-
Euro Surveillance : Bulletin Europeen... Jun 2024We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent...
We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.
Topics: Humans; Female; Pregnancy; Denmark; Parvovirus B19, Human; Pregnancy Complications, Infectious; Adult; Incidence; Parvoviridae Infections; Epidemics; Hydrops Fetalis; Severity of Illness Index; Young Adult; Erythema Infectiosum; Adolescent; Abortion, Spontaneous; Population Surveillance
PubMed: 38873795
DOI: 10.2807/1560-7917.ES.2024.29.24.2400299 -
BMC Research Notes Jun 2024This study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients.
PURPOSE
This study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients.
METHODS
A total of 101 patients with thalassemia major were involved in this cross-sectional survey. A deep medication review was done, and participants' knowledge, attitude, and practice were evaluated by a validated instrument based on a 20-scoring system.
RESULTS
Statistical analyses showed 52 patients (51.5%) had a poor knowledge level (scores < 10) about their medications, 37 (36.6%) had a moderate level (scores 10-15), and 12 (11.9%) had a satisfactory level (scores > 15). Seventy-seven (76.2%) patients have positive beliefs regarding the dependence of their current health status on taking iron chelators, and 63 (62.4%) believed that they would become very ill without taking medication. The results also showed that the mean practice score in patients who received deferoxamine was 5.81 ± 3.50; in the patients who received deferiprone and those who received deferasirox, the mean scores were 7.36 ± 5.15 and 14.94 ± 4.14. Also, the knowledge and practice level had a direct linear correlation based on the regression analyses (P < 0.001).
CONCLUSION
In conclusion, results of the present research suggests that the patients' knowledge about the administration, adverse events, and necessity of ICAs was not satisfactory. Improving the knowledge of thalassemia patients toward their medicines through educational interventions is highly recommended to improve their practice level.
Topics: Humans; Iron Chelating Agents; Iran; Male; Female; Adult; Cross-Sectional Studies; Health Knowledge, Attitudes, Practice; Young Adult; Adolescent; beta-Thalassemia; Thalassemia; Deferiprone; Deferasirox; Deferoxamine; Triazoles; Middle Aged; Pyridones
PubMed: 38872196
DOI: 10.1186/s13104-024-06819-3 -
Croatian Medical Journal Jun 2024To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.
AIM
To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing.
METHODS
We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF.
RESULTS
We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software.
CONCLUSION
The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.
Topics: Humans; Female; Pregnancy; High-Throughput Nucleotide Sequencing; Haplotypes; Polymorphism, Single Nucleotide; Prenatal Diagnosis; beta-Thalassemia; Noninvasive Prenatal Testing; beta-Globins; Genotype; Hemoglobinopathies; Anemia, Sickle Cell
PubMed: 38868964
DOI: 10.3325/cmj.2024.65.180 -
Nature Communications Jun 2024Sickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible...
Sickle cell disease is a devastating blood disorder that originates from a single point mutation in the HBB gene coding for hemoglobin. Here, we develop a GMP-compatible TALEN-mediated gene editing process enabling efficient HBB correction via a DNA repair template while minimizing risks associated with HBB inactivation. Comparing viral versus non-viral DNA repair template delivery in hematopoietic stem and progenitor cells in vitro, both strategies achieve comparable HBB correction and result in over 50% expression of normal adult hemoglobin in red blood cells without inducing β-thalassemic phenotype. In an immunodeficient female mouse model, transplanted cells edited with the non-viral strategy exhibit higher engraftment and gene correction levels compared to those edited with the viral strategy. Transcriptomic analysis reveals that non-viral DNA repair template delivery mitigates P53-mediated toxicity and preserves high levels of long-term hematopoietic stem cells. This work paves the way for TALEN-based autologous gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Gene Editing; Animals; Hematopoietic Stem Cells; Humans; Female; Mice; Genetic Therapy; Transcription Activator-Like Effector Nucleases; Hematopoietic Stem Cell Transplantation; beta-Globins; Tumor Suppressor Protein p53; DNA Repair; Mutation; beta-Thalassemia; Disease Models, Animal; Gene Transfer Techniques
PubMed: 38862518
DOI: 10.1038/s41467-024-49353-3 -
Lipids in Health and Disease Jun 2024Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction...
