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Background: Anti-CD19 chimeric antigen receptors (CARs) T-cell therapy has been shown to have excellent efficacy in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL). But many patients are refractory to anti-CD19-CAR T-cell therapy or relapse again., Methods: Five patients with R/R B-ALL did not respond to anti-CD19-CAR T-cell therapy or had a disease progression again after CAR-T cell therapy. They received a salvage therapy of Blinatumomab. The clinical response, CD19 expression on ALL cells, the proportion of CD3 + T cells, level of cytokine levels of interleukin-6 (IL-6), hematological toxicity, grade of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxic syndrome (ICANS) were observed in salvage therapy of Blinatumomab., Results: Four patients obtained CR/CRi, even in patients without high expression of CD19 in B-ALL cells, while the other patient received NR after Blinatumomab therapy. The CD19 expression on ALL cells, the proportion of CD3 + T cells, and CD3 + CD8 + T cells were deficient in Pt 5, who obtained PR in Blinatumomab therapy. One patient (Pt 3) was diagnosed with grade 0 hematological toxicity. The other four patients were diagnosed with grades 2-3 of hematological toxicity. The CRS was grade 0/one patient, grade 1/three, and grade 2/one. The ICANS was grade 0/four patients, grade 1/one. Rhizopus microsporus pneumonia and cryptococcal encephalopathy in two patients were controlled during Blinatumomab therapy., Conclusions: Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in R/R B-ALL patients without high expression of CD19 in B-ALL cells, patients with CNS leukemia or co-infection.Key messagesSome R/R B-ALL patients did not respond to anti-CD19 CAR T-cell therapy or had a disease progression again. Effective and safe salvage therapy for such patients remains to be explored.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients without high expression of CD19 in B-ALL cells.Blinatumomab could be an effective and safe salvage therapy in patients with R/R B-ALL who failed/progressed after anti-CD19-CAR T therapy, even in patients with CNS leukemia or co-infection.

This study aimed to explore the risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy procedures to prevent their occurrence and improve surgical outcomes. A retrospective analysis was conducted on 356 patients who underwent lateral decubitus percutaneous nephrolithotomy for the treatment of kidney stones and upper ureteral stones from January 2015 to August 2022. Among them, 290 patients had complete clinical data. General clinical data, perioperative data, and stone characteristics were collected for each patient. Univariate and multivariate logistic regression analyses were performed to identify risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy. The postoperative infection rate after lateral decubitus percutaneous nephrolithotomy was 19.31%, and the postoperative bleeding rate was 12.07%. Independent risk factors for postoperative infection were multiple stones (P < .001), stone size (P < .001), and stone co-infection (P = .012). Independent risk factors for postoperative bleeding were multiple stones (P = .008) and stone size (P = .014). Multiple stones, stone size, and stone co-infection are independent risk factors for postoperative infection after lateral decubitus percutaneous nephrolithotomy. Multiple stones and stone size are independent risk factors for postoperative bleeding after lateral decubitus percutaneous nephrolithotomy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets., Methods: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed., Findings: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032)., Interpretation: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications., Funding: French Ministry of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Peritoneal dialysis (PD) is a valuable means to increase access to kidney replacement therapy in South Africa (SA). An increased rate of modality discontinuation related to an increased risk of peritonitis in patients of black African ethnicity, in those with diabetes and in those living with HIV has previously been suggested, which may lead to hesitancy in adoption of 'PD first' programmes., Objectives: To analyse the safety of a PD-first programme in terms of 5-year peritonitis risk and patient and modality survival at the outpatient PD unit at Helen Joseph Hospital, Johannesburg., Methods: After exclusions, clinical data from 120 patients were extracted for analysis. The effects of patient age at PD initiation, ethnicity, gender, diabetes mellitus and HIV infection on patient and modality survival and peritonitis risk were analysed using Cox proportional hazards modelling and logistic regression analysis. Five-year technique and patient Kaplan-Meier survival curves for peritonitis and comorbidity groups were compared using the Cox-Mantel test. The Mann-Whitney U-test and Fisher's exact test were used to compare continuous and categorical variables where appropriate., Results: Five-year patient survival was 49.9%. Black African ethnicity was associated with reduced mortality hazard (hazard ratio (HR) 0.33; 95% confidence interval (CI) 0.15 - 0.71; p=0.004), and patients with diabetes had poorer 5-year survival (19.1%; p=0.097). Modality survival at 5 years was 48.1%. Neither Black African ethnicity nor HIV infection increased the risk of PD discontinuation. Peritonitis was associated with increased modality failure (HR 2.99; 95% CI 1.31 - 6.87; p=0.009). Black African ethnicity did not increase the risk of peritonitis. HIV was not independently associated with an increased risk of peritonitis. Patient and PD survival were generally similar to other contemporaneous cohorts, and the peritonitis rate in this study was within the International Society for Peritoneal Dialysis acceptable range., Conclusion: PD is a safe and appropriate therapy in a low socioeconomic setting with a high prevalence of HIV infection. Consideration of home circumstances and training in sterile technique reduce peritonitis risk and improve PD modality survival. Patients with diabetes may be at risk of poorer outcomes on PD.

BACKGROUND The interaction of viral infection may be associated with increased morbidity after renal transplantation. This study aimed to identify the incidence and risk factors of viruria infections in renal transplant recipients. MATERIAL AND METHODS In this longitudinal study, 502 episodes recorded in 81 kidney transplant patients from 1/2019 to 12/2021 in a hospital in Vietnam were included. BK, JC polyomaviruses, CMV, EBV, and HSV were detected. Multivariable Cox regression analysis was performed to evaluate risk factors for the viruria infection. RESULTS Fifty-six patients (69.1%) had viruria co-infection. The incidence of JC, CMV, and BK infection was the most common viruria, with 67.9%, 61.7%, and 56.8%, respectively. Cox regression revealed that the risk factors for JC were single infection, dose of MMF (HR 1.002), corticoid (HR 1.02), hypertension (HR 1.65), and hematuria (HR 2.03); risk factors for CMV infection were male sex (HR 1.92) and eGFR (HR 0.98); risk factors for BK single infection were hypertension (HR 1.67), proteinuria (HR 3.80), higher tacrolimus trough level (HR 1.17), and dose of MMF (HR 1.002). Hypertension (HR 1.68), fasting plasma glucose (HR 1.13), proteinuria (HR 6.01), tacrolimus trough level (HR 1.12), and dose of MMF (HR 1.004) were independent risk factors for the viruria co-infection. CONCLUSIONS Kidney function was associated with the incidence of viruria. Higher tacrolimus trough level and dose of MMF were associated with higher risk of BK, JC, and co-infection.

