Rosanne W. Wieten

Health risks of travelers with medical conditions - a retrospective analysis.

BACKGROUND Traveling the world may result in infection with tropical or other travel-associated diseases. This applies increasingly also to people with immune-compromising and other medical conditions, as well as to elderly individuals. To reduce exposure and susceptibility to health risks, there is a need for appropriate pre-travel advice for these particular groups of travelers. METHODS In this observational study, we analyzed the overall risk of health problems among travelers with underlying medical conditions who attended the University of Amsterdams Academic Medical Centers (AMC) travel clinic from January to October 2010. Telephone questionnaires were administered to 345 travelers with underlying conditions and 100 healthy travelers. RESULTS The most common underlying medical conditions studied included: (1) diabetes mellitus; (2) impaired immunity due to use of immune-suppressing medication; (3) reduced gastric barrier; and (4) HIV infection. The overall incidence of travel-related diseases (TRDs) was higher among those patients with underlying medical conditions compared to healthy travelers [incidence rate ratio (IRR) 2.26, 95% CI (1.29-3.98)]. Of all diseases reported, gastrointestinal disease, fever, and respiratory problems were reported most frequently. Travel to Central America, South Central Asia, Northeast Asia, and North Africa was associated with increased risk of contracting TRD. Hepatitis B protection was absent or unknown in 75% of these travelers. CONCLUSIONS Travelers with medical conditions had a higher risk of obtaining TRD, predominantly gastrointestinal in nature.

Serum lipids and lipoproteins in malaria - a systematic review and meta-analysis

BackgroundSerum lipid profile changes have been observed during malaria infection. The underlying biological mechanisms remain unclear. The aim of this paper is to provide an overview on those serum lipid profile changes, and to discuss possible underlying biological mechanisms and the role of lipids in malaria pathogenesis.MethodsA systematic review and meta-analysis to determine lipid profile changes during malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to 11 July, 2013, that measured serum lipid parameters in malaria patients. Also, major trial registries were searched. Mean differences in lipid profile parameters were combined in fixed and random effects meta-analysis, with a separate analysis for different groups of controls (healthy, other febrile illnesses or very low parasitaemia). These parameters were also compared between severe malaria and uncomplicated malaria. Funnel plots were used to test for publication bias.ResultsOf 2,518 studies reviewed, 42 met the criteria for inclusion in the qualitative analysis, and of these, 15 reported the necessary data for inclusion in the meta-analysis for cholesterol; nine for high-density lipoprotein (HDL), eight for low-density lipoprotein (LDL), and nine for triglycerides, respectively. Total cholesterol, HDL and LDL concentrations were lower in malaria and other febrile diseases compared to healthy controls. The decline was more pronounced and statistically significant during malaria compared to other febrile diseases. These results were consistent across included studies. Triglycerides were raised compared to healthy controls, but not statistically significant when compared to symptomatic controls.ConclusionsThis meta-analysis suggests that the observed lipid profile changes are characteristic for malaria. Although a definite link with the pathogenesis of malaria cannot yet be demonstrated, plausible hypotheses of biological mechanisms involving host lipid alterations and the pathogenesis of malaria exist. An increased research effort to elucidate the precise pathways is warranted, since this could lead to better understanding of malaria pathophysiology and consequently to novel treatment approaches.

Efficacy and safety of artemisinin combination therapy (ACT) for non-falciparum malaria: a systematic review

BackgroundArtemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.MethodsA PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.ResultsThe literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.ConclusionACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.Trial registrationCRD42014009103

Response to Hepatitis A Vaccination in Immunocompromised Travelers

BACKGROUND Hepatitis A vaccines are highly immunogenic in healthy patients, but there is uncertainty about their immunogenicity in immunocompromised patients. METHODS Our study included immunocompromised patients who received 1 or 2 hepatitis A vaccinations between January 2011 and June 2013. We assessed factors that influenced the serologic response to vaccination. We performed a literature review of previous studies on hepatitis A vaccination in immunocompromised patients. RESULTS Of 85 immunocompromised patients, 65 used immunosuppressive drugs, 13 had received stem cell transplants, and 7 were infected with human immunodeficiency virus. After vaccination, 65 of 85 (76.5%) developed antibodies. Tumor necrosis factor α blocker use was associated with better serologic responses than other immunosuppressive drugs. Female patients were more compliant than male patients with postvaccination antibody titer measurements. In 11 relevant studies, antibody responses after the first and second vaccination averaged 37% and 82%, respectively. Factors that negatively influenced serologic response rates were high doses of immunosuppressive drugs, fewer hepatitis A vaccinations, and a short interval between vaccination and antibody measurement. CONCLUSIONS Immunocompromised patients showed moderate to good serologic responses to hepatitis A vaccination, but may need more time to develop immunity. Tumor necrosis factor α blocker use was associated with better antibody responses than other drugs. Specifically, male patients should be motivated to return for antibody titer measurements.

