Unveiling the Burden of Hepatitis A in Salerno, Italy: A Comprehensive 9-Year Retrospective Study (2015-2023) on the Seroprevalence of HAV Antibodies and Age/Sex Distribution.

Background: Hepatitis A virus (HAV) infection is a significant global cause of viral hepatitis. At present, the anti-HAV vaccine in Italy is proposed exclusively for specific high-risk groups, and a universal vaccination program is not implemented. Objectives: This study aimed to assess the level of immunity against HAV in patients of both sexes across age groups ranging from 0 to 95 years admitted to the San Giovanni di Dio e Ruggi d'Aragona Hospital in Salerno, Italy, over a 9-year period (2015-2023). Methods: The total HAV seroprevalence by chemiluminescence Vitros system immunodiagnostics (ortho-diagnostics) was obtained by database analysis, stratifying patients for gender and age group in both the pre-pandemic (2015-2019) and pandemic (2020-2023) periods. Results: Out of 28,104 samples collected in 2015-2023, 20,613 resulted positive by total HAV immune screening, with a significant reduction in the annualized proportion of events during the pandemic period compared to the pre-pandemic period. HAV was more abundant in males than females in both periods (exceeding the 70%), with a statistically significant decrease in HAV in females in 2015-2019. The 61-70-year-old age group is more susceptible for both genders, with a strong deviation from the 41-50-year-old age group compared to the 51-60-year-old group. The pandemic period affected the number of analyzed samples in 2020. Conclusions: The study revealed high HAV seroprevalence, especially in males and individuals aged 61-70 years. There was a notable decrease in seroprevalence during the pandemic compared to pre-pandemic years. These results emphasize the need for ongoing monitoring and suggest that a universal vaccination program could address regional immunity gaps and lower disease incidence.

Impact of ESKAPE Pathogens on Bacteremia: A Three-Year Surveillance Study at a Major Hospital in Southern Italy.

BACKGROUND/OBJECTIVES: ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pose a serious public health threat as they are resistant to multiple antimicrobial agents. Bloodstream infections (BSIs) caused by ESKAPE bacteria have high mortality rates due to the limited availability of effective antimicrobials. This study aimed to evaluate the prevalence and susceptibility of ESKAPE pathogens causing BSIs over three years in a large tertiary hospital in Salerno. METHODS: Conducted at the Clinical Microbiology Laboratory of San Giovanni di Dio e ''Ruggi D'Aragona'' Hospital from January 2020 to December 2022, blood culture samples from different departments were incubated in the BD BACTEC™ system for 5 days. Species identification was performed using MALDI-TOF MS, and antimicrobial resistance patterns were determined by the VITEK2 system. RESULTS: Out of 3197 species isolated from positive blood cultures, 38.7% were ESKAPE bacteria. Of these, 59.9% were found in blood culture samples taken from men, and the most affected age group was those aged >60 years. (70.6%). Staphylococcus aureus was the main BSI pathogen (26.3%), followed by Klebsiella pneumoniae (15.8%). Significant resistance rates were found, including 35% of Staphylococcus aureus being resistant to oxacillin and over 90% of Acinetobacter baumannii being resistant to carbapenems. CONCLUSIONS: These results highlight the urgent need for antimicrobial stewardship programs to prevent incurable infections.

Lamotrigine vs levetiracetam in female patients of childbearing age with juvenile absence epilepsy: A Bayesian reanalysis.

OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.

