Rapid Infectious Diseases Diagnostics in the Critical Care Unit
Cheston B. Cunha, Burke A. Cunha in Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
Identification of a respiratory virus as a cause of illness has significant implications for patient management. However, it is impossible for clinicians to differentiate between bacterial and viral LRTIs based on signs and symptoms alone. Although the presence of lobar consolidation on a chest radiograph is suggestive of bacterial pneumonia, interstitial infiltrates can be more difficult to interpret and may be present in a variety of viral and non-infectious diseases. Additionally, coinfection with bacterial and viral pathogens is possible. NAATs have revolutionized the diagnosis of respiratory viral illnesses, owing to their speed and high-level sensitivity and specificity. NAAT is now preferred to rapid viral antigen testing, direct fluorescent antibody staining, and viral culture for critically ill adult patients with suspected pneumonia.
Viral-Induced Asthma and Chronic Obstructive Pulmonary Disease
Sunit K. Singh in Human Respiratory Viral Infections, 2014
It is increasingly realized that viral and bacterial coinfection could be an important causative factor in exacerbations. Interaction between influenza and bacterial infection is known to promote the development of pneumonia40 and patients with asthma have a known risk of developing invasive pneumonia. Further, individuals with COPD co-infected with RV and Haemophilus influenzae have exhibited increased severity of exacerbations compared to those without coinfection.41,42 Johnston and colleagues recently demonstrated that experimental inoculation–infection with RV in COPD was followed by secondary bacterial infection in more than half of the inoculated patients.43 Thus, both influenza and RV infection may impede bacterial host defense mechanisms and increase the risk of exacerbations as well as secondary pneumonia. The potential importance of coinfection is reflected by increasing number of research approaches in the field with revelation of intriguing molecular mechanisms and clinical observations. For example, experimental data have identified a potential role of the transcription factor IRF3 in reduced antibacterial defense evoked by viral infection. Thus, inducement of IRF3 by dsRNA, produced by viral infection and acting on cytoplasmic RIG-I-like receptors, reduced toll-like receptor (TLR)-mediated antibacterial defense by the suppression of the expression of IL-12 and IL-23.44 This finding increases the interest in the pharmacology of IRF3 inhibition.45
Herpes Simplex Virus Infections in Immunocompromised Patients
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
The great majority of the cases of encephalitis occur in concomitance with CMV encephalitis, which also involves preferentially the periventricular areas. In a postmortem study of 82 cases of CMV encephalitis, 16% of these were actually found to be mixed HSV and CMV encephalitis (106). These mixed forms are not distinguishable from pure CMV encephalitis, both histologically and clinically. Histopathological examination shows necrotic lesions in the periventricular areas and, occasionally, foci of necrosis deep in the brain parenchyma. Inclusion-bearing cells are always present within or peripheral to the lesions, although cannot be attributed to either virus. The diagnosis of coinfection is usually established by immunocytochemistry (Fig. 2). The relative contribution of either virus to the clinical picture is not clear, although immunohistochemical studies show a greater or equal prevalence of CMV-positive cells compared to HSV-positive cells (106,109).
The management of Babesia, amoeba and other zoonotic diseases provoked by protozoa
Published in Expert Opinion on Therapeutic Patents, 2023
Clemente Capasso, Claudiu T. Supuran
Utilizing mouse models of infection that produce pathological symptoms similar to those seen in human babesiosis is an opportunity to examine the effects of coinfection on the host. Acute phase control of this parasite in humans has been linked to innate immune responses mediated by macrophages and natural killer (NK) cells, which presumably benefited from the generation of IL-2, IL-12, TNF-, and IFN- by these cells [34]. Mouse models of coinfection, which may be easily studied in the lab, can shed light on the pathogenic processes and host immune responses during simultaneous or consecutive infections with pathogens. The capacity to manipulate infectious dosages, infection timing, and host and pathogen genotypes offer a rare window of opportunity to gain insights applicable to human diseases [34]. Considering this aspect, the evaluation of drugs, such as atovaquone, azithromycin, clindamycin, and quinine, in animal models of babesiosis has raised concerns about their efficacy in achieving parasite elimination [16]. In 2016, it was demonstrated the potency of ELQ-271 and ELQ-316 in the short-term ex vivo culture system of B. microti as well as in the in vivo SCID (Severe Combined Immunodeficiency) model of B. microti infection. In B. microti-infected mice, a seven-day oral administration of 10 mg/kg of ELQ-271 or ELQ-316 resulted in clearance of parasitemia, followed by recrudescence by day 12 post-drug removal [16].
Case report: nanopore targeted sequencing in the diagnosis of invasive pulmonary Aspergillus infection in a patient with acute promyelocytic leukemia
Published in Hematology, 2023
Qiuxia Huang, Yaohui Wu, Xuan Lu, Linghui Xia
In the present case, we first suspected bacterial and fungal coinfection; however, the corresponding treatment was not effective. The NTS of blood samples detected Aspergillus flavus and several other pathogens, and that of pleural effusion samples confirmed this infection. The patient's symptoms improved after adjusting the antifungal regimen. Ten days thereafter, the patient presented with new-onset fever and dyspnea, and CT scan findings showed increased levels of pleural fluid. However, the second pleural effusion NTS presented no evidence of Aspergillus flavus. Adjustments to the antibacterial regimen improved the patient’s symptoms. Clinical practice guidelines suggest voriconazole as the primary treatment for most IPA cases [1]. However, voriconazole showed poor efficacy in the present case. Finally, we combined micafungin and amphotericin B to achieve a better therapeutic effect [13,19].
Novel therapeutic approaches for targeting TB and HIV reservoirs prevailing in lungs
Published in Expert Opinion on Drug Delivery, 2019
Mrunal Jadhav, Tabassum Khan, Chintan Bhavsar, Munira Momin, Abdelwahab Omri
Tuberculosis is one of the leading causes of mortality in HIV positive people. The replication rate of HIV is higher in HIV-TB coinfection with higher viral and bacterial load in the lungs. The therapeutic regimen available for treatment of coinfection suffers from drawbacks of toxicity and poor patient compliance due to long duration of treatment regimen. There are few new drug combinations currently in clinical trials which could provide new options of therapeutic intervention in management of this coinfection. Nanotechnology offers a viable platform for development of existing and new therapeutic interventions into pulmonary targeted drug delivery systems that specifically and effectively target both viral and bacterial reservoirs in the lungs. Additionally, recent evidence on gallium nanoparticles for simultaneous targeting of HIV and M. tuberculosis has opened up new vistas for development of dual targeting drug delivery systems. However further studies are needed to provide mechanistic insight for its selective toxicity in the coinfection.