Malaria in Appalachia? A Rare Case of Plasmodium vivax in an Adolescent Exchange Student From South Korea.

Cultural globalization, including the resumption of international travel post-SARS-CoV-2 pandemic, emphasizes the importance of regional infectious disease variation, especially when considering a differential diagnosis for fever in a traveler. Prompt diagnosis is often imperative to initiate proper treatment and reduce morbidity and mortality associated with many environmental and vector-borne pathogens. The Anopheles mosquito transmits malaria in areas endemic to malaria. Malaria, while not endemic to the United States, can be seen in a traveler. This illness can be deadly if left untreated. Symptoms of malaria include but are not limited to jaundice, cyclic fever, and flu-like illness. In this case report, we describe a unique presentation of Plasmodium vivax malaria in a 17-year-old traveler from South Korea with a negative rapid malaria test. A peripheral smear from microscopy demonstrated the presence of gametocytes, which are pathognomonic for malaria. Despite the presence of a very low parasitemia (<1%), the patient was noted to have some severe features such as significant thrombocytopenia, acute kidney injury, as well as relapsed disease several months later despite adequate treatment. A high clinical index of suspicion and a detailed history allowed prompt treatment and no permanent sequelae.

A Comprehensive Narrative Review of Drug Interactions Between Traveler's Diarrhea Medications and Chronic Therapies: Implications for Clinical Practice.

Diarrhea is a common illness for travelers. Traveler's diarrhea is typically defined as experiencing at least three unformed stools per day during a stay abroad or within 10 days of returning from the destination. In this review, we consulted five databases, namely, Medicine Complete, Medscape, Drugs.com, Epocrates, and DDInter, to conduct a comprehensive drug interaction analysis. We selected commonly prescribed medications used for the treatment of traveler's diarrhea, including ciprofloxacin, levofloxacin, norfloxacin, ofloxacin, azithromycin, rifaximin, bismuth salicylate, and loperamide. The antidiabetic medications chosen included metformin, glipizide, glimepiride, sitagliptin, linagliptin, dapagliflozin, empagliflozin, and acarbose. The chosen antihypertensive drugs were telmisartan, olmesartan, amlodipine, nifedipine, enalapril, ramipril, metoprolol, and propranolol. Aspirin, clopidogrel, ticagrelor, rivaroxaban, warfarin, atorvastatin, and rosuvastatin were also chosen as they play an essential role in cardiovascular treatment. We performed comprehensive interaction checks across all five databases for each combination of a traveler's diarrhea medication and medication from one of the three comorbid conditions (antidiabetic, antihypertensive, or cardioprotective). We categorized the severity of interactions as mild, moderate, or severe. Similarly, we used colors to highlight the number of databases reporting drug interactions, providing insights into the reliability of these interactions across sources. Interactions with antidiabetic drugs revealed that fluoroquinolones and sulfonylureas produce severe interaction effects. Comparatively, rifaximin can be safer as it exhibited mild interaction only with metformin, whereas the other antidiabetic drugs showed no interaction effect. Levofloxacin was found to be the safest drug among hypertensive individuals as it exerted no interaction effects with any of the antihypertensive medications. Levofloxacin and rifaximin were considered to be safe as these drugs interacted with only two cardioprotective drugs. This review features the importance of a precise approach in prescribing medications for traveler's diarrhea, especially for patients with chronic comorbidities. These findings play a pivotal role in improving awareness and providing tailored treatment for the interaction to ensure patient well-being.

What Do Travelers Know about Traveler's Diarrhea? Impact of a Pre-Travel Consultation in the Lisbon Area, Portugal.

