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Virulence Dec 2023Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus,... (Review)
Review
Monkeypox (Mpox) was mostly limited to Central and Western Africa, but recently it has been reported globally. The current review presents an update on the virus, including ecology and evolution, possible drivers of transmission, clinical features and management, knowledge gaps, and research priorities to reduce the disease transmission. The origin, reservoir(s) and the sylvatic cycle of the virus in the natural ecosystem are yet to be confirmed. Humans acquire the infection through contact with infected animals, humans, and natural hosts. The major drivers of disease transmission include trapping, hunting, bushmeat consumption, animal trade, and travel to endemic countries. However, in the 2022 epidemic, the majority of the infected humans in non-endemic countries had a history of direct contact with clinical or asymptomatic persons through sexual activity. The prevention and control strategies should include deterring misinformation and stigma, promoting appropriate social and behavioural changes, including healthy life practices, instituting contact tracing and management, and using the smallpox vaccine for high-risk people. Additionally, longer-term preparedness should be emphasized using the One Health approach, such as systems strengthening, surveillance and detection of the virus across regions, early case detection, and integrating measures to mitigate the socio-economic effects of outbreaks.
Topics: Animals; Humans; Mpox (monkeypox); Virulence; Ecosystem; Monkeypox virus; Ecology; Disease Outbreaks
PubMed: 36864002
DOI: 10.1080/21505594.2023.2186357 -
Indian Journal of Pediatrics Jul 2024Tuberculosis (TB) is a communicable disease that is a major cause of ill health and one of the leading causes of death worldwide. Children act as reservoirs of infection... (Review)
Review
Tuberculosis (TB) is a communicable disease that is a major cause of ill health and one of the leading causes of death worldwide. Children act as reservoirs of infection out of which future cases develop. Without the successful detection and treatment of TB infection and disease in children, elimination strategies for TB will be ineffective. India has a severe problem with TB in children, which accounts for around 31% of the global pediatric TB load. However, over the past 10 y, children have consistently made up 6-7% of all patients treated yearly under the National Tuberculosis Elimination Programme (NTEP). There is an estimated detection gap of 56% in India, which is the reason for many missed cases of TB in children. Only 3% of children less than 14 y with MDR/RR-TB, are reported from India, which again is an underestimation of the actual incident cases. Population density, housing and living conditions, environmental conditions, cultural practices, age of the child, exposure to tobacco and other environmental pollutants, the virulence of the mycobacterial strain and their genetics, host genetics, BCG vaccination, malnutrition, immunodeficiency are some of the risk factors for TB exposure, infection and disease in children. Understanding the natural history as well as the epidemiology of childhood TB is important to assess which children are the most vulnerable. It would also guide us in understanding the burden of pediatric TB on a regional, national, or global level, thus facilitating the appropriate targeting of health resources and also guiding policy-making decisions.
Topics: Humans; India; Child; Tuberculosis; Risk Factors; Adolescent; Child, Preschool; Tuberculosis, Multidrug-Resistant
PubMed: 37919487
DOI: 10.1007/s12098-023-04910-4 -
Global Pediatrics Dec 2023The pediatric population, especially under-five children, is highly susceptible to malaria and accounts for 76 % of global malaria deaths according to the World Malaria... (Review)
Review
PURPOSE
The pediatric population, especially under-five children, is highly susceptible to malaria and accounts for 76 % of global malaria deaths according to the World Malaria Report 2022. The purpose of this manuscript is to discuss the various factors involved in the susceptibility of the pediatric population to Malaria and the importance of this age group for malaria elimination.
METHODOLOGY
Data on pediatric malaria epidemiology that includes prevalence, risk factors, immune factors, socioeconomic factors, control methods, etc. were extracted from published literature using PubMed and Google Scholar. This data was further correlated with malaria incidence data from the World Health Organization (WHO) and the National Center for Vector Borne Diseases Control (NCVBDC).
RESULTS
The younger age group is vulnerable to severe malaria due to an immature immune system. The risk of infection and clinical disease increases after the waning of maternal immunity. In the initial years of life, the developing brain is more susceptible to malaria infection and its after-effects. The pediatric population may act as a malaria transmission reservoir due to parasite density and asymptomatic infections. WHO recommended RTS,S/AS01 has limitations and may not be applicable in all settings to propel malaria elimination.
CONCLUSION
The diagnosis of malaria is based on clinical suspicion and confirmed with microscopy and/or rapid diagnostic testing. The school-age pediatric population serves as a transmission reservoir in the form of asymptomatic malaria since they have acquired some immunity due to exposure in early childhood. Targeting the hidden reservoir in the pediatric population and protecting this vulnerable group will be essential for malaria elimination from the countries targeting elimination.
