Alfons Van Gompel

Vaccinations in patients with immune-mediated inflammatory diseases

Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals.

Personal protection against European disease vectors

tions that, up until that time, had only received an episodic focus. One drawback of the book is that the authors cover a wide gamut of topics. Consequently, disease-specifi c topics are presented without adequately providing the necessary background on the disease entity to the reader. Not all readers may fully understand the necessary disease-specifi c background that would make the discussions of public health intervention understandable. For instance, the chapter on TB presents a history of the disease from the turn of the 20th century. But if the reader were unaware of the public health threat posed by the undiagnosed or nonadherent TB patient, the reader would understandably question the authority of public health practitioners to occasionally take extraordinary steps to ensure that infection is not transmitted within the community. Even without a comprehensive background on specifi c diseases, this book will interest a wide audience, not only public health practitioners but the medical and legal community with whom we partner. Searching Eye tackles a topic that deserves more of our respective attention, for as noted by the authors, “The vitality of democratic communities necessitates an ongoing effort to negotiate and renegotiate the boundaries between privacy, society’s limiting principle, and public health, which at its best has sought to expand the role of government as a guardian against disease and suffering.” I congratulate the authors on their wellresearched and thorough discourse on this core public health activity.

Likelihood ratios: A real improvement for clinical decision making?

The concept of likelihood ratio has been advocated for several years as one of the better means to evaluate diagnostic tests and as a practical and valuable tool in clinical decision making. In this paper we review the basic concepts underlying the evaluation of diagnostic tests and we explore the properties and usefulness of both positive and negative likelihood ratios compared with sensitivity and specificity. Particular attention is given to the use of likelihood ratios in the clinical setting. Likelihood ratios have three main advantages: they are intuitive, they simplify the predictive value calculation and the overall evaluation of sequential testing. Disadvantages are the non-linearity and the necessity to recalculate probabilities in odds. Although they summarize the information contained in sensitivity and specificity, these characteristics are still necessary for certain clinical decisions. Since likelihood ratios have been promoted among physicians and medical students, we discuss examples of inappropriate use and misunderstandings in the medical literature: the frequent omission of confidence intervals, the choice of cut-off points based on likelihood ratios for positive test results only and the confusion between likelihood ratios for ranges and those for cut-off points.

Schistosomiasis in travellers and migrants.

Schistosomiasis is a tropical parasitic disease caused by blood-dwelling fluke worms of the genus Schistosoma whose infective stages, the cercariae, are amplified through mollusks acting as intermediate hosts. People are infected when exposed to fresh water containing cercariae that penetrate the skin. There are however considerable differences in intensity of infection and morbidity, depending on the pattern of exposure and the infective species. In travellers, schistosomiasis differs substantially from infection in endemic populations in many aspects: geography, morbidity, treatment and prevention. In migrants, schistosomiasis manifests itself in a way more akin to what is seen in endemic populations. In this paper we will review the specific issues associated with schistosomiasis in travellers and migrants, with emphasis on the acute disease manifestations in non-immune persons, and on neuroschistosomiasis as a potential severe complication. We discuss new trends in diagnosis and treatment with respect to the specific disease stage, and summarize precautionary measures and novel ways to prevent Schistosoma infection in travellers.

Imported Relapsing Fever in European Tourists

Two imported cases of relapsing fever after a trip through Senegal are described. Two women developed a tick-borne relapsing fever after having slept outdoors on a terrace in Zinguichor, Senegal. The first patient was rapidly cured after a course of doxycycline. The second patient initially received erythromycin, but despite this treatment she developed neurological symptoms and Borrelia persisted in the thick-smear examination. After treatment with doxycycline she developed a Jarish-Herxheimer reaction. Treatment with doxycycline was continued and finally all symptoms disappeared within 36 hours after starting this treatment. A diagnosis of relapsing fever should be considered in all patients returning from the tropics with recurrent fever, especially if no malaria parasites are found.