Traveler's diarrhea (TD) is one of the most common travel-related health problems, largely interfering with planned activities and potentially contributing to antimicrobial resistance. This study aimed to characterize the knowledge about TD among pre-travel consultation users of one Portuguese travel clinic and determine the impact of the consultation on knowledge levels. Using a quasi-experimental, separate-sample pretest-posttest design, participants were randomly assigned to two groups: control/pre-consultation group (CG) or experimental/post-consultation group (EG). An anonymous self-administered questionnaire was used. A total of 470 participants were analyzed (227 CG; 243 EG). The EG/post-consultation group showed significant improvement in knowledge, with correct answers increasing from 63% to 75% (p < 0.001). However, knowledge gaps persisted: over 50% were unaware of TD's self-limited nature, 30% did not recognize loperamide as a symptom reliever, and 36% believed all travelers should take antibiotics to prevent TD. The educational level and previous travel outside Europe influenced baseline knowledge; previous travel medicine consultations and information on TD improved knowledge in both groups and made it easier to acquire knowledge on the subject. Thus, a pre-travel consultation effectively increased travelers' TD knowledge. However, post-consultation knowledge levels remained suboptimal, indicating the need for targeted interventions to increase travelers' literacy and optimize pre-travel consultations.

Iquitos Virus in Traveler Returning to the United States from Ecuador.

We describe the case of a returned traveler to the United States from Ecuador who had an acute febrile illness, initially diagnosed as Oropouche fever. This illness was later confirmed to be a rare infection with Iquitos virus, a related bunyavirus that shares 2 of 3 genome segments with Oropouche virus.

Reducing intrusive memories and promoting posttraumatic growth with Traveler: A randomized controlled study.

Over recent decades, serious games have become a promising intervention approach for addressing psychological problems by providing users with computerized, engaging, and interactive experiences. An innovative serious game, Traveler, has been developed specifically as an intervention tool for managing posttraumatic responses immediately after trauma. The game incorporates the principle of visuospatial interference, the core elements of Tetris, such as spatial displacement and mental rotation, and the critical phases of eye movement desensitization and reprocessing. To test the intervention efficacy and feasibility of Traveler, we conducted a randomized controlled trial involving 105 young adults. Participants were randomly assigned into three groups: a wait-list control group, a group undergoing five-session written exposure therapy, or a group engaging in one session of Traveler gameplay. Outcome measures included intrusive memories (i.e. vividness of traumatic images, disgust at traumatic images, flashback frequency, and flashback impact) and posttraumatic growth measured by the Posttraumatic Growth Inventory. Traveler significantly outperformed the control and written exposure therapy groups in reducing intrusive memories and enhancing posttraumatic growth, with effects persisting at a 30-day follow-up. Thus, Traveler offers a promising brief and early intervention technique for addressing posttraumatic responses. Yet, its clinical applicability requires further investigation.

Primary Varicella Infection in a Young Adult from the Democratic Republic of the Congo: A Case Report and Mini-Review.

We describe a case of an immunocompetent adult male patient originally from the Democratic Republic of Congo (DRC), who was referred to our unit for a several-day history of fever and a pruritic, vesicular rash. There was initial concern in the Emergency Department for Mpox (formerly known as "monkeypox") given the current epidemiology versus other viral etiologies. Primary varicella zoster virus (pVZV) infection was ultimately diagnosed by PCR from a swabbed, unroofed lesion, and he recovered completely with supportive management and without antiviral therapy. We herein describe how common viral exanthems may best be differentiated in an emergency or outpatient setting.

Extended-spectrum ß-lactamase-producing Plesiomonas shigelloides isolated from the stool of a Japanese traveler returning from Rwanda: A case report.

A 21-year-old previously healthy Japanese woman visited an outpatient clinic because of abdominal pain, watery diarrhea, vomiting, and mild fever that had started on the previous day. She traveled to rural and urban areas of Rwanda and returned to Japan 3 days before. Stool culture yielded the Plesiomonas shigelloides strain TMCH301018, against which minimum inhibitory concentrations of cefotaxime and cefotaxime-clavulanate were 128 and ≤0.12/4 µg/mL, respectively. The strain had the blaCTX-M-27 gene and an IncA/C replicon-type plasmid. Moreover, a transformant produced by introduction of an IncA/C plasmid extracted from TMCH301018 into Escherichia coli DH5α was positive for the blaCTX-M-27 gene and fulfilled the criteria of extended-spectrum ß-lactamase (ESBL) production described by the Clinical and Laboratory Standards Institute, indicating that TMCH301018 produced ESBL of CTX-M-27 and the ESBL-encoding gene was located on an IncA/C plasmid. Pathogenicity of TMCH301018 for the patient's complaints was uncertain because a molecular assay detected other enteropathogens in the stool specimen and the symptoms improved within 2 days with administration of oral ciprofloxacin, to which TMCH301018 was not susceptible. To our knowledge, this is the first report describing the isolation of ESBL-producing P. shigelloides.