BACKGROUND
Obesity is a metabolic syndrome where allelic and environmental variations together determine the susceptibility of an individual to the disease. Caloric restriction (CR) is a nutritional dietary strategy recognized to be beneficial as a weight loss regime in obese individuals. Preconceptional parental CR is proven to have detrimental effects on the health and development of their offspring. As yet studies on maternal CR effect on their offspring are well established but paternal CR studies are not progressing. In current study, the impact of different paternal CR regimes in diet-induced obese male Wistar rats (WNIN), on their offspring concerning metabolic syndrome are addressed.
METHODS
High-fat diet-induced obese male Wistar rats were subjected to caloric restriction of 50% (HFCR-I) and 40% (HFCR-II) and then they were mated with normal females. The male parent's reproductive function was assessed by sperm parameters and their DNMT's mRNA expression levels were also examined. The offspring's metabolic function was assessed by physiological, biochemical and molecular parameters.
RESULTS
The HFCR-I male parents have shown reduced body weights, compromised male fertility and reduced DNA methylation activity. Further, the HFCR-I offspring showed attenuation of the AMPK/SIRT1 pathway, which is associated with the progression of proinflammatory status and oxidative stress. In line, the HFCR-I offspring also developed altered glucose and lipid homeostasis by exhibiting impaired glucose tolerance & insulin sensitivity, dyslipidemia and steatosis. However, these effects were largely mitigated in HFCR-II offspring. Regarding the obesogenic effects, female offspring exhibited greater susceptibility than male offspring, suggesting that females are more prone to the influences of the paternal diet.
CONCLUSION
The findings highlight that HFCR-I resulted in paternal undernutrition, impacting the health of offspring, whereas HFCR-II largely restored the effects of a high-fat diet on their offspring. As a result, moderate caloric restriction has emerged as an effective weight loss strategy with minimal implications on future generations. This underscores the shared responsibility of fathers in contributing to sperm-specific epigenetic imprints that influence the health of adult offspring.
Topics: Animals; Sirtuin 1; Diet, High-Fat; Obesity; Male; Rats, Wistar; Female; Caloric Restriction; Rats; DNA Methylation; AMP-Activated Protein Kinases; Signal Transduction; Pregnancy
PubMed: 38851752
DOI: 10.1186/s12944-024-02161-6 -
Transfusion Clinique Et Biologique :... Jun 2024Systematic transfusions coupled with iron chelation therapy have substantially improved the life expectancy of thalassemia patients in developed nations. As the human... (Review)
Review
Systematic transfusions coupled with iron chelation therapy have substantially improved the life expectancy of thalassemia patients in developed nations. As the human organism does not have a protective mechanism to remove excess iron, iron overload is a significant concern in thalassemia, leading to organ damage, especially in the heart and liver. Thus, iron chelation therapy is crucial to prevent or reverse organ iron overload. There are three widely used iron chelators, either as monotherapy or in combination. The choice of iron chelator depends on several factors, including local guidelines, drug availability, and the individual clinical scenario. Despite treatment advancements, challenges persist, especially in resource-limited settings, highlighting the need for improved global healthcare access. This review discusses clinical management, current treatments, and future directions for thalassemia, focusing on iron overload and its complications. Furthermore, it underscores the progress in transforming thalassemia into a manageable chronic condition and the potential of novel therapies to further enhance patient outcomes.
PubMed: 38849068
DOI: 10.1016/j.tracli.2024.06.001 -
PloS One 2024Evidence supports the benefits of hydroxyurea (HU) in adults with sickle cell disease (SCD), but reservations remain due to long-term concerns of fertility.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence supports the benefits of hydroxyurea (HU) in adults with sickle cell disease (SCD), but reservations remain due to long-term concerns of fertility. Retrospective analysis of clinical records of SCD patients (haemoglobin SS genotype) have identified gender-related differences in disease progression. This could inform risk stratification during SCD at diagnosis with the possibility to guide therapeutic decisions.
