Predictors of mortality among TB-HIV co-infected children attending anti-retroviral therapy clinics of selected public hospitals in southern, Ethiopia: retrospective cohort study

Background Co-infection of tuberculosis and HIV has a significant impact on public health. TB is the most common opportunistic infection and the leading cause of death in HIV-positive children worldwide. But there is paucity of studies concerning the predictors of mortality among TB-HIV co-infected children. This study aimed to determine the predictors of mortality among TB-HIV co-infected children attending ART clinics of public hospitals in Southern Nation, Nationalities and Peoples Region (SNNPR), Ethiopia. Methods A hospital-based retrospective cohort study design was used among 284 TB-HIV co-infected children attending ART clinics at selected public hospitals in SNNPR, Ethiopia, from January 2009 to December 2019. Then, medical records of children who were TB/HIV co-infected and on ART were reviewed using a structured data extraction tool. Data were entered using Epidata 4.6 and analyzed using SPSS version 23. The Kaplan Meier survival curve along with log rank tests was used to estimate and compare survival time. Bivariable and multivariable analyses were conducted to identify predictors of mortality among TB/HIV co-infected children. Adjusted Hazard Ratio with p value < 0.05 and 95% confidence interval was considered statistically significant. Result A total of 284 TB/HIV co-infected children were included in the study. Among these, 35 (12.3%) of them died during the study period. The overall mortality rate was 2.78 (95%CI = 1.98-3.99) per 100 child years of observation. The predictors of mortality were anemia (AHR = 3.6; 95%CI: 1.39-9.31), fair or poor ART drug adherence (AHR = 2.9; 95%CI = 1.15-7.43), extrapulmonary TB (AHR = 3.9; 95%CI: 1.34-11.45) and TB drug resistance (AHR = 5.7; 95%CI: 2.07-15.96). Conclusion Mortality rate of TB/HIV co-infected children in selected public hospitals in SNNPR, Ethiopia was documented as 2.78 per child years of observation as a result of this study. Moreover, Anemia, drug resistant tuberculosis, extrapulmonary TB and poor adherence to ART drugs were identified as the predictors of mortality among these children.

1404. Tuberculosis and HIV Coinfection: A Review of 135 Cases Experience of the Infectious Diseases Department- CHU Mohamed VI- Marrakech

Background Tuberculosis is a health problem in Morocco, which is increasingly indicative of human immunodeficiency virus (HIV) infection. Objective To determine the epidemiological, clinical and paraclinical, therapeutic and evolutionary aspects of tuberculosis and HIV co-infection. Methods we report 135 cases co-infected with HIV and tuberculosis, collected by the infectious diseases department at the Mohammed VI University Hospital in Marrakech. This is a 12-year retrospective study (2007 to 2020) that involved all HIV-infected patients hospitalized for tuberculosis regardless of its location. Results The mean age of the patients was 40 years (17-73 years). A male predominance was noted in 69% of cases. In 74.6% of cases, tuberculosis was indicative of HIV infection. Nine patients were receiving antiretroviral (ARV) treatment at the time of the discovery of tuberculosis. There were 24% pulmonary tuberculosis, 25.3% extrapulmonary tuberculosis and 49% disseminated tuberculosis. Tuberculosis was confirmed in 31.7% of cases. At the time of tuberculosis diagnosis, the average CD4 count was 86 cells / mm. Quadruple therapy with isoniazid, rifampicin, pyrazinamide and ethambutol was started in 83% of patients. The average time to start ARVs was 7 weeks. All patients who received ARVs received a combination therapy comprising the combination of 2 nucleoside analogs and one non-nucleoside analog. At the end of our work, the evolution was favorable in 53% of cases, death occurred in 25% of cases, 18.6% of patients were lost to follow-up, two cases of failure and another of relapse. Immune restoration syndrome was noted in 8 cases. Drug toxicity was observed in 24.5% of patients, 73% of which was related to hepato-toxicity of antibacillary drugs. Conclusion Tuberculosis is the most common opportunistic infection in people with HIV. Despite the advent of highly active triple therapy, tuberculosis is still a major cause of death in HIV positive people. Disclosures All Authors: No reported disclosures

Oral Candidiasis in Patients with Hematological Diseases: Diagnosis Through Clinical and Cytopathological Exams

