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.

Human African trypanosomiasis in a Belgian traveller returning from the Masai Mara area, Kenya, February 2012.

A Belgian traveller was diagnosed with human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense nine days after visiting the Masai Mara area in Kenya. He presented with an inoculation chancre and was treated with suramin within four days of fever onset. Two weeks earlier, HAT was also reported in a German traveller who had visited the Masai Mara area. Because no cases have occurred in the area for over 12 years, this may indicate a focal cluster of HAT.

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.

Imported human African trypanosomiasis in Europe, 2005-2009.

Physicians in Europe are likely to see more African trypanosomiasis cases because of the increasing popularity of travel to Africa. In this paper the literature on imported cases in Europe, since 2005 is reviewed. Because of the high mortality risk associated with acute Rhodesian trypanosomiasis, travellers should be informed about preventive measures and the early disease manifestations.

Risk factors for delay in the diagnosis and treatment of tuberculosis at a referral hospital in Rwanda.

SETTING: Kigali University Hospital, the main referral centre for TB in Rwanda. OBJECTIVE: To evaluate delays in the diagnosis and treatment of tuberculosis (TB) and associated risk factors. DESIGN: Prospective data collection of patients treated for pulmonary TB (PTB) or extra-pulmonary TB (EPTB) between June and September 2006. RESULTS: Of 104 patients with a mean age of 35 years (range 17-84) recruited into the study, 62% were HIV-positive. EPTB was diagnosed in 60 cases. The median total, health care and patient delays were respectively 57, 28 and 25 days. The health system delay before referral was significantly longer than the delay at our institution (18 vs. 6 days, P<0.0001). Risk factors for a longer health system delay at our institution were smear-negative PTB or EPTB (OR 5.12) and a trial of antibiotics (OR 2.96). The latter was also found to significantly prolong total delay (OR 2.85), as did rural residence (OR 4.86). No significant association was found between patient delay and age, sex, profession or health insurance status. CONCLUSION: Smear-negative PTB and EPTB were associated with longer health system delays. A trial of antibiotics significantly increased the health system delay. Its use, recommended by the World Health Organization in case of smear-negative TB and EPTB in developing countries, needs validation at the tertiary health care level.

Pulmonary cryptococcosis associated with HIV-1 infection in Rwanda: a retrospective study of 37 cases.

OBJECTIVES: To study the demographic, clinical, radiographic and diagnostic features, the clinical course and therapeutic response of pulmonary cryptococcosis in HIV-1-infected patients. DESIGN: Retrospective review. SETTING: The Department of Medicine of an urban reference hospital in Central Africa. METHODS: All the records of HIV-1-infected patients with pulmonary cryptococcosis were reviewed retrospectively with regard to the parameters described above. RESULTS: Over a 3-year period, pulmonary cryptococcosis was diagnosed in 37 HIV-1-infected Rwandan patients (21 men, 16 women; mean age, 35 years; range, 26-55 years). Twenty-nine patients (78%) had primary pulmonary cryptococcosis. Cough (94%), weight loss (65%), fever (51%), dyspnoea (46%), thoracic pain (30%), headache (13%) and haemoptysis (8%) were the predominant clinical findings. A diffuse interstitial infiltrate on chest radiograph was observed in 76% of the patients, an alveolar pattern in 19%, mediastinal and/or hilar adenopathy in 11%, nodules and pleural effusion each in 5%. Bronchoalveolar lavage, with a yield of 82%, was found to be the most sensitive diagnostic procedure. Screening of cryptococcal antigen in the serum failed to detect cases of primary pulmonary cryptococcosis. Twelve patients with primary pulmonary cryptococcosis treated with itraconazole as acute and maintenance therapy were all protected against disseminated cryptococcal disease; seven out of 10 (70%) of those who did not receive a specific anticryptococcal drug developed disseminated cryptococcal disease. CONCLUSION: Pulmonary cryptococcosis is not a rare complication of HIV-1 infection in Rwanda. Its clinical and radiographic patterns are non-specific and bronchoalveolar lavage is the procedure of choice for its diagnosis. The natural history of untreated primary pulmonary cryptococcosis is disseminated cryptococcal disease. Itraconazole is highly effective in the prevention of disseminated cryptococcal disease in patients with primary pulmonary cryptococcosis.

Epidemiology and clinical features of imported dengue fever in Europe: sentinel surveillance data from TropNetEurop.

