Infectious Medicine最新文献

Background

West Nile virus is a severe zoonotic pathogen that can cause severe central nervous system symptoms in humans and horses, and is fatal for birds, chickens and other poultry. With no specific drugs or vaccines available, antibody-based therapy is a promising treatment. This study aims to develop neutralizing antibodies against West Nile virus and assess their cross-protective potential against Japanese encephalitis virus.

Methods

Monoclonal antibodies against WNV and JEV were isolated by hybridoma technology. The therapeutic efficacy of these antibodies was evaluated using a mouse model, and a humanized version of the monoclonal antibody was generated for potential human application.

Results

In this study, we generated eight monoclonal antibodies that exhibit neutralizing activity against WNV. Their therapeutic effects against WNV were validated both in vivo and in vitro. Among these antibodies, C9-G11-F3 also exhibited cross-protective activity against JEV. We also humanized the antibody to ensure that it could be used for WNV infection treatment in humans.

Conclusion

This study highlights the importance of neutralizing antibodies as a promising approach for protection against West Nile virus infection and suggests their potential utility in the development of therapeutic interventions.

Background

Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus, is endemic to tropical and subtropical areas such as Vietnam. Morphological methods only identify the genus, while DNA-molecular techniques are susceptible in Strongyloides spp. detection. The study aims to determine the prevalence of dominant Strongyloides species among the population in Duc Hoa district, Long An, Vietnam.

Methods

A cross-sectional study used 1190 stool specimens collected from July 2017 to November 2018. All samples were transported within 2 h, stored at 2–8°C, and processed within 48 h for microscopy smear and culture at the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine (PNT). Then all positive samples with the above 2 methods were verified by real-time PCR technique. Real-time PCR amplification was conducted at the Laboratory of Molecular Biology, PNT.

Results

Direct microscopy and modified Harada-Mori culture detected Strongyloides spp. larvae in 79/1190 samples (6.6%). About 94.2% of the DNA samples were Strongyloides stercoralis, 2.9% were co-infections with Strongyloides ratti and S. stercoralis, and 2.9% were patients with S. ratti. The identity of 12/14 sequences was confirmed as S. stercoralis with a high level of similarity (91.3%–100%) and over 98% for S. ratti.

Conclusion

DNA-molecular techniques and sequence analysis are highly suitable for identifying Strongyloides species isolated from stool samples. It is remarkable evidence of the presence of zoonosis S. ratti disease in human, not just the known S. stercoralis. It is likely to result in a certain proportion of people being infected by this animal-borne infectious pathogen.

Dengue is amongst the most prevalent viral diseases which globally affects millions of individuals annually and renders billions at risk, particularly in tropical and sub-tropical nations. WHO estimated 100–400 million infections each year and reported 4.2 million active cases in 2019 worldwide. The infection is caused by arthropod-transmitted dengue virus which is known to have 5 serotypes (DENV1-5). Most of the cases show mild clinical symptoms; though others may develop severe forms viz; dengue hemorrhagic fever and dengue shock syndrome. Though limited literature suggests the population-specific genetic influence on susceptibility and the clinical course of dengue; the genetic propensity of dengue is largely unknown in most ethnicities. In this context, the human leukocyte antigen (HLA) system represents the most polymorphic region of the human genome and is crucial for the initiation of an appropriate immune response. In most of the genome-wide association studies, the HLA complex is the most significantly linked genetic region with susceptibility or protection towards various infectious and noninfectious diseases. Killer immunoglobulin-like receptors represent another highly variable system present on the surface of natural killer (NK) cells which regulate the activity of NK cells through interactions with their cognate HLA ligands. It is conceivable that the interaction of HLA-Killer immunoglobulin-like receptors systems influences the host susceptibility towards dengue infection as well the disease outcome. Here we attempt to review these parameters in dengue infection and disease outcome. Further detailed investigations are warranted towards the identification of novel susceptibility markers and targeted therapeutic interventions.

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus SFTSV with case fatality up to 30%. The reactivation of Epstein-Barr virus (EBV) has been proven to occur in individuals with various immune suppression conditions.

Methods

Here, we diagnosed 22 SFTSV infected patients with PCR in a hospital in Shandong Province, China in 2020. To understand the consequences of SFTSV infection leading to EBV reactivation, we examined EBV reactivation in SFTSV-infected patients with PCR and RT-PCR.

Results

We found that EBV was reactivated in 18.2% (4/22) of SFTS patients, suggesting that EBV reactivation is common in SFTS patients. Compared with SFTS patients without EBV reactivation, SFTS patients with EBV-reactivation had a significantly lower median level of serum albumin (32.45 g/L vs. 26.95 g/L, p = 0.03) and a significantly higher median number of urine red blood cells (0 cells/μL vs. 9 cells/μL, p = 0.04).

Conclusion

SFTS infection can reactivate EBV in patients, which may make the clinical condition of patients worsen.