Background: This study aimed to systemically explore the risk factors of secondary infection/recurrence after ablation in patients with liver cancer., Methods: Relevant literature in PubMed, EMbase, and Cochrane Library databases were searched with keywords including "liver cancer or carcinoma," "ablation," "infectious or infection or recurrence," and "risk factor or relevant factor or correlative factor or influencing factor." Meta-analyses were performed and forest plots were drawn for risk factors, including the tumor size and location, number of tumor nodules, hepatitis B virus (HBV) DNA levels, serum alpha fetal protein (AFP) levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy. A funnel plot was drawn to assess the publication bias., Results: A total of 23 studies were included from the initial 701 potentially relevant articles. Our meta-analyses showed that a large tumor size (odds ratio [OR] = 1.58; 95% confidence interval [CI]: 1.31-1.92); proximity to the colon, large vessels, and large hepatic vein (OR = 4.10; 95% CI: 2.26-7.43); multinodular tumor (OR = 2.10; 95% CI: 1.46-3.03), the higher HBV DNA levels (OR = 1.34; 95% CI: 1.09-0.64); higher serum AFP levels (OR = 1.56; 95% CI: 1.18-2.05), lower serum albumin levels (OR = 1.67; 95% CI: 1.06-2.65); Child-Pugh Class B and Class C (OR = 1.27; 95% CI: 1.05-1.54); and lack of antiviral therapy (OR = 1.75; 95% CI: 0.93-3.28) were associated with an increased risk of post-ablation infection/recurrence in patients with liver cancers., Conclusion: Our results indicated that the tumor size and location, number of tumor nodules, HBV DNA levels, serum AFP levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy were the risk factors for post-ablation infection/recurrence in patients with liver cancer. Here, we have provided directions for the clinical prevention of secondary infection/recurrence in patients with liver cancer who underwent ablation therapy., Competing Interests: None

Background: COVID-19 infection is considered to cause high mortality in kidney transplant recipients (KTR). Old age, comorbidities and acute kidney injury are known risk factors for increased mortality in KTR. Nevertheless, mortality rates have varied across different regions. Differences in age, comorbidities and varying standards of care across geographies may explain some variations. However, it is still unclear whether post-transplant duration, induction therapy, antirejection therapy and co-infections contribute to increased mortality in KTR with COVID-19. The present study assessed risk factors in a large cohort from India., Methods: A matched case-control study was performed to analyze risk factors for death in KTR (N = 218) diagnosed with COVID-19 between April 2020 to July 2021 at the study centre. Cases were KTR who died (non-survivors, N = 30), whereas those who survived were taken as controls (survivors, N = 188)., Results: A high death-to-case ratio of 13.8% was observed amongst study group KTR infected with COVID-19. There was a high incidence (12.4%) of co-infections, with cytomegalovirus being the most common co-infection among non-survivors. Diarrhea, co-infection, high oxygen requirement, and need for mechanical ventilation were significantly associated with mortality on regression analyses. Antirejection therapy, lymphopenia and requirement for renal replacement therapy were associated with worse outcomes., Conclusions: The mortality was much higher in KTR who required mechanical ventilation and had co-infections. Mortality did not vary with the type of transplant, post-transplant duration and usage of depletion induction therapy. An aggressive approach has to be taken for an early diagnosis and therapeutic intervention of associated infections., (© 2022. The Author(s).)

Background: Ethiopia is one of the high burden countries for extrapulmonary tuberculosis (EPTB); however, the prompt diagnosis of EPTB remains challenging. This study is aimed to evaluate the diagnostic performance of Xpert MTB/RIF and DetermineTM TB-LAM Ag (TB-LAM) for the prompt diagnosis of EPTB in Ethiopia., Methods: A total of 147 presumptive EPTB patients, including 23 HIV- positive participants were enrolled. Extra-pulmonary samples were collected from all presumptive EPTB cases and tested for Mycobacterium tuberculosis complex (MTBC) using fluorescent microscopy, Xpert MTB/RIF, and culture. Additionally, urine samples were also collected from 126 participants and were tested by DetermineTM TB-LAM Ag (Alere Inc, Waltham, USA). The Sensitivity and specificity of Xpert and TB- LAM tests were calculated by comparing with a composite reference standard (CRS), which comprises smear microscopy, culture and response to empirical anti-TB treatment., Results: Of 147 patients, 23 (15.6%) were confirmed EPTB cases (culture-positive), 14 (9.5%) were probable EPTB (clinically, radiologically or cytologically positive and received anti-TB treatment with good response), and 110 (74.8%) were classified as "non- TB" cases. Compared to the composite reference standard (CRS), the overall sensitivity and specificity of Xpert MTB/RIF were 43.2% and 100%, respectively with the highest sensitivity for Lymph node aspirate (85.7%) and lower sensitivity for pleural fluid (14.3%) and 100% specificity for all specimen types. The sensitivity and specificity of TB-LAM were 33.3% and 94.4% respectively with the highest sensitivity for HIV co-infected participants (83.3%). The sensitivity of the combination of Xpert MTB/RIF and TB-LAM tests regardless of HIV status was 61.1% whereas the sensitivity was improved to 83.3% for HIV-positive cases., Conclusion: TB-LAM alone has low sensitivity for EPTB diagnosis; however, the combination of TB-LAM and Xpert MTB/RIF improves the diagnosis of EPTB particularly for countries with high EPTB and HIV cases., Competing Interests: NO authors have competing interests.

Background: Worldwide tuberculosis (TB) takes more lives than any other infectious diseases. WHO estimates around 68,000 incident TB cases in Nepal. However, in 2018 only around 27,232 new TB cases were reported in the national system, resulting around 40,768 incident TB cases missing every year in Nepal. National Tuberculosis Control Center carried out this study in anti-retroviral therapy (ART) sites to estimate the prevalence of TB and identify the associated risk factors for TB among the people living with Human Immunodeficiency Virus (PLHIVs) in Nepal., Methods: It was a cross-sectional institution-based study conducted between March and August 2018. Six ART sites with high caseloads of PLHIVs were selected. PLHIVs who were equal or above 18 years of age and were in ART program at the selected study sites were considered eligible for the study. Diagnosis of tuberculosis among PLHIVs who agreed to participate in the study was carried out as per the National Tuberculosis Management Guideline of National Tuberculosis Program of Nepal., Results: Among 403 PLHIVs, tuberculosis was diagnosed in 40 (9.9%) individuals. Median age of the participants was 36 (30-43) years. Prevalence of TB was significantly higher among male PLHIVs than female PLHIVs (13.6% Vs 5.8%; P = 0.02) and Dalit ethnic group compared to Brahmin/Chettri (22.0%Vs5.9%, P = 0.01). The risk of developing TB was found significant among those with HIV stage progressed to WHO stage 3 and 4 (OR = 4.85, P<0.001) and with the family history of TB (OR = 4.50, P = 0.002)., Conclusions: Prevalence of TB among PLHIVs in Nepal was found 9.9%. Risk of developing TB was higher among PLHIVs who were male, Dalit, with HIV stage progressed to WHO stage 3 and 4 and with family history of TB. Hence, targeted interventions are needed to prevent the risk of developing TB among PLHIVs. Similarly, integrated, and comprehensive TB and HIV diagnosis and treatment services are needed for the management of TB/HIV co-infection in Nepal., Competing Interests: The authors have declared that no competing interests exist.

Vector-borne pathogens commonly establish multistrain infections, also called complex infections. How complex infections are established, either before or after the development of an adaptive immune response, termed coinfection or superinfection, respectively, has broad implications for the maintenance of genetic diversity, pathogen phenotype, epidemiology, and disease control strategies. Anaplasma marginale, a genetically diverse, obligate, intracellular, tick-borne bacterial pathogen of cattle, commonly establishes complex infections, particularly in regions with high transmission rates. Both coinfection and superinfection can be established experimentally; however, it is unknown how complex infections develop in a natural transmission setting. To address this question, we introduced naive animals into a herd in southern Ghana with a high infection prevalence and high transmission pressure and tracked the strain acquisition of A. marginale through time using multilocus sequence typing. As expected, the genetic diversity among strains was high, and 97% of animals in the herd harbored multiple strains. All the introduced naive animals became infected, and three to four strains were typically detected in an individual animal prior to seroconversion, while one to two new strains were detected in an individual animal following seroconversion. On average, the number of strains acquired via superinfection was 16% lower than the number acquired via coinfection. Thus, while complex infections develop via both coinfection and superinfection, coinfection predominates in this setting. These findings have broad implications for the development of control strategies in high-transmission settings.

