-
BMJ Open Jul 2024Toxoplasmosis is a zoonotic parasitic disease caused by . It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to...
BACKGROUND
Toxoplasmosis is a zoonotic parasitic disease caused by . It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence of infection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia.
METHODS
This was a cross-sectional study where blood was collected, and the serum was tested for IgG and IgM. A questionnaire was administered to participants on demographic characteristics and risk factors. Data were entered in Microsoft Excel and exported to STATA version 14 for analysis.
RESULTS
A total of 401 women were enrolled in the study from 3 March to 5 August 2021. The seroprevalence of IgG was 4.2% (n=17), while the seroprevalence of IgM was 0.7% (n=3). The median age was 27 (IQR: 24-30) years, and a larger proportion had primary-level education (n=223, 55.6%). The majority (81.6%) of the women were married. None of the risk factors investigated in this study were significant for infection.
CONCLUSION
There was a low seroprevalence of infection among pregnant women in the Namwala district of Southern Province, Zambia, and regular screening may not be warranted in this population. Continued research on toxoplasmosis is recommended to understand its epidemiology across Zambia.
Topics: Humans; Female; Zambia; Cross-Sectional Studies; Seroepidemiologic Studies; Adult; Pregnancy; Toxoplasmosis; Risk Factors; Toxoplasma; Young Adult; Immunoglobulin M; Antibodies, Protozoan; Pregnancy Complications, Parasitic; Immunoglobulin G; Prenatal Care
PubMed: 38950992
DOI: 10.1136/bmjopen-2024-084582 -
The Journal of Clinical Investigation Jun 2024Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML),...
Activating mutations of FLT3 contribute to deregulated hematopoietic stem and progenitor cell (HSC/Ps) growth and survival in patients with acute myeloid leukemia (AML), leading to poor overall survival. AML patients treated with investigational drugs targeting mutant FLT3, including Quizartinib and Crenolanib, develop resistance to these drugs. Development of resistance is largely due to acquisition of cooccurring mutations and activation of additional survival pathways, as well as emergence of additional FLT3 mutations. Despite the high prevalence of FLT3 mutations and their clinical significance in AML, there are few targeted therapeutic options available. We have identified 2 novel nicotinamide-based FLT3 inhibitors (HSN608 and HSN748) that target FLT3 mutations at subnanomolar concentrations and are potently effective against drug-resistant secondary mutations of FLT3. These compounds show antileukemic activity against FLT3ITD in drug-resistant AML, relapsed/refractory AML, and in AML bearing a combination of epigenetic mutations of TET2 along with FLT3ITD. We demonstrate that HSN748 outperformed the FDA-approved FLT3 inhibitor Gilteritinib in terms of inhibitory activity against FLT3ITD in vivo.
Topics: Humans; Leukemia, Myeloid, Acute; fms-Like Tyrosine Kinase 3; Drug Resistance, Neoplasm; Animals; Mice; Niacinamide; Cell Line, Tumor; Xenograft Model Antitumor Assays; Female; Antineoplastic Agents; Mutation; Mice, SCID; Mice, Inbred NOD
PubMed: 38950330
DOI: 10.1172/JCI169245 -
PloS One 2024Feral populations of aoudad (Ammotragus lervia) occur in Texas bighorn sheep (Ovis canadensis) habitat and pose several conceptual ecological threats to bighorn sheep...
Evaluating the transmission dynamics and host competency of aoudad (Ammotragus lervia) experimentally infected with Mycoplasma ovipneumoniae and leukotoxigenic Pasteurellaceae.
