Acute myocarditis: an overview of pathogenesis, diagnosis and management.

Acute myocarditis encompasses a diverse presentation of inflammatory cardiomyopathies with infectious and non-infectious triggers. The clinical presentation is heterogeneous, from subtle symptoms like mild chest pain to life-threatening fulminant heart failure requiring urgent advanced hemodynamic support. This review provides a comprehensive overview of the current state of knowledge regarding the pathogenesis, diagnostic approach, management strategies, and directions for future research in acute myocarditis. The pathogenesis of myocarditis involves interplay between the inciting factors and the subsequent host immune response. Infectious causes, especially cardiotropic viruses, are the most frequently identified precipitants. However, autoimmune processes independent of microbial triggers, as well as toxic myocardial injury from drugs, chemicals or metabolic derangements also contribute to the development of myocarditis through diverse mechanisms. Furthermore, medications like immune checkpoint inhibitor therapies are increasingly recognized as causes of myocarditis. Elucidating the nuances of viral, autoimmune, hypersensitivity, and toxic subtypes of myocarditis is key to guiding appropriate therapy. The heterogeneous clinical presentation coupled with non-specific symptoms creates diagnostic challenges. A multifaceted approach is required, incorporating clinical evaluation, electrocardiography, biomarkers, imaging studies, and endomyocardial biopsy. Cardiovascular magnetic resonance imaging has become pivotal for non-invasive assessment of myocardial inflammation and fibrosis. However, biopsy remains the gold standard for histological classification and definitively establishing the underlying etiology. Management relies on supportive care, while disease-specific therapies are limited. Although some patients recover well with conservative measures, severe or fulminant myocarditis necessitates aggressive interventions such as mechanical circulatory support devices and transplantation. While immunosuppression is beneficial in certain histological subtypes, clear evidence supporting antiviral or immunomodulatory therapies for the majority of acute viral myocarditis cases remains insufficient. Substantial knowledge gaps persist regarding validated diagnostic biomarkers, optimal imaging surveillance strategies, evidence-based medical therapies, and risk stratification schema. A deeper understanding of the immunopathological mechanisms, rigorous clinical trials of targeted therapies, and longitudinal outcome studies are imperative to advance management and improve the prognosis across the myocarditis spectrum.

Monoclonal antibodies for the prevention of Plasmodium falciparum malaria: a multi-target approach?

This article discusses the need for novel additional preventative strategies in malaria focusing on the potential role for monoclonal antibodies in disease prevention and putative strategies for their development and use in Plasmodium falciparum malaria.

Toxoplasma gondii infection in HIV-infected pregnant women: epidemiology and risks of mother-to-child transmission.

Toxoplasma gondii (T. gondii) infects approximately one third of the world's population. Globally there are an estimated 13.1 million cases of T. gondii co-infection in HIV-infected people with 87.1% of these individuals living in sub-Saharan Africa. The risk of T. gondii infection in HIV-infected women rises significantly with lower CD4+ T cell counts (particularly under 100 cells/µl). Mother-to-child transmission (MTCT) occurs in approximately 30% of cases of maternal T. gondii infection during pregnancy. The global prevalence of latent toxoplasmosis in HIV-infected pregnant women is 47.5% but the overall risk in HIV-infected mothers of MTCT of T. gondii is however, estimated to be low at < 5%. MTCT in HIV-infected mothers not only occurs due to T. gondii primary infection in pregnancy but also due to reactivation. Infants with congenital toxoplasmosis born to HIV-infected mother may have a more rapid onset and greater dissemination of disease thus having potentially devastating effects. This article discusses the key risks for MTCT of T. gondii infection in HIV-infected mothers as well highlighting the many knowledge gaps for which further study is required.

Increased imported severe Plasmodium falciparum malaria involving hyperparasitaemia (>10%) in a UK hospital following relaxation of COVID-19 restrictions compared to the pre-pandemic period.

We identified and compared patients diagnosed with Plasmodium falciparum malaria at a large hospital in London, UK prior to the COVID-19 pandemic versus following relaxation of COVID-19-associated restrictions. We found that parasitaemias, rates of hyperparasitaemia and severe malaria were significantly higher in the period post-relaxation of COVID-19 restrictions.

Sofosbuvir in the Treatment of Hepatitis E virus Infection: A Review of in vitro and in vivo Evidence.

Chronic hepatitis E virus (HEV) infection, which occurs almost exclusively in immunocompromised patients, if untreated may progress to cirrhosis and possibly hepatocellular carcinoma. The reduction of immunosuppression and/or administration of ribavirin is frequently curative but there remain many immunocompromised individuals whose HEV infection is refractory to these therapeutic strategies. Moreover, the haematological toxicity of ribavirin limits its use. Pegylated interferon has demonstrated success in a small number of patients with chronic HEV infection; however, the potentially increased risk of graft rejection associated with its use renders it unsuitable for many transplant recipients. Alternative therapeutic strategies are therefore required. This article reviews the in vitro and in vivo literature to date of the antiviral agent sofosbuvir (well established in the treatment of hepatitis C) in the treatment of HEV infection.

Nosocomial transmission of hepatitis E virus and development of chronic infection: The wider impact of COVID-19.

BACKGROUND: Transmission of hepatitis E virus (HEV) within the healthcare setting is extremely rare. Additionally, the development of chronic HEV infection in association with severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection and/or its immunomodulatory therapy has not been reported previously. AIMS: To describe the investigation and management of a nosocomial HEV transmission incident during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Epidemiological and molecular investigation of two individuals hospitalised with COVID-19 who were both diagnosed with HEV infection. RESULTS: Findings from our investigation were consistent with transmission of HEV from one patient with a community-acquired HEV infection to another individual (identical HEV sequences were identified in the two patients), most likely due to a breach in infection control practices whilst both patients shared a bed space on the intensive care unit (ICU). Chronic HEV infection requiring treatment with ribavirin developed in one patient with prolonged lymphopaenia attributable to COVID-19 and/or the immunomodulators received for its treatment. Further investigation did not identify transmission of HEV to any other patients or to healthcare workers. CONCLUSIONS: The extraordinary demands that the COVID-19 pandemic has placed on all aspects of healthcare, particularly within ICU settings, has greatly challenged the ability to consistently maintain optimal infection prevention and control practices. Under the significant pressures of the COVID-19 pandemic a highly unusual nosocomial HEV transmission incident occurred complicated further by progression to a chronic HEV infection in one patient.