The racial composition of road users, traffic citations, and police stops.

This paper exploits the potential of Global Positioning System datasets sourced from mobile phones to estimate the racial composition of road users, leveraging data from their respective Census block group. The racial composition data encompasses approximately 46 million trips in the Chicago metropolitan region. The research focuses on the relationship between camera tickets and racial composition of drivers vs. police stops for traffic citations and the racial composition in these locations. Black drivers exhibit a higher likelihood of being ticketed by automated speed cameras and of being stopped for moving violations on roads, irrespective of the proportion of White drivers present. The research observes that this correlation attenuates as the proportion of White drivers on the road increases. The citation rate measured by cameras better matches the racial composition of road users on the links with cameras than do stops by police officers. This study therefore presents an important contribution to understanding racial disparities in moving violation stops, with implications for policy interventions and social justice reforms.

Exploring the utilization and perceptions of pre-travel health consultations in primary care settings in Saudi Arabia: a cross-sectional study.

BACKGROUND: International travel exposes individuals to diverse health risks, necessitating proactive pre-travel health preparations. Saudi Arabia has witnessed increased outbound travel. This study addresses a critical gap in knowledge by investigating the utilization and perceptions of pre-travel health consultations among adults in the Eastern Province of Saudi Arabia. METHODS: This cross-sectional study surveyed patients at the Family and Community Medicine Center of Imam Abdulrahman Bin Faisal University during January 2024 to explore perceptions of pre-travel health consultations among the Saudi Arabian population. Adults aged 18 years or older in the waiting area were invited to complete a self-administered questionnaire. RESULTS: Of the 772 participants, 624 (80.8%) engaged in international travel within the last year. However, 593 (76.8%) had never sought pre-travel health consultations. Age, gender, and education level significantly influenced the pursuit of pre-travel health advice, with older individuals, females, and those with higher educational attainment more likely to seek consultations. Participants perceived vaccination recommendations (597, 77.4%) and disease prevention information (678, 87.8%) as crucial parts of pre-travel health consultations. However, barriers to seeking advice included perceived low risk (445, 74.8%), lack of awareness (215, 36.3%), time constraints (128, 21.6%), and cost concerns (92, 15.5%). CONCLUSION: The low prevalence of pre-travel health consultations among travelers highlights the need for targeted educational campaigns and the integration of travel health services into primary healthcare. Addressing the identified barriers and leveraging preferred information sources are crucial steps towards enhancing the uptake of pre-travel health consultations, ultimately improving the health and safety of international travelers from the region.

Dengue: A focused review for the emergency clinician.

Dengue is an arbovirus transmitted by the Aedes spp. mosquito. Approximately 390 million infections occur annually per World Health Organization estimates, with significant increases in infections throughout the last decade. The disease is endemic in warmer climates throughout the world, though cases may also be imported to non-endemic regions by returning travelers. Patients experience a wide variety of symptoms ranging from asymptomatic infection to severe disease requiring critical care. Emergency clinicians should consider the diagnosis of dengue in patients from endemic areas presenting with a flu-like illness, rash, and evidence of bleeding.

Malaria during COVID-19 Travel Restrictions in Makkah, Saudi Arabia.

