Chikungunya virus and West Nile virus infections imported into Belgium, 2007-2012.

Arboviral infections are emerging among tourists travelling to (sub)tropical regions. This study aims to describe the importation of chikungunya virus (CHIKV) and West Nile virus (WNV) into Belgium over a 6-year period from 2007 to 2012. Clinical samples were obtained from travellers presenting at the outpatient clinic of the Institute of Tropical Medicine (ITM), Antwerp, Belgium or submitted to the Central Laboratory for Clinical Biology of the ITM. Testing was performed by serology and/or by real-time reverse transcriptase-polymerase chain reaction. A total of 1288 returning travellers were investigated for CHIKV infection resulting in 34 confirmed and two probable diagnoses (2·80%). Out of 899 patients, four confirmed and one probable imported WNV infections were diagnosed (0·55%). No locally acquired cases have been registered in Belgium until now and the geographical origin of the imported infections reflects the global locations where the viruses are circulating.

Heat-shock protein 70 gene sequencing for Leishmania species typing in European tropical infectious disease clinics.

We describe Leishmania species determination on clinical samples on the basis of partial sequencing of the heat-shock protein 70 gene (hsp70), without the need for parasite isolation. The method is especially suited for use in non-endemic infectious disease clinics dealing with relatively few cases on an annual basis, for which no fast high throughput diagnostic tests are needed. We show that the results obtained from this gene are in nearly perfect agreement with those from multilocus enzyme electrophoresis, which is still considered by many clinicians and the World Health Organization (WHO) as the gold standard in Leishmania species typing. Currently, 203 sequences are available that cover the entire hsp70 gene region analysed here, originating from a total of 41 leishmaniasis endemic countries, and representing 15 species and sub-species causing human disease. We also provide a detailed laboratory protocol that includes a step-by-step procedure of the typing methodology, to facilitate implementation in diagnostic laboratories.

Epidemiology and outcome of Shigella, Salmonella and Campylobacter infections in travellers returning from the tropics with fever and diarrhoea.

INTRODUCTION: During a study on fever after a stay in the tropics, we aimed at investigating the epidemiology and outcome of invasive bacterial enteritis due to Shigella, Salmonella or Campylobacter spp. in patients diagnosed with febrile traveller's diarrhoea. METHODS: From April 2000 to September 2006, we evaluated prospectively 594 travellers presenting with fever and diarrhoea within a month after a stay in the tropics. Patients not found with a systemic infection were assumed to have febrile traveller's diarrhoea (TD). Invasive bacterial enteritis was confirmed by isolation of Shigella, Campylobacter or nontyphoidal Salmonella in stool cultures. RESULTS: Systemic infections (mainly malaria) were diagnosed in 259 (44%) evaluated travellers. Invasive bacterial enteritis, either alone or with another infection, was confirmed in 114 (34%) of the 335 remaining patients with febrile TD. Aetiologies were distributed between Campylobacter jejuni (47, 41%), Shigella spp. (43, 38%), Salmonella spp. (22, 19%) and mixed Campylobacter-Salmonella infection (2, 2%). Invasive bacterial enteritis accounted for about a third of febrile TD cases occurring after a stay in sub-Saharan Africa, North Africa/Middle East or Latin America, and for half of those occurring after a travel to southern Asia (including 33% only due to C. jejuni). Resistance to fluoroquinolones was exclusively observed in C. jejuni isolates, but at an overall rate of 53%. Clinical failure occurred in 33% of the patients with C. jejuni infection empirically treated with a fluoroquinolone. CONCLUSION: Invasive bacterial enteritis was a frequent aetiology of febrile TD. C. jejuni was the leading pathogen after a travel to southern Asia, and was associated with high rate of resistance to fluoroquinolones and of clinical failure.

Chikungunya infection confirmed in a Belgian traveller returning from Phuket (Thailand).

Chikungunya infection has been increasingly reported in international travellers following its epidemic re-emergence in the Indian Ocean islands in 2006 and its spread to southern Asia thereafter. We describe the first case of chikungunya in a Belgian traveller returning from Phuket, Thailand and discuss the potential implications of chikungunya cases imported to European countries for patient management and public health.

