Replication-Competent Oropouche Virus in Semen of Traveler Returning to Italy from Cuba, 2024.

A febrile man in Italy who had traveled to Cuba in July 2024 was diagnosed with Oropouche fever. Reverse transcription PCR detected prolonged shedding of Oropouche virus RNA in whole blood, serum, urine, and semen. Sixteen days after symptom onset, replication-competent virus was detected in semen, suggesting risk for sexual transmission.

Analysis of Monkeypox Virus Exposures and Lesions by Anatomic Site.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Clinical Characteristics and Outcomes Among Travelers With Severe Dengue : A GeoSentinel Analysis.

BACKGROUND: Dengue virus is a flavivirus transmitted by Aedes mosquitoes and is an important cause of illness worldwide. Data on the severity of travel-associated dengue illness are limited. OBJECTIVE: To describe the epidemiology, clinical characteristics, and outcomes among international travelers with severe dengue or dengue with warning signs as defined by the 2009 World Health Organization classification (that is, complicated dengue). DESIGN: Retrospective chart review and analysis of travelers with complicated dengue reported to GeoSentinel from January 2007 through July 2022. SETTING: 20 of 71 international GeoSentinel sites. PATIENTS: Returning travelers with complicated dengue. MEASUREMENTS: Routinely collected surveillance data plus chart review with abstraction of clinical information using predefined grading criteria to characterize the manifestations of complicated dengue. RESULTS: Of 5958 patients with dengue, 95 (2%) had complicated dengue. Eighty-six (91%) patients had a supplemental questionnaire completed. Eighty-five of 86 (99%) patients had warning signs, and 27 (31%) were classified as severe. Median age was 34 years (range, 8 to 91 years); 48 (56%) were female. Patients acquired dengue most frequently in the Caribbean (n = 27 [31%]) and Southeast Asia (n = 21 [24%]). Frequent reasons for travel were tourism (46%) and visiting friends and relatives (32%). Twenty-one of 84 (25%) patients had comorbidities. Seventy-eight (91%) patients were hospitalized. One patient died of nondengue-related illnesses. Common laboratory findings and signs were thrombocytopenia (78%), elevated aminotransferase (62%), bleeding (52%), and plasma leakage (20%). Among severe cases, ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2), and neurologic symptoms (n = 2) were reported. Of 44 patients with serologic data, 32 confirmed cases were classified as primary dengue (IgM+/IgG-) and 12 as secondary (IgM-/IgG+) dengue. LIMITATIONS: Data for some variables could not be retrieved by chart review for some patients. The generalizability of our observations may be limited. CONCLUSION: Complicated dengue is relatively rare in travelers. Clinicians should monitor patients with dengue closely for warning signs that may indicate progression to severe disease. Risk factors for developing complications of dengue in travelers need further prospective study. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention, International Society of Travel Medicine, Public Health Agency of Canada, and GeoSentinel Foundation.

Oropouche fever cases diagnosed in Italy in two epidemiologically non-related travellers from Cuba, late May to early June 2024.

Oropouche fever is caused by Oropouche virus (OROV), transmitted primarily through the bite of infected midges, particularly of the genus Culicoides. The virus is mainly circulating in Central and South America where several countries reported an ongoing outbreak. We report here two imported cases of OROV infection identified in Italy, late May-early June 2024. These cases indicate that in the shadow of a massive dengue outbreak in the Americas, the Oropouche outbreak might be more widespread than previously estimated.

Investigation of an airport-associated cluster of falciparum malaria in Frankfurt, Germany, 2022.

Airport malaria is uncommon but increasing in Europe and often difficult to diagnose. We describe the clinical, epidemiological and environmental investigations of a cluster of airport malaria cases and measures taken in response. Three Frankfurt International Airport employees without travel histories to malaria-endemic areas were diagnosed with Plasmodium falciparum malaria in Germany in 2022. Two cases were diagnosed within 1 week, and the third one after 10 weeks. Two cases had severe disease, all three recovered fully. The cases worked in separate areas and no specific location for the transmissions could be identified. No additional cases were detected among airport employees. In June and July, direct flights from Equatorial Guinea, Nigeria and Angola and one parcel originating in Ghana arrived at Frankfurt airport. No vector-competent mosquitoes could be trapped to identify the source of the outbreak. Whole genome sequencing of P. falciparum genomes showed a high genetic relatedness between samples of the three cases and suggested the geographical origin closest to Ghana. A diagnosis of airport malaria should prompt appropriate and comprehensive outbreak investigations to identify the source and to prevent severe forms of falciparum malaria.