Malaria is a parasitic infection that may result in an acute, life-threatening illness. It is a major public health problem in the tropical world. The disease is caused by the parasites of the genus Plasmodium and is transmitted by female Anopheles mosquitoes. Saudi Arabia is in the elimination phase of malaria control. Several parts of Saudi Arabia report cases of imported malaria among travelers and visitors. The city of Makkah in Saudi Arabia has a population of about 2.3 million. Moreover, over 6 million religious visitors from different parts of the world visit Makkah annually. During the COVID-19 outbreak, travel restrictions were enforced in Makkah to contain the spread of COVID-19. We compare the total reported cases of malaria in Makkah before, during, and after COVID-19 travel restrictions in this retrospective cross-sectional study. Data on demographics, clinical data, and laboratory parameters were collected from the medical records of the Ministry of Health, Saudi Arabia. The annual malaria incidence rates in Makkah were 29.13/million people (2018), 37.82/million people (2019), 15.65/million people (2020), 12.61/million people (2021), and 48.69/million people (2022). Most of the malaria cases in Makkah were caused by Plasmodium falciparum, followed by P. vivax. Sudan, Nigeria, Yamen, Pakistan, and India are the top five countries contributing to malaria cases in Makkah. Weekly malaria case analyses revealed that COVID-19-related travel restrictions resulted in zero malaria cases in Makkah, indicating the magnitude of the travel-related malaria burden in the city.

A severe case of Plasmodium falciparum malaria in a traveler returning from Kazakhstan, a malaria-free country.

Following a 2-week trip to Kazakhstan, a 42-year-old woman presented at the emergency department in Germany with fever, headache, nausea, and neurological symptoms. An infection with Plasmodium falciparum was rapidly diagnosed. The patient was immediately treated with intravenous artesunate and transferred to an intensive care unit. The initial parasite density was as high as 30% infected erythrocytes with 845,880 parasites/µL. Since Kazakhstan was declared malaria-free in 2012, molecular testing for Plasmodium has been initiated to identify a possible origin. Genotyping of the msp-1 gene and microsatellite markers showed that the parasites are of African origin, with two different alleles indicating a polyclonal infection. After a hospitalization of 10 days, the patient was discharged in good health. Overall, our results emphasize that malaria must be on the list of differential diagnoses for patients with fever of unknown origin, even if they come from countries where malaria does not commonly occur.

cGMP-dependent kinase 2, Na+/H+ exchanger NHE3, and PDZ-adaptor NHERF2 co-assemble in apical membrane microdomains.

AIM: Trafficking, membrane retention, and signal-specific regulation of the Na+/H+ exchanger 3 (NHE3) are modulated by the Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adapter proteins. This study explored the assembly of NHE3 and NHERF2 with the cGMP-dependent kinase II (cGKII) within detergent-resistant membrane microdomains (DRMs, "lipid rafts") during in vivo guanylate cycle C receptor (Gucy2c) activation in murine small intestine. METHODS: Small intestinal brush border membranes (siBBMs) were isolated from wild type, NHE3-deficient, cGMP-kinase II-deficient, and NHERF2-deficient mice, after oral application of the heat-stable Escherichia coli toxin (STa) analog linaclotide. Lipid raft and non-raft fractions were separated by Optiprep density gradient centrifugation of Triton X-solubilized siBBMs. Confocal microscopy was performed to study NHE3 redistribution after linaclotide application in vivo. RESULTS: In the WT siBBM, NHE3, NHERF2, and cGKII were strongly raft associated. The raft association of NHE3, but not of cGKII, was NHERF2 dependent. After linaclotide application to WT mice, lipid raft association of NHE3 decreased, that of cGKII increased, while that of NHERF2 did not change. NHE3 expression in the BBM shifted from a microvillar to a terminal web region. The linaclotide-induced decrease in NHE3 raft association and in microvillar abundance was abolished in cGKII-deficient mice, and strongly reduced in NHERF2-deficient mice. CONCLUSION: NHE3, cGKII, and NHERF2 form a lipid raft-associated signal complex in the siBBM, which mediates the inhibition of salt and water absorption by Gucy2c activation. NHERF2 enhances the raft association of NHE3, which is essential for its close interaction with the exclusively raft-associated activated cGKII.

Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.