Background: Candidiasis is a common opportunistic infection that may interfere with oncologic patients’ prognosis, especially those with hematologic diseases. This study is the first to analyse the prevalence of oral candidiasis in onco-hematological patients by physical and oral cytopathological exams. Methods: This is a cross-sectional and observational study with a retrospective sample composed of participants hospitalized in the hematology clinic, diagnosed with hematologic diseases. All patients were submitted to an oral mucosal exam and scraps from oral mucosa were obtained. Results: Of the 62 participants, 56.5% were male, 82.3% were white, with mean age of 57 years. Lymphoma was the most common hematologic disease (24.2%). In total, 48.3% of the sample was diagnosed with oral candidiasis. Of these participants with oral candidiasis, 13 (21.0%) had clinical diagnosis, where erythematous subtype was present in all cases and pseudomembranous subtype in 12 individuals. Cytopathological analysis revealed more 17 (27.4%) cases, without oral lesion indicative of candidiasis. Conclusions: Oral candidiasis is common among patients with hematologic disease, and the cytopathological exam proved to be a useful tool, confirming clinical diagnosis of candidiasis and identifying subclinical cases. These data are of great relevance considering the possible complications that these patients may develop such as longer hospitalizations, worsening of the general condition due to candidemia and even death.

On the Treatment of Pneumocystis jirovecii Pneumonia: Current Practice Based on Outdated Evidence

Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection causing more than 400,000 cases annually worldwide. While antiretroviral therapy has reduced the burden of PCP in persons living with HIV, an increasing proportion of cases occur in other immunocompromised populations. In this review we synthesize the available randomized controlled trial (RCT) evidence-base for PCP treatment. We identified 14 RCTs that were conducted 25-35 years ago, principally in 40-year-old men with HIV. Trimethoprim-sulfamethoxazole (TMP-SMX), at a dose of 15-20mg/kg/day, is the treatment of choice based on historical practice rather than on quality comparative dose finding studies. Treatment duration is similarly based on historical practice and is not evidence-based. Corticosteroids have a demonstrated role in hypoxemic patients with HIV but have yet to be studied in RCTs as an adjunctive therapy in non-HIV populations. The echinocandins are potential synergistic treatments in need of further investigation.

The Evaluation of the Factors Affecting Mortality in Cases of HIV-infected Pneumocystis Jiroveci Pneumonia

Objective: Pneumocystis jiroveci pneumonia (PJP) is a common opportunistic infection in human immunodeficiency virus (HIV) infection cases. This study aimed to investigate the mortality rate and the factors affecting mortality in HIV-infected PJP cases followed in our clinic. Methods: In this study HIV (+) cases followed up in our clinic between 2012-2019 were included. Age, sex, comorbidity status, LDH, CD4, lymphocyte, albumin, values, and blood gas results of these patients were recorded at the time of diagnosis. Results: Twenty-eight patients with the diagnosis of HIV-infected PJP were included in the study. The mean age of the patients was 45.7 years, and the male ratio was 78.6% (18/28). The overall hospital mortality rate was 35.7% (10/28) among the cases. Conclusions: As a result, performing studies involving many patients may be beneficial in these patients for diagnosis, follow-up and early treatment.

Etiologies of Fever of Unknown Origin in HIV/AIDS Patients, Hanoi, Vietnam

Background: Prolonged fever is a challenge for clinicians in managing patients with HIV/AIDS. Their TCD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of prolonged fever and their distribution in different TCD4 count levels in HIV/AIDS patients.Methods: A cross-sectional, retrospective and prospective study was conducted on 195 HIV/AIDS patients with fever of unknown origin admitted to National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratio was used to compare the distribution of common etiologies in two different TCD4 count levels, including <50 cells/mm3 and ≥50 cells/mm3.Results: The proportion of opportunistic infections and non-infectious etiologies was 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by Talaromycosis (29.2%) and Pneumocystis jiroveci (20.5%). Tuberculosis was predominant in all stratified CD4 levels. Most cases with Talaromycosis had CD4 counts below 50 cells/mm3. 53.8% of cases were infected by one pathogen. There was no difference between the number of concurrent etiologies and T-CD4 levels. Conclusions: Opportunistic infections, especially tuberculosis, are still the leading cause of prolonged fever in HIV/AIDS patients. Talaromyces marnefei should be screened in patients with CD4 <50 cells/mm3. This study implies that guidelines regarding providing the appropriate treatment for FUO-HIV patients based on the CD4 cells count should be developed that may reduce the burden of clinicians in managing HIV/AIDS patients.