Human Filariasis in Travelers and Migrants: A Retrospective 25-year Analysis at the Institute of Tropical Medicine, Antwerp, Belgium.

BACKGROUND: Information on human filariasis in international travelers is scarce. We describe the epidemiology, clinical presentation, and outcome of these infections in a reference travel clinic over the past decades. METHODS: We reviewed all cases of filariasis diagnosed at the Institute of Tropical Medicine, Antwerp, Belgium, from 1994 to 2018. Diagnosis was obtained by either parasitological methods (confirmed) or strict clinical case definitions (probable). We assessed the characteristics of cases at diagnosis and response to therapy within 3-12 months. RESULTS: A total of 320 patients (median age: 41 years; 71% males) were diagnosed with 327 filarial infections (Wuchereria bancrofti = 6, Onchocerca volvulus = 33, Loa loa = 150, Mansonella perstans = 130, unspecified species = 8). Diagnosis was confirmed in 213/320 (67%) patients. European long-term travelers accounted for 166 patients (52%) and visitors/migrants from tropical countries for another 110 (34%). Central Africa was the likely region of acquisition for 294 (92%) patients. The number of filariasis cases decreased from 21.5/year on average in the 1990s to 6.3/year in the past decade, when loiasis became predominant. Cases reported symptoms in >80% of all filarial infections but mansonellosis (45/123 single infections; 37%). Lymphatic filariasis and onchocerciasis cases responded well to conventional therapy. However, 30% of patients with loiasis and mansonellosis experienced treatment failure (with diethylcarbamazine and levamisole-mebendazole, respectively). CONCLUSIONS: The burden and species distribution of filariasis in travelers evolved in the past decades. Most presentations were symptomatic. Case management would benefit from more effective therapies for loiasis and mansonellosis.

Mitigation of benznidazole toxicity and oxidative stress following ascorbic acid supplementation in an adult traveller with chronic indeterminate Chagas' disease.

BACKGROUND: Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas' disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment. OBJECTIVES: We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity. METHODS: We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000 mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation. RESULTS: AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient. CONCLUSIONS: We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage.

Detection of Zika Virus Replication in Human Semen by Reverse-Transcription Polymerase Chain Reaction Targeting of Antisense Ribonucleic Acid.

BACKGROUND: Persistence of Zika virus (ZIKV) ribonucleic acid (RNA) in semen is common after infection. METHODS: We designed a reverse-transcription polymerase chain reaction assay that targets antisense ZIKV RNA (asRNA) to assess ZIKV replication competence in ZIKV RNA-positive semen samples. RESULTS: We detected ZIKV asRNA in semen of 9 of 19 men (47.4%) diagnosed with ZIKV infection. All asRNA-positive samples had high ZIKV loads (cycle threshold values <26) and were obtained within 21 days of symptom onset. CONCLUSIONS: The sensitivity of the asRNA assay for detection of ZIKV replication was higher than that of conventional virus isolation methods (47.4% vs 21.1%, P = .032).

Epidemiological and Clinical Characteristics of International Travelers with Enteric Fever and Antibiotic Resistance Profiles of Their Isolates: a GeoSentinel Analysis.

