Coinfections and antimicrobial treatment in a cohort of falciparum malaria in a non-endemic country: a 10-year experience.

INTRODUCTION: Falciparum malaria remains one of the deadliest infectious diseases worldwide. In Germany, it is mainly an imported infection among travellers. Rates of coinfection are often unknown, and a clinical rationale for the beneficial use of calculated antibiotic therapy in patients with malaria and suspected coinfection is lacking. METHODS: We conducted an analysis of all in-patients treated with falciparum malaria at a German infectious diseases centre in vicinity to one of Europe's major airports for 2010-2019. Logistic regression and time-to-event analysis were used to evaluate predictors for bacterial coinfection, the use of antibacterial substances, as well as their influence on clinical course. RESULTS: In total, 264 patients were included. Of those, 64% received an additional antibacterial therapy (n = 169). Twenty-nine patients (11.0%) were found to have suffered from a relevant bacterial coinfection, while only a small fraction had relevant bacteremia (n = 3, 1.4%). However, patients with severe malaria did not suffer from coinfections more frequently (p = 0.283). CRP levels were not a reliable predictor for a bacterial coinfection (OR 0.99, 95% CI 0.94-1.06, p = 0.850), while another clinical focus of infection was positively associated (OR 3.86, 95% CI 1.45-11.55, p = 0.010). CONCLUSION: Although bacterial coinfections were rare in patients with malaria at our centre, the risk does not seem negligible. These data point rather towards individual risk assessment in respective patients than to general empiric antibiotic use.

Predictors of aetiology and outcomes of acute gastrointestinal illness in returning travellers: a retrospective cohort analysis.

BACKGROUND: Gastrointestinal illness is a major cause of morbidity in travellers and is a common reason for presentation to healthcare services on return. Whilst the aetiology of imported gastrointestinal disease is predominantly infectious, outcomes are variable due to a range of phenomena such as post-infectious irritable bowel syndrome, drug resistance and occult pathology (both infectious and non-infectious). Previous studies have focussed on predictors of aetiology of gastrointestinal disease in travellers; we present a retrospective study combining both aetiological and early outcome data in a large cohort of returned travellers. METHOD: We identified 1450 patients who attended our post-travel walk-in clinic with gastrointestinal symptoms between 2010 and 2016. Demographic, travel, clinical and laboratory data was collected through case note review. Logistic regression analysis to examine correlates of aetiology and outcome were performed in R (CRAN Project 2017). RESULTS: Of 1450 patients in our cohort 153 reported bloody diarrhoea and 1081 (74.6%) reported non-bloody diarrhoea. A definitive microbiological diagnosis was made in 310 (20.8%) of which 137 (9.4%) had a parasite identified and 111 (7.7%) had a bacterial cause identified. Factors associated with a parasitological diagnosis included history of travel to South Asia (aOR = 2.55; 95%CI 1.75-3.70, p < 0.0001) and absence of bloody diarrhoea (aOR = 0.22; 95%CI 0.066-0.53, p < 0.005). Factors associated with a bacteriological diagnosis included male gender (aOR = 1.69; 95%CI 1.10-2.62, p < 0.05), an age < 37 years on presentation (aOR = 2.04; 95%CI 1.25-3.43, p < 0.01), white cells on stool microscopy (aOR = 3.52; 95%CI 2.09-5.86, p < 0.0001) and a C-reactive protein level of >5iu/dL (aOR = 4.68; 95%CI 2.91-7.72, p < 0.0001). The majority (1235/1450, 82.6%) reported full symptomatic resolution by the first follow up visit; factors associated with lack of symptomatic resolution included female gender (aOR = 1.45 95%CI 1.06-1.99, p < 0.05), dysenteric diarrhoea (aOR = 2.14 (95%CI 1.38-3.25, p < 0.0005) and elevated peripheral leukocyte count (aOR = 1.58 95%CI 1.02-2.40, p < 0.05). CONCLUSIONS: In a cohort of returned travellers, we were able to identify multiple factors that are correlated with both aetiology and outcome of imported gastrointestinal syndromes. We predict these data will be valuable in the development of diagnostic and therapeutic pathways for patients with imported gastrointestinal infections.

