. Twelve (92%) centers responded to the survey. All centers used prophylaxis for the donor-positive/recipient-negative (D+/R-) group. For R + patients, 54% used prophylaxis, 37% used a pre-emptive strategy. In the low-risk group, D-/R-, 50% used a pre-emptive approach and 50% had no specific prevention strategy. The antiviral used by all centers for prophylaxis was valganciclovir (VGCV). The duration of prophylaxis varied from 3 to 7 months and the duration of viral load monitoring varied from 6 months to indefinitely. No center used a hybrid/sequential approach. For the treatment of CMV DNAemia, VGCV or intravenous GCV were used. Therapeutic drug monitoring of VGCV was performed in 5 centers (42%). Five centers reported drug resistance. Eight centers (67%) administered VGCV during the treatment of acute graft rejection. There is uniformity in CMV management in some areas among pediatric KT centers in France but not in others which remain diverse and are not up to date with current guidelines, suggesting unnecessary variation which could be reduced with better evidence to inform practice.

Demographic, Clinical, and Laboratory Characteristics of HIV Patients with Cerebral Toxoplasmosis at Haji Adam Malik General Hospital Medan

Cerebral toxoplasmosis is one of the frequent opportunistic infections of the central nervous system of Human Immunodeficiency Virus (HIV) patients in the presence of Toxoplasma Gondii infection. In Indonesia, the incidence of HIV patients with cerebral toxoplasmosis is 45%. This study was done to determine the demographic, clinical, and laboratory characteristics of HIV patients with cerebral toxoplasmosis at Haji Adam Malik Hospital, Medan, based on medical record data in 2022. The total sample was 23 patients with time periods from January to March 2022. Demographically, the data showed that most of the HIV patients with cerebral toxoplasmosis were male (91.3%), a mean age of 36.48 ± 5.74 years, married (87%), high school graduates (69.6%), and working (91.3%). The most common clinical characteristics were headache (69.6%) and cognitive impairment (56.5%). Laboratory characteristics found were (56.5%) non-reactive (<0.8 COI) and (43.5%) reactive (≥1 COI) anti toxoplasma IgM, while reactive anti-toxoplasma IgG (≥3 IU/ml) was obtained in all research samples (100%).

Effect and Mechanism of Cotrimoxazole Against Talaromyces marneffei in vitro.

Talaromyces marneffei (formerly Penicillium marneffei) is an important thermally dimorphic fungus endemic which is characterized by one of the most frequent opportunistic infections in HIV/AIDS patients, mainly prevalent in Southeast Asia, southern China, and northeastern India. Cotrimoxazole(CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi, thereby commonly used to prevent several opportunistic infections among HIV/AIDS patients. In addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis are considered to have the potential to prevent T. marneffei infection in HIV/AIDS patients receiving antiretroviral therapy (ART). However, the effect of cotrimoxazole towards T. marneffei fungus in vitro remains unclear. Human THP-1 macrophages were used as cell model in vitro to explore the effect and mechanism of cotrimoxazole resistance towards T. marneffei. Cell viability assay and drug sensitivity colony forming units (CFU) experiments were conducted to determine the minimum inhibitory concentration (MIC) of cotrimoxazole inside and outside THP-1 macrophages respectively. Enzyme-linked immunosorbent assay (Elisa) was used to measure the concentration of Dihydropteroic acid synthetase (DHPS), Dihydrofolate synthetase (DHFS) and Dihydrofolate reductase (DHFR) between T. marneffei adding TMP/SMX and without adding TMP/SMX group respectively. Real-time fluorescence quantitative PCR(qPCR) was performed to detect the mRNA expression levels in Dectin-1 mediated signaling pathway and downstream inflammatory cytokines including IL-6, IL-10, IL-23A, CXCL8 and TNF-α released by T. marneffei-infected macrophages between adding TMP/SMX and without adding TMP/SMX group respectively. Cotrimoxazole can inhibit the proliferation of T. marneffei within safe concentration inside and outside THP-1 macrophages. Drug susceptibility results showed the minimal inhibit concentration(MIC) of 1:5 TMP/SMX was ranging from 14/70 to 68/340μg/ml. The MIC of SMX was ranging from 100 to 360μg/ml. The MIC of TMP was ranging from 240 to 400μg/ml outside macrophages. The MIC of TMP/SMX was ranging from 36/180 to 68/340μg/ml. The MIC of SMX was ranging from 340 to 360μg/ml. The MIC of TMP was ranging from 320 to 400μg/ml inside macrophages. The synergistic interaction of 1:5 TMP/SMX was more effective in inhibiting T. marneffei than separate SMX and TMP. DHPS, DHFS and DHFR can be inhibited by cotrimoxazole within safe and effective concentration. Dectin-1 expression is increased following T. marneffei infection, leading to the increase of IL-6, IL-10, IL-23A and the decrease of CXCL8 and TNF-α. Conversely, cotrimoxazole decrease the levels of Dectin-1, IL-6, IL-10, IL-23A and increase the levels of CXCL8 and TNF-α, thereby enhancing the intracellular killing-T. marneffei capacity of macrophages. Our findings indicated that cotrimoxazole directly inhibited T. marneffei growth by blocking DHPS, DHFS and DHFR and indirectly inhibited T. marneffei growth perhaps by regulating the Dectin-1 signaling pathway, which may effectively interfere with the defense ability of the host against T. marneffei infection.

P002 Antifungal activity of antimicrobial synthetic peptides against Candida species of public health importance

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMBackgroundCandidiasis is one of the most frequent opportunistic infections in immunosuppressed and/or hospitalized patients. In countries like Colombia, candidiasis is associated with a mortality rate of ∼ 46%. Growing pharmacological resistance of Candida spp., and the appearance of the emerging pathogen Candida auris, have turned candidiasis into a major public health problem. Different types of antimicrobial peptides have been investigated as a therapeutic alternative to control candidiasis effectively and safely.ObjectiveThis work aimed at evaluating the in vitro antifungal activity of three synthetic antimicrobial peptides (35 409, 1609, and 29 009) obtained from Plasmodium falciparum Rif1 protein against C. auris, C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis, species with worldwide clinical importance.MethodsThe minimum inhibitory concentrations (MIC) of the three peptides against Candida species were determined by the plate microdilution method; the peptides’ effect on biofilm formation in C. auris and C. albicans species was also evaluated through the XTT metabolic activity assay. Additionally, the structural damages in C. auris and C. albicans caused by the action of the peptides were observed by transmission electron microscopy (TEM) and finally, the in vitro peptides’ cytotoxicity against L929 murine fibroblasts was verified.ResultsOur findings showed that the three peptides herein evaluated, displayed antifungal activity in both planktonic and sessile Candida cells. Likewise, the TEM evidenced morphological alterations induced by the peptides, both in the membrane and at the intracellular level of the yeasts. As well, total safety against the murine cell line L929 with 24 h of treatment was observed.ConclusionsFrom these results, we conclude that the antimicrobial peptides 35 409, 1609, and 29 009 are potential therapeutic alternatives against the most important Candida species in Colombia and the world.