Enteric fever, caused by Salmonella enterica serovar Typhi (S Typhi) and S. enterica serovar Paratyphi (S Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site's national guidelines. A total of 889 travelers (S Typhi infections, n = 474; S Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of <18 years old. Most individuals (41%) traveled to visit friends and relatives (VFRs) and acquired the infection in South Asia (71%). Child travelers with S Typhi infection were most frequently VFRs (77%). The median trip duration was 31 days (interquartile range, 18 to 61 days), and 448 of 691 travelers (65%) had no pretravel consultation. Of 143 S Typhi and 75 S Paratyphi isolates for which there were susceptibility data, nonsusceptibility to antibiotics varied (fluoroquinolones, 65% and 56%, respectively; co-trimoxazole, 13% and 0%; macrolides, 8% and 16%). Two S Typhi isolates (1.5%) from India were nonsusceptible to third-generation cephalosporins. S Typhi fluoroquinolone nonsusceptibility was highest when infection was acquired in South Asia (70 of 90 isolates; 78%) and sub-Saharan Africa (6 of 10 isolates; 60%). Enteric fever is an important travel-associated illness complicated by AMR. Our data contribute to a better understanding of region-specific AMR, helping to inform empirical treatment options. Prevention measures need to focus on high-risk travelers including VFRs and children.

Promising application of monoclonal antibody against chikungunya virus E1-antigen across genotypes in immunochromatographic rapid diagnostic tests.

BACKGROUND: Three different genotypes of chikungunya virus (CHIKV) have been classified: East/Central/South African (ECSA), West African (WA), and Asian. Previously, a rapid immunochromatographic (IC) test detecting CHIKV E1-antigen showed high sensitivity for certain ECSA-genotype viruses, but this test showed poor performance against the Asian-genotype virus that is spreading in the American continents. We found that the reactivity of one monoclonal antibody (MAb) used in the IC rapid diagnostic test (RDT) is affected by a single amino acid substitution in E1. Therefore, we developed new MAbs that exhibited specific recognition of all three genotypes of CHIKV. METHODS: Using a combination of the newly generated MAbs, we developed a novel version of the IC RDT with improved sensitivity to Asian-genotype CHIKV. To evaluate the sensitivity, specificity, and cross-reactivity of the new version of the IC RDT, we first used CHIKV isolates and E1-pseudotyped lentiviral vectors. We then used clinical specimens obtained in Aruba in 2015 and in Bangladesh in 2017 for further evaluation of RDT sensitivity and specificity. Another alphavirus, sindbis virus (SINV), was used to test RDT cross-reactivity. RESULTS: The new version of the RDT detected Asian-genotype CHIKV at titers as low as 10^4 plaque-forming units per mL, a concentration that was below the limit of detection of the old version. The new RDT had sensitivity to the ECSA genotype that was comparable with that of the old version, yielding 92% (92 out of 100) sensitivity (95% confidence interval 85.0-95.9) and 100% (100 out of 100) specificity against a panel of 100 CHIKV-positive and 100 CHIKV-negative patient sera obtained in the 2017 outbreak in Bangladesh. CONCLUSIONS: Our newly developed CHIKV antigen-detecting RDT demonstrated high levels of sensitivity and lacked cross-reactivity against SINV. These results suggested that our new version of the CHIKV E1-antigen RDT is promising for use in areas in which the Asian and ECSA genotypes of CHIKV circulate. Further validation with large numbers of CHIKV-positive and -negative clinical samples is warranted. (323 words).

Challenges in diagnosing Zika-experiences from a reference laboratory in a non-endemic setting.

Diagnosing a patient with Zika infection is not always straightforward. Here, we aim to describe our data collected from December 2015 to December 2017 and discuss the implemented algorithm and diagnostic challenges we encountered. At the National Reference Center for Arboviruses at the Institute of Tropical Medicine, Antwerp, Belgium (ITM), a commercial Zika virus (ZIKV) enzyme-linked immunosorbent assay (ELISA) detecting immunoglobulin (Ig) M and IgG, a commercial ZIKV immunofluorescence assay (IFA) detecting IgM, and an in-house Zika virus neutralization test (VNT) were implemented. For molecular detection of ZIKV, an in-house and a commercial real-time RT-PCR were applied. An algorithm, adapted from the European Centre for Disease Control and Prevention (ECDC), was implemented. Between December 2015 and December 2017, we tested 6417 patients for ZIKV. Of those, according to ECDC criteria, 127 (2.0%) were classified as a confirmed Zika infection of which 39 by RT-PCR (0.6%), 15 (0.2%) as a probable Zika infection, 73 (1.1%) as undefined, and 65 (1.0%) as false positive reactions. Main challenges were the brief window for detection of IgM, cross-reactivity of antibodies with other flaviviruses and malaria, and low VNT titers in the acute phase. In RT-PCR negative samples, classification of ZIKV infection as recent or past proved difficult, when IgM was negative. The majority of patients could be classified according to ECDC criteria, though 1.1% of patients remained "undefined" and 1.0% were ELISA false positive reactions. Complementary IFA IgM was of added value to increase IgM detection rates. Improved serological assays and more longitudinal data on antibody kinetics are needed.