Sexual Risk Behavior of Travelers who Consulted a Pretravel Clinic

OBJECTIVEnThe objective of this study was to determine to which degree travelers who received pretravel advice at a travel clinic have protected or unprotected sexual contact with a new partner and what factors influence this behavior.nnnMETHODnAn anonymous questionnaire was sent to travelers who came to a pretravel clinic between June 1 and August 31, 2005. Risk factors for casual travel sex and predictors of protected sex were studied in a multivariate model.nnnRESULTSnA total of 1,907 travelers were included (response rate 55%) in the study. Only 4.7% of the respondents had sexual contact with a new partner, and 63.1% of these new partners were from the country of destination. Of those who had casual travel sex, 52.4% did not expect this (women 75%), 30.9% did not always use condoms, and 41% were not protected against hepatitis B. Independent risk factors for casual travel sex were traveling without steady partner (OR 14.4), expecting casual travel sex (OR 9.2), having casual sexual contacts in the home country (OR 2.4), non-tourist journeys (OR 2.2), being male (OR 2.1), the fact that the information on sexually transmitted infections (STI) had been read (OR 2.0), and traveling to South and Central America (OR 2.0). Taking condoms along (OR 5.4) and reading the information on STI (OR 3.3) were identified as independent predictors of protected sex.nnnCONCLUSIONSnTravelers have substantial sexual risk behavior. Casual sex is usually not expected, and the most important predictor is traveling without a steady partner. We would advice every client of a travel clinic who will travel without a steady partner to read the STI information, to take condoms along, and to be vaccinated against hepatitis B.

Recurrence of blackwater fever: triggering of relapses by different antimalarials.

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.

Trends of norfloxacin and erythromycin resistance of Campylobacter jejuni/Campylobacter coli isolates recovered from international travelers, 1994 to 2006.

BACKGROUNDnCampylobacter sp. is a major cause of bacterial enterocolitis and travelers diarrhea. Empiric treatment regimens include fluoroquinolones and macrolides.nnnMETHODSnOver the period 1994 to 2006, 724 Campylobacter jejuni/Campylobacter coli isolates recovered from international travelers at the outpatient clinic of the Institute of Tropical Medicine, Antwerp, Belgium, were reviewed for their susceptibility to norfloxacin and erythromycin.nnnRESULTSnNorfloxacin resistance increased significantly over time in isolates from travelers returning from Asia, Africa, and Latin America. For the years 2001 to 2006, norfloxacin resistance rates were 67 (70.5%) of 95 for Asia, 20 (60.6%) of 33 for Latin America, and 36 (30.6%) of 114 for Africa. The sharpest increase was noted for India, with no resistance in 1994, but 41 (78.8%) of 52 resistant isolates found during 2001 to 2006. Erythromycin resistance was demonstrated in 20 (2.7%) isolates, with a mean annual resistance of 3.1% +/- 2.8%; resistance increased over time, with up to 3(7.5%) of 40 and 3 (8.6%) of 35 resistant isolates in 2004 and 2006, respectively (p < 0.05); there was no apparent geographic association. Combined resistance to norfloxacin and erythromycin was observed in five isolates.nnnCONCLUSIONSnThe high resistance rates to fluoroquinolones warrant reconsideration of their use as drugs of choice in patients with severe gastroenteritis when Campylobacter is the presumed cause. Continued monitoring of the incidence and the spread of resistant Campylobacter isolates is warranted.

Falciparum malaria in patient 9 years after leaving malaria-endemic area.