Background: HIV-1 infection predisposes to an increased burden of pneumonia caused by community-acquired and opportunistic pathogens., Methods: Within the context of the Pneumonia Etiology Research for Child Health case-control study of under 5 pneumonia, we investigated the etiology of World Health Organization-defined severe/very severe pneumonia requiring hospitalization in South African HIV-infected children. Nasopharyngeal-oropharyngeal swabs and blood, collected from cases and age- and season-matched HIV-infected controls attending outpatient antiretroviral therapy (ART) clinics, were analyzed using molecular diagnostic methods. Cases were also investigated for tuberculosis. Etiologic fractions among cases with radiologically confirmed pneumonia were derived using Bayesian analytic techniques., Results: Of 115 HIV-infected cases, 89 (77.4%) had radiologically confirmed pneumonia. Severe immunosuppression (adjusted odds ratio, 32.60; 95% confidence interval, 7.25-146.64) was significantly associated with radiologically confirmed pneumonia. Cotrimoxazole prophylaxis (46.4% vs. 77.4%) and ART (28.2% vs. 83.1%) coverage were significantly lower in cases compared with ART-clinic controls. An etiologic agent was identified in 99.0% of the radiologically confirmed cases. The 'top 4' pathogens associated with radiologically confirmed pneumonia were Pneumocystis jirovecii [23.0%; 95% credible interval (CrI), 12.4%-31.5%], Staphylococcus aureus (10.6%; 95% CrI, 2.2%-20.2%), pneumococcus (9.5%; 95% CrI, 2.2%-18.0%) and respiratory syncytial virus (9.3%; 95% CrI, 2.2%-14.6%). Bacteremia (6.7%) and in-hospital death (10.1%) were frequent among those with radiologically confirmed disease., Conclusions: Pneumocystis jirovecii, S. aureus, pneumococcus and respiratory syncytial virus contribute a considerable burden of radiologically confirmed pneumonia in South African HIV-infected children under 5 years. Expediting access to ART and cotrimoxazole prophylaxis would decrease the burden of pneumonia in these children., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: There likely are several predisposing factors to secondary infections in patients with Coronavirus disease 2019 (COVID-19), some of which may be preventable. The aim of this review is to explore the literature, summarize potential predisposing factors to secondary infections and their incidence. It also summarizes a variety of healthcare scenarios in which different kinds of secondary infections occur., Recent Findings: Apart from immune dysregulation, severe resource limitations in healthcare settings have made COVID-19 units conducive to a variety of secondary infections. Long-term effect of excess antibiotic use in COVID-19 patients is yet to be studied. Very few studies have assessed secondary infections as the primary outcome measure making it difficult to know the true incidence. Mortality attributable to secondary infections in COVID-19 patients is also unclear., Summary: Incidence of secondary infections in COVID-19 patients is likely higher than what is reported in the literature. Well designed studies are needed to understand the incidence and impact of secondary infections in this patient population. Many of these may be preventable especially now, as personal protective equipment and other healthcare resources are recovering. Infection prevention and control (IPC) and antimicrobial stewardship programmes (ASP) must reassess current situation to correct any breaches that could potentially cause more harm in these already vulnerable patients as we brace for a future surge with another pandemic wave., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Granulicatella adiacens is facultative anaerobic Gram-positive bacteria, which mainly involve bacterial endocarditis and bacteremia, but there are few reports of local suppurative infection. A case of lung abscess with a coinfection of Granulicatella adiacens and other bacteria in a lung cancer patient will be reported in this paper. To our knowledge, this is the first case report describing lung abscess due to G.adiacens., Case Presentation: A 52-year-old Chinese woman was admitted to the hospital, She complained of coughing and expectoration for 1 month, shortness of breath for half a month, and dyspnea for 1 day. After a series of examinations, she was diagnosed with lung abscess, pleural effusion, and bronchogenic carcinoma. Draining pus culture demonstrated Granulicatella adiacens. After more than 5 weeks of antibiotic therapies in total, she gradually recovered to fight against lung cancer., Conclusion: This is the first reported lung abscess caused by G.adiacens. In immunosuppressed hosts, G.adiacens is a virulent pathogen associated with a spectrum of intrathoracic suppurative. Earlier diagnosis and proper drainage surgery with effective antibiotics treatment are very important, and antimicrobial treatment should be more than 5 weeks. When complex pulmonary infection interferes with the CT diagnosis, clinical suspicion of lung cancer should be increased if G.adiacens or Eikenella corrodens is detected from a pulmonary infection.

Although a growing number of studies suggest interactions between Schistosoma parasites and viral infections, the effects of schistosome infections on the host response to viruses have not been evaluated comprehensively. In this systematic review, we investigated how schistosomes impact incidence, virulence, and prevention of viral infections in humans and animals. We also evaluated immune effects of schistosomes in those coinfected with viruses. We screened 4,730 studies and included 103. Schistosomes may increase susceptibility to some viruses, including HIV and Kaposi's sarcoma-associated herpesvirus, and virulence of hepatitis B and C viruses. In contrast, schistosome infection may be protective in chronic HIV, Human T-cell Lymphotropic Virus-Type 1, and respiratory viruses, though further research is needed. Schistosome infections were consistently reported to impair immune responses to hepatitis B and possibly measles vaccines. Understanding the interplay between schistosomes and viruses has ramifications for anti-viral vaccination strategies and global control of viral infections., Competing Interests: The authors have declared that no competing interests exist.

Animal and human bite injuries are a public health burden. Dog bites outnumber cat bites, but cat bites pose the greatest risk for infection. Skin and soft tissue infections are the most frequent infectious manifestations resulting from bite injury, although invasive infection may occur through direct inoculation or dissemination through the bloodstream. Although contemporary, well-designed trials are needed to inform clinical practice, preemptive antibiotic therapy after a bite injury is warranted for injuries posing high risk for infection and for patients at risk of developing severe infection; antibiotics should target aerobic and anaerobic microbes that comprise the oral and skin flora., Competing Interests: Disclosure This work was supported in part by a grant from the Agency for Healthcare Research and Quality (R01-HS024269). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Strongyloidiasis and HTLV-I (human T-lymphotropic virus-1) are important infections that are endemic in many countries around the world with an estimated 370 million infected with Strongyloides stercoralis alone, and 5-10 million with HTVL-I. Co-infections with these pathogens are associated with significant morbidity and can be fatal. HTLV-I infects T-cells thus causing dysregulation of the immune system which has been linked to dissemination and hyperinfection of S. stercoralis leading to bacterial sepsis which can result in death. Both of these pathogens are endemic in Australia primarily in remote communities in Queensland, the Northern Territory, and Western Australia. Other cases in Australia have occurred in immigrants and refugees, returned travellers, and Australian Defence Force personnel. HTLV-I infection is lifelong with no known cure. Strongyloidiasis is a long-term chronic disease that can remain latent for decades, as shown by infections diagnosed in prisoners of war from World War II and the Vietnam War testing positive decades after they returned from these conflicts. This review aims to shed light on concomitant infections of HTLV-I with S. stercoralis primarily in Australia but in the global context as well., (© 2021 Elsevier Ltd. All rights reserved.)