PubMed: 38440360
DOI: 10.1016/j.gpeds.2023.100085 -
Transactions of the Royal Society of... Sep 2023Cutaneous leishmaniasis (CL) is a parasitic vector-borne disease affecting mostly low- and middle-income countries. CL is endemic in Guatemala, where an increase in the... (Review)
Review
Cutaneous leishmaniasis (CL) is a parasitic vector-borne disease affecting mostly low- and middle-income countries. CL is endemic in Guatemala, where an increase in the number of cases and incidence and a changing disease distribution in the past decade have been reported. Important research was conducted in Guatemala in the 1980s and 1990s to understand the epidemiology of CL and two Leishmania species were identified as the aetiologic agents. Several species of sand flies have been reported, five of which are naturally infected with Leishmania. Clinical trials conducted in the country evaluated different treatments against the disease and provided solid evidence for CL control strategies that are applicable worldwide. More recently, in the 2000s and 2010s, qualitative surveys were conducted to understand community perceptions of the disease and to highlight the challenges and enablers for disease control. However, limited recent data have been generated regarding the current CL situation in Guatemala, and key information necessary for effective disease control, such as incrimination of vectors and reservoirs, is still lacking. This review describes the current state of knowledge of CL in Guatemala, including the main parasite and sand fly species, disease reservoirs, diagnosis and control, as well as the perceptions of communities in endemic regions.
Topics: Animals; Guatemala; Leishmaniasis, Cutaneous; Leishmania; Phlebotomus; Psychodidae; Leishmaniasis
PubMed: 37103337
DOI: 10.1093/trstmh/trad024 -
Journal of Dental Research Mar 2024The oral cavity is an epidemiologically relevant route of viral transmission due to the shedding of viruses in saliva. With advancements in salivary diagnostics, an... (Review)
Review
The oral cavity is an epidemiologically relevant route of viral transmission due to the shedding of viruses in saliva. With advancements in salivary diagnostics, an increasing number of viruses have been detected. However, the anatomic source of virus in saliva is still largely unknown. Some viruses have a well-established tropism for the salivary glands (SGs), and recent studies have emphasized the importance of the glands as potential reservoirs for infectious viruses. Viral infections of the SGs have been linked to acute and chronic SG pathology and may be associated with SG dysfunction, with phenotypes similar to those seen in SjÖgren's disease (SjD), an autoimmune condition that affects the salivary and lacrimal glands. Understanding the breadth of viruses that infect the SG and the conserved or distinct host responses to these infections may provide insights into the pathogenesis of virus-mediated SG diseases. There is a need for further research to fully understand the molecular mechanisms by which viruses enter and replicate in the glands, their physiologic impact on SG function, and whether the SGs can serve as a long-term reservoir for infectious viral particles. The purpose of this review is to highlight a group of viruses that infect the salivary gland: hepatitis C virus, hepatitis D virus, severe acute respiratory syndrome coronavirus 2, enteric viruses, human T-cell leukemia virus type I, human immunodeficiency virus, human cytomegalovirus, and BK polyomavirus. We focus on the effects of viral infection on salivary gland (SG) inflammation, function, and its association with SjD.
Topics: Humans; Salivary Glands; Sjogren's Syndrome; Saliva; Inflammation
PubMed: 38344753
DOI: 10.1177/00220345231222871 -
Nature Medicine Oct 2023The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon...
The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4 T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.
Topics: Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Macaca mulatta; Anti-Retroviral Agents; Virus Latency; Virus Replication; HIV-1; Antibodies; Lymph Nodes; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37783968
DOI: 10.1038/s41591-023-02570-7 -
Heliyon Aug 2023Ebola virus disease (EVD) is a severe and highly fatal zoonotic disease caused by viruses in the family and genus . The disease first appeared in Zaire near the Ebola... (Review)
Review
Ebola virus disease (EVD) is a severe and highly fatal zoonotic disease caused by viruses in the family and genus . The disease first appeared in Zaire near the Ebola River in 1976, now in the Democratic Republic of the Congo. Since then, several outbreaks have been reported in different parts of the world, mainly in Africa, leading to the identification of six distinct viral strains that cause disease in humans and other primates. Bats are assumed to be the main reservoir hosts of the virus, and the initial incidence of human epidemics invariably follows exposure to infected forest animals through contact or consumption of bush meat and body fluids of forest animals harboring the disease. Human-to-human transmission occurs when contaminated body fluids, utensils, and equipment come in contact with broken or abraded skin and mucous membranes. EVD is characterized by sudden onset of 'flu-like' symptoms (fever, myalgia, chills), vomiting and diarrhea, then disease rapidly evolves into a severe state with a rapid clinical decline which may lead potential hemorrhagic complications and multiple organ failure. Effective EVD prevention, detection, and response necessitate strong coordination across the animal, human, and environmental health sectors, as well as well-defined roles and responsibilities evidencing the significance of one health approach; the natural history, epidemiology, pathogenesis, and diagnostic procedures of the Ebola virus, as well as prevention and control efforts in light of one health approach, are discussed in this article.