To the Editor: A 30-year-old African man, without any specific medical history, came to the emergency department of Brugmann University Hospital in Brussels, Belgium, on March 18, 2008, because of malaise, profuse transpiration, and dizziness that day. He also reported a 3-day history of muscle pain and pain while urinating, for which his general practitioner prescribed ciprofloxacin. Originally from Guinea-Conakry, the patient reported no travel outside Belgium after his arrival >9 years earlier. No recurrent fever episodes were noted during this period. Two weeks before becoming ill, a friend visiting from Guinea-Conakry stayed at his home for 7 days. n nResults of a physical examination were normal, except for a temperature of 37.5°C. Blood analysis showed moderate anemia (hemoglobin 12.9 g/dL) and thrombocytopenia (platelet count 73,000/μL) with total bilirubin and C-reactive protein levels of 1.5 mg/dL and 7.0 mg/dL, respectively. Because we suspected subfebrile malaria in this patient, a blood smear was prepared. It showed ring-shaped trophozoites of Plasmodium falciparum with a parasite density of 0.1%. Serologic tests showed an antibody titer to Plasmodium spp. of 3,200. A blood sample was sent to the national reference laboratory at the Institute of Tropical Medicine in Antwerp. The diagnosis of P. falciparum malaria was confirmed by microscopy and real-time PCR. Follow-up was uneventful because the patient responded to a 7-day course of oral quinine and doxycycline. n nMalaria, a potential life-threatening disease caused by P. falciparum, usually occurs within 2 months after the bite of an infective mosquito. A few reports mention a delay of >1 year between exposure and initial clinical symptoms, probably related to the disappearance of residual protective immunity in immigrants (1,2). Impaired immunity has also been linked to late malaria, implicating a chronic low-grade P. falciparum infection that becomes clinically evident in an immunocompromised person (3). In addition, several cases of malaria without any travel history to a malaria-endemic region have been described. A possible explanation for this type of malaria is exposure to an imported Anopheles spp. mosquito, referred to as airport, luggage, or container malaria (4). Transmission by indigenous anopheline mosquitoes when weather conditions are favorable has been reported in some European countries (5,6). Cases of P. falciparum malaria without any evidence of a mosquito bite have been reported and related to transfusion of parasitized erythrocytes, intravenous drug use, or accidental needlestick injuries (4). n nWe report a clinically atypical case of late P. falciparum malaria that may have been contracted by the bite of an anopheline mosquito captured in the luggage of the patient’s visiting friend (7). Unreported travel to a malaria-endemic region was possible but unlikely because our patient stayed illegally in Belgium and leaving the country would risk being repatriated to Guinea-Conakry. Indigenous malaria was excluded because he became ill during the winter, a time when proliferation of local Anopheles spp. in Belgium is difficult. The patient did not receive any recent blood transfusions and denied being an intravenous drug user, although this possibility cannot be excluded. n nThis type of malaria, also known as luggage or suitcase malaria, makes adequate and timely diagnosis difficult because a history of exposure to a possibly malaria-infected mosquito is apparently absent. Moreover, our patient had few classic symptoms or signs, such as high-grade fever, chills, or headaches; this pattern complicates diagnosis. This lack of typical malaria symptoms may be related to the fact that before coming to the hospital, the patient took ciprofloxacin, which has in vitro activity against P. falciparum. Another possible reason is residual immunity to malaria, which was no longer protective but still capable of attenuating symptoms or signs of malaria. This finding implicates recrudescence of disease after a long period of asymptomatic infection with P. falciparum. Serologic analysis detected high levels of antibodies to Plasmodium spp., which suggests a chronic infection rather than a new one. n nIt is generally accepted that protective immunity wanes after several months of nonexposure. Support for this thesis is the frequency of clinical malaria in African adults who visit their families after a long stay in a country where the disease is not endemic. However, these cases might be caused by antigenic variation of P. falciparum in the area visited, which would enable the parasite to evade the host’s immune response (8). Residual immunologic memory against P. falciparum has been suggested, which would link persistent immunity with late recrudescence or with less severe or complicated disease in immigrants (2,9). Moreover, P. falciparum has been transmitted through blood transfusions from donors from malaria-endemic regions several years after exposure, which suggests long subpatent periods (10). n nThis case highlights the problem of diagnosing P. falciparum malaria in patients without a recent travel history to malaria-endemic areas. In such cases, autochthonous malaria, whether transmitted by an imported or an indigenous mosquito or by infected blood cells or needles, should be excluded. Residual protective immunity, even after several years of nonexposure to P. falciparum, may explain persistent asymptomatic infection and late recrudescence of disease.

Eosinophilic meningitis due to Angiostrongylus cantonensis in a Belgian traveller

Eosinophilic meningitis is a rare clinical entity. The most frequent cause in travellers to the tropics is infection with the rat lungworm Angiostrongylus cantonensis. In this report, we describe a case of eosinophilic meningitis due to infection with this nematode in a traveller who presented with slight headache, diarrhoea, general malaise and thoracic radicular pain after a trip through Latin America and the Fiji Islands. She responded less than optimally to repeated steroid and albendazole treatments, but finally recovered completely.