Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

A retrospective study on intracranial mixed infection with tuberculous meningitis in Shenzhen, China.

Tuberculous meningitis (TBM) is a prevalent global intracranial infection and the most lethal and disabling form of tuberculosis. TBM with mixed intracranial infections is clinically rare but has a higher mortality rate. To investigate the clinical characteristics of TBM with mixed intracranial infections, demographic and clinical data of TBM and pulmonary tuberculosis (PTB) patients admitted to Shenzhen Third People's Hospital between January 2015 and October 2022 were collected anonymously. A total of 207 cases of TBM were diagnosed, of which 16 cases (7.73%) were TBM with mixed intracranial infections. The overall mortality rate of TBM cases was 16.4%, while the mortality rate of TBM cases with mixed intracranial infections was as high as 35.7%. Compared to simple TBM cases, TBM cases with mixed intracranial infections had severer clinical symptoms. The percentage of human immune deficiency virus (HIV)-positive TBM cases with mixed intracranial infections reached up to 68.8%. HIV co-infection, CD4+/CD8+ T-cell counts less than 1, cranial nerve impairment, paralysis, cerebral infarction, PRO less than 450 mg/L, WBC less than 10 × 106 /L, and CL more than 120 mmol/L were risk factors for TBM cases with mixed intracranial infections. Compared to PTB, HIV co-infection, CD4+ T cell less than 550 /uL, and age less than 45 years were risk factors for TBM, and TBM was associated with higher mortality rates. Our study provides additional data to better understand single TBM and TBM with mixed intracranial infections. More than two-thirds of TBM cases with mixed intracranial infections were HIV-positive. Clinicians should consider the possibility of multiple infections in people with TBM/HIV co-infection. IMPORTANCE: TBM can cause severe neurological damage and death, and TBM with mixed intracranial infections can exacerbate the damage and poor prognosis of the disease. TBM with mixed intracranial infections is a rare disease, which has led to an incomplete understanding of its clinical features. This study investigated the clinical features of TBM and its associated factors by comparing the characteristics of TBM with mixed intracranial infections, single TBM and pulmonary tuberculosis. This information will help to improve the understanding of TBM, diagnostic accuracy and treatment outcomes.

Tuberculosis Coinfection among COVID-19 Patients: Clinical Presentation and Mortality in a Tertiary Lung Hospital in Indonesia.

BACKGROUND: Tuberculosis (TB) and coronavirus disease 2019 (COVID-19) are the top two killers of infectious disease. We aimed to determine the association of TB coinfection with the inhospital mortality of COVID-19 patients in Indonesia as a TB-endemic country. METHODS: We conducted a retrospective cohort study in a tertiary lung hospital in Indonesia. All TB-coinfected COVID-19 patients who were hospitalized between January 2020 and December 2021 were included in the study. COVID-19 patients without TB were randomly selected for the control group. Clinical characteristics and laboratory results were assessed. Survival analysis was performed to determine the estimated death rate and median survival time (MST). Multivariate Cox regression analysis was conducted to define the association of TB coinfection with the in-hospital mortality of COVID-19. RESULTS: We included 86 (8.3%) TB coinfections among 1034 confirmed COVID-19 patients. TB coinfection patients had younger age, malnutrition, and different symptoms compared to the COVID-19 group. TB-coinfected patients had a lower estimated death rate than the COVID-19 group (6.5 vs. 18.8 per 1000 population). MST in the COVID-19 group was 38 (interquartile range 16-47) days, whereas the same observation time failed to determine the MST in the TB coinfection group. TB coinfection had a crude hazard ratio of mortality 0.37 (95% confidence interval [CI] 0.15-0.94, P = 0. 004). The final model analysis including age, sex, and lymphocyte as confounding factors resulted in an adjusted HR of mortality 0.31 (95% CI 0.1-0.9). CONCLUSION: This study showed TB coinfection was negatively associated with the in-hospital mortality of COVID-19.

Systematic review and meta-analysis of Tuberculosis and COVID-19 Co-infection: Prevalence, fatality, and treatment considerations.