Outpatient management of uncomplicated enteric fever: A case series of 93 patients from the Hospital of Tropical Diseases, London.

OBJECTIVES: Enteric fever is predominantly managed as an outpatient condition in endemic settings but there is little evidence to support this approach in non-endemic settings. This study aims to review the outcomes of outpatients treated for enteric fever at the Hospital of Tropical Diseases in London, UK. METHODS: We conducted a retrospective analysis of all patients with confirmed enteric fever between August 2009 and September 2020. Demographic, clinical, laboratory and microbiological data were collected and compared between the inpatient and outpatient populations. Outcomes investigated were complicated enteric fever, treatment failure and relapse. RESULTS: Overall, 93 patients (59% male, median age 31) were identified with blood and/or stool culture confirmed enteric fever and 49 (53%) of these were managed as outpatients. The commonest empirical treatment for outpatients was azithromycin (70%) and for inpatients was ceftriaxone (84%). Outpatients were more likely than inpatients to receive only one antibiotic (57% vs 19%, p < 0.01) and receive a shorter duration of antibiotics (median 7 vs 11 days, p <0.01). There were no cases of complicated disease or relapse in either the inpatient or outpatient groups. There was one treatment failure in the outpatient group. Azithromycin was well-tolerated with no reported side effects. CONCLUSIONS: Our findings suggest that outpatient management of uncomplicated imported enteric fever is safe and effective with the use of oral azithromycin. Careful monitoring of patients is recommended as treatment failure can occur.

Performance of rapid tests in the management of dengue fever imported cases in Lazio, Italy 2014-2019.

BACKGROUND: In Italy, dengue virus is the most frequent agent of imported viral infections. The use of rapid diagnostic tests (RDTs) may be of help as a preliminary user-friendly quick assay to facilitate dengue diagnosis, as ordinary laboratory diagnosis of dengue fever may require special efforts in terms of tools availability, interpretation of results, and skilled personnel. The performance of RDTs, however, may vary according to different epidemiological and laboratory background. METHODS: We reviewed five years of laboratory records of two dengue RDT results (Colorimetric SD-Bioline Dengue-Duo-RDT and Fluorimetric SD-Biosensor-STANDARD-F-Dengue-RDT), able to detect viral NS1 antigen and specific IgM and IgG. Diagnostic parameters were calculated using as reference the results of molecular (RT-PCR) and serological (immunofluorescence, IFA) tests. Overall performance, calculated considering the final case definition, was included in the accuracy assessment of RDTs. RESULTS: The combined use of NS1 and IgM/IgG RDT for the detection of acute dengue cases resulted in an overall sensitivity and specificity of 87.2% and 97.9% for Colorimetric RDT, 96.2% and 96.2% for Fluorimetric RDT. NS1 was the most reliable marker of acute infection, while IgM resulted falsely positive in nine samples, including sera derived from 2 Zika and 4 non-arbovirus infected patients. CONCLUSIONS: The inclusion of RDT in the diagnostic algorithm is of undeniable help in the prompt management and surveillance of dengue infection in non-endemic areas. Confirmatory tests are, however, necessary to rule in or rule out dengue fever diagnosis.

Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers.

OBJECTIVES: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. METHODS: Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. RESULTS: In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. CONCLUSIONS: MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. SUMMARY: Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods.

Diagnostic approach to encephalitis and meningoencephalitis in adult returning travellers.

BACKGROUND: Encephalitis and meningoencephalitis are severe, sometime life-threatening infections of the central nervous system. Travellers may be exposed to a variety of neurotropic pathogens. AIMS: We propose to review known infectious causes of encephalitis in adults acquired outside Europe, and how to identify them. SOURCES: We used Pubmed and Embase, to search the most relevant publications over the last years. CONTENT: Microbiologic tests and radiological tools to best identify the causative pathogen in travellers presenting with encephalitis and ME are presented in this narrative review, as well as a diagnostic approach tailored to the visited area and types of exposures. IMPLICATIONS: This review highlights the diagnostic difficulties inherent to exotic causes of central nervous system infections, and attempts to guide clinicians with respect to which microbiological tests to consider, in addition to brain MRI, when approaching a returning traveller presenting with encephalitis.