METHODS
This systemic review and meta-analysis evaluated fertility parameters in both children (aged ≥ 6 years) and adults with SCD receiving HU therapy. Studies were sourced from PubMed and EMBASE from inception to July 2023. A total of 160 potentially relevant articles were identified.
RESULTS
Four studies were included that evaluated the effects of HU on sperm parameters in males. A further 4 studies assessed anti-mullerian hormone (AMH) levels and ovarian reserves in females. Differences from baseline values were used to identify compromised fertility. Amongst males, HU treatment negatively impacted the concentration of spermatozoa (MD = -15.48 million/mL; 95% CI: [-20.69, -10.26]; p< 0.001), which continued following treatment cessation (MD = -20.09 million/mL; 95% CI: [-38.78, -1.40]; P = 0.04). HU treatment also led to lower total sperm counts (MD = -105.87 million; 95% CI: [-140.61, -71.13]; P< 0.001) which persisted after treatment (MD = -53.05 million; 95% CI: [-104.96, -1.14]; P = 0.05). Sperm volume, initial forward motility and morphology were unaffected by HU treatment. In females, HU treatment decreased the mean AMH levels 1.83 (95% CI [1.42, 2.56]. A total of 18.2.% patients treated with HU showed reduced ovarian reserves.
INTERPRETATION & CONCLUSIONS
This systemic review and meta-analysis suggest that the use of HU for SCD impacts seminal fluid parameters in males and can diminish AMH levels and ovarian reserves in females.
Topics: Adult; Child; Female; Humans; Male; Anemia, Sickle Cell; Anti-Mullerian Hormone; Antisickling Agents; Fertility; Hydroxyurea; Ovarian Reserve; Sperm Count; Spermatozoa
PubMed: 38848387
DOI: 10.1371/journal.pone.0304241 -
Annals of Medicine and Surgery (2012) Jun 2024Alpha thalassemia, resulting from nondeletional mutations, typically presents a more severe clinical manifestation compared to deletional mutations. Severe outcomes,...
INTRODUCTION AND IMPORTANCE
Alpha thalassemia, resulting from nondeletional mutations, typically presents a more severe clinical manifestation compared to deletional mutations. Severe outcomes, such as hydrops fetalis, are associated with two specific nondeletional mutations. Therefore, DNA-based investigation is crucial for suspected carriers exhibiting subtle hematological abnormalities to facilitate proper diagnosis and effective family counseling.
CASE PRESENTATION
In this report, the authors describe a phenotypically normal 1-year-old girl with a rare and unique alpha-thalassemia genotype due to the presence of Hb Adana, a nondeletional alpha-chain mutation compounded with Hb SEA, an alpha-globin gene deletion.
CLINICAL DISCUSSION
Mutations determine the clinical manifestations of alpha-thalassemia. DNA testing is recommended for suspected carriers with relatively small hematological abnormalities, for precise diagnosis and family counseling. To provide clinicians with a reference for diagnostic assessment, the authors established a genotype-phenotype correlations based on reported cases of Hb Adana following an exhaustive literature review. Being interested in determining which ethnicities and genotypes are associated with a higher risk of complications, including hydrops fetalis and transfusion dependence, the authors formalized a diagnostic evaluation guide and a guide for early screening to improve outcomes.
CONCLUSION
Precise genetic evaluation is important for the diagnosis of alpha thalassemia. Hematologists play a critical role in managing these disorders, understanding genotype-phenotype correlations, and highlighting the significance of genetic counseling for high-risk patients. Extensive studies on these various genophenotypes are required to improve the diagnosis and prognosis of such medical conditions and advocate preventative strategies.
PubMed: 38846854
DOI: 10.1097/MS9.0000000000002101 -
Medecine Tropicale Et Sante... Mar 2024Although a protective effect of hemoglobin S has been described, malaria has frequently been associated with increased morbidity and mortality in sickle cell disease...