[Screening the asymptomatic traveler returning from the tropics]. / Bilan de santé chez le voyageur asymptomatique de retour des tropiques.

Travelers to developing countries may be exposed to several infectious pathogens sometimes leading to complications after a long latency period. Screening of asymptomatic returning travelers is only justified in case of specific risks during travel or after a long tropical stay (> 3 months). Based mainly on the history taking of risk patterns, some occult infections have to be looked for: tuberculosis, sexual transmitted infections and some parasitic conditions (schistosomiasis, amebiasis, strongyloidosis,...). Post-travel screening is most effective about 3 months after return, and may be even more beneficial if associated with screening of major western morbidities and preventive counseling for future travels.

Selective ambulatory management of imported falciparum malaria: a 5-year prospective study.

The ambulatory management of imported Plasmodium falciparum malaria is controversial because criteria for safe selection of patients are imprecise. The aim of the present study was to investigate the evolution and outcome of patients diagnosed with Plasmodium falciparum malaria at a Belgian referral institute in order to assess the safety of the institute's current selective ambulatory management protocol. From 2000 to 2005, all patients diagnosed with P. falciparum infection at the Institute of Tropical Medicine and the University Hospital of Antwerp were enrolled prospectively. Ambulatory treatment was offered to nonvomiting patients if they exhibited none of the 2000 World Health Organization criteria of severity and had parasitemia below 1% at the initial assessment. The treatment of choice was quinine (plus doxycycline or clindamycin) for inpatients and atovaquone-proguanil for outpatients. P. falciparum malaria was diagnosed in 387 patients, of whom 246 (64%) were Western travelers or expatriates and 117 (30%) were already on antimalarial therapy. At diagnosis, 60 (15%) patients had severe malaria. Vital organ dysfunction was initially seen in 34 and developed later in five others. Five patients died. Of the 327 patients initially assessed as having uncomplicated malaria, 113 (35%) were admitted immediately; of these, 4 developed parasitemia >/=5% at a later stage but without any clinical consequence. None of the 214 individuals initially treated as outpatients experienced any malaria-related complications, including 10 who were admitted later. Vital organ dysfunction was observed in only 2 of the 214 patients with initial parasitemia <1% who had not taken antimalarial agents (both patients had impaired consciousness at presentation). Ambulatory treatment is safe in treatment-naive malaria patients with parasitemia <1% who do not vomit and who do not exhibit any criteria of severe malaria.

A case of multiple amoebic liver abscesses: clinical improvement after percutaneous aspiration.

Amoebic liver abscesses are by far the most common extra-intestinal manifestation of invasive amoebiasis. The classical clinical picture consists of fever, right upper quadrant pain and hepatomegaly. Ultrasound and serology make an early diagnosis possible. Amoebic liver abscesses usually appear singly and are normally situated in the right lobe of the liver. This case report refers to a white Belgian woman, living in an endemic area for amoebiasis, presenting with 25 amoebic liver abscesses, who did not improve clinically despite appropriate anti-amoebic therapy, is described. Only percutaneous drainage of the larger abscesses led to clinical recovery. Amoebic abscess aspiration and evacuation under ultrasonographic guidance is of limited risk, but in experienced hands may enhance clinical recovery, particularly in patients with large abscesses not responding to conservative medical treatment. Aspiration of large abscesses (> 5 cm) is rarely necessary but should be considered if there is no clinical improvement after 3 days of nitroimidazole treatment with amoebicides.

Treatment of acute diarrhoea: update of guidelines based on a critical interuniversity assessment of medications and current practices.

Further to a thorough analysis of the problem of acute diarrhoea and the therapeutic options, recommendations were defined following a multidisciplinary approach. These guidelines take into account the reality of frequent self-medication. They further differ as a function of age (children, primarily treated by ORS and for whom self-medication is not advised versus adults who can self-medicate), symptoms (uncomplicated diarrhoea versus dysentery) and location where the diarrhoea is contracted (at home or when travelling).

A Belgian traveler who acquired yellow fever in the Gambia.