Feral populations of aoudad (Ammotragus lervia) occur in Texas bighorn sheep (Ovis canadensis) habitat and pose several conceptual ecological threats to bighorn sheep re-establishment efforts. The potential threat of disease transmission from aoudad to bighorn sheep may exacerbate these issues, but the host competency of aoudad and subsequent pathophysiology and transmissibility of pneumonic pathogens involved in the bighorn sheep respiratory disease complex is largely unknown. Because the largest population-limiting diseases of bighorn sheep involve pathogens causing bronchopneumonia, we evaluated the host competency of aoudad for Mycoplasma ovipneumoniae and leukotoxigenic Pasteurellaceae. Specifically, we described the shedding dynamics, pathogen carriage, seroconversion, clinical patterns, and pathological effects of experimental infection among wild aoudad held in captivity. We found that aoudad are competent hosts capable of maintaining and intraspecifically transmitting Mycoplasma ovipneumoniae and Pasteurellaceae and can shed the bacteria for 53 days after exposure. Aoudad developed limited clinical signs and pathological findings ranged from mild chronic lymphohistiocytic bronchointerstitial pneumonia to severe and acute suppurative pneumonia, similarly, observed in bighorn sheep infected with Mycoplasma spp. and Pasteurellaceae bacteria, respectively. Furthermore, as expected, clinical signs and lesions were often more severe in aoudad inoculated with a combination of Mycoplasma ovipneumoniae and Pasteurellaceae as compared to aoudad inoculated with only Mycoplasma ovipneumoniae. There may be evidence of interindividual susceptibility, pathogenicity, and/or transmissibility, indicated by individual aoudad maintaining varying severities of chronic infection who may be carriers continuously shedding pathogens. This is the first study to date to demonstrate that aoudad are a conceptual disease transmission threat to sympatric bighorn sheep populations due to their host competency and intraspecific transmission capabilities.
Topics: Animals; Mycoplasma ovipneumoniae; Pasteurellaceae; Pneumonia, Mycoplasma; Sheep; Sheep, Bighorn; Ruminants; Sheep Diseases; Pasteurellaceae Infections; Female
PubMed: 38950318
DOI: 10.1371/journal.pone.0294853 -
PLoS Pathogens Jul 2024An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value...
An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value remains poorly characterized for influenza A virus (IAV), commonly known as the flu. In this study, we screened tens of thousands of cells using a microfluidic method called droplet quantitative PCR (dqPCR). The high-throughput capability of dqPCR enabled the measurement of a large population of infected cells producing progeny virus. By measuring the fully assembled and successfully released viruses from these infected cells, we discover that the viral burst sizes for both the seasonal H3N2 and the 2009 pandemic H1N1 strains vary significantly, with H3N2 ranging from 101 to 104 viruses per cell, and H1N1 ranging from 101 to 103 viruses per cell. Some infected cells produce average numbers of new viruses, while others generate extensive number of viruses. In fact, we find that only 10% of the single-cell infections are responsible for creating a significant portion of all the viruses. This small fraction produced approximately 60% of new viruses for H3N2 and 40% for H1N1. On average, each infected cell of the H3N2 flu strain produced 709 new viruses, whereas for H1N1, each infected cell produced 358 viruses. This novel method reveals insights into the flu virus and can lead to improved strategies for managing and preventing the spread of viruses.
PubMed: 38950082
DOI: 10.1371/journal.ppat.1012257 -
PLoS Pathogens Jul 2024The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro-...
The regulation of inflammatory responses and pulmonary disease during SARS-CoV-2 infection is incompletely understood. Here we examine the roles of the prototypic pro- and anti-inflammatory cytokines IFNγ and IL-10 using the rhesus macaque model of mild COVID-19. We find that IFNγ drives the development of 18fluorodeoxyglucose (FDG)-avid lesions in the lungs as measured by PET/CT imaging but is not required for suppression of viral replication. In contrast, IL-10 limits the duration of acute pulmonary lesions, serum markers of inflammation and the magnitude of virus-specific T cell expansion but does not impair viral clearance. We also show that IL-10 induces the subsequent differentiation of virus-specific effector T cells into CD69+CD103+ tissue resident memory cells (Trm) in the airways and maintains Trm cells in nasal mucosal surfaces, highlighting an unexpected role for IL-10 in promoting airway memory T cells during SARS-CoV-2 infection of macaques.
PubMed: 38950078
DOI: 10.1371/journal.ppat.1012339 -
PLoS Neglected Tropical Diseases Jul 2024The scarcity of reliable devices for diagnosis of Animal African trypanosomiasis (AAT) presents a limitation to control of the disease. Existing high-sensitivity...