Background: Infection with high-risk human papillomavirus (HR-HPV) has been shown to be more prevalent and persistent in female adolescents with HIV. However, data among male adolescents with perinatally acquired HIV (PHIV) are limited., Setting: We investigated the incidence and persistence of HR-HPV in anogenital compartments and associated factors among PHIV in comparison to HIV-uninfected (HU) male adolescents in Thailand., Methods: PHIV and HU males aged 12-24 years were enrolled. At baseline and 3 subsequent annual visits, specimens from the scrotum, penis, and anal area were obtained for HPV and other testing., Results: From June 2013 to October 2017, 49 PHIV and 47 HU male adolescents with a median age of 18 (interquartile range 17-20) years were enrolled. PHIV had higher incidence of any HR-HPV infection than HU adolescents {33.05 [95% confidence interval (CI): 20.82 to 52.46] vs. 15.73 [95% CI: 8.18 to 30.22] per 100 person-years, P = 0.04}. The persistence of any HR-HPV genotypes (detected at ≥2 annual visits) was not different by group (PHIV 27% vs. HU 23%, P = 0.75). Having ≥3 sex partners in past 6 months (adjusted prevalence ratio 2.39, 95% CI: 1.14 to 5.05; P = 0.02) and co-infection with other sexually transmitted infections (syphilis, chlamydia, and/or gonorrhea) were associated with persistent HR-HPV infection (adjusted prevalence ratio 6.21, 95% CI: 2.87 to 13.41; P < 0.001)., Conclusions: Thai PHIV male adolescents had a higher incidence of HR-HPV infection than those without HIV. Having multiple sex partners and co-infection with sexually transmitted infections was associated with persistent HR-HPV infection. These data demonstrate the need to prioritize PHIV male adolescents in routine and catch-up HPV vaccination programs.

Mesenchymal stromal cells (MSCs) have a multimodal, immunomodulatory mechanism of action and are now in clinical trials for single organ and systemic sepsis. However, a number of practicalities around source, homogeneity and therapeutic window remain to be determined. Here, we utilised conditioned medium from CD362 + -sorted umbilical cord-human MSCs (UC-hMSCs) for a series of in vitro anti-inflammatory assays and the cryopreserved MSCs themselves in a severe (Series 1) or moderate (Series 2+3) caecal ligation and puncture (CLP) rodent model. Surviving animals were assessed at 48 h post injury induction. MSCs improved human lung, colonic and kidney epithelial cell survival following cytokine activation. In severe systemic sepsis, MSCs administered at 30 min enhanced survival (Series 1), and reduced organ bacterial load. In moderate systemic sepsis (Series 2), MSCs were ineffective when delivered immediately or 24 h later. Of importance, MSCs delivered 4 h post induction of moderate sepsis (Series 3) were effective, improving serum lactate, enhancing bacterial clearance from tissues, reducing pro-inflammatory cytokine concentrations and increasing antimicrobial peptides in serum. While demonstrating benefit and immunomodulation in systemic sepsis, therapeutic efficacy may be limited to a specific point of disease onset, and repeat dosing, MSC enhancement or other contingencies may be necessary.

In COVID-19, respiratory infection with SARS-CoV-2 plus another virus (viral co-infection) or with SARS-CoV-2 plus a bacterial pathogen (combined viral and bacterial pneumonia) has been described. Secondary bacterial pneumonia can follow the initial phase of viral respiratory infection or occur during the recovery phase. No obvious pattern or guidelines exist for viral co-infection, combined viral and bacterial pneumonia, or secondary bacterial pneumonia in COVID-19. Based on existing clinical data and experience with similar viruses such as influenza and SARS-CoV, the management approach in COVID-19 should, ideally, take into consideration the overall presentation and the trajectory of illness., (Copyright © 2020 The Cleveland Clinic Foundation. All Rights Reserved.)

Globally, it is estimated that of the 36.7 million people infected with human immunodeficiency virus (HIV), 6.3% are coinfected with hepatitis C virus (HCV). Coinfection with HIV reduces the chance of HCV spontaneous clearance. In this work, we formulated and analysed a deterministic model to study the HIV and HCV coinfection dynamics in absence of therapy. Due to chronic stage of HCV infection being long, asymptomatic, and infectious, our model formulation was based on the splitting of the chronic stage into the following: before onset of cirrhosis and its complications and after onset of cirrhosis. We computed the basic reproduction numbers using the next generation matrix method. We performed numerical simulations to support the analytical results. We carried out sensitivity analysis to determine the relative importance of the different parameters influencing the HIV-HCV coinfection dynamics. The findings reveal that, in the long run, there is a substantial number of individuals coinfected with HIV and latent HCV. Therefore, HIV and latently HCV-infected individuals need to seek early treatment so as to slow down the progression of HIV to AIDS and latent HCV to advanced HCV., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Edison Mayanja et al.)

The aim of the present study was to identify the clinical efficacy of glucocorticoid therapy on the treatment of patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Clinical and laboratory parameters were collected from 308 patients with COVID-19 pneumonia from the fever clinic of Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between January 14, 2020 and February 9, 2020, of which 216 patients received low-dose (equivalent of methylprednisolone 0.75-1.5 mg/kg/d) glucocorticoid treatment. The effect of glucocorticoid on imaging progress, adverse events, nucleic acid results and the outcomes were investigated. Lymphocyte count and C-reactive protein (CRP) significantly differed between the glucocorticoid therapy and non-glucocorticoid therapy groups. Compared with the non-glucocorticoid therapy group, glucocorticoid therapy did not significantly influence the clinical course of COVID-19 pneumonia, including imaging progress and the time duration for negative transformation of nucleic acid. Glucocorticoid therapy did not significantly influence the outcomes nor the adverse events of COVID-19 pneumonia. For the treatment of COVID-19 pneumonia, systemic and in-depth investigation is needed to determine the timing and dosage of glucocorticoids needed to inhibit overwhelming inflammatory response and not the protective immune response to COVID-19 pneumonia., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background and Objective: The spread of an infection from the paranasal sinuses is rare but severe. Between 4% and 20% of all rhinosinusitis can become complicated, orbital involvement being the most frequent (60-75%). Orbital complications are more common in children but more severe in adults. We aim to analyse the epidemiological characteristics of these patients and to propose a management algorithm., Materials and Methods: We carried out a retrospective review of 21 patients with orbital complications of acute rhinosinusitis diagnosed in the same institution from 2005 to 2018. The diagnosis was based on clinical history, endoscopic examination and imaging tests. All patients received an intravenous antibiotic and were assessed by ophthalmology. An immediate surgical treatment was performed in the case of an abscess or poor response to medical management., Results: The average age was 24 years. Fifty-two percent were males and 48% females. According to Chandler's classification, 43% (9/21) had preseptal cellulitis (7 adults and 2 children), 10% (2/21) orbital cellulitis (one adult and one child), 43% (9/21) subperiosteal abscess (2 adults and 7 children), there was one case of orbital abscess in an adult and there were no cases of cavernous sinus thrombosis. A CT scan was performed in all patients and the cases of subperiosteal or orbital abscess were treated surgically, except 2 paediatric patients (<4 years) with a small and medial subperiosteal abscess (<4mm) who responded well to medical treatment. The surgical approach is performed by endonasal endoscopy, perforating the lamina papyracea in cases of subperiosteal abscess and also opening the periorbita in orbital abscess. It was combined with an external palpebral approach in the 4 cases that presented a superior or lateral abscess. Two young adults (10%) presented an intracranial complication concomitantly., Conclusion: Orbital complications of acute rhinosinusitis are rare but potentially severe. It is important to be aware of and suspect them in order to act quickly. It is essential to define the location and extension of the infection for correct management, as well as multidisciplinary treatment. The surgical approach is performed by endonasal endoscopy. It is limited by abscesses located on the roof of the orbit or on the lateral wall, when a combined external palpebral approach is required., (Copyright © 2020 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