Rabies vaccinations: are abbreviated intradermal schedules the future?

Rabies is a deadly disease, and current preexposure vaccination schedules are lengthy and expensive. We identified nine studies investigating abbreviated schedules. Although initial responses were lower, accelerated adequate immune responses were elicited after booster vaccinations. Lower-dose (and therefore cheaper) vaccination schedules may constitute a valid alternative to current vaccination schedules.

Towards improved uptake of malaria chemoprophylaxis among West African travellers: identification of behavioural determinants

BackgroundMalaria is a potentially lethal illness for which preventive measures are not optimally used among all travellers. Travellers visiting friends and relatives in their country of origin (VFRs) are known to use chemoprophylaxis less consistently compared to tourist travellers. In this study, factors explaining the low use of chemoprophylaxis were pursued to contribute to improving uptake of preventive measures among VFRs.MethodsFollowing in-depth interviews with Ghanaians living in Amsterdam, a questionnaire was developed to assess which behavioural determinants were related to taking preventive measures. The questionnaire was administered at gates of departing flights from Schiphol International Airport, Amsterdam (the Netherlands) to Kotoka International Airport, Accra (Ghana).ResultsIn total, 154 questionnaires were eligible for analysis. Chemoprophylaxis had been started by 83 (53.9%) and bought by 93 (60.4%) travellers. Pre-travel advice had been obtained by 104 (67.5%) travellers. Those who attended the pre-travel clinic and those who incorrectly thought they had been vaccinated against malaria were more likely to use preventive measures. Young-, business- and long-term travellers, those who had experienced malaria, and those who thought curing malaria was easier than taking preventive tablets were less likely to use preventive measures.ConclusionAlmost half of the VFRs travelling to West Africa had not started chemoprophylaxis; therefore, there is room for improvement. Risk reduction strategies could aim at improving attendance to travel clinics and focus on young-, business and long term travellers and VFRs who have experienced malaria during consultation. Risk reduction strategies should focus on improving self-efficacy and conceptions of response efficacy, including social environment to aim at creating the positive social context needed.

Molecular Diagnostics of Rickettsia africae Infection in Travelers Returning from South Africa to The Netherlands

BACKGROUND African tick-bite fever (ATBF) is frequently diagnosed in The Netherlands in travelers returning from South Africa. It is caused by Rickettsia africae and diagnosis is based on travel history and clinical presentation and usually confirmed by detecting serum antibodies against rickettsiae of the spotted fever group. However, these typically occur late in the course of the disease, and a mild clinical course or early antibiotic treatment can diminish antibody production. METHODS AND RESULTS Four travelers presented with (sub)febrile temperatures and eschar(s), several days after returning from South Africa. R. africae DNA was amplified and sequenced from skin biopsies of the eschars of all patients. Initial immunofluorescence assays yielded no immunoglobulin M (IgM)/IgG antibodies directed against spotted fever group rickettsiae; however, serology in the convalescent phase-several weeks after the patients had fully recovered-was positive. CONCLUSIONS ATBF should be considered in travelers returning from South Africa to The Netherlands with febrile illness and (multiple) skin lesions. The diagnosis can be confirmed by (paired) serology; however, polymerase chain reaction and sequencing on skin biopsies could be a (faster and more accurate) confirmatory test. Advantages of molecular methods over serology are species identification and high sensitivity early in the course of the disease.

Yellow fever revaccination guidelines change – a decision too feverish?

M. P. Grobusch, A. Goorhuis, R. W. Wieten, J. D. M. Verberk, E. F. F. Jonker, P. J. J. van Genderen and L. G. Visser 1) Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, 2) Department of Infectious Diseases, Leiden University Medical Center, Leiden University, Leiden and 3) Institute for Tropical Diseases, Harbour Hospital Rotterdam, Rotterdam, the Netherlands E-mail: m.p.grobusch@amc.uva.nl Article published online: 13 July 2013

A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination.

Introduction Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as a proxy for potentially longer lasting immunity. Methods and Findings PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07–3.1%). On day 180, these cells were still present (median 0.06%, range 0.02–0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells. Conclusion The presence of a functionally competent YF-specific memory T-cell pool 18 years and sufficient titers of neutralizing antibodies 35–40 years after first vaccination suggest that single vaccination may be sufficient to provide long-term immunity.

Dengue in travellers: applicability of the 1975–1997 and the 2009 WHO classification system of dengue fever

Objectives  The aim of this study was to assess the applicability and benefits of the new WHO dengue fever guidelines in clinical practice, for returning travellers.