INTRODUCTION
Although a protective effect of hemoglobin S has been described, malaria has frequently been associated with increased morbidity and mortality in sickle cell disease patients in Africa. Various cytopenias are frequently found on the haemograms of these patients. In Benin, a malaria-endemic zone with a high prevalence of sickle cell disease, the aim of this study was to establish and compare the blood count profile according to hemoglobin type in the association of sickle cell disease and malaria.
MATERIAL AND METHOD
This was a prospective descriptive study. It covered a 24-month period from October 2020 to October 2022. It included all patients with major sickle cell syndrome seen in clinical haematology and with a positive thick drop/parasite density, whatever the parasitaemia value. For each patient, a blood count was performed on the Sysmex XT 4000i machine, supplemented by a smear study after staining with May-Grunwald Giemsa. Data were analyzed using R 3.6.1 software.
RESULTS
Three hundred non-redundant cases with a positive thick smear were identified in sickle cell patients, including 208 SS homozygotes (69.3%) and 92 SC heterozygotes (30.7%). In contrast, there were 181 non-redundant cases with a negative thick smear, including 119 SS homozygotes (65.7%) and 62 SC heterozygotes (34.3%). Among subjects with a positive thick smear, the majority of patients (70%) exhibited clinical symptoms. Severe malaria was observed in 58% of the cases. The proportion of severe malaria was higher in SS homozygote patients than in double heterozygote SC patients (p < 0.0001). The mean parasite density was higher in SS individuals (4 320.7 ± 2 185 trophozoites/pL) compared to SC individuals (1 564.4 ± 1 221 trophozoites/pL; p < 0.0001). was the only species identified. The mean hemoglobin level in impaludated SS subjects was 6.1 g/dL, significantly lower than that in non-impaludated SS subjects (p < 0.0001). The average white blood cell count in impaludated SS subjects was 16.58 G/L, compared to 13.2 G/L in those with a negative thick smear (p < 0.0001). Twenty cases of thrombocytopenia were found in SS subjects with a positive thick smear, compared to 6 cases in those with a negative thick smear. As for SC subjects with a positive thick smear, the average hemoglobin levels and white blood cell counts were 9.8 g/dL and 10.63 G/L, respectively, compared to 11.27 g/dL and 7.3 G/L in SC subjects with a negative thick smear. Eighteen cases of thrombocytopenia were found in subjects with a positive thick smear, compared to 17 cases in those with a negative thick smear.
DISCUSSION
Sickle cell disease and malaria represent two major public health problems. However, contrary to popular belief, sickle cell disease is not immune to malaria infestation. Malaria is recognized as one of the main causes of morbidity and mortality in sickle cell patients, particularly children. In Benin, its association with sickle cell emergencies has already been reported.Our study found that malaria was predominantly associated with the homozygous SS form (p < 0.00001). Severe malaria was the most common clinical form. All malaria infestations in our series were due to and parasitaemia was significantly higher in SS patients (p < 0.0001).The hematological profile of the association of sickle cell disease and malaria in homozygous SS individuals in our series showed characteristics of a normocytic normochromic anemia with neutrophil-predominant leukocytosis. Compared to non-malaria-infected SS individuals, there was a significant worsening of anemia, neutrophil-predominant leukocytosis, and a decrease in the average platelet count. In SC individuals, there was rather a microcytic normochromic regenerative anemia associated with neutrophil-predominant leukocytosis. Compared to non-malaria-infected SC individuals, there was a significant decrease in the rate of anemia and neutrophil-predominant leukocytosis. Anemia is a constant feature in homozygous sickle cell disease, and the low values recorded illustrate the hemolytic nature of malaria, especially in SS individuals, and the better tolerance of SC individuals. Furthermore, the low baseline hemoglobin levels make SS individuals more vulnerable to malaria-induced anemia compared to SC individuals. The observed leukocytosis is generally accompanied by reticulocytosis in the case of major sickle cell syndrome, which must be taken into account for result validation. It is the expression of compensatory bone marrow reaction to anemia and inflammatory mechanisms resulting from malaria infestation. Finally, thrombocytopenia was significantly more common in SC patients, even though they were adults living in malaria-endemic areas. Malaria can frequently induce thrombocytopenia through platelet consumption during the "rosetting" phenomenon. In SS patients, the effects of "rosetting" could be compensated for by the bone marrow stimulation induced by anemia. In our series with adult subjects living in an endemic area, thrombocytopenia is not a frequent biological disturbance. In a clinicalbiological context combining a systemic inflammatory response syndrome with anemia and neutrophil-predominant leukocytosis in a SS or SC sickle cell patient, the clinician should be able to consider malaria and confirm or rule out this diagnosis.