Acute influenza virus infections are a global public health concern accounting for millions of illnesses worldwide ranging from mild to severe with, at time, severe complications. Once an individual is infected, the immune system is triggered in response to the pathogen. This immune response can be beneficial ultimately leading to the clearance of the viral infection and establishment of immune memory mechanisms. However, it can be detrimental by increasing susceptibility to secondary bacterial infections and resulting in permanent changes to the lung architecture, in the form of fibrotic sequelae. Here, we review influenza associated bacterial super-infection, the formation of T-cell memory, and persistent lung injury resulting from influenza infection., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Co-infections commonly arise when two or multiple different pathogens infect the same host, either as simultaneous or as secondary concurrent infection. This potentiates their pathogenic effects and leads to serious negative consequences on the exposed host. Numerous studies on the occurrence of the bacterial, parasitic, fungal and viral co-infections were conducted in various tilapia species. Co-infections have been associated with serious negative impacts on susceptible fish because they increase the fish susceptibility to diseases and the likelihood of outbreaks in the affected fish. Co-infections can alter the disease course and increase the severity of disease through synergistic and, more rarely, antagonistic interactions. In this review, reports on the synergistic co-infections and their impacts on the affected tilapia species are highlighted. Additionally, their pathogenic mechanisms are briefly discussed. Tilapia producers should be aware of the possible occurrence of co-infections and their effects on the affected tilapia species and in particular of the clinical signs and course of the disease. To date, there is still limited information regarding the pathogenicity mechanisms and pathogen interactions during these co-infections. This is generally due to low awareness regarding co-infections, and in many cases, a dominant pathogen is perceived to be of vital importance and hence becomes the target of treatment while the treatment of the co-infectious agents is neglected. This review article aimed at raising awareness regarding co-infections and helping researchers and fish health specialists pay greater attention to these natural cases, leading to increased research and more consistent diagnosis of co-infectious outbreaks in order to improve control strategies to protect tilapia when infected with multiple pathogens., (© 2020 John Wiley & Sons Ltd.)

This study aims to identify the pathogens of diarrhea in Vientiane Capital, Lao People's Democratic Republic (Lao PDR). The data of 2482 patients who visited eight health facilities due to diarrhea in 2012-2015 were retrospectively reviewed. Stool or rectal swabs collected from all patients were tested for bacteria. Children who were under 5 years old were additionally tested for rotavirus. Of 2482 cases, 1566 cases were under 5 years old, and at least one enteropathogen was detected in 475 cases (19.1%). Salmonella species was the most commonly detected bacterial pathogen. Enteropathogenic Escherichia coli (EPEC) and Salmonella species was the major pathogen in the dry season and the wet season, respectively. Eighty-seven patients tested positive for multiple bacteria. Rotavirus was detected in 291 children under 5 years old (32.4%), mostly from October to April. The major bacteria of coinfection with rotavirus were EPEC followed by Salmonella species. Salmonella species was the predominant bacterial pathogen of diarrhea of all ages, and rotavirus was the predominant pathogen among children under 5 years old. Further studies examining other types of pathogens for diarrhea and the introduction of a rotavirus vaccine for children are needed in Lao PDR.

Objectives: Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) cause the majority of non-gonococcal urethritis (NGU). The role of Ureaplasma urealyticum (UU) in NGU is unclear. Prior case-control studies that examined the association of UU and NGU may have been confounded by mixed infections and less stringent criteria for controls. The objective of this case-control study was to determine the prevalence and aetiology of mixed infections in men and assess if UU monoinfection is associated with NGU., Methods: We identified 155 men with NGU and 103 controls. Behavioural and clinical information was obtained and men were tested for Neisseria gonorrhoeae and CT, MG, UU and Trichomonas vaginalis (TV). Men who were five-pathogen negative were classified as idiopathic urethritis (IU)., Results: Twelve per cent of NGU cases in which a pathogen was identified had mixed infections, mostly UU coinfections with MG or CT; 27% had IU. In monoinfected NGU cases, 34% had CT, 17% had MG, 11% had UU and 2% had TV. In controls, pathogens were rarely identified, except for UU, which was present in 20%. Comparing cases and controls, NGU was associated with CT and MG monoinfections and mixed infections. UU monoinfection was not associated with NGU and was almost twice as prevalent in controls. Men in both the case and control groups who were younger and who reported no prior NGU diagnosis were more likely to have UU (OR 0.97 per year of age, 95% CI 0.94 to 0.998 and OR 6.3, 95% CI 1.4 to 28.5, respectively)., Conclusions: Mixed infections are common in men with NGU and most of these are UU coinfections with other pathogens that are well-established causes of NGU. UU monoinfections are not associated with NGU and are common in younger men and men who have never previously had NGU. Almost half of NGU cases are idiopathic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Effective combination antiretroviral therapy (cART) has tremendously reduced HIV-associated morbidity, mortality and mother-to-child transmission. However, the benefits of cART are threatened by comorbidities, adverse drug reactions and virus resistance to existing treatment regimens. One of the most occurring comorbidities is cytomegalovirus (CMV) infection., Objectives: To investigate the effects of cART on the occurrence of CMV infection among pregnant women., Methods: Using a cross-sectional study design, 175 HIV-infected pregnant women were recruited, and data were obtained from their clinical records. Blood samples were collected for host DNA, CMV DNA and plasma efavirenz (EFV) measurement. CMV DNA was measured using real-time polymerase chain reaction (PCR). CYP2B6 c.516G&gt;T and CYP2B6 c.983T&gt;C single nucleotide polymorphisms were characterised using PCR/restriction fragment length polymorphism and TaqMan assays, respectively. Plasma EFV concentrations were determined using high-performance liquid chromatography., Results: There was an inverse association between plasma EFV concentration and CMV DNA. Participants with lower plasma EFV concentrations were significantly (p&lt;0.001) more likely to be CMV DNA positive than those with higher plasma concentrations. This result is also supported by the observation that carriers of CYP2B6 poor-metaboliser genotypes (CYP2B6 c.516T/T and CYP2B6 c.983T/C) were less likely to be positive for CMV DNA. Furthermore, poor metabolism as denoted by CYP2B6 c.516T/T and CYP2B6 c.983T/C genotypes was significantly associated with lower CMV viral load., Conclusions: HIV treatment disrupts the balance between host and co-infecting microbes. Reduced or subtherapeutic levels of antiretroviral drugs, which could be exacerbated by genetic polymorphisms in drug metabolism genes and non-adherence, predispose infected individuals to an increased risk of CMV infection in pregnancy.