Long-term outcomes and adaptive behavior in adult patients with Lennox-Gastaut syndrome.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy characterized by difficult-to-control seizures and cognitive dysfunction. Previous studies mainly focused on pediatric populations, and little is known about the long-term cognitive outcome in adult patients with LGS. The objective of this study was to investigate the long-term functional and adaptive behavior in adult patients with LGS. METHODS: This cross-sectional study enrolled adult patients diagnosed with LGS according to the recently published International League Against Epilepsy (ILAE) diagnostic criteria. The adaptive behavior of participants was assessed using the Vineland Adaptive Behavior Scales, Survey Interview, Second Edition (VABS-II). Demographic, clinical, electroencephalography (EEG), and antiseizure medication (ASM) data were also collected at different timepoints, to investigate their association with VABS-II scores. RESULTS: The study included 38 adult patients with LGS. A low score on the Adaptive Behavior Composite Scale was found in all patients. When considering single VABS-II domains, particularly low scores were found in daily living skills and socialization, whereas slightly higher performances were observed in communication. An earlier age at LGS diagnosis was identified as the most significant predictor of worse adaptive outcomes in adult life. At the time of study evaluation, high seizure frequency, higher EEG background slowing, and multifocal EEG epileptiform abnormalities were significantly associated with lower VABS-II raw scores. Furthermore, in an exploratory correlation analysis with ASM regimen at the study visit, treatment with cannabidiol was associated with higher adaptive behavior scores, whereas benzodiazepine intake correlated with lower scores. SIGNIFICANCE: This study provides relevant insights into the long-term challenges faced by adults with Lennox-Gastaut syndrome (LGS), highlighting significant impairments in adaptive behavior as well as the associated clinical and electroencephalography features. Additionally, this study provides a more specific neuropsychological profile in adults with LGS and underscores the importance of comprehensive care approaches that go beyond seizure control in this population. PLAIN LANGUAGE SUMMARY: This study examined adults with Lennox-Gastaut syndrome (LGS), a severe type of epilepsy, to understand their long-term abilities to perform daily tasks and adapt socially. We found that these adults have significant difficulties with daily living and social skills, although not all areas were equally affected. They performed somewhat better in communication, particularly in understanding others (receptive communication). Importantly, the younger the age at which LGS was diagnosed, the worse their outcomes were as adults. This study highlights the need for research and treatment approaches that focus not only on controlling seizures but also on improving daily life skills.

Identification of Chagas disease biomarkers using untargeted metabolomics.

Untargeted metabolomic analysis is a powerful tool used for the discovery of novel biomarkers. Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease that affects 6-7 million people with approximately 30% developing cardiac manifestations. The most significant clinical challenge lies in its long latency period after acute infection, and the lack of surrogate markers to predict disease progression or cure. In this cross-sectional study, we analyzed sera from 120 individuals divided into four groups: 31 indeterminate CD, 41 chronic chagasic cardiomyopathy (CCC), 18 Latin Americans with other cardiomyopathies and 30 healthy volunteers. Using a high-throughput panel of 986 metabolites, we identified three distinct profiles among individuals with cardiomyopathy, indeterminate CD and healthy volunteers. After a more stringent analysis, we identified some potential biomarkers. Among peptides, phenylacetylglutamine and fibrinopeptide B (1-13) exhibited an increasing trend from controls to ICD and CCC. Conversely, reduced levels of bilirubin and biliverdin alongside elevated urobilin correlated with disease progression. Finally, elevated levels of cystathionine, phenol glucuronide and vanillactate among amino acids distinguished CCC individuals from ICD and controls. Our novel exploratory study using metabolomics identified potential biomarker candidates, either alone or in combination that if confirmed, can be translated into clinical practice.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Depressive symptoms in children and adolescents with epilepsy and primary headache: a cross-sectional observational study.

Background: The primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels. Methods: 68 pediatric patients aged 6-18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF). Results: The group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only. Conclusion: Depressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management.

Screening blood donors for malaria, can we increase the number of eligible donors? An observational retrospective study.