Cyclic nucleotide elevation in intestinal epithelial cells is the key pathology causing intestinal fluid loss in secretory diarrheas such as cholera. Current secretory diarrhea treatment is primarily supportive, and oral rehydration solution is the mainstay of cholera treatment. There is an unmet need for safe, simple and effective diarrhea treatments. By promoting cAMP hydrolysis, extracellular calcium-sensing receptor (CaSR) is a regulator of intestinal fluid transport. We studied the antidiarrheal mechanisms of FDA-approved CaSR activator cinacalcet and tested its efficacy in clinically relevant human cell, mouse and intestinal organoid models of secretory diarrhea. By using selective inhibitors, we found that cAMP agonists-induced secretory short-circuit currents (Isc) in human intestinal T84 cells are mediated by collective actions of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) and Clc-2 Cl- channels, and basolateral membrane K+ channels. 30 µM cinacalcet pretreatment inhibited all 3 components of forskolin and cholera toxin-induced secretory Isc by ∼75%. In mouse jejunal mucosa, cinacalcet inhibited forskolin-induced secretory Isc by ∼60% in wild type mice, with no antisecretory effect in intestinal epithelia-specific Casr knockout mice (Casr-flox; Vil1-cre). In suckling mouse model of cholera induced by oral cholera toxin, single dose (30 mg/kg) oral cinacalcet treatment reduced intestinal fluid accumulation by ∼55% at 20 hours. Lastly, cinacalcet inhibited forskolin-induced secretory Isc by ∼75% in human colonic and ileal organoids. Our findings suggest that CaSR activator cinacalcet has antidiarrheal efficacy in distinct human cell, organoid and mouse models of secretory diarrhea. Considering its excellent clinical safety profile, cinacalcet can be repurposed as a treatment for cyclic nucleotide-mediated secretory diarrheas including cholera.

Malaria: A focused review for the emergency medicine clinician.

INTRODUCTION: Malaria is a potentially fatal parasitic disease transmitted by the Anopheles mosquito. A resurgence in locally acquired infections has been reported in the U.S. OBJECTIVE: This narrative review provides a focused overview of malaria for the emergency clinician, including the epidemiology, presentation, diagnosis, and management of the disease. DISCUSSION: Malaria is caused by Plasmodium and is transmitted by the Anopheles mosquito. Disease severity can range from mild to severe. Malaria should be considered in any returning traveler from an endemic region, as well as those with unexplained cyclical, paroxysms of symptoms or unexplained fever. Patients most commonly present with fever and rigors but may also experience cough, myalgias, abdominal pain, fatigue, vomiting, and diarrhea. Hepatomegaly, splenomegaly, pallor, and jaundice are findings associated with malaria. Although less common, severe malaria is precipitated by microvascular obstruction with complications of anemia, acidosis, hypoglycemia, multiorgan failure, and cerebral malaria. Peripheral blood smears remain the gold standard for diagnosis, but rapid diagnostic tests are available. Treatment includes specialist consultation and antimalarial drugs tailored depending on chloroquine resistance, geographic region of travel, and patient comorbidities. Supportive care may be required, and patients with severe malaria will require resuscitation. Most patients will require admission for treatment and further monitoring. CONCLUSION: Emergency medicine clinicians should be aware of the presentation, diagnosis, evaluation, and management of malaria to ensure optimal outcomes.

Japanese Encephalitis Vaccine Acceptance and Strategies for Travelers: Insights from a Scoping Review and Practitioners in Endemic Countries.

Japanese encephalitis (JE) remains the cause of vaccine-preventable encephalitis in individuals living in endemic areas and international travelers. Although rare, the disease's high fatality rate emphasizes the need for effective immunization. This review aims to provide updated data on the JE burden between 2017 and 2023, vaccine acceptance, and vaccine strategies for travelers. We prospectively identified studies, using MEDLINE and PubMed, published through 2023. JE incidence has decreased in local populations and remains low among travelers from non-endemic countries. The local JE risk cannot be utilized to determine traveler risk. Adult travelers naïve to JEV infection or immunization may be at potentially higher risk. The JE vaccine acceptance rates among international travelers visiting JE endemic areas range from 0.2% to 28.5%. The cost of the vaccine and low risk perception could be barriers to JE vaccination. For travelers, an accelerated two-dose regimen of inactivated Vero cell JE vaccine (JE-VC) or a single dosage of live attenuated JE vaccine (JE-LV) may be an option. In conclusion, the JE burden among residents and travelers is lower, but the risk is not negligible. Practitioners should prioritize sharing knowledge, increasing awareness, and promoting vaccinations and preventive measures to reduce tourists' risk of JE along their journey.