The scarcity of reliable devices for diagnosis of Animal African trypanosomiasis (AAT) presents a limitation to control of the disease. Existing high-sensitivity technologies such as PCR are costly, laborious, time-consuming, complex, and require skilled personnel. Hence, utilisation of most diagnostics for AAT is impracticable in rural areas, where the disease occurs. A more accessible point-of-care test (POCT) capable of detecting cryptic active infection, without relying on expensive equipment, would facilitate AAT detection. In turn, early management, would reduce disease incidence and severity. Today, several ongoing research projects aim at modifying complex immunoassays into POCTs. In this context, we report the development of an antigen (Ag) detection sandwich ELISA prototype for diagnosis of T. congolense infections, which is comprised of nanobody (Nb) and monoclonal antibody (mAb) reagents. The Nb474H used here, originated from a past study. Briefly, the Nb was engineered starting from mRNA of peripheral blood lymphocytes of an alpaca immunized with soluble lysate of Trypanosoma congolense (TC13). T. congolense glycosomal fructose-1,6-bisphosphate aldolase (TcoALD) was discovered as the cognate Ag of Nb474H. In this study, splenocytes were harvested from a mouse immunized with recombinant TcoALD and fused with NS01 cells to generate a hybridoma library. Random screening of the library on TcoALD retrieved a lone binder, designated IgM8A2. Using Nb474H as Ag-capture reagent in combination with the IgM8A2 monoclonal antibody Ag-detection reagent resulted in a tool that effectively detects native TcoALD released during infection by T. congolense parasites. Hitherto, development of POCT for detection of active trypanosome infection is elusive. The Nanobody/Monoclonal Antibody (Nb/mAb) "hybrid" sandwich technology offers prospects for exploration, using the unique specificity of Nb as a key determinant in Ag capturing, while using the versatility of monoclonal Ab to adapt to various detection conditions.
PubMed: 38950072
DOI: 10.1371/journal.pntd.0012294 -
PloS One 2024More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions....
BACKGROUND
More than a year after recovering from COVID-19, a large proportion of individuals, many of whom work in the healthcare sector, still report olfactory dysfunctions. However, olfactory dysfunction was common already before the COVID-19 pandemic, making it necessary to also consider the existing baseline prevalence of olfactory dysfunction. To establish the adjusted prevalence of COVID-19 related olfactory dysfunction, we assessed smell function in healthcare workers who had contracted COVID-19 during the first wave of the pandemic using psychophysical testing.
METHODS
Participants were continuously tested for SARS-CoV-2 IgG antibodies since the beginning of the pandemic. To assess the baseline rate of olfactory dysfunction in the population and to control for the possibility of skewed recruitment of individuals with prior olfactory dysfunction, consistent SARS-CoV-2 IgG naïve individuals were tested as a control group.
RESULTS
Fifteen months after contracting COVID-19, 37% of healthcare workers demonstrated a quantitative reduction in their sense of smell, compared to only 20% of the individuals in the control group. Fifty-one percent of COVID-19-recovered individuals reported qualitative symptoms, compared to only 5% in the control group. In a follow-up study 2.6 years after COVID-19 diagnosis, 24% of all tested recovered individuals still experienced parosmia.
CONCLUSIONS
In summary, 65% of healthcare workers experienced parosmia/hyposmia 15 months after contracting COVID-19. When compared to a control group, the prevalence of olfactory dysfunction in the population increased by 41 percentage points. Parosmia symptoms were still lingering two-and-a half years later in 24% of SARS-CoV-2 infected individuals. Given the amount of time between infection and testing, it is possible that the olfactory problems may not be fully reversible in a plurality of individuals.
Topics: Humans; COVID-19; Health Personnel; Male; Female; Olfaction Disorders; Adult; Prevalence; Case-Control Studies; Middle Aged; SARS-CoV-2; Smell
PubMed: 38950019
DOI: 10.1371/journal.pone.0306290 -
PloS One 2024Medical students must have robust educational experiences, graduate and commence timely employment. Here, we describe how the Royal College of Surgeons in Ireland (RCSI)...