BACKGROUND: Tuberculosis (TB) and COVID-19 co-infection poses a significant global health challenge with increased fatality rates and adverse outcomes. However, the existing evidence on the epidemiology and treatment of TB-COVID co-infection remains limited. METHODS: This updated systematic review aimed to investigate the prevalence, fatality rates, and treatment outcomes of TB-COVID co-infection. A comprehensive search across six electronic databases spanning November 1, 2019, to January 24, 2023, was conducted. The Joanna Briggs Institute Critical Appraisal Checklist assessed risk of bias of included studies, and meta-analysis estimated co-infection fatality rates and relative risk. RESULTS: From 5,095 studies screened, 17 were included. TB-COVID co-infection prevalence was reported in 38 countries or regions, spanning both high and low TB prevalence areas. Prevalence estimates were approximately 0.06% in West Cape Province, South Africa, and 0.02% in California, USA. Treatment approaches for TB-COVID co-infection displayed minimal evolution since 2021. Converging findings from diverse studies underscored increased hospitalization risks, extended recovery periods, and accelerated mortality compared to single COVID-19 cases. The pooled fatality rate among co-infected patients was 7.1% (95%CI: 4.0% ~ 10.8%), slightly lower than previous estimates. In-hospital co-infected patients faced a mean fatality rate of 11.4% (95%CI: 5.6% ~ 18.8%). The pooled relative risk of in-hospital fatality was 0.8 (95% CI, 0.18-3.68) for TB-COVID patients versus single COVID patients. CONCLUSION: TB-COVID co-infection is increasingly prevalent worldwide, with fatality rates gradually declining but remaining higher than COVID-19 alone. This underscores the urgency of continued research to understand and address the challenges posed by TB-COVID co-infection.

Molecular and serological evidence of chikungunya virus infection with high case fatality among pediatric population with acute encephalitis syndrome: first report from Eastern Uttar Pradesh, India.

Acute encephalitis syndrome (AES) outbreaks in children of Eastern Uttar Pradesh (E-UP) region of India have been a longstanding public health issue, with a significant case fatality rate of 20-25%. Since past decade, a rise in chikungunya (CHIK) cases has been occurring, which is a reported etiology of AES. However, the burden of chikungunya virus (CHIKV) among pediatric AES (pAES) is unknown from E-UP. We included 238 hospitalized pAES cases. The presence of IgM antibodies for CHIKV, and Dengue virus (DENV) was tested, and RT-PCR was performed for CHIKV and DENV in serologically confirmed CHIKV and DENV pAES cases. Positive samples were sequenced using Sangers sequencing. Further, to check for co-infection, IgM antibodies for other AES etiologies including Japanese encephalitis virus (JEV), Leptospira and Orientia tsutsugamushi (OT) in serum were also investigated. IgM ELISA demonstrated 5.04% (12) positivity for CHIKV. Among CHIKV IgM positive, 3 (25%, 3/12) pAES patients died. CHIKV genome was detected in 3 pAES specimens. Among which, 2 CHIKV cases were also positive for OT DNA. Partially sequenced CHIKV were genotyped as ECSA. The overall finding indicates evidence of CHIKV infection with high case fatality among pAES patients from E-UP. This study advocates constant serological and molecular surveillance of CHIKV in AES endemic regions of India.

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021.

BACKGROUND: Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. METHODS: We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. FINDINGS: We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths. INTERPRETATION: Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups. FUNDING: Bill & Melinda Gates Foundation.

Mortality of children and adolescents co-infected with tuberculosis and HIV: a systematic review and meta-analysis.

OBJECTIVE: Children and adolescents with HIV infection are well known to face a heightened risk of tuberculosis. However, the exact mortality rates and temporal trends of those with HIV-tuberculosis (TB) co-infection remain unclear. We aimed to identify the overall mortality and temporal trends within this population. METHODS: PubMed, Web of Science, and Embase were employed to search for publications reporting on the mortality rates of children and adolescents with HIV-TB co-infection from inception to March 2, 2024. The outcome is the mortality rate for children and adolescents with HIV-TB co-infection during the follow-up period. In addition, we evaluate the temporal trends of mortality. RESULTS: During the follow-up period, the pooled mortality was 16% [95% confidence interval (CI) 13-20]. Single infection of either HIV or TB exhibit lower mortality rates (6% and 4%, respectively). We observed elevated mortality risks among individuals aged less than 12 months, those with extrapulmonary TB, poor adherence to ART, and severe immunosuppression. In addition, we observed a decreasing trend in mortality before 2008 and an increasing trend after 2008, although the trends were not statistically significant ( P  = 0.08 and 0.2 respectively). CONCLUSIONS: Children and adolescents with HIV-TB co-infection bear a significant burden of mortality. Timely screening, effective treatment, and a comprehensive follow-up system contribute to reducing the mortality burden in this population.

Synergistic Pathogenicity by Coinfection and Sequential Infection with NADC30-like PRRSV and PCV2 in Post-Weaned Pigs.

Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are frequently reported in most outbreaks, with clinical presentations involving dyspnea, fever, reduced feed intake, weight loss, and death in fattening pigs. The NADC30-like PRRSV and PCV2d are the main circulating virus strains found in China. This study determines the impact of NADC30-like PRRSV and PCV2d mono-infection and coinfection on the immune system, organ pathology, and viral shedding in five-week-old post-weaned pigs. Pigs were randomly divided into six groups: PBS, PRRSV, PCV2, PRRSV-PCV2 coinfection (co), and PRRSV-PCV2 or PCV2-PRRSV sequential infections. Fever, dyspnea, decreased feed intake, weight loss, and pig deaths occurred in groups infected with PRRSV, Co-PRRSV-PCV2, and PRRSV-PCV2. The viral load was higher in Co-PRRSV-PCV2, PRRSV-PCV2, and PCV2-PRRSV than those mono-infected with PRRSV or PCV2. Additionally, cytokines (IFN-γ, TNF-α, IL-4, and IL-10) produced by pigs under Co-PRRSV-PCV2 and PRRSV-PCV2 groups were more intense than the other groups. Necropsy findings showed hemorrhage, emphysema, and pulmonary adhesions in the lungs of pigs infected with PRRSV. Smaller alveoli and widened lung interstitium were found in the Co-PRRSV-PCV2 and PRRSV-PCV2 groups. In conclusion, PRRSV and PCV2 coinfection and sequential infection significantly increased viral pathogenicity and cytokine responses, resulting in severe clinical signs, lung pathology, and death.

Prevalence and Clinical Impact of Coinfection in Patients with Coronavirus Disease 2019 in Korea.

Coinfection rates with other pathogens in coronavirus disease 2019 (COVID-19) varied during the pandemic. We assessed the latest prevalence of coinfection with viruses, bacteria, and fungi in COVID-19 patients for more than one year and its impact on mortality. A total of 436 samples were collected between August 2020 and October 2021. Multiplex real-time PCR, culture, and antimicrobial susceptibility testing were performed to detect pathogens. The coinfection rate of respiratory viruses in COVID-19 patients was 1.4%. Meanwhile, the rates of bacteria and fungi were 52.6% and 10.5% in hospitalized COVID-19 patients, respectively. Respiratory syncytial virus, rhinovirus, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were the most commonly detected pathogens. Ninety percent of isolated A. baumannii was non-susceptible to carbapenem. Based on a multivariate analysis, coinfection (odds ratio [OR] = 6.095), older age (OR = 1.089), and elevated lactate dehydrogenase (OR = 1.006) were risk factors for mortality as a critical outcome. In particular, coinfection with bacteria (OR = 11.250), resistant pathogens (OR = 11.667), and infection with multiple pathogens (OR = 10.667) were significantly related to death. Screening and monitoring of coinfection in COVID-19 patients, especially for hospitalized patients during the pandemic, are beneficial for better management and survival.

Bacterial and viral coinfection in idiopathic pulmonary fibrosis patients: the prevalence and possible role in disease progression.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial pneumonia of unknown aetiology with a mean survival rate of less than 3 years. No previous studies have been performed on the role of co-infection (viral and bacterial infection) in the pathogenesis and progression of IPF. In this study, we investigated the role of viral/bacterial infection and coinfection and their possible association with pathogenesis and progression of IPF. METHODS: We investigated the prevalence and impact of bacterial and viral coinfection in IPF patients (n = 67) in the context of pulmonary function (FVC, FEV1 and DLCO), disease status and mortality risk. Using principal component analysis (PCA), we also investigated the relationship between distribution of bacterial and viral co-infection in the IPF cohort. RESULTS: Of the 67 samples, 17.9% samples were positive for viral infection, 10.4% samples were positive for bacterial infection and 59.7% samples were positive coinfection. We demonstrated that IPF patients who were co-infected had a significantly increased risk of mortality compared (p = 0.031) with IPF patients who were non-infected [Hazard ratio: 8.12; 95% CI 1.3-26.9]. CONCLUSION: In this study, we report for the first time that IPF patients who were coinfected with bacterial and viral infection have significantly decreased FVC and DLCO (% predicted). Besides, the results demonstrated the increased AE-IPF, increased incidence of death and risk of mortality in infected/coinfected patients compared to non-infected IPF patients.

Estimation of lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest, Ethiopia, 2021; a multicentre historical follow-up study.