PubMed: 37600424
DOI: 10.1016/j.heliyon.2023.e19036 -
International Journal of Molecular... Aug 2023In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years... (Review)
Review
In the era of personalized medicine greatly improved by molecular diagnosis and tailor-made therapies, the survival rate of acute myeloid leukemia (AML) at 5 years remains unfortunately low. Indeed, the high heterogeneity of AML clones with distinct metabolic and molecular profiles allows them to survive the chemotherapy-induced changes, thus leading to resistance, clonal evolution, and relapse. Moreover, leukemic stem cells (LSCs), the quiescent reservoir of residual disease, can persist for a long time and activate the recurrence of disease, supported by significant metabolic differences compared to AML blasts. All these points highlight the relevance to develop combination therapies, including metabolism inhibitors to improve treatment efficacy. In this review, we summarized the metabolic differences in AML blasts and LSCs, the molecular pathways related to mitochondria and metabolism are druggable and targeted in leukemia therapies, with a distinct interest for Venetoclax, which has revolutionized the therapeutic paradigms of several leukemia subtype, unfit for intensive treatment regimens.
Topics: Humans; Mitochondria; Cell Division; Clonal Evolution; Clone Cells; Leukemia
PubMed: 37685874
DOI: 10.3390/ijms241713069 -
Frontiers in Microbiology 2023Hendra virus (HeV) and Nipah virus (NiV) are biosafety level 4 zoonotic pathogens causing severe and often fatal neurological and respiratory disease. These agents have... (Review)
Review
Hendra virus (HeV) and Nipah virus (NiV) are biosafety level 4 zoonotic pathogens causing severe and often fatal neurological and respiratory disease. These agents have been recognized by the World Health Organization as top priority pathogens expected to result in severe future outbreaks. HeV has caused sporadic infections in horses and a small number of human cases in Australia since 1994. The NiV Malaysia genotype (NiV-M) was responsible for the 1998-1999 epizootic outbreak in pigs with spillover to humans in Malaysia and Singapore. Since 2001, the NiV Bangladesh genotype (NiV-B) has been the predominant strain leading to outbreaks almost every year in Bangladesh and India, with hundreds of infections in humans. The natural reservoir hosts of HeV and NiV are fruit bats, which carry the viruses without clinical manifestation. The transmission pathways of henipaviruses from bats to humans remain poorly understood. Transmissions are often bridged by an intermediate animal host, which amplifies and spreads the viruses to humans. Horses and pigs are known intermediate hosts for the HeV outbreaks in Australia and NiV-M epidemic in Malaysia and Singapore, respectively. During the NiV-B outbreaks in Bangladesh, following initial spillover thought to be through the consumption of date palm sap, the spread of infection was largely human-to-human transmission. Spillover of NiV-B in recent outbreaks in India is less understood, with the primary route of transmission from bat reservoir to the initial human infection case(s) unknown and no intermediate host established. This review aims to provide a concise update on the epidemiology of henipaviruses covering their previous and current outbreaks with emphasis on the known and potential role of livestock as intermediate hosts in disease transmission. Also included is an up-to-date summary of newly emerging henipa-like viruses and animal hosts. In these contexts we discuss knowledge gaps and new challenges in the field and propose potential future directions.
PubMed: 37529329
DOI: 10.3389/fmicb.2023.1167085 -
International Journal of Cardiology Dec 2023Hypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is...
BACKGROUND
Hypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is emerging as a potential marker of disease severity in both cardiomyopathies. The present study compares HCM and FD cardiomyopathy with similar degree of LVH, exploring LA morpho-functional parameters and the correlates of clinical outcome.
METHODS
We performed a comprehensive CMR-based comparison between 30 HCM and 30 FD patients matched on age, sex, BSA, LV mass and major cardiovascular risk factors affecting LA remodeling (arterial hypertension and diabetes). 30 healthy controls were also included. CMR feature tracking (CMR-FT) analysis, T1 mapping and conventional parameters were evaluated. Patients also underwent transthoracic echocardiography for LV diastolic function assessment. Clinical events at follow-up were collected (atrial and ventricular events, bradyarrhythmia, heart failure (HF) hospitalization and death).
RESULTS
HCM patients showed greater LA remodeling compared to FD patients, namely higher LA end-systolic volume index (LAVi max), lower LA-ejection fraction (LA-EF) and worse reservoir (εs) and booster function (εa) (all p < 0.05). Accordingly, these parameters have demonstrated good potential for distinguishing between FD and HCM (AUC 0.68-0.73, all p < 0.05), with LAVi max being an independent predictor for HCM diagnosis (OR 1.07, 95%CI 1.011-1.132, p 0.02). Moreover, in HCM patients a significant association between εs and HF occurrence was observed at 2-year follow-up (OR 0.85, 95%CI 0.72-0.99, p 0.04).
CONCLUSIONS
In HCM, LA remodeling is greater than in FD cardiomyopathy with similar LVH, and reservoir strain is associated with HF at follow-up.
PubMed: 37696360
DOI: 10.1016/j.ijcard.2023.131357