Travellers returning ill from the tropics - a descriptive retrospective study.

International travel continues to increase in frequency. Health care providers need a wide understanding of the spectrum of travel related diseases and their management. This retrospective study analyses the demographic and clinical data of 360 travellers returning from the tropics presenting to an outpatient clinic at a tertiary hospital between 2003 - 2007. The aim of this study was to analyse the frequency of presenting symptoms and diseases in ill returning travellers and to correlate them to the areas visited and the duration and purpose of travel. The main symptoms during travel were diarrhoea (n = 200, 56 %) and fever (n = 124, 34 %). Travellers not visiting friends and relatives but with close contact to the local population were at more than two-fold increased risk of diarrhoea (Odds Ratio [OR] 2.5; 95 % confidence interval [CI] 1.1-6.0, p = 0.03) and fever (OR 2.4; 95 % CI 1.1-5.3; p = 0.02) compared to tourist travellers. Travellers visiting friends and relatives (VFR) were not at increased risk for diarrhoea (OR 0.6; 95 % CI 0.3-1.3; p = 0.17), or fever (OR 1.5; 95 % CI 0.7-3.4; p = 0.28). Thirty-two percent of all travellers (n = 115) were diagnosed with a specific pathogen. Malaria (6 %), giardiasis (6 %) and amebiasis (4 %) were the most frequently detected pathogens. The odds of malaria as a cause of the presenting illness was lower among travellers reporting pre-travel advice. Specific antimicrobial treatment was required in around one third of the patients.

Skin lesions in returning travellers.

Skin lesions, apart from diarrhoeas, fever of unknown origin, and respiratory tract infections belong to the most frequent medical problems in travellers returned from tropical and subtropical destinations, accounting more than 10% of reported cases. Most dermatoses have their clinical onset during travel, although some of them can occur after return. Travel-related dermatological problems can have a wide spectrum of clinical picture, from macular, popular or nodular rash, linear and migratory lesions, to plaques, vesicles, bullae, erosions or ulcers. Skin conditions in returning travellers may be of infectious and non-infectious aetiologies. Infectious lesions may be originally tropical (e.g. dengue, chikungunya, schistosomiasis, leishmaniasis, myiasis, tungiasis, loiasis), although the majority are cosmopolitan (arthropod bites, sunburns, allergic rashes). The evaluation of skin lesions depends on many factors, including immune status of patients, use of medicines, exposure on health hazards (fauna, flora, risky behaviours), as well as the time, duration and location of travel. As the number of travellers to tropical and subtropical destinations has been continuously rising, the number of skin illnesses has also been increasing. This means that specialists in travel medicine need to extend their knowledge of epidemiology, clinical features and diagnosis of travel-related health problems including skin lesions in returning travellers.

Laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers.

The gold standard for laboratory diagnosis of schistosomiasis is the presence of typical eggs in stool or urine. The laboratory diagnosis of schistosomiasis and Katayama syndrome in returning travellers is difficult because the number of excreted eggs is often very limited. In early infections and in patients with only a few contacts with contaminated water, the total number of parasites, migrating larvae or schistosomulae, and adult worms, is very low. Eggs can only be found in faeces or urine when there is at least one pair of adult worms at the final location. The number of parasites increases as a function of the number of contacts with infected water. The exact latency between contamination and egg production is unknown. It is estimated that excretion of eggs starts after 40-50 days. The specific diagnosis of early schistosomiasis and Katayama fever relies essentially on serologic tests or preferably on PCR (if available). These assays are much more sensitive (up to four times) in the early phase of schistosomiasis than microscopic examination for typical eggs. Eosinophilia (sometimes exceeding 50%) is often present in patients with acute schistosomiasis (Katayama fever), but may be limited or absent in late fibrotic manifestations of the disease.