INTRODUCTION: In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021. METHODS: Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable. RESULTS: From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9-4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64-8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14-78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21-6.45)] were significant predictors of mortality. CONCLUSION: In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals.

COVID-19-Associated Pulmonary Aspergillosis, Fungemia, and Pneumocystosis in the Intensive Care Unit: a Retrospective Multicenter Observational Cohort during the First French Pandemic Wave.

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (P < 10-4). For CAPA, the presence of several mycological criteria was associated with death (P < 10-4). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (P = 0.001). Antimold treatment did not alter prognosis (P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Identifying Risk Factors for Secondary Infection Post-SARS-CoV-2 Infection in Patients With Severe and Critical COVID-19.

Emerging evidence has unveiled the secondary infection as one of the mortal causes of post-SARS-CoV-2 infection, but the factors related to secondary bacterial or fungi infection remains largely unexplored. We here systematically investigated the factors that might contribute to secondary infection. By clinical examination index analysis of patients, combined with the integrative analysis with RNA-seq analysis in the peripheral blood mononuclear cell isolated shortly from initial infection, this study showed that the antibiotic catabolic process and myeloid cell homeostasis were activated while the T-cell response were relatively repressed in those with the risk of secondary infection. Further monitoring analysis of immune cell and liver injury analysis showed that the risk of secondary infection was accompanied by severe lymphocytopenia at the intermediate and late stages and liver injury at the early stages of SARS-CoV-2. Moreover, the metagenomics analysis of bronchoalveolar lavage fluid and the microbial culture analysis, to some extent, showed that the severe pneumonia-related bacteria have already existed in the initial infection.

Clinical profile and mortality in patients with T. cruzi/HIV co-infection from the multicenter data base of the "Network for healthcare and study of Trypanosoma cruzi/HIV co-infection and other immunosuppression conditions".

OBJECTIVE: Chagas disease (CD) globalization facilitated the co-infection with Human Immunodeficiency Virus (HIV) in endemic and non-endemic areas. Considering the underestimation of Trypanosoma cruzi (T. cruzi)-HIV co-infection and the risk of life-threatening Chagas Disease Reactivation (CDR), this study aimed to analyze the major co-infection clinical characteristics and its mortality rates. METHODS: This is a cross-sectional retrospective multicenter study of patients with CD confirmed by two serological or one parasitological tests, and HIV infection confirmed by immunoblot. CDR was diagnosed by direct microscopy with detection of trypomastigote forms in the blood or other biological fluids and/or amastigote forms in inflammatory lesions. RESULTS: Out of 241 patients with co-infection, 86.7% were from Brazil, 47.5% had <200 CD4+ T cells/µL and median viral load was 17,000 copies/µL. Sixty CDR cases were observed. Death was more frequent in patients with reactivation and was mainly caused by CDR. Other causes of death unrelated to CDR were the manifestation of opportunistic infections in those with Acquired Immunodeficiency Syndrome. The time between the co-infection diagnosis to death was shorter in patients with CDR. Lower CD4+ cells count at co-infection diagnosis was independently associated with reactivation. Similarly, lower CD4+ cells numbers at co-infection diagnosis and male sex were associated with higher lethality in CDR. Additionally, CD4+ cells were lower in meningoencephalitis than in myocarditis and milder forms. CONCLUSION: This study showed major features on T. cruzi-HIV co-infection and highlighted the prognostic role of CD4+ cells for reactivation and mortality. Since lethality was high in meningoencephalitis and all untreated patients died shortly after the diagnosis, early diagnosis, immediate antiparasitic treatment, patient follow-up and epidemiological surveillance are essentials in T. cruzi/HIV co-infection and CDR managements.

Ascariasis complicada en un infante / Complicated ascariasis in an infant

Introducción: La ascariasis es una enteroparasitosis con alta prevalencia en la población pediátrica tercermundista, la cual puede asociarse a otras enfermedades intestinales y tener graves complicaciones que requieren tratamiento quirúrgico. Objetivo: Informar el caso de un infante operado por coinfección de ascariasis intestinal y fiebre tifoidea complicadas. Presentación del caso: Paciente masculino de 9 años de edad asistido y operado en el hospital provincial N´gola Kimbanda de la provincia Namibe, Angola, por presentar evidencia clínica de peritonitis aguda generalizada por perforación intestinal de causa tifoidea y por cuyo orificio salían además áscaris lumbricoides vivos. Su evolución no fue satisfactoria y falleció 24 horas después de la operación. Conclusiones: El diagnóstico y tratamiento quirúrgico oportuno de la coinfección letal de ascariasis y fiebre tifoidea complicadas permitirá disminuir la morbilidad y mortalidad por esta prevalente asociación(AU)