BACKGROUND: In non-endemic countries, malaria can be transmitted through blood donations from imported cases. To ensure standards of quality and safety of human blood, the European Union and Spanish national law, requires a deferral period, or a screening by immunological or genomic test among those donors with potential risk of malaria. Scientific societies, European Committee on Blood Transfusion, and Spanish Society of Haematology and Haemotherapy, refer only to the result of the immunological test. METHODS: An observational retrospective study was performed in potential donors with a positive immunological test for malaria done in the Regional Transfusion Center in Madrid and referred to the National Reference Unit for Tropical Diseases in Madrid between 2015-2020. At consultation a Polymerase Chain Reaction (PCR) for malaria was performed. RESULTS: During the study period, 121 possible donors attended for consultation at NRU-Trop. Median age: 38.5 (IQR:33-48); median time to consultation was 32 months (IQR:12.5-110). Eighty-two (67.8%) donors were migrants and thirty-nine were travellers (32.2%). ELISA values were available for 109 subjects (90.1%), 56 individual left malaria endemic area > 3 years before. All donors tested negative for Plasmodium spp PCR test (n = 121, 100%). CONCLUSIONS: None of the subjects with a positive immunologic test deferred as blood donors had a positive genomic test. The presence of Plasmodium spp in collected blood was not detected by molecular techniques. To avoid the loss of potential blood donors, especially those with low incidence red blood cell antigens, as more precise microbiology techniques become available, updating the existing legislation becomes necessary to increase the availability of donated blood.

Trends in imported infections among migrants and travellers to Spain: a decade of analysis through the +Redivi network (2012-2022).

BACKGROUND: High-speed global travel, increased trade, world population growth, migration, urbanization and climate change have favoured the emergence and spread of pathogens. We aimed to analyse the evolution of imported infections in Spain during 2012-2022 and the potential impact of some of the abovementioned factors on differential morbidity patterns. METHODS: In this retrospective study (January 2012 to December 2022), we analysed data collected by the +Redivi network across 25 health centres. The network's standardised database records new cases of imported infections, including patient demographics, travel history, pre-travel advice and diagnostic information. To assess outcome rates over time and potential interactions, we constructed penalized weighted models to reduce the bias related to a low event rate and used weighted logistic regression for morbidity outcomes. RESULTS: We recorded 25 632 episodes, comprising 13 913 migrants, 4047 visiting friends and relatives (VFR) immigrants, 392 VFR travellers and 7280 travellers. Most immigrants came from South America (48.3%), Sub-Saharan Africa (28.5%), North Africa (6.6%), South Central Asia (5.4%) and Central America/Caribbean (5.3%). The most common regions visited by travellers were Sub-Saharan Africa (33.5%), South America (24.5%), Central America/Caribbean (13.5%), Southeast Asia (12%) and South Central Asia (10%). The proportion of diagnoses of malaria, strongyloidiasis and unspecified self-limiting febrile syndrome < 3 weeks remained unchanged during the study period. An increased frequency of diagnosis was reported for schistosomiasis, blastocystosis, giardiasis, dengue, diarrhoea, new cases of HIV, latent and pulmonary tuberculosis, whereas a decrease was reported for syphilis, chikungunya fever, Chagas disease and eosinophilia. We detected interactions between time and sex or type of participant across the different diagnoses. CONCLUSIONS: Our study underscores the importance of epidemiological data in understanding infectious diseases dynamics among travellers and migrants, emphasizing how demographic shifts, migration trends and healthcare policies affect disease profiles. Comprehensive data play an essential role in enhancing public health policies and travel advice.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

Pulmonary infections in the returning traveler.

PURPOSE OF REVIEW: The recent COVID-19 pandemic has shaped the epidemiology of other infectious diseases globally. International tourist arrivals are increasing and recovering to prepandemic levels. This review focuses on respiratory infections in travelers, highlighting the characteristics of the main imported viral, bacterial, fungal, and parasitic infections with pulmonary involvement. RECENT FINDINGS: A recent systematic review estimated a prevalence of respiratory symptoms in travelers of around 35%, increasing to nearly 65% in the context of mass gatherings. Common viral and bacterial pathogens account for the majority of respiratory infections with an identified cause; however, recent data focus on the need for surveillance of emerging infections such as MERS-CoV, henipaviruses and multidrug resistant bacteria, which may be spread through travel. Fungal and parasitic respiratory infections are less common, and acquisition is usually associated with specific risk factors or exposure in endemic areas. Special risk groups, such as immunocompromised travelers, may be particularly vulnerable, presenting with severe disease or reactivation of latent infections. SUMMARY: The next significant international epidemic could involve another new infectious agent causing respiratory disease and spreading via mobile populations. Official protocols should be adhered to, and public health interventions implemented for effective control. Continued and globally coordinated investments in research for new vaccines, therapeutic agents, disease modeling, and digital tracking strategies are essential.

