Neurogenic inflammation and colliquative lymphadenitis with persistent orthopox virus DNA detection in a human case of cowpox virus infection transmitted by a domestic cat.

Cowpox viruses are orthopoxviruses that may survive in the environment for years. Rodents are regarded as the primary hosts, but transmission to other species has been reported. This report describes a cowpox virus infection in a cat with subsequent transmission to its owner leading to protracted, atypical and severe clinical signs. A young cat presented with multiple crusts and plaques on the neck, muzzle and tail base. The owner developed an erythematous lesion with elevated margins, central necrosis and crust formation below the left breast, a neurogenic inflammation, enlarged regional lymph nodes, a colliquative lymphadenitis and concomitant flu-like symptoms. Cultures were taken at the first visit from the cat's lesional skin and the patient's skin, and polymerase chain reaction with sequencing of the haemagglutinin region of both were positive for cowpox virus. The patient was treated with various antibiotics and methylprednisolone and was in clinical remission after 7 months.

[Vaccinations for international travelers]. / Reiseimpfungen.

Vaccinations are a prominent part of health preparations before international travel. They can avoid or significantly reduce the risk of numerous infectious diseases. Until recently, vaccination against yellow fever was the only obligatory vaccination. However, according to updated international health regulations, other vaccinations and prophylactic measures may be required at entry from certain countries. For all routine vaccinations as recommended in Germany, necessary revaccination and catch-up of missed vaccinations should be administered before travel. At most destinations the risk of infection is higher than in Germany. Hepatitis A vaccine is generally recommended for travelers to areas of increased risk, polio vaccine for all destinations where eradication is not yet confirmed (Asia and Africa). The indications for other travel vaccines must take into consideration travel destination and itinerary, type and duration of travel, individual risk of exposure as well as the epidemiology of the disease to be prevented. Several vaccines of potential interest for travel medicine, e.g., new vaccines against malaria and dengue fever, are under development.

Infection-induced anaemia: a cross-sectional study of 14,636 German travellers aged 20-49 years.

BACKGROUND: Anaemia is a frequently diagnosed condition which can develop as a consequence of numerous factors, including infectious diseases (IDs). Travelling, especially in sub-/tropical regions, leads to an elevated risk of contracting IDs. The aim of our study was to assess the epidemiological significance of IDs in inducing anaemia among a large cohort of returned travellers. METHODS: This was a cross-sectional study in which data on 17,009 returned travellers aged 20-49 years who consulted the travel medicine clinic of the University of Munich between 1999 and 2011 were retrieved and analysed. RESULTS: Of the returned travellers, 8.3 % (6.0 % of males/10.4 % of females) were diagnosed with anaemia. The prevalence of anaemia was significantly elevated among patients of African (21.4/28.3 %) and Asian (11.6/15.7 %) origin. When the study population was restricted to the 14,636 travellers of German origin, 7.1 % of the returned travellers (4.6/9.6 %) were diagnosed with anaemia. The prevalence was significantly elevated among patients who travelled for >30 days (5.7 of males/10.6 % of females) and for male travellers visiting friends and relatives (7.7 %). However, these correlations were confounded by malaria. The prevalence of anaemia was significantly elevated only among returned travellers diagnosed with malaria (36.1 of males/26.9 % of females) and with symptomatic intestinal Entamoeba histolytica infections (30.0/33.3 %). CONCLUSION: Following the exclusion of confounding by malaria from the statistical analysis, the prevalence of anaemia was found to be significantly elevated among patients of African and Asian origin, and among patients of German origin who had travelled for >30 days, it could be mainly attributable to chronic, long-lasting causes. Although more than 550 travel-associated IDs were assessed in our study, only symptomatic intestinal Entamoeba histolytica infections and, to an even larger extent, malaria were determined to be of epidemiological significance for inducing anaemia among travellers.

Comparative study on infection-induced thrombocytopenia among returned travellers.

BACKGROUND: Thrombocytopenia is a frequent finding among ill returned travellers and may be caused by a large number of different conditions, including infectious diseases specific or typical for tropical and subtropical regions. In order to assess the diagnostic significance of thrombocytopenia we investigated a large cohort of returned travellers. METHODS: This was a comparative study in which data collected on 19,473 returned travellers who consulted the outpatient travel clinic of the the University of Munich Hospital between 1999 and 2009 were analysed. Of these, 732 (3.8%) travellers were diagnosed with thrombocytopenia, and their data were compared with those of the remaining 18,741 travellers with normal platelet counts. RESULTS: Thrombocytopenia was significantly more frequent among patients with malaria (63%), acute human immunodeficiency virus infection (48%), dengue fever/dengue haemorrhagic fever (DF/DHF; 47%), Epstein-Barr virus infectious mononucleosis (23%), paratyphoid/typhoid fever (14%), and rickettsiosis (12%). Malaria and DF/DHF caused 25% of all cases of thrombocytopenia (platelet count <140,000/µl) and 75% of all cases of severe thrombocytopenia (platelet count <30,000/µl). Sex, age, country of origin, duration and type of travel were not significantly correlated with thrombocytopenia. The most frequent travel destinations