Introduction: More than 1200 different types of microbes were found in the human mouth, only some of these microorganisms were associated with intracranial bacterial infection. However, there are limited data available about the Pseudoramibacter alactolyticus (P alactolyticus) or Mycobacterium tuberculosis (MTB) intracranial infections oral origin., Patient Concerns: Here, we reported a rarely case with P alactolyticus and MTB coinfection in central nervous after dental extraction. The 44-year-old man presented with progressive headache over the last 2 weeks and a sustained fever >39°C, with a dental extraction performed 2 days before the onset of headache., Diagnosis: P alactolyticus and MTB were confirmed by real-time polymerase chain reaction targeting the16S ribosomal RNA gene. The presence of MTB was also demonstrated by positive acid-fast staining of the purulent discharge., Interventions: The patient was treated by metronidazole and anti-TB treatment OUTCOMES:: The patient fully recovered without sequela., Conclusion: In conclusion there should be awareness of the possibility of P alactolyticus or MTB intracranial infections following tooth extraction.

Background: Viral bronchiolitis is the most common cause of respiratory failure requiring invasive ventilation in young children. Bacterial co-infections may complicate and prolong paediatric intensive care unit (PICU) stay. Data on prevalence, type of pathogens and its association with disease severity are limited though. These data are especially important as bacterial co-infections may be treated using antibiotics and could reduce disease severity and duration of PICU stay. We investigated prevalence of bacterial co-infection and its association with disease severity and PICU stay., Methods: Retrospective cohort study of the prevalence and type of bacterial co-infections in ventilated children performed in a 14-bed tertiary care PICU in The Netherlands. Children less than 2 years of age admitted between December 2006 and November 2014 with a diagnosis of bronchiolitis and requiring invasive mechanical ventilation were included. Tracheal aspirates (TA) and broncho-alveolar lavages (BAL) were cultured and scored based on the quantity of bacteria colony forming units (CFU) as: co-infection (TA > 10 ^5 /BAL > 10 ^4 CFU), low bacterial growth (TA < 10 ^5 /BAL < 10 ^4 CFU), or negative (no growth). Duration of mechanical ventilation and PICU stay were collected using medical records and compared against the presence of co-infection using univariate and multivariate analysis., Results: Of 167 included children 63 (37.7%) had a bacterial co-infection and 67 (40.1%) low bacterial growth. Co-infections occurred within 48 h from intubation in 52 out 63 (82.5%) co-infections. H.influenza (40.0%), S.pneumoniae (27.1%), M.catarrhalis (22.4%), and S.aureus (7.1%) were the most common pathogens. PICU stay and mechanical ventilation lasted longer in children with co-infections than children with negative cultures (9.1 vs 7.7 days, p = 0.04 and 8.1vs 6.5 days, p = 0.02)., Conclusions: In this large study, bacterial co-infections occurred in more than a third of children requiring invasive ventilation for bronchiolitis and were associated with longer PICU stay and mechanical ventilation. These findings support a clinical trial of antibiotics to test whether antibiotics can reduce duration of PICU stay.

Background: Scabies is a WHO neglected tropical disease common in children in low- and middle-income countries. Excoriation of scabies lesions can lead to secondary pyoderma infection, most commonly by Staphyloccocus aureus and Streptococcus pyogenes (group A streptococcus, GAS), with the latter linked to acute post-streptococcal glomerulonephritis (APSGN) and potentially rheumatic heart disease (RHD). There is a paucity of data on the prevalence of these skin infections and their bacterial aetiology from Africa., Methodology/principal Findings: A cross-sectional study, conducted over a four-month period that included the dry and rainy season, was conducted to determine the prevalence of common skin infections in Sukuta, a peri-urban settlement in western Gambia, in children <5 years. Swabs from pyoderma lesions were cultured for S. aureus and GAS. Of 1441 children examined, 15.9% had scabies (95% CI 12.2-20.4), 17.4% had pyoderma (95% CI 10.4-27.7) and 9.7% had fungal infections (95% CI 6.6-14.0). Scabies was significantly associated with pyoderma (aOR 2.74, 95% CI 1.61-4.67). Of 250 pyoderma swabs, 80.8% were culture-positive for S. aureus, and 50.8% for GAS. Participants examined after the first rains were significantly more likely to have pyoderma than those examined before (aRR 2.42, 95% CI 1.38-4.23), whereas no difference in scabies prevalence was seen (aRR 1.08, 95% CI 0.70-1.67). Swab positivity was not affected by the season., Conclusions/significance: High prevalence of scabies and pyoderma were observed. Pyoderma increased significantly during the rainy season. Given the high prevalence of GAS pyoderma among children, further research on the association with RHD in West Africa is warranted., Competing Interests: The authors have declared that no competing interests exist.

Background: Rotavirus vaccine efficacy (VE) estimates in low-resource settings are lower than in developed countries. We detected coinfections in cases of severe rotavirus diarrhea in a rotavirus VE trial to determine whether these negatively impacted rotavirus VE estimates., Methods: We performed TaqMan Array Card assays for enteropathogens on stools from rotavirus enzyme immunoassay-positive diarrhea episodes and all severe episodes (Vesikari score ≥11), from a phase 3 VE trial of Rotavac, a monovalent human-bovine (116E) rotavirus vaccine, carried out across 3 sites in India. We estimated pathogen-specific etiologies of diarrhea, described associated clinical characteristics, and estimated the impact of coinfections on rotavirus VE using a test-negative design., Results: A total of 1507 specimens from 1169 infants were tested for the presence of coinfections. Rotavirus was the leading cause of severe diarrhea even among vaccinated children, followed by adenovirus 40/41, Shigella/enteroinvasive Escherichia coli, norovirus GII, sapovirus, and Cryptosporidium species. Bacterial coinfections in rotavirus-positive diarrhea were associated with a longer duration of diarrhea and protozoal coinfections with increased odds of hospitalization. Using the test-negative design, rotavirus VE against severe rotavirus gastroenteritis increased from 49.3% to 60.6% in the absence of coinfections (difference, 11.3%; 95% confidence interval, -10.3% to 30.2%)., Conclusions: While rotavirus was the dominant etiology of severe diarrhea even in vaccinated children, a broad range of other etiologies was identified. Accounting for coinfections led to an 11.3% increase in the VE estimate. Although not statistically significant, an 11.3% decrease in VE due to presence of coinfections would explain an important fraction of the low rotavirus VE in this setting., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)

We evaluated the association between human pegivirus-2 (HPgV-2) infection and hepatitis C virus (HCV)/hepatitis B virus (HBV) co-infection in 745 plasma samples collected from HCV-positive but human immunodeficiency virus type one (HIV-1)-negative people who inject drugs in Hunan, China. The prevalence of anti-HPgV-2 was 4.43  % (33/745) and, within this, the HCV 6a genotype showed significantly higher prevalence as compared with the HCV non-6a genotypes, 6.29  % (18/286) vs. 1.69  % (4/236), respectively (P=0.009). HPgV-2 RNA was detected in 2.15  % (16/745), and was not significantly different between the HCV 6a and non-6a genotypes, 2.45  % (7/286) vs. 2.54  % (6/236), respectively (P =0.945). HBV single infection did not increase the risk of HPgV-2 infection. Compared with HCV single infection, HCV/HBV co-infection increased the risk of HPgV-2 infection by about three-fold: odds ratio (OR)=3.24 [95  % confidence interval (CI) 1.34-7.82, P=0.014] according to anti-HPgV-2 positivity or OR=3.51 (95  % CI 1.15-10.74, P=0.051) according to HPgV-2 viraemia. HPgV-2 infection did not increase the levels of liver-specific enzymes. Our study provides new findings regarding the association between HPgV-2 and HCV genotypes as well as HCV/HBV co-infection.