Intestinal protozoa in returning travellers: a GeoSentinel analysis from 2007 to 2019.

BACKGROUND: Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. METHODS: We analysed records of returning international travellers with illness caused by Giardia duodenalis, Cryptosporidium spp., Cyclospora cayetanensis or Cystoisospora belli, reported to the GeoSentinel Network during January 2007-December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. RESULTS: There were 2517 cases, 82.3% giardiasis (n = 2072), 11.4% cryptosporidiosis (n = 287), 6.0% cyclosporiasis (n = 150) and 0.3% cystoisosporiasis (n = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18-30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. CONCLUSIONS: This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported.

Chikungunya infection in returned travellers: results from the geosentinel network, 2005-2020.

BACKGROUND: Chikungunya is an important travel-related disease because of its rapid geographical expansion and potential for prolonged morbidity. Improved understanding of the epidemiology of travel-related chikungunya infections may influence prevention strategies including education and vaccination. METHODS: We analysed data from travellers with confirmed or probable chikungunya reported to GeoSentinel sites from 2005 to 2020. Confirmed chikungunya was defined as a compatible clinical history plus either virus isolation, positive nucleic acid test or seroconversion/rising titre in paired sera. Probable chikungunya was defined as a compatible clinical history with a single positive serology result. RESULTS: 1202 travellers (896 confirmed and 306 probable) with chikungunya were included. The median age was 43 years (range 0-91; interquartile range [IQR]: 31-55); 707 (58.8%) travellers were female. Most infections were acquired in the Caribbean (28.8%), Southeast Asia (22.8%), South Central Asia (14.2%) and South America (14.2%). The highest numbers of chikungunya cases reported to GeoSentinel were in 2014 (28.3%), 2015 (14.3%) and 2019 (11.9%). The most frequent reasons for travel were tourism (n = 592; 49.3%) and visiting friends or relatives (n = 334; 27.7%). The median time to presentation to a GeoSentinel site was 23 days (IQR: 7-52) after symptom onset. In travellers with confirmed chikungunya and no other reported illnesses, the most frequently reported symptoms included musculoskeletal symptoms (98.8%), fever/chills/sweats (68.7%) and dermatologic symptoms (35.5%). Among 917 travellers with information available, 296 (32.3%) had a pretravel consultation. CONCLUSIONS: Chikungunya was acquired by international travellers in almost 100 destinations globally. Vector precautions and vaccination where recommended should be integrated into pretravel visits for travellers going to areas with chikungunya or areas with the potential for transmission. Continued surveillance of travel-related chikungunya may help public health officials and clinicians limit the transmission of this potentially debilitating disease by defining regions where protective measures (e.g. pretravel vaccination) should be strongly considered.

Topiramate ban in women of childbearing potential with idiopathic generalized epilepsy: Does effectiveness offset the teratogenic risks?