Zika virus in semen: a prospective cohort study of symptomatic travellers returning to Belgium.

OBJECTIVE: To prospectively monitor Zika viral loads in semen from Belgian travellers with confirmed Zika virus infection, who returned from the Americas during the 2016 Zika virus epidemic. METHODS: We recruited symptomatic travellers consulting our clinic and we confirmed infection with either reverse-transcriptase (RT) polymerase chain reaction (PCR) assay or virus neutralization test. The participants produced semen samples weekly, either at the clinic or at home. For the initial sample, the laboratory staff did a microscopy analysis if they received the sample within an hour of production. Using RT-PCR, we monitored Zika virus ribonucleic acid (RNA) loads in semen until we obtained two negative results. FINDINGS: We detected Zika virus RNA in nine of 15 participants' semen, one of whom was vasectomized. The median time to loss of RNA detection in semen was 83 days after symptom onset (95% confidence interval, CI: 57-108). The longest duration of viral shedding in semen before obtaining the first negative RT-PCR result was 144 days after symptom onset. All of the 11 participants, for whom we microscopically analysed their semen, had presence of leukocytes, 10 showed haematospermia and six showed oligospermia. These abnormalities occurred irrespective of Zika virus detection in semen. CONCLUSION: The majority of men in our study had detectable Zika virus RNA in their semen. We recommend that semen from Zika virus-infected men should be analysed with RT-PCR and that health professionals should advise infected men, even if they are vasectomized, about current recommendations for prevention of sexual transmission of the virus.

Acute-phase diagnosis of murine and scrub typhus in Belgian travelers by polymerase chain reaction: a case report.

BACKGROUND: Rickettsiosis is a potential life threatening infectious disease in travelers. Clinical recognition is not always straightforward, as typical manifestations such as rash and/or eschar may be absent. Definite diagnosis is based on seroconversion and therefore often delayed until the convalescent phase of disease. CASE PRESENTATION: In this case report, we describe four patients with severe travel-related rickettsiosis (two patients with murine- and two patients with scrub typhus), in whom acute- phase diagnosis was possible by real-time polymerase chain reaction on serum or blood. CONCLUSIONS: Despite its limitations, we think that polymerase chain reaction can contribute significantly to the early diagnosis and treatment of rickettsial disease in travelers.

Patient characteristics and antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae infections in international travellers: a GeoSentinel analysis.

BACKGROUND: Antimicrobial resistance (AMR) is a global health crisis, with Enterobacterales including Escherichia coli and Klebsiella pneumoniae playing significant roles. While international travel to low- and middle-income countries is linked to colonisation with AMR Enterobacterales, the clinical implications, particularly the risk of subsequent infection, remain unclear due to limited data. We aimed to characterise E. coli and K. pneumoniae infections in travellers and the antimicrobial susceptibility profiles of their isolates. METHODS: We analysed data on E. coli and K. pneumoniae infections in travellers collected at GeoSentinel sites between 2015 and 2022, focusing on epidemiological, clinical and microbiological characteristics. We defined multi-drug resistance (MDR) as non-susceptibility to agents from at least three drug classes. RESULTS: Over the 8-year period, we included 655 patients (median age 41 years; 74% female) from 57 sites in 27 countries, with 584 E. coli and 72 K. pneumoniae infections. Common travel regions included Sub-Saharan Africa, Southeast Asia, and South-Central Asia. Urinary tract infections predominated. Almost half (45%) were hospitalised. Among infections with antimicrobial susceptibility data across three or more drug classes, 203/544 (37%) E. coli and 19/67 (28%) K. pneumoniae demonstrated MDR. Over one-third of E. coli and K. pneumoniae isolates were non-susceptible to third-generation cephalosporins and cotrimoxazole, with 38% and 28% non-susceptible to fluoroquinolones, respectively. Travellers to South-Central Asia most frequently had isolates non-susceptible to third-generation cephalosporins, fluoroquinolones and carbapenems. We observed increasing frequencies of phenotypic extended spectrum beta-lactamase and carbapenem resistance over time. CONCLUSIONS: E. coli and K. pneumoniae infections in travellers, particularly those to Asia, may be challenging to empirically treat. Our analysis highlights the significant health risks these infections pose to travellers and emphasises the escalating global threat of AMR. Enhanced, systematic AMR surveillance in travellers is needed, along with prospective data on infection risk post travel-related AMR organism acquisition.