Secondary bacterial infections following Viperidae snakebite envenomation in children are common. Among 75 patients admitted because of snakebites at the only pediatric hospital in Costa Rica, 16 (21.3%) had a culture-confirmed secondary bacterial infection. Morganella morganii (37.5%), Aeromonas hydrophila (31.2%), and Providencia rettgeri (18.7%) were the most common pathogens. Empiric prophylaxis is still recommended and should be based on local etiological agents and antimicrobial susceptibilities.

Enteric disease in pigs is usually of multifactorial etiology, including infectious and non-infectious factors. In many cases of endemic diarrhea in weaner-to-finisher pigs, the combination of 2 or more microorganisms leads to aggravation of intestinal lesions and, consequently, clinical signs. We autopsied a 4-mo-old fattening pig with diarrhea and diagnosed severe fibrinonecrotizing typhlocolitis. Numerous spiral-shaped bacteria and amoeba-like PAS-positive protozoa were observed in the cecal and colonic mucosa and submucosa. Brachyspira hyodysenteriae was detected by PCR from colonic content. By in situ hybridization, large numbers of Entamoeba polecki were found within the lamina propria and submucosa; moderate numbers of Blastocystis sp. and scattered trichomonads were present in intestinal content. In addition, Entamoeba polecki, Balantidium spp., Blastocystis sp., and Trichomonas sp. were also detected by PCR.

Chikungunya virus (CHIKV) infection is spatiotemporally related to dengue virus (DENV) infection and mostly undiagnosed due to similar primary symptoms. In 2013, a high rate (36%) of coinfection of DENV and CHIKV was reported in Odisha. Hence, the hospital-based study was continued to synthesis current epidemiological understanding of their single distribution or coinfection. Suspected DENV patients serum samples were tested for DENV and CHIKV by serology and reverse-transcription polymerase chain reaction. The positive samples were used for analysis of mutation, selection pressure, and phylogenetic relationship. Clinical information was also analyzed. Among 648 (2015 and 2016) suspected DENV patients, 141 (21.7%) were positive for DENV (serotypes 1-3), 22 (3.4%) were positive for CHIKV (ECSA) and 4 (2.8%) were coinfected with both. Sequence analysis showed four consistent mutations (M104V, V112A, K166N, and F169L) in CprM gene of DENV 2 and two consistent mutations (M269V, D284E) in E1 gene of CHIKV. Interestingly, the CHIKV- E1 A226V mutation was absent in the studied population. It was also noticed that the peak incidence of both the infections occurs in August-September in 2015-16. Moreover, Plasmodium species, Salmonella typhi, and Rickettsial typhi infections were also observed in DENV patients. Different etiology was also detected in other undifferentiated fever patients as mixed infections (malaria, S. typhi, and R. typhi ). Hence, this investigation shows the significant reduction of DENV-CHIKV coinfection as compared with previous report, the burden of arboviruses and acute undifferentiated fever in Odisha in 2015-2016, highlighting the importance of epidemiological picture of febrile patients for appropriate patient management., (© 2018 Wiley Periodicals, Inc.)

Background: Visceral leishmaniasis (VL) is becoming endemic in São Paulo state, in the southeastern region of Brazil. Unusual manifestations with non-specific signs and symptoms may make diagnosis difficult and delay treatment, increasing the risk of severity and death, particularly in new endemic areas. There are few studies on patients with these characteristics in Brazil. We describe a case series of unusual manifestations of VL in children and its spatial dispersion in the western region of São Paulo state., Cases Presentation: From 2009 to 2014, five clinical cases involving children treated in the Regional Hospital of Presidente Prudente (RH) were selected. Two patients had multiple relapses requiring liposomal amphotericin B; one patient had VL-cytomegalovirus-dengue co-infection and liver injury; one patient was diagnosed with X-linked agammaglobulinemia, a primary immunodeficiency; and one patient was diagnosed with VL-human immunodeficiency virus/acquired immunodeficiency syndrome (VL-HIV/AIDS) co-infection. Primary or secondary immunodeficiencies were found in four children, and associated viral infections were found in three children. Three patients were referred from other hospitals to RH. With regard to the geographic spread of VL, more cases were found in the northern area, in the epicenter of the infection where the first cases were registered, flowing south; a spatial-temporal occurrence was found., Conclusions: Primary and secondary immunodeficiencies and viral co-infectious should be considered among unusual manifestations of VL, especially in those with multiple relapses. Spatial-temporal occurrence was found. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices to stem the tide of the epidemic.

Background: Treponema pallidum subsp pertenue and Haemophilus ducreyi are causative agents of cutaneous ulcer (CU) in yaws-endemic regions in the tropics. However, a significant proportion of CU patients remain polymerase chain reaction (PCR) negative for both bacterial agents. We aimed to identify potential additional etiological agents of CU in a yaws-endemic region., Methods: This population-based cohort study included children in Lihir Island (Papua New Guinea) examined during a yaws eradication campaign in October 2013-October 2014. All consenting patients with atraumatic exudative ulcers of >1 cm diameter were enrolled. Lesional swabs were collected for real-time PCR testing for T. pallidum subsp pertenue and H. ducreyi. We then performed shotgun whole DNA metagenomics sequencing on extracted DNA and taxonomically assigned shotgun sequences using a human microbiome reference., Results: Sequence data were available for 122 samples. Shotgun sequencing showed high classification agreement relative to PCR testing (area under the curve for T. pallidum/H. ducreyi was 0.92/0.85, respectively). Clustering analysis of shotgun data revealed compositional clusters where the dominant species (median relative abundance ranged from 32% to 66%) was H. ducreyi (23% of specimens), T. pallidum subsp pertenue (16%), Streptococcus dysgalactiae (12%), Arcanobacterium haemolyticum (8%), and Corynebacterium diphtheriae (8%). Sample clustering derived from ulcer microbial composition did not show geographical patterns., Conclusions: These data suggest a diverse etiology of skin ulcers in yaws-endemic areas, which may help design more accurate diagnostic tools and more effective antimicrobial treatment approaches to the cutaneous ulcer syndrome.

The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients' information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts &lt;50 cells/μl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916-21.215, P = 0.003), CD4 counts 50-199 cells/μl (OR: 6.303, 95% CI = 1.874-21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349-5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147-15.299, P &lt; 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.