Efficacy of an Enterotoxigenic Escherichia coli (ETEC) Vaccine on the Incidence and Severity of Traveler's Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score.

The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers' Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score and alternative clinical endpoints were evaluated as part of an initial validation effort to access the efficacy of a vaccine intervention for the first time in travelers to an ETEC endemic area. A randomized, double-blind, placebo-controlled trial followed travelers to Guatemala or Mexico up to 28 days after arrival in the country following vaccination (two doses two weeks apart) with an ETEC vaccine. Fecal samples were collected upon arrival, departure, and during TD for pathogen identification. Serum was collected in a subset of subjects to determine IgA cholera toxin B subunit (CTB) antibody titers upon their arrival in the country. The ETEC vaccine's efficacy, utilizing a TD severity score and other alternative endpoints, including the relationship between antibody levels and TD risk, was assessed and compared to the per-protocol primary efficacy endpoint. A total of 1435 subjects completed 7-28 days of follow-up and had available data. Vaccine efficacy was higher against more severe (≥5 unformed stools/24 h) ETEC-attributable TD and when accounting for immunologic take (PE ≥ 50%; p < 0.05). The vaccine protected against less severe (3 and 4 unformed stools/24 h) ETEC-attributable TD when accounting for symptom severity or change in activity (PE = 76.3%, p = 0.01). Immunologic take of the vaccine was associated with a reduced risk of infection with ETEC and other enteric pathogens, and with lower TD severity. Clear efficacy was observed among vaccinees with a TD score of ≥4 or ≥5, regardless of immunologic take (PE = 72.0% and 79.0%, respectively, p ≤ 0.03). The vaccine reduced the incidence and severity of ETEC, and this warrants accelerated evaluation of the improved formulation (designated ETVAX), currently undergoing advanced field testing. Subjects with serum IgA titers to CTB had a lower risk of infection with ETEC and Campylobacter jejuni/coli. Furthermore, the TD severity score provided a more robust descriptor of disease severity and should be included as an endpoint in future studies.

Profiles of travelers to intermediate-high health risk areas following the reopening of borders in the COVID-19 crisis: A clustering approach.

BACKGROUND: The reactivation of international travel in 2021 has created a new scenario in which the profile of the traveler to medium-high health risk areas may well have changed. However, few studies have analyzed this new profile since the reopening of borders in that year. METHODS: We designed an ad hoc questionnaire that was administered face-to-face by our medical team during appointments with 330 travelers in the second half of 2021. Information was collected on the following topics: sociodemographic and socioeconomic status; type of travel and previous travel experience; health status and risk perception (of COVID-19 and tropical infectious diseases). Using all features simultaneously, an unsupervised machine learning approach (k-means) is implemented to characterize groups of travelers. Pairwise chi-squared tests were performed to identify key features that showed statistically significant differences between clusters. RESULTS: The travelers were clustered into seven groups. We associated the clusters with different intensities of perceived risk of acquiring COVID-19 and tropical infectious diseases on the trip. The perceived risk of both diseases was low in the group "middle or lower middle class young inexperienced male tourist" but high in the group "middle or lower middle-class young with children inexperienced business traveler". CONCLUSIONS: Broadening our knowledge of the profiles of travelers to intermediate-high health risk areas would help to tailor the health advice provided by practitioners to their characteristics and type of travel. In a changing health context, the k-means approach supposes a flexible statistical method that calculates travelers' profiles and can be easily adapted to process new information.