Medical students must have robust educational experiences, graduate and commence timely employment. Here, we describe how the Royal College of Surgeons in Ireland (RCSI) delivered clinical placements in medical programmes over the first three waves of the COVID-19 pandemic in Ireland, including a student-centred, holistic approach to students' educational, social and health needs with strong student involvement, re-organising the university's primary care team, developing COVID-19 PCR testing on site and re-focusing communications and student services. This resulted in re-arranging the students into learning communities, and students and staff electronically recorded their COVID-19 symptom status daily. In-person observed structured clinical examination and other clinical exams progressed. No lockdown of any campus occurred. Over the two senior years, 693 students completed 15,000 weeks of clinical and experiential learning across 104 sites, similar to previous years, including anatomy practicals, procedural skills training, simulated ward rounds and patient encounters, case-based presentations and small group tutorials. The compliance rate with the daily symptom tracker was 91%. The percentage response rate and the number of students providing feedback from October 2020 to April 2021 was as high as 50%. The overall response rate was 33%. By mid-May, 93-95% of students in the two senior years had had at least one dose of the SARS-CoV-2 vaccine, with 99% fully vaccinated by the start of the next academic year in autumn 2021. Over the period of testing for SARS-CoV-2, just over 22,000 samples were processed, of which 0.79% were positive; no medical student acquired COVID-19 or was associated with nosocomial transmission. The total investment by the RCSI in Dublin, was €9.3m (€1.2 in capital expenditure and €8.1 in operational expenses). Continuing face-to-face clinical placements during a pandemic was possible through a multi-model approach that prioritised two-way communication, compliance with national public health advice and student screening.
Topics: COVID-19; Humans; Students, Medical; Pandemics; SARS-CoV-2; Education, Medical; Ireland; Education, Distance
PubMed: 38950018
DOI: 10.1371/journal.pone.0306129 -
PLoS Pathogens Jul 2024Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to...
Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis. Ultimately, mice succumbed to infection. Dual loss of IL-17RA and IL-22RA impaired expression of small proline rich proteins (SPRRs), a class of antimicrobial effectors not previously linked to fungal immunity. Sprr2a1 exhibited direct candidacidal activity in vitro, and Sprr1-3a-/- mice were susceptible to OPC. Thus, cooperative actions of Type 17 cytokines mediate oral mucosal anti-Candida defenses and reveal a role for SPRRs.
Topics: Animals; Interleukin-22; Mice; Candidiasis, Oral; Interleukins; Interleukin-17; Mice, Knockout; Mice, Inbred C57BL; Candida albicans; Receptors, Interleukin; Receptors, Interleukin-17
PubMed: 38949991
DOI: 10.1371/journal.ppat.1012302 -
Microbial Genomics Jul 2024species are common inhabitants of the 'healthy' female urinary and vaginal communities, often associated with a lack of symptoms in both anatomical sites. Given...
species are common inhabitants of the 'healthy' female urinary and vaginal communities, often associated with a lack of symptoms in both anatomical sites. Given identification by prior studies of similar bacterial species in both communities, it has been hypothesized that the two microbiotas are in fact connected. Here, we carried out whole-genome sequencing of 49 strains, including 16 paired urogenital samples from the same participant. These strains represent five different species: , , , , and . Average nucleotide identity (ANI), alignment, single-nucleotide polymorphism (SNP), and CRISPR comparisons between strains from the same participant were performed. We conducted simulations of genome assemblies and ANI comparisons and present a statistical method to distinguish between unrelated, related, and identical strains. We found that 50 % of the paired samples have identical strains, evidence that the urinary and vaginal communities are connected. Additionally, we found evidence of strains sharing a common ancestor. These results establish that microbial sharing between the urinary tract and vagina is not limited to uropathogens. Knowledge that these two anatomical sites can share lactobacilli in females can inform future clinical approaches.
Topics: Humans; Female; Vagina; Lactobacillus; Microbiota; Polymorphism, Single Nucleotide; Genome, Bacterial; Phylogeny; Urinary Tract; Whole Genome Sequencing; Urine
PubMed: 38949867
DOI: 10.1099/mgen.0.001267