Opportunistic infections (OIs) are a significant cause of morbidity and mortality in immunosuppressed patients and may be due to bacteria, virus, protozoa, or fungi. Toxoplasmosis is a common cause of central nervous system infection in human immunodeficiency virus (HIV) patients. Coccidioidomycosis is a relatively common fungal infection that may lead to disseminated disease and fungemia in immune-compromised hosts living in endemic regions. This single-patient case report documents the presentation, diagnosis, management, and outcome of concomitant central nervous system toxoplasmosis and diffuse miliary pneumonia with fungemia due to disseminated seronegative Coccidioides immitis in a 33-year-old male patient recently diagnosed with chronic advanced HIV. Impaired cellular immune function, such as defects in the IL-12/IFN-γ pathway or T-helper IL-17-mediated response, is associated with increased severity of coccidioidomycosis. Fungemia and acute respiratory distress syndrome are both associated with very high mortality in coccidioidomycosis. In HIV hosts, negative Coccidioides serology can be seen in up to 25% of cases and therefore other diagnostic modalities should be initiated promptly and simultaneously. This case demonstrates simultaneous OI in the setting of advanced acquired immune deficiency syndrome and emphasizes the need for early diagnosis of HIV and OI in order to ensure prompt initiation of antiretroviral therapy, prophylactic, and therapeutic medications.

Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function ("dysbiosis") in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections.

Background: Dengue fever is a mosquito-borne viral disease with a very high incidence in Southeast Asia. Most patients with dengue fever recover following a self-limiting febrile illness, while a small proportion may progress to develop severe disease with complications such as acute liver failure, acute kidney injury, and multiorgan failure. Secondary bacterial infections and thrombotic events are very rare., Case Presentation: A 38-year-old previously healthy Sri Lankan woman from Colombo, Sri Lanka, presented with dengue shock syndrome leading to acute liver failure and kidney injury. She was managed with intravenously administered fluid resuscitation with close monitoring of her hemodynamic status, and hemodialysis. Her renal and liver functions and platelet count improved gradually, but the fever persisted and there was a neutrophil leukocytosis. A clinical examination and investigations to identify a focus of secondary infection revealed staphylococcal infective endocarditis. She was started on intravenously administered vancomycin, but as the response was poor the antibiotic was changed to intravenously administered linezolid, to which the response was good. She also developed right proximal femoral deep vein thrombosis, and was commenced on subcutaneous enoxaparin and warfarin. Enoxaparin was stopped after her international normalized ratio reached the desirable range, and warfarin was continued for 3 months., Conclusions: Dengue virus is known to cause endothelial dysfunction that allows bacteria to invade tissues, defective functioning and reduction in the number of cells of the immune system, and alteration of cytokines leading to immune dysregulation, predisposing patients to develop secondary bacterial infections. Evidently, patients with dengue fever who have prolonged fever (more than 5 days) and acute kidney injury are at high risk for concurrent bacteremia. Dengue virus interferes with the components of the anti-clotting pathway, such as thrombomodulin-thrombin-protein C complex. It also activates endothelial cells and increases the expression of procoagulant factors. These factors may predispose patients with dengue viral infections to develop thrombotic complications. Therefore it is important to be aware of the possibility of serious secondary bacterial infections occurring following dengue viral infections, especially in patients with prolonged fever and acute kidney injury, and to keep in mind that thrombotic events may occur as complications of dengue viral infections.

Background: The causes of acute febrile illness (AFI) in Latin America are diverse and their complexity increases as the proportion of fever due to malaria decreases, as malaria control measures and new pathogens emerge in the region. In this context, it is important to shed light on the gaps in the epidemiological characteristics and the geographic range for many AFI aetiologies., Objectives: To review studies on community-acquired fever aetiology other than malaria in Latin America, and to highlight knowledge gaps and challenges needing further investigation., Sources: PubMed from 2012 to April 2018., Content: We found 17 eligible studies describing 13 539 patients. The median number of pathogens tested per individual was 3.5 (range 2-17). A causative pathogen could be determined for 6661 (49.2%) individuals. The most frequently reported pathogen during the study periods was dengue virus (DENV) (14 studies), followed by chikungunya virus (nine studies) and Zika virus (seven studies). Among the studies reporting concurrent infections, 296 individuals (2.2%) were found to have co-infections. In-hospital mortality was reported in eight (47%) studies, ranging between 0% and 18%., Implications: DENV fever is the febrile illness most frequently reported, reflecting its importance, while chikungunya and zika viruses present increasing trends since their emergence in the region. Studies with systematic and harmonized approaches for detection of multiple pathogens are needed and would probably reveal a higher burden of neglected pathogens such as Rickettsia spp. and arenaviruses. The lack of point-of-care tests and harmonized approach limits the care provided by health professionals and the efficacy of surveillance for AFI in the region., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: We aimed to assess the effects of amoxicillin treatment in adult patients presenting to primary care with a lower respiratory tract infection (LRTI) who were infected with a potential bacterial, viral, or mixed bacterial/viral infection., Methods: This multicentre randomized controlled trial focused on adults with LRTI not suspected for pneumonia. Patients were randomized to receive either antibiotic (amoxicillin 1 g) or placebo three times daily for 7 consecutive days using computer-generated random numbers (follow-up 28 days). In this secondary analysis of the trial, symptom duration (primary outcome), symptom severity (scored 0-6), and illness deterioration (reconsultation with new or worsening symptoms, or hospital admission) were analysed in pre-specified subgroups using regression models. Subgroups of interest were patients with a (strictly) bacterial, (strictly) viral, or combined infection, and patients with elevated values of procalcitonin, C-reactive protein, or blood urea nitrogen., Results: 2058 patients (amoxicillin n = 1036; placebo n = 1022) were randomized. Treatment did not affect symptom duration (n = 1793). Patients from whom a bacterial pathogen only was isolated (n = 207) benefited from amoxicillin in that symptom severity (n = 804) was reduced by 0.26 points (95% CI -0.48 to -0.03). The odds of illness deterioration (n = 2024) was 0.24 (95% CI 0.11 to 0.53) times lower from treatment with amoxicillin when both a bacterial and a viral pathogen were isolated (combined infection; n = 198)., Conclusions: Amoxicillin may reduce the risk of illness deterioration in patients with a combined bacterial and viral infection. We found no clinically meaningful benefit from amoxicillin treatment in other subgroups., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine the main predictors of death in multidrug-resistant (MDRTB) patients from Brazil., Design: Retrospective cohort study, a survival analysis of patients treated between 2005 and 2012., Results: Of 3802 individuals included in study, 64.7% were men, mean age was 39 (1-93) years, and 70.3% had bilateral pulmonary disease. Prevalence of human immunodeficiency virus (HIV) was 8.3%. There were 479 (12.6%) deaths. Median survival time was 1452 days (4 years). Factors associated with increased risk of death were age greater than or equal to 60 years (hazard rate [HR] = 1.6, confidence interval [CI] = 1.15-2.2), HIV co-infection (HR = 1.46; CI = 1.05-1.96), XDR resistance pattern (HR = 1.74, CI = 1.05-2.9), beginning of treatment after failure (HR = 1.72, CI = 1.27-2.32), drug abuse (HR = 1.64, CI = 1.22-2.2), resistance to ethambutol (HR = 1.30, CI = 1.06-1.6) or streptomycin (HR = 1.24, CI = 1.01-1.51). Mainly protective factors were presence of only pulmonary disease (HR = 0.57, CI = 0.35-0.92), moxifloxacin use (HR = 0.44, CI = 0.25-0.80), and levofloxacin use (HR = 0.75; CI = 0.60-0.94)., Conclusion: A more comprehensive approach is needed to manage MDRTB, addressing early diagnostic, improving adhesion, and comorbidities, mainly HIV infection and drug abuse. The latest generation quinolones have an important effect in improving survival in MDRTB., (Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance., Methods: We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics., Results: A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings., Conclusions: Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.