Travelers have the potential both to acquire and to spread dengue virus infection. The incidence of dengue fever (DF) among European travelers certainly is underestimated, because few centers use standardized diagnostic procedures for febrile patients. In addition, DF is currently not reported in most European public health systems. Surveillance has commenced within the framework of a European Network on Imported Infectious Disease Surveillance (TropNetEurop) to gain information on the quantity and severity of cases of dengue imported into Europe. Descriptions of 294 patients with DF were analyzed for epidemiological information and clinical features. By far the most infections were imported from Asia, which suggests a high risk of DF for travelers to that region. Dengue hemorrhagic fever occurred in 7 patients (2.4%) all of whom recovered. Data reported by member sites of the TropNetEurop can contribute to understanding the epidemiology and clinical characteristics of imported DF.

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Persistent arthralgia and its association with HIV infection in Rwanda.

A prospective study of persistent arthralgia was carried out on 331 consecutive female patients admitted to the Department of Internal Medicine of the Centre Hospitalier de Kigali in Kigali, Rwanda. The aim of this study was to determine its association with HIV-1 infection and to describe its clinical characteristics. Ten additional HIV-1-seropositive patients with this condition attending the outpatient clinic were also included in the clinical study. Persistent arthralgia was significantly more common in HIV-1-seropositive hospitalized patients (14 of 209, 6.7%) than in HIV-1-seronegative hospitalized patients (one of 122, 0.8%; p = 0.02) and had a specificity and a positive predictive value for HIV-1 infection of 99.1% and 93.3%, respectively. HIV-1-related persistent arthralgia, studied in 24 patients in early as well as late stages of HIV-1 infection, commonly affected several and mainly large joints, was mostly distributed symmetrically, and was usually relieved with nonsteroidal antiinflammatory drugs. Recurrencies were noted in eight patients. In areas highly endemic for HIV-1, persistent arthralgia should be considered a probable manifestation of HIV-1 infection, and although it is uncommon, it can be regarded as a predictor of HIV-1 infection.

Epidemiology and clinical features of vivax malaria imported to Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Plasmodium vivax is the second most common species among malaria patients diagnosed in Europe, but epidemiological and clinical data on imported P. vivax malaria are limited. The TropNetEurop surveillance network has monitored the importation of vivax malaria into Europe since 1999. OBJECTIVES: To present epidemiological and clinical data on imported P. vivax malaria collected at European level. MATERIAL AND METHODS: Data of primary cases of P. vivax malaria reported between January 1999 and September 2003 were analysed, focusing on disease frequency, patient characteristics, place of infection, course of disease, treatment and differences between network-member countries. RESULTS: Within the surveillance period 4,801 cases of imported malaria were reported. 618 (12.9%) were attributed to P. vivax. European travellers and immigrants were the largest patient groups, but their proportion varied among the reporting countries. The main regions of infection in descending order were the Indian subcontinent, Indonesia, South America and Western and Eastern Africa, as a group accounting for more than 60% of the cases. Regular use of malaria chemoprophylaxis was reported by 118 patients. With 86 (inter-quartile range 41-158) versus 31 days (inter-quartile range 4-133) the median symptom onset was significantly delayed in patients with chemoprophylaxis (p < 0.0001). Common complaints were fever, headache, fatigue, and musculo-skeletal symptoms. All patients survived and severe clinical complications were rare. Hospitalization was provided for 60% and primaquine treatment administered to 83.8% of the patients, but frequencies varied strongly among reporting countries. CONCLUSIONS: TropNetEurop data can contribute to the harmonization of European treatment policies.

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.

Imported schistosomiasis in Europe: sentinel surveillance data from TropNetEurop.

BACKGROUND: Schistosomiasis is a major parasitic disease, increasingly imported into temperate climates by immigrants from and travelers to endemic areas. METHOD: To generate valid data on imported infectious diseases to Europe and to recognize trends over time, the European Network on Imported Infectious Diseases Surveillance (TropNetEurop) was founded in 1999. Three hundred and thirty-three reports of schistosomiasis were analyzed for epidemiologic and clinical features. RESULTS: Male patients accounted for 64% of all cases. The average age of all patients was 29.5 years. The majority of patients were of European origin (53%). Europeans traveled predominantly for tourism (52%). Main reasons for travel for people from endemic areas were immigration and refuge (51%) and visits to relatives and friends (28%). The majority of infections were acquired in Africa; 92 infections were clearly attributable to Schistosoma haematobium, 130 to Schistosoma mansoni, and 4 to Schistosoma intercalatum. Praziquantel was the only treatment used. No deaths were recorded. CONCLUSION: TropNetEurop sentinel provides valuable epidemiologic and clinical data on imported schistosomiasis to Europe.

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.