Topics: Humans; Anemia, Sickle Cell; Prospective Studies; Male; Female; Benin; Adult; Adolescent; Young Adult; Child; Malaria; Blood Cell Count; Middle Aged; Child, Preschool; Hemoglobin, Sickle
PubMed: 38846115
DOI: 10.48327/mtsi.v4i1.2024.404 -
Medecine Tropicale Et Sante... Mar 2024Sickle cell disease is one of the most common genetic diseases in France. In French Guiana, neonatal screening was introduced in 1992, at the same time as other...
BACKGROUND
Sickle cell disease is one of the most common genetic diseases in France. In French Guiana, neonatal screening was introduced in 1992, at the same time as other screening programs for childhood diseases. The aim of this study is to describe the organization of newborn screening for sickle cell disease in French Guiana.
MATERIALS AND METHODS
We used several data sources: data collected from hospital records since 2005, activity reports from the national neonatal screening program and data from screening campaigns organized by the Drepaguyane association between 2010 and 2021 on 1,300 subjects. Blood samples from newborns are collected by capillary or venous sampling and absorbed on blotting paper (Guthrie) at the same time as those for other neonatal screenings. The dried papers are sent to the inter-regional laboratory in Lille, for further processing. In Saint-Laurent-du-Maroni, in order to reduce the proportion of people lost to follow-up, a double screening is carried out and the results are returned before discharge from the maternity hospital. All data were entered into an anonymous Excel file. The data were analyzed using STATA software.
RESULTS
Among the 175,593 screened neonates between 1992 and 2021, screening detected 823 infants with sickle cell disease and 17,950 heterozygotes. Sickle cell genotypes include 493 SS (60%), 302 SC (37%) and 28 S-Beta-thalassemia (3%). The incidence of sickle cell disease was 1/213, 95% CI [1/236-1/204], and that of heterozygotes 1/10, IC 95% [1/12-1/8]. The majority of these children (52%) were from the Maroni region. The delay between screening and test results was 7 days. Only pathological results (homozygous, heterozygous) were communicated to parents and/or the attending physician by post. These data confirm the upward trend in the number of children screened for sickle cell disease in French Guiana. Data from screening campaigns organized by the Drepaguyane association have enabled to describe the distribution of the various abnormal hemoglobin fractions, and to confirm that HbS is more frequent in Western French Guiana. In Cayenne, in 2021, the active file comprised 699 patients, including 266 children under 18 years old.
DISCUSSION AND CONCLUSION
This study provides valuable data on 30 years of neonatal screening for sickle cell disease in French Guiana, and on the evolution of sickle cell disease patients. It confirms that French Guiana is the French territory with the highest incidence of sickle cell disease. This incidence continues to rise over time. The study reveals the improvement in the organization of sickle cell disease management in French Guiana between 1992, when screening was introduced, and the present day. It highlights the role of patient associations in the fight against this disease, by organizing awareness and screening campaigns. These data will be used to guide public health policies in the pursuit of improved care and primary prevention.
Topics: Humans; Anemia, Sickle Cell; French Guiana; Neonatal Screening; Infant, Newborn; Female; Time Factors
PubMed: 38846113
DOI: 10.48327/mtsi.v4i1.2024.488