A 47-year-old Belgian woman acquired yellow fever during a 1-week vacation in The Gambia; she had never been vaccinated against yellow fever. She died of massive gastrointestinal bleeding 7 days after the onset of the first symptoms. This dramatic case demonstrates that it is important for persons to be vaccinated against yellow fever before they travel to countries where yellow fever is endemic, even if the country, like The Gambia, does not require travelers to be vaccinated.

Changing epidemiological and clinical aspects of imported malaria in Belgium.

BACKGROUND: In the early nineties the increase of imported malaria in some European countries was temporarily halted, but it resumed in 1994. More Africans, more European travelers, and fewer long-term residents were counted amongst patients. A shift towards more subacute disease has been noted. This study intends to assess whether the same trends were observed in Belgium. METHODS: Clinical and epidemiological data of 128 patients treated for malaria in 1997 at the Institute of Tropical Medicine and the University Hospital of Antwerp were compared with 209 malaria patients treated in 1988/1989. Risk factors for clinical presentation and parasitemia were analysed. RESULTS: In Belgium the number of reported imported malaria cases remained almost stable between 1988 and 1997. In 1997, there were more African patients, less infections from Central Africa, and 50% less residents. Less patients reported prophylaxis use. The causative agent shifted from Plasmodium falciparum to other species. Subacute and atypical malaria became less frequent. In both years, there were no deaths, and severe malaria did not increase significantly. Mefloquine disappeared almost as a curative treatment, and was replaced by quinine, with or without a long acting agent, or by halofantrine. The ethnic origin, nor the use of chemoprophylaxis, influenced disease characteristics. In 1988, malaria attacks in the previous months predisposed to subacute disease; longer residence, and attacks in the previous months, protected against high parasitemia; longer symptom duration correlated with absence of fever, and with splenomegaly. None of these risk factors was correlated with severe malaria. CONCLUSION: The incidence of subacute malaria dropped significantly in the last decade. Although this presentation is almost limited to residents, the decline in malaria can not be explained by an overall shorter duration of stay, since the decline in this particular clinical presentation of malaria was also spectacular in residents. Apparently, insufficient treatment of malaria attacks in the previous months is the only independent risk factor.

Hyperreactive malaria in expatriates returning from sub-Saharan Africa.

The extreme presentation of hyperreactive malaria is hyperreactive malarial splenomegaly syndrome (HMS). Some patients present with a less pronounced syndrome. To investigate whether the degree of splenomegaly correlates with the degree of immune stimulation, whether prophylaxis or recent treatment play a role, and whether short therapy alone is effective, we examined retrospectively the medical records of expatriates with exposure to P. falciparum who attended our outpatient department from 1986 to 1997, particularly subacute symptoms or signs, strongly elevated malarial antibodies and elevated total serum IgM. We analysed duration of stay, prophlyaxis intake, spleen size, serum IgM levels and response to antimalarial treatment. Serum IgM levels were significantly higher in patients with larger splenomegaly. The use of chloroquine alone as treatment for presumptive or proved malaria attacks was correlated with larger spleen size. Short adequate antimalarial therapy resulted in marked improvement or complete recovery. In nine patients the hyperreactive response reappeared after re-exposure, in four of them twice. We conclude that patients with subacute symptoms but without gross splenomegaly may have very high levels of IgM and malarial antibodies, and relapse on re-exposure, suggesting the existence of a variant of the hyperreactive malarial splenomegaly syndrome without gross splenomegaly.

Diarrheagenic Escherichia coli and acute and persistent diarrhea in returned travelers.

To determine the role of diarrheagenic Escherichia coli in acute and persistent diarrhea in returned travelers, a case control study was performed. Enterotoxigenic E. coli (ETEC) was detected in stool samples from 18 (10.7%) of 169 patients and 4 (3.7%) of 108 controls. Enteroaggregative E. coli (EAggEC) was detected in 16 (9.5%) patients and 7 (6.5%) controls. Diffuse adherent E. coli strains were commonly present in both patients (13%) and controls (13.9). Campylobacter and Shigella species were the other bacterial enteropathogens most commonly isolated (10% of patients, 2% of controls). Multivariate analysis showed that the presence of ETEC was associated with acute diarrhea (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.5 to 29.1; P = 0.005), but not with persistent diarrhea (OR, 1.6; 95% CI, 0.4 to 7.4). EAggEC was significantly more often present in patients with acute diarrhea than in controls (P = 0.009), but no significant association remained after multivariate analysis. ETEC and EAggEC are frequently detected in returned travelers with diarrhea. The presence of ETEC strains is associated with acute but not with persistent diarrhea.

