Haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis infection in a patient with HIV.

A male in his 30s who was recently diagnosed with HIV arrived at the emergency department exhibiting an altered mental state and acute respiratory distress. Initial laboratory tests revealed a high anion gap metabolic acidosis, elevated liver enzyme levels and bicytopenia. A CT scan identified a miliary pattern. Bronchoscopy with bronchoalveolar lavage displayed epithelial and inflammatory cells. However, subsequent tests ruled out the presence of fungi, Pneumocystis organisms, malignancies, granulomas and viral inclusions. Broad-spectrum antibiotics with emphasis on Mycobacterium tuberculosis and antifungal treatments were administered. The regimen was adjusted after a positive urine test for the Histoplasma antigen.The patient later manifested signs and symptoms, including increased ferritin level, fever, splenomegaly, diminished natural killer cell function and heightened interleukin-2 receptor levels, confirming haemophagocytic lymphohistiocytosis. Given the patient's gravely decompensated state, the treatment incorporated dexamethasone, and the patient's vasopressor-resistant septic shock was addressed with methylene blue.

Disseminated Histoplasma captulatum infection in a patient with HIV.

Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy.

CROI 2024: Tuberculosis, Mpox, and Other Infectious Complications in People With HIV.

Several novel antituberculosis agents, including long-acting injectable agents in mouse models, have shown promise in preclinical and early clinical studies. This encouraging news is offset by the failures of a tuberculosis (TB) vaccine to prevent disease recurrence and a 3-month clofazimine-based treatment regimen for drug-susceptible TB. Clinically focused insights regarding TB, mpox, and other HIV-associated infectious complications that were presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) are summarized in this review.

Opportunistic infections among people living with HIV/AIDS attending antiretroviral therapy clinics in Gedeo Zone, Southern Ethiopia.

INTRODUCTION: Opportunistic infections (OIs) are more common and severe among people with suppressed immunity like those living with HIV/AIDS (PLWH). This study aimed to assess the prevalence of OIs and associated factors among PLWH attending antiretroviral therapy (ART) clinics in the Gedeo zone, Southern Ethiopia. METHODS: A facility based retrospective cohort study was conducted from April to June 2018 among PLWH attending ART clinics in Gedeo zone, Ethiopia from November 2016 - November 2017. A simple random sampling method was used to select the both paper based and electronic study participants' charts. Adjusted odds ratios were calculated using multivariable logistic regression analysis for variables statistically significant at 95% confidence interval under bivariable logistic regression analysis, and significance was declared at P < 0.05. RESULTS: a total of 266 PLWH attended the selected ART clinics of Gedeo zone during the one year period were participated in the current study. The majority 104(39.1%) were within the age group 30-39, 106(60.2%) male, 184(69.2%) married, and 167(62.9%) urban residents. The study revealed the prevalence of OIs was 113(42.5%) with oral candidiasis 28(24.5%) the most prevalent followed by pulmonary tuberculosis 22(19.5%) and herpes zoster 15(13.4%). Further, study participants with ambulatory [AOR = 2.40(95% CI: 1.14, 5.03)], and bedridden [AOR = 3.27(95% CI:1.64, 6.52)] working functional status; with lower CD4 count: less than 200cells/mm3 [AOR = 9.14(95% CI: 2.75, 30.39)], 200-350cells/mm3 [AOR = 9.45(95% CI: 2.70,33.06)], 351-500cells/mm3 [AOR = 5.76(95% CI: 1.71, 19.39)]; being poor in ART adherence level [AOR = 10.05(95% CI: 4.31,23.46)]; being in stage III/IV WHO clinical stage of HIV/AIDS [AOR = 2.72(95% CI: 1.42, 5.20)]; and being chewing khat [AOR = 2.84(95% CI: 1.21, 6.65)] were found positively predicting the occurrence of OIs. CONCLUSION: This study speckled a high prevalence of OIs with several predicting factors. Therefore, the study acmes there should be interventional means which tackles the higher prevalence of OIs with focus to the predicting factors like lower CD4 count level, less/bedridden working functional status, poor ART adherence level, advanced stage of HIV/AIDS stage and chewing khat.