A Case of Disseminated Cutaneous Mycobacterium chelonae Infection During Treatment With Tofacitinib

Janus kinase ( JAK) inhibitors, like other immunomodulators, are known to be associated with an increased risk of infections.1 An analysis of long-term clinical trial data has shown tuberculosis to be the most common opportunistic infection associated with tofacitinib use.2

Frosted branch angiitis due to cytomegalovirus-associated unmasking immune reconstitution inflammatory syndrome: a case report and literature review

Background Cytomegalovirus (CMV) retinitis is a common opportunistic infection in patients with acquired immunodeficiency syndrome. The common funduscopic manifestations are haemorrhagic necrotising variety and granular variety. Frosted branch angiitis (FBA), as a special form, when it occurred after antiretroviral therapy(ART), could possibly be associated with immune reconstitution. We report a case of FBA secondary to CMV infection-associated unmasking immune reconstitution inflammatory syndrome (IRIS). Case presentation A 27-year-old man with human immunodeficiency virus infection developed FBA after 35 days of ART. The left Aqueous humour (AqH) tested positive for CMV DNA, and the patient was diagnosed with CMV retinitis. The degree of intraocular inflammation was reflected by increased levels of interleukin (IL)-6 and IL-8 in AqH. After anti-CMV treatment and continuous ART for several months, his FBA and vision significantly improved. CMV DNA became undetectable in the left AqH, and the IL-6 and IL-8 levels in AqH decreased. Conclusion FBA could be a sign of CMV-associated unmasking IRIS. Anti-CMV treatment alone or combination with steroid treatment may be administered, depending on the changes in CMV DNA load and immunologic profile of AqH.

A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis

Background Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Despite the wide use of effective antiretroviral and antifungal therapy in AIDS patients, CM is still a major morbidity and mortality cause. Understanding the immune response in cryptococcal infection may help to improve the treatment strategies. Methods We established a prospective cohort of twelve AIDS patients with CM (HIV + CM+) admitted to the hospital from 2019 to 2020. All patients were examined at the baseline, 2 weeks, and 4 weeks thereafter. The level of 19 cytokines in cerebrospinal fluid (CSF) were recorded to analyze the characteristics and dynamic changes of Th1/Th2 immune response. Meanwhile, six AIDS patients without CM (HIV + CM-) and seventeen healthy subjects (HIV-CM-) were included as control groups for CSF assessment. Results The HIV+ CM+ group had higher CSF IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the HIV-CM- group at baseline. And they also had a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- patients. Except one patient dropped out of the study, eleven HIV + CM+ patients received induction antifungal therapy and regular CSF testing, and the mortality rate was 9.1% (1/11) and 18.2% (2/11) respectively at week 2 and week 4. Compared with baseline CSF cytokines, IL-2, IL-13, IL-17A, and VEGF-A decreased in week 2, and the VEGF-A levels further decreased in week 4. But there was no difference in the levels of all cytokines between survivors and the dead. Conclusion No evidence of Th1/Th2 imbalance was found in AIDS patients with CM. However, the CSF cytokine network may provide new clues for the treatment of AIDS patients with CM. Trial registration This trial was prospectively registered in 2019.7.16. The registered number is ChiCTR1900024565.

Cryptococcal Meningitis in an HIV-Negative Puerperal Woman

Cryptococcal meningitis is a common opportunistic infection in HIV-infected patients and other immunocompromised people. Pregnancy, which is a state of relative immunosuppression, can also be a risk factor for the development of cryptococcal meningitis. We report a clinical case of a 41-year-old woman who developed a severe meningeal syndrome after an otherwise normal pregnancy. Cerebrospinal fluid (CSF) cytochemical analysis presented hypoglycorrhachia, high protein levels, and pleocytosis. Cryptococcal antigen tested positive in serum and CSF, and Cryptococcus neoformans was identified in the CSF culture. The diagnosis of cryptococcal meningitis was confirmed, and antifungal induction therapy was started with liposomal amphotericin B and flucytosine. After clinical improvement, induction therapy was discontinued, and the patient was discharged under maintenance therapy with fluconazole. While under antifungal maintenance therapy, the patient presented worsening of symptoms and a new brain magnetic resonance showed the development of multiple cryptococcoma. Despite sterile CSF cultures, there was a deterioration of the cytochemical parameters. The diagnosis of immune reconstitution inflammatory syndrome was assumed, and after initiation of corticotherapy, the patient improved considerably. This is a rare case of cryptococcal meningitis in a puerperal woman with a challenging management.