The hypereosinophilic syndrome after residence in a tropical country: report of 4 cases.

Severe eosinophilia may be complicated by acute or chronic visceral damage. The underlying origin of the hypereosinophilia may be infectious, allergic, toxic, malignant or systemic (the secondary or reactive hypereosinophilic syndrome), but in a number of cases no cause can be found (the idiopathic hypereosinophilic syndrome). We describe 4 cases with hypereosinophilia and secondary visceral damage after residence in a tropical region. In three cases a helminthic infection was the obvious cause, the brain and the heart were the target organs. After treatment of the infection both the hypereosinophilia and the neurological and cardiac lesions disappeared. The fourth patient died of multi-organ disease. No definite trigger of the hypereosinophilia could be found. We discuss clinical findings, necessary investigations and therapeutic strategies.

Inhibition of various steps in the replication cycle of vesicular stomatitis virus contributes to its photoinactivation by AlPcS4 or Pc4 and red light.

Vesicular stomatitis virus (VSV) was used as a model virus to study the processes involved in photoinactivation by aluminum phthalocyanine tetrasulfonate (AlPcS4) or silicon phthalocyanine HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc4) and red light. Previously a very rapid decrease in the intracellular viral RNA synthesis after photodynamic treatment was observed. This decrease was correlated to different steps in the replication cycle. Binding of VSV to host cells and internalization were only slightly impaired and could be visualized by electron microscopy. The capability of the virus to fuse with membranes in an acidic endosomal environment was studied using both pyrene-labeled liposomes and a hemolysis assay as a model. These tests indicate a rapid decrease of fusion capacity after AlPcS4 treatment, which correlated with the decrease in RNA synthesis. For Pc4 treatment no such correlation was found. The fusion process is the first step in the replication cycle, affected by AlPcS4 treatment, but also in vitro RNA polymerase activity was previously shown to be inhibited. Inactivation of VSV by Pc4 treatment is apparently caused by damage to a variety of viral components. Photodynamic treatment of virus suspensions with both sensitizers causes formation of 8-oxo-7,8-dihydroguanosine in viral RNA as measured by HPLC with electrochemical detection. This damage might be partly responsible for inhibition of the in vitro viral RNA polymerase activity by photodynamic treatment.

Evaluation of two tests based on the detection of histidine rich protein 2 for the diagnosis of imported Plasmodium falciparum malaria.

The ParaSight-F dipstick test (Becton Dickinson, USA) and the ICT Malaria Pf test (ICT, Australia) both detect histidine rich protein 2 (HRP-2), a water-soluble antigen expressed by Plasmodium falciparum trophozoites. The present study compared the diagnostic performance of both tests in persons returning to Belgium from countries endemic for malaria. During a period of 18 months both tests were performed on all patients returning from the tropics with a positive malaria blood film. Patients with fever without an obvious cause were used as controls. For the ParaSight-F test, considering P. falciparum trophozoites only, sensitivity was 95% and specificity 90%. Considering trophozoites of all species of Plasmodium, sensitivity was 71% and specificity 87%. Finally, considering patients with clinical malaria, the sensitivity of the test was 72% and specificity 87%. For the ICT Malaria Pf test, sensitivity was 95% and specificity 89% for P. falciparum trophozoites only, 71% and 86% for trophozoites of all species, and 72% and 87% for clinical malaria. Both tests gave highly comparable results. However, antigen detection assays cannot replace conventional microscopy in diagnosing imported malaria. Thick blood film examination is more sensitive and more specific, it allows estimation of parasitaemia and distinction between parasite growth stages, and it covers all species. Moreover, with treated patients the use of antigen tests might lead to problems in determining the efficacy of therapy.