Direct antiglobulin (Coombs) test in HIV-positive Talaromycosis marneffei patients.

Talaromycosis marneffei (T.M) is the primary opportunistic infection of AIDS patients, and its morbidity and mortality are extremely high. To further clarify the disease characteristics of patients and provide a solid basis for in-depth exploration of their pathogenic mechanisms, we retrospectively summarized and analyzed their clinical data. We included all T.M patients tested for direct antiglobulin test (DAT) in the study. Interestingly, we found that AIDS-T.M patients had an extremely high rate of DAT positivity (92/127, 72.44%). In univariate analysis, a positive DAT was associated with blood culture of TM (P = .021), hypoproteinemia (P = .001), anemia (P = .001), thrombocytopenia (P = .003), sepsis (P = .007), and Sequential Organ Failure Assessment (SOFA) (P = .001). Hypoproteinemia, anemia, SOFA, APTT > 32.6 s, and AST > 40 U/l were studied by logistic regression. Logistic regression revealed that SOFA (OR = 1.311, P = .043), hypoproteinemia (OR = 0.308, P = .021), and anemia (OR = 0.19, P = .044) were associated with positive DAT. Positive DAT was associated with severe disease manifestations such as sepsis, and the DAT test is crucial in patients with fungemia.

Talaromycosis marneffei (T.M) is the primary opportunistic infection of AIDS patients and causes high morbidity and mortality. AIDS-T.M patients who were positive for direct antiglobulin test had higher manifestations of inflammation, abnormal liver function, coagulation dysfunction, and hematologic abnormalities.

Incidence and pattern of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) in patients on anti-retroviral therapy: An observational study.

BACKGROUND: Tuberculosis-immune reconstitution inflammatory syndrome is an atypical, immoderate immune response mounted by the refurbishing immune system against the mycobacterium tuberculosis, commonly seen in HIV-infected individuals. ART significantly enhances one's immunity. However, this enhancement in immunity also sets off a number of inflammatory processes termed as Immune Reconstitution Inflammatory Syndrome (IRIS). METHODS: This observational study was conducted with the aim of assessing the incidence and pattern of TB-IRIS in people living with HIV/AIDS on ART registered at the ART Centre of S.C.B. Medical College and Hospital, Cuttack. They were evaluated for their plasma viral load and CD4 count at baseline. Thereafter, the plasma viral load was assessed every week and the CD4 count was assessed fortnightly. Each study participant was followed-up for a period of three months to look for any onset of TB-IRIS. RESULTS: A total of 286 patients were included the study. The overall incidence of TB-IRIS was 7.7%. The occurrence of paradoxical TB-IRIS was nearly double than ART-associated TB-IRIS. There was a significant rise in the CD4 cell count in the patients of both paradoxical (p = 0.001) and ART-associated (p = 0.017) TB-IRIS. The plasma viral load at baseline also showed significant differences from the levels documented at the appearance of the TB-IRIS both in both the types i.e. paradoxical (p = 0.001) and ART-associated (p = 0.012) TB-IRIS. CONCLUSION: People with HIV/TB coinfection experience high morbidity and death from all kinds of TB-IRIS, necessitating specific attention. As HIV-positive cases and implementation of ART continue to rise, it's vital to quickly rule out TB coinfection.

Difficulty in diagnosing intracranial infection caused by Mycobacterium avium in an AIDS patient: case report and review of the literature.