Introduction: Ascariasis is an enteroparasitosis with high prevalence in the third-world pediatric population, which can be associated with other bowel diseases and have serious complications that require surgical treatment. Objective: Report the case of an infant operated by the co-infection of complicated intestinal ascariasis and typhoid fever. Case presentation: 9-year-old male patient attended and operated at N'gola Kimbanda Provincial Hospital in Namibe Province, Angola, after presenting clinical evidence of generalized acute peritonitis due to intestinal perforation of typhoid-causing and through which live ascaris lumbricoide also came out. His evolution was unsatisfactory and he died 24 hours after the operation. Conclusions: The timely diagnosis and surgical treatment of lethal co-infection of complicated ascariasis and typhoid fever will reduce morbidity and mortality from this prevalent association(AU)

Mortality during tuberculosis treatment in South Africa using an 8-year analysis of the national tuberculosis treatment register.

In 2011, the South African HIV treatment eligibility criteria were expanded to allow all tuberculosis (TB) patients lifelong ART. The impact of this change on TB mortality in South Africa is not known. We evaluated mortality in all adults (≥ 15 years old) treated for drug-susceptible TB in South Africa between 2009 and 2016. Using a Cox regression model, we quantified risk factors for mortality during TB treatment and present standardised mortality ratios (SMR) stratified by year, age, sex, and HIV status. During the study period, 8.6% (219,618/2,551,058) of adults on TB treatment died. Older age, male sex, previous TB treatment and HIV infection (with or without the use of ART) were associated with increased hazard of mortality. There was a 19% reduction in hazard of mortality amongst all TB patients between 2009 and 2016 (adjusted hazard ratio: 0.81 95%CI 0.80-0.83). The highest SMR was in 15-24-year-old women, more than double that of men (42.3 in 2016). Between 2009 and 2016, the SMR for HIV-positive TB patients increased, from 9.0 to 19.6 in women, and 7.0 to 10.6 in men. In South Africa, case fatality during TB treatment is decreasing and further interventions to address specific risk factors for TB mortality are required. Young women (15-24-year-olds) with TB experience a disproportionate burden of mortality and interventions targeting this age-group are needed.

Influenza co-infection associated with severity and mortality in COVID-19 patients.

BACKGROUND: In COVID-19 patients, undetected co-infections may have severe clinical implications associated with increased hospitalization, varied treatment approaches and mortality. Therefore, we investigated the implications of viral and bacterial co-infection in COVID-19 clinical outcomes. METHODS: Nasopharyngeal samples were obtained from 48 COVID-19 patients (29% ICU and 71% non-ICU) and screened for the presence of 24 respiratory pathogens using six multiplex PCR panels. RESULTS: We found evidence of co-infection in 34 COVID-19 patients (71%). Influenza A H1N1 (n = 17), Chlamydia pneumoniae (n = 13) and human adenovirus (n = 10) were the most commonly detected pathogens. Viral co-infection was associated with increased ICU admission (r = 0.1) and higher mortality (OR 1.78, CI = 0.38-8.28) compared to bacterial co-infections (OR 0.44, CI = 0.08-2.45). Two thirds of COVID-19 critically ill patients who died, had a co-infection; and Influenza A H1N1 was the only pathogen for which a direct relationship with mortality was seen (r = 0.2). CONCLUSIONS: Our study highlights the importance of screening for co-infecting viruses in COVID-19 patients, that could be the leading cause of disease severity and death. Given the high prevalence of Influenza co-infection in our study, increased coverage of flu vaccination is encouraged to mitigate the transmission of influenza virus during the on-going COVID-19 pandemic and reduce the risk of severe outcome and mortality.

Predictors of mortality in patients with drug-resistant tuberculosis: A systematic review and meta-analysis.