Mpox (monkeypox) virus (MPXV), which causes a mild smallpox-like disease, has been endemic in Africa for several decades, with sporadic cases occurring in other parts of the world. However, the most recent outbreak of mpox mainly among men that have sex with men has affected several continents, posing serious global public health concerns. The infections exhibit a wide spectrum of clinical presentation, ranging from asymptomatic infection to mild, severe disease, especially in immunocompromised individuals, young children, and pregnant women. Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models. However, the continued evolution of MPXV has produced multiple lineages, leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines. MPXV infections in various animal models have provided a central platform for identification and comparison of diseased pathogenesis between the contemporary and historic isolates. In this review, we discuss the susceptibility of various animals to MPXV, and describe the key pathologic features of rodent, rabbit and nonhuman primate models. We also provide application examples of animal models in elucidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs. These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures. Finally, we list some remaining scientific questions of MPXV that can be resolved by animal models.

Background

Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19, we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein.

Methods

Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB, and IRF were differentiated into macrophages over 3 days using phorbol 12-myristate 13-acetate, or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α. Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours.

Results

Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein.

Conclusions

Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflammatory transcription factors upon stimulation with S-glycoprotein. BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19. Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.

Background

COVID-19 caused by SARS-CoV-2 virus is characterized by respiratory compromise and immune system involvement, even leading to serious disorders, such as cytokine storm.

Methods

We then conducted a literature review on the topic of sepsis and covid-19, and in parallel conducted an experimental study on the histological finding of patients who died from SARS-Covid 19 infection and a control group.

Results

Sepsis associated with covid-19 infection has some similarities and differences from that from other causes.

Conclusion

In this paper the complex interplay between the 2 disorders was discussed, focusing on the similarities and on the effect that one could have on the other. A preliminary experimental section that demonstrates the multisystemic involvement in subjects who die from SARS-CoV-2 is also proposed.

Background

During the course of an epidemic of a potentially fatal disease, it is difficult to accurately estimate the case fatality rate (CFR) because many calculation methods do not account for the delay between case confirmation and disease outcome. Taking the coronavirus disease-2019 (COVID-19) as an example, this study aimed to develop a new method for CFR calculation while the pandemic was ongoing.

Methods

We developed a new method for CFR calculation based on the following formula: number of deaths divided by the number of cases T days before, where T is the average delay between case confirmation and disease outcome. An objective law was found using simulated data that states if the hypothesized T is equal to the true T, the calculated real-time CFR remains constant; whereas if the hypothesized T is greater (or smaller) than the true T, the real-time CFR will gradually decrease (or increase) as the days progress until it approaches the true CFR.

Results

Based on the discovered law, it was estimated that the true CFR of COVID-19 at the initial stage of the pandemic in China, excluding Hubei Province, was 0.8%; and in Hubei Province, it was 6.6%. The calculated CFRs predicted the death count with almost complete accuracy.

Conclusions

The method could be used for the accurate calculation of the true CFR during a pandemic, instead of waiting until the end of the pandemic, whether the pandemic is under control or not. It could provide those involved in outbreak control a clear view of the timeliness of case confirmations.

Background

In Brazil, the Ministry of Health (MH) monitors leprosy using 15 indicators, with the aim of implementing and evaluating evidence-based public policies. However, an excessive number of variables can complicate the definition of objectives and verification of epidemiological goals.

Methods

In this paper, we develop the Global Leprosy Assessment Index (GLAI), a composite measure that integrates two key dimensions for the control the disease: epidemiological and operational. Using a confirmatory factor analysis model to examine 2020 state-level data, we have standardized GLAI to a range of 0 to 1.

Results

Higher values within this range indicate a greater severity of the disease. The mean value of the GLAI was 0.67, with a standard deviation of 0.22. Roraima has the highest value, followed by Paraíba with 0.88 while Tocantins records the lowest value of the indicator, followed by Mato Grosso with 0.14. The epidemiological and operational indicators have a positive but statistically insignificant correlation (r = 0.25; p-value = 0.20).

Conclusions

The development of evidence-based public policies depends on the availability of valid and reliable indicators. The GLAI presented in this paper is easily reproducible and can be used to monitor the disease with disaggregated information. Furthermore, the GLAI has the potential to serve as a more robust parameter for evaluating the impact of actions designed to eradicate leprosy in Brazil.

In this current case series, all Coronavirus disease 2019 patients had predominant ophthalmological presentation. Only one patient sough care for concomitant respiratory symptoms. We reported herein 2 cases with cranial oculomotor nerve palsy, one patient with confirmed diagnosis of branch retinal vein occlusion, and the last one patient presenting for acute kareto-conjunctivitis with several recurrences, which was unsuccessfully treated with steroids and requiring cliclosporin. These case series highlights the importance of collecting a careful history of ocular presentation, including exposures to possible infected patients with SARS-CoV-2. This this will lead to an early diagnosis and treatment and to make appropriate infection control measures.