BACKGROUND: Mycobacterium avium complex (MAC) is an uncommon clinical pathogen, especially in the central nervous system (CNS), and carries a poor prognosis. MAC infections commonly present as immune reconstitution disease (IRD) in HIV patients. Herein, we report a case of intracranial infection caused by MAC in an AIDS patient without disseminated MAC (DMAC) and immune reconstitution inflammatory syndrome (IRIS). CASE PRESENTATION: A 31-year-old HIV-positive male presented us with progressively worsening CNS symptoms, and neuroimaging revealed ring-enhancing lesions. The intracranial lesions worsened after the empirical therapy for toxoplasma encephalitis and fungal infection. Due to the rapid progression of the disease, the patient died. Mycobacterium avium was the only pathogen in brain tissue after cultures and molecular biology tests. CONCLUSION: MAC infection in CNS is challenging to diagnose in HIV patients. Our findings emphasize that obtaining tissue samples and applying molecular biology methods is essential to help diagnose the patient as soon as possible to receive adequate treatment.

Ocular involvement in highly treatment-experienced patients with HIV.

Introduction: Ocular involvement in human immunodeficiency virus (HIV) infected and treatment-experienced patients is a significant concern, despite the advancements in antiretroviral therapy (ART) medication. The extended life expectancy of HIV patients has altered the spectrum of HIV-associated ocular diseases, ranging from minor issues to severe vision impairment or blindness. Therefore, understanding these complications becomes crucial in providing comprehensive medical care and quality of life improvement. HIV patients on multiple ARTs can experience various ocular disorders due to the complexity of their treatment regimens, drug toxicities, immune reconstitution, and opportunistic infections. Most worthy to consider are: cytomegalovirus (CMV) retinitis, immune recovery uveitis (IRU), keratoconjunctivitis sicca (dry eye syndrome), and HIV-associated neuroretinal disorders. Materials and methods: A retrospective clinical investigation was conducted on HIV/AIDS-infected patients from January 1, 2013, to December 31, 2023. The study included 62 patients over 18 years, who tested HIV-positive via enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot (WB), with assessments of HIV plasma viral load (VL) and CD4+ T cell counts (CD4). Data collected included demographics, pathological histories, clinical characteristics, blood tests, assessments for opportunistic infections, patient staging, antiretroviral therapy initiation, and disease prognosis. Results: The study found that of most patients, 37 were aged 30-39 (59.7%), with 59.7% males and 40.3% females. Most had been living with HIV for 10-19 years (35.5%). Initial CD4 counts were < 200 cells/mm3 in 46.8% of patients, which improved to 19.3% when the study was done. CMV retinitis prevalence decreased from 46.8% initially to 35.5% despite ART. Other conditions included ocular toxoplasmosis (3.22%), tuberculosis-related uveitis (1,6%), keratoconjunctivitis sicca (19.3%), and HIV retinopathy (29%). Notably, 62.1% of CMV retinitis patients experienced significant visual acuity reduction. Oral valganciclovir was beneficial for patients with CMV disease affecting multiple sites and effective for both induction and maintenance therapy of CMV retinitis. Conclusions: Managing ocular complications in HIV-experienced patients requires a multidisciplinary approach with regular ophthalmologic evaluations, prompt treatment of infections, and continuous monitoring of ART effectiveness. Early detection and intervention are crucial for preserving vision and improving outcomes. The study highlighted the importance of constant monitoring even after viral suppression. Abbreviations: HIV = Human immunodeficiency virus, ART = antiretroviral therapy, CMV = cytomegalovirus, IRU = immune recovery uveitis, ELISA = enzyme-linked immunosorbent assay, WB = Western Blot, VL = viral load, CD4 = CD4+ T cells.

Characteristics of HIV-associated cryptococcal meningitis in a tertiary Chilean hospital: An observational retrospective study.

BACKGROUND: Central nervous system opportunistic infections can be the first presentation of an HIV infection. Our aim is to describe clinical and laboratory characteristics of HIV-associated Cryptococcal Meningitis (CM), in-hospital outcomes and analyze associations of these parameters with adverse outcomes. METHODS: Observational study of local cohort of HIV-associated cryptococcal meningitis in a high complexity tertiary urban hospital in Santiago, Chile. Descriptive analysis through chart review of all episodes of HIV-associated CM in adults, from 1995 to 2019. Inclusion criteria were confirmed CM with cerebrospinal fluid culture or India ink in the appropriate clinical context and HIV diagnosis. We selected relevant variables that have been described as predictors of adverse outcomes in the literature and explore associations in our cohort. RESULTS: There were 37 HIV associated CM cases, occurring from 2000 to 2019. Majority were men (86 %) with a median age of 35 years. CM was the first HIV manifestation in 32 %. Opening pressure was measured in 10 % of patients at admission. Most CSF parameters were mildly altered, and two patients presented with completely normal CSF findings. Most patients -94,4 %- suffered adverse events secondary to antifungal therapy. Despite of recommendations against their use, steroids were frequently prescribed. Mortality was 18,9 %, and was associated with older age, and more days of headache prior to admission. CONCLUSIONS: CM clinical presentation and CSF characteristics are variable at presentation, which can lead to delayed diagnosis. Inappropriate use of corticosteroids, antifungal toxicity and suboptimal management of elevated intracranial pressure are key aspects to improve.

Miscellaneous ophthalmic conditions related to low CD4 cell count in HIV-positive patients.

Introduction: Management of patients living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (AIDS) (PLWHA) still represents a challenge for doctors in various medical fields. The presence of co-infections, with different degrees of immune system impairment, raises the need for a multi-disciplinary approach to the PLWHA. Methods: In this paper, we present three cases of PLWHA with various ophthalmological conditions, who were admitted to "Prof. Dr. Matei Balș" National Institute for Infectious Diseases (INBIMB). Three of them were late presenters, recently diagnosed with AIDS. All three were in immuno-virological failure. The ophthalmic conditions were either related to the HIV infection, or the result of other complications. Discussion: The diversity and complexity of ocular involvement in PLWHA were deeply linked to the patient's immunological status at the ophthalmological evaluation moment. Thus, antiretroviral therapy (ART) played an important immune status recovery role. Encountered ocular conditions vary, some being directly caused by the presence of the virus, and the others were the result of opportunistic infections (cytomegalovirus, Varicella virus) or other co-infections (Treponema pallidum). Neurological conditions disturbing the natural defense mechanism, prolonged hospital stay, and exposure to multiple antibiotic regimens are risk factors for difficult-to-treat eye infections with multidrug-resistant bacteria. Some ocular conditions can be the reason that leads to HIV infection diagnosis, while others can appear during the time, especially in patients with low ART adherence. The prognostic is conditioned by the early recognition and correct management of the disease and the immunological status recovery under ART. Conclusions: Correct and early diagnosis of HIV-related eye conditions is mandatory to establish the most appropriate medical management to obtain an increase in the quality of life of the patient. Abbreviations: HIV = Human Immunodeficiency Virus, AIDS = Acquired Immunodeficiency Syndrome, ART = Antiretroviral Therapy.

Systematic Review of Prevalence of Histoplasma Antigenuria in Persons with HIV in Latin America and Africa.

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma--caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

Comparison of clinical outcomes of pulmonary nocardiosis between AIDS and non-AIDS patients.

BACKGROUND: Nocardia species can affect both immunocompetent and immunocompromised people. METHOD: This retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand. RESULTS: A total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1-198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61-24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74-5.87, p = 0.162)). CONCLUSION: AIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.

HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study.

Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010-37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.

Improving disseminated histoplasmosis diagnosis in HIV/AIDS patients in Suriname: The role of a urine lateral flow assay.

Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions.

Drug-resistant oral candidiasis in patients with HIV infection: a systematic review and meta-analysis.

BACKGROUND: Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients. METHODS: Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model. RESULTS: Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I2 > 50.00%, P < 0.01), except for caspofungin (I2 = 0.00%, P = 0.65). CONCLUSIONS: Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin. REGISTRATION: The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial.

BACKGROUND: HIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB. METHODS: This is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events. DISCUSSION: Disseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04951986. Registered on 7 July 2021 https://clinicaltrials.gov/study/NCT04951986.