Regulatory agencies have recently discouraged the prescription of topiramate (TPM) to women of childbearing potential with epilepsy due to growing evidence of the teratogenic and neurodevelopmental risks associated with its use during pregnancy. It remains, however, unclear whether the use of TPM in this population can be supported to some extent by its high effectiveness. In this multicenter, retrospective, cohort study performed at 22 epilepsy centers, we investigated the comparative effectiveness of TPM and levetiracetam (LEV) given as first-line antiseizure medication in a cohort of women of childbearing potential with idiopathic generalized epilepsy (IGE). A total of 336 participants were included, of whom 24 (7.1%) received TPM and 312 (92.9%) LEV. Women treated with TPM had significantly higher risks of treatment failure and treatment withdrawal and were less likely to achieve seizure freedom at 12 months compared to women treated with LEV. In conclusion, this study highlighted a low tendency among clinicians to use TPM in women of childbearing potential with IGE, anticipating the recently released restrictions on its use. Furthermore, the available data on effectiveness do not appear to support the use of TPM in this population.

Chagas Disease in Europe.

Chagas disease is currently present in many non-endemic countries and remains a neglected tropical disease globally. A review of the literature identified significant gaps and scarcity of updated information from European countries, with most studies reporting data from Spain and Italy. The index of underdiagnosis may be as high as 70%, affecting mainly females of child-bearing age. Standardized screening of fertile, non-pregnant, women from endemic countries and subsequent treatment is considered an essential strategy to control transmission and prevent new cases, yet no uniform legislation for screening risk groups exists. There is heterogeneity in Europe in terms of preventive strategies to avoid transfusion-related transmission of Chagas disease, not necessarily in line with the European directives, with some countries conducting systematic screening for T. cruzi infection in blood donors, whilst others rely on pre-transfusion questionnaires. The growing burden of the infection in resource-rich areas may provide an opportunity for progress in certain aspects of control and prevention. Options for improving screening strategies, management and linkage to care are reviewed.

Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean.

Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.

Levetiracetam vs Lamotrigine as First-Line Antiseizure Medication in Female Patients With Idiopathic Generalized Epilepsy.

Importance: After the recent limitations to prescribing valproate, many studies have highlighted the challenging management of female patients of reproductive age with idiopathic generalized epilepsy (IGE). However, no study, to the authors' knowledge, has addressed the comparative effectiveness of alternative antiseizure medications (ASMs) in these patients. Objective: To compare the effectiveness and safety of levetiracetam and lamotrigine as initial monotherapy in female patients of childbearing age with IGE. Design, Setting, and Participants: This was a multicenter, retrospective, comparative effectiveness cohort study analyzing data from patients followed up from 1994 to 2022. Patients were recruited from 22 primary, secondary, and tertiary adult and child epilepsy centers from 4 countries. Eligible patients were female individuals of childbearing age, diagnosed with IGE according to International League Against Epilepsy (2022) criteria and who initiated levetiracetam or lamotrigine as initial monotherapy. Patients were excluded due to insufficient follow-up after ASM prescription. Exposures: Levetiracetam or lamotrigine as initial monotherapy. Main Outcomes and Measures: Inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards regression was performed to compare treatment failure (TF) among patients who received levetiracetam or lamotrigine as initial monotherapy. Results: A total of 543 patients were included in the study, with a median (IQR) age at ASM prescription of 17 (15-21) years and a median (IQR) follow-up of 60 (24-108) months. Of the study population, 312 patients (57.5%) were prescribed levetiracetam, and 231 (42.5%) were prescribed lamotrigine. An IPTW-adjusted Cox model showed that levetiracetam was associated with a reduced risk of treatment failure after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04). However, after stratification according to different IGE syndromes, the higher effectiveness of levetiracetam was confirmed only in patients with juvenile myoclonic epilepsy (JME; IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas no significant differences were found in other syndromes. Patients treated with levetiracetam experienced adverse effects more frequently compared with those treated with lamotrigine (88 of 312 [28.2%] vs 42 of 231 [18.1%]), whereas the 2 ASMs had similar retention rates during follow-up (IPTW-adjusted HR, 0.91; 95% CI, 0.65-1.23; P = .60). Conclusions and Relevance: Results of this comparative effectiveness research study suggest the use of levetiracetam as initial alternative monotherapy in female patients with JME. Further studies are needed to identify the most effective ASM alternative in other IGE syndromes.