Full Genome Characterization of the First Oropouche Virus Isolate Imported in Europe from Cuba.

On 27 May 2024, the Cuban Ministry of Health reported the first outbreak of Oropouche fever on the island. The etiologic agent, Oropouche virus (OROV), is a poorly understood arbovirus that has been known since the 1960s and represents a public health burden in Latin America. We report the whole-genome characterization of the first European OROV isolate from a returning traveler from Cuba with Oropouche fever-like symptoms. The isolate was obtained from the patient's serum; whole-genome sequencing was performed by next-generation sequencing, followed by phylogenetic analysis and genetic variability studies. The analysis showed that the most closely related sequence was from the French Guiana 2020 outbreak. Interestingly, our isolate is a reassortant virus, included in a highly supported monophyletic clade containing recent OROV cases (Brazil 2015-Colombia 2021), separated from the other four previously known genotypes. More deeply, it was found to be included in a distinct branch containing the sequences of the Brazil 2022-2024 outbreak. The reassortment event involved the S and L segments, which have high similarity with sequences belonging to a new cluster (here defined as OROV_SCDC_2024), while the M segment shows high similarity with older sequences. These results likely describe the viral strain responsible for the current outbreak in Cuba, which may also reflect the ongoing outbreak in Latin America. Further studies are needed to understand how OROV evolves towards traits that facilitate its spread and adaptation outside its original basin, and to track its spread and evolution in the European continent.

Impact of dengue fever on depression, anxiety, and stress symptoms in Esmeraldas Province, Ecuador: a prospective cohort study.

BACKGROUND: Physical symptoms of dengue have been documented extensively, but knowledge gaps on dengue-associated mental health hazards remain. We investigated the frequency of psychiatric symptoms (depression, anxiety, and stress) and neurocognitive performance during the first year after a dengue episode. METHODS: Using DASS-21 scores at 3, 6, and 12 months, we assessed depression, anxiety, and stress in anti-dengue IgM-positive adults and matched controls during the 2021 dengue season in Esmeraldas Province, Ecuador. Patients with DASS-21 scores ≤ 4 were considered normal; those with scores of 5-7, 8-10, and ≥ 11 indicated mild, moderate, and severe depression, respectively; cutoff scores for anxiety and stress were ≥ 5 and ≥ 9, respectively. We also assessed 'delayed matching to sample' (DMS) and 'spatial working memory' (SWM) using the Cambridge Neuropsychological Test Automated Battery. RESULTS: We enrolled 102 cases and 78 controls. At 3 months, 90 cases and 70 controls were available for follow-up, among these 40/90 (44.4%) cases and 12/70 (17.1%) controls had DASS-21 scores ≥ 5 (RR 2.7, 95% CI [1.5-4.7]). Dengue remained a predictor for depression after adjusting for age, sex, and COVID-19 status. We observed no difference in anxiety between the groups, but stress scores increased at month 3 (RR 1.87, 95% CI [1.01-3.4]). DASS-21 scores normalized during follow-up. DMS and SWM did not differ between groups at 3 and 6 months. At month 12, cases had lower SWM than controls did (p value < 0.001). CONCLUSIONS: Care providers should be aware of dengue-associated mood disorders and facilitate timely referral to mental health services. Future longitudinal studies are warranted to validate our observations regarding the impact of dengue on mental health and neurocognitive status in affected patients.