Incidence rate of tuberculosis among HIV infected children in Ethiopia: systematic review and meta-analysis.

BACKGROUND: Tuberculosis is one the leading causes of death from a single infectious disease, caused by the bacillus mycobacterium tuberculosis. In Ethiopia, even though several primary studies have been conducted on the incidence of tuberculosis among HIV-infected children, the pooled incidence rate of tuberculosis among HIV-infected children (aged 0-14 years) is unknown. Therefore, the main objectives of this systematic review and meta-analysis are to estimate the pooled incidence rate of tuberculosis among HIV-infected children and its predictors in Ethiopia. METHOD: International electronic databases such as PubMed, HINARI, Science Direct, Google Scholar, and African Journals Online were searched using different search engines.  Quality of primary studies was checked using the Joanna Briggs Institute checklist. The heterogeneity of studies was tested using I-square statistics. Publication bias was tested using a funnel plot and Egger's test. Forest plots and tables were used to present the results. The random effect model was used to estimate the pooled incidence of tuberculosis among children living with HIV. RESULT: A total of 13 studies were included in this systematic review and meta-analysis. The pooled incidence of tuberculosis among HIV-infected children was 3.77 (95% CI: 2.83, 5.02) per 100-person-year observations. Advanced HIV disease (HR: 2.72, 95% CI: 1.9; 3.88), didn't receive complete vaccination (HR: 4.40, 95% CI: 2.16; 8.82), stunting (HR: 2.34, 95% CI: 1.64, 3.33), underweight (HR: 2.30, 95% CI: 1.61; 3.22), didn't receive Isoniazid preventive therapy (HR: 3.64, 95% CI: 2.22, 5.96), anemia (HR: 3.04, 95% CI: 2.34; 3.98), fair or poor antiretroviral therapy adherence (HR: 2.50, 95% CI: 1.84; 3.40) and didn't receive cotrimoxazole preventive therapy (HR: 3.20, 95% CI: 2.26; 4.40) were predictors of tuberculosis coinfection among HIV infected children. CONCLUSION: This systematic review and meta-analysis concluded that the overall pooled incidence rate of tuberculosis among HIV-infected children was high in Ethiopia as compared to the END TB strategy targets. Therefore, emphasis has to be given to drug adherence (ART and Isoniazid) and nutritional counseling. Moreover, early diagnosis and treatment of malnutrition and anemia are critical to reduce the risk of TB coinfection. REGISTRATION: Registered in PROSPERO with ID: CRD42023474956.

Predictive models-assisted diagnosis of AIDS-associated Pneumocystis jirovecii pneumonia in the emergency room, based on clinical, laboratory, and radiological data.

We assessed predictive models (PMs) for diagnosing Pneumocystis jirovecii pneumonia (PCP) in AIDS patients seen in the emergency room (ER), aiming to guide empirical treatment decisions. Data from suspected PCP cases among AIDS patients were gathered prospectively at a reference hospital's ER, with diagnoses later confirmed through sputum PCR analysis. We compared clinical, laboratory, and radiological data between PCP and non-PCP groups, using the Boruta algorithm to confirm significant differences. We evaluated ten PMs tailored for various ERs resource levels to diagnose PCP. Four scenarios were created, two based on X-ray findings (diffuse interstitial infiltrate) and two on CT scans ("ground-glass"), incorporating mandatory variables: lactate dehydrogenase, O2sat, C-reactive protein, respiratory rate (> 24 bpm), and dry cough. We also assessed HIV viral load and CD4 cell count. Among the 86 patients in the study, each model considered either 6 or 8 parameters, depending on the scenario. Many models performed well, with accuracy, precision, recall, and AUC scores > 0.8. Notably, nearest neighbor and naïve Bayes excelled (scores > 0.9) in specific scenarios. Surprisingly, HIV viral load and CD4 cell count did not improve model performance. In conclusion, ER-based PMs using readily available data can significantly aid PCP treatment decisions in AIDS patients.