BACKGROUND: Even though the lives of millions have been saved in the past decades, the mortality rate in patients with drug-resistant tuberculosis is still high. Different factors are associated with this mortality. However, there is no comprehensive global report addressing these risk factors. This study aimed to determine the predictors of mortality using data generated at the global level. METHODS: We systematically searched five electronic major databases (PubMed/Medline, CINAHL, EMBASE, Scopus, Web of Science), and other sources (Google Scholar, Google). We used the Joanna Briggs Institute Critical Appraisal tools to assess the quality of included articles. Heterogeneity assessment was conducted using the forest plot and I2 heterogeneity test. Data were analyzed using STATA Version 15. The pooled hazard ratio, risk ratio, and odd's ratio were estimated along with their 95% CIs. RESULT: After reviewing 640 articles, 49 studies met the inclusion criteria and were included in the final analysis. The predictors of mortality were; being male (HR = 1.25,95%CI;1.08,1.41,I2;30.5%), older age (HR = 2.13, 95%CI;1.64,2.62,I2;59.0%,RR = 1.40,95%CI; 1.26, 1.53, I2; 48.4%) including a 1 year increase in age (HR = 1.01, 95%CI;1.00,1.03,I2;73.0%), undernutrition (HR = 1.62,95%CI;1.28,1.97,I2;87.2%, RR = 3.13, 95% CI; 2.17,4.09, I2;0.0%), presence of any type of co-morbidity (HR = 1.92,95%CI;1.50-2.33,I2;61.4%, RR = 1.61, 95%CI;1.29, 1.93,I2;0.0%), having diabetes (HR = 1.74, 95%CI; 1.24,2.24, I2;37.3%, RR = 1.60, 95%CI;1.13,2.07, I2;0.0%), HIV co-infection (HR = 2.15, 95%CI;1.69,2.61, I2; 48.2%, RR = 1.49, 95%CI;1.27,1.72, I2;19.5%), TB history (HR = 1.30,95%CI;1.06,1.54, I2;64.6%), previous second-line anti-TB treatment (HR = 2.52, 95% CI;2.15,2.88, I2;0.0%), being smear positive at the baseline (HR = 1.45, 95%CI;1.14,1.76, I2;49.2%, RR = 1.58,95%CI;1.46,1.69, I2;48.7%), having XDR-TB (HR = 2.01, 95%CI;1.50,2.52, I2;60.8%, RR = 2.44, 95%CI;2.16,2.73,I2;46.1%), and any type of clinical complication (HR = 2.98, 95%CI; 2.32, 3.64, I2; 69.9%). There are differences and overlaps of predictors of mortality across different drug-resistance categories. The common predictors of mortality among different drug-resistance categories include; older age, presence of any type of co-morbidity, and undernutrition. CONCLUSION: Different patient-related demographic (male sex, older age), and clinical factors (undernutrition, HIV co-infection, co-morbidity, diabetes, clinical complications, TB history, previous second-line anti-TB treatment, smear-positive TB, and XDR-TB) were the predictors of mortality in patients with drug-resistant tuberculosis. The findings would be an important input to the global community to take important measures.

Interleukin-4 protects mice against lethal influenza and Streptococcus pneumoniae co-infected pneumonia.

Streptococcus pneumoniae co-infection post-influenza is a major cause of mortality characterized by uncontrolled bacteria burden and excessive immune response during influenza pandemics. Interleukin (IL)-4 is a canonical type II immune cytokine known for its wide range of biological activities on different cell types. It displays protective roles in numerous infectious diseases and immune-related diseases, but its role in influenza and S. pneumoniae (influenza/S. pneumoniae) co-infected pneumonia has not been reported. In our study, we used C57BL/6 wild-type (WT) and IL-4-deficient (IL-4-/- ) mice to establish co-infection model with S. pneumoniae after influenza virus infection. Co-infected IL-4-/- mice showed increased mortality and weight loss compared with WT mice. IL-4 deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of IL-4 in decreasing post-influenza susceptibility to S. pneumoniae co-infection. Loss of IL-4 also resulted in aggravated lung damage together with massive proinflammatory cytokine production and immune cell infiltration during co-infection. Administration of recombinant IL-4 rescued the survival and weight loss of IL-4-/- mice in lethal co-infection. Additionally, IL-4 deficiency led to more immune cell death in co-infection. Gasdermin D (GSDMD) during co-infection was induced in IL-4-/- mice that subsequently activated cell pyroptosis. Treatment of recombinant IL-4 or inhibition of GSDMD activity by disulfiram decreased immune cell death and bacterial loads in lungs of IL-4-/- co-infected mice. These results suggest that IL-4 decreases post-influenza susceptibility to S. pneumoniae co-infection via suppressing GSDMD-induced pyroptosis. Collectively, this study demonstrates the protective role of IL-4 in influenza/S. pneumoniae co-infected pneumonia.

Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis.

INTRODUCTION: The recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection. PATIENTS AND METHODS: We searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763. RESULTS: Of 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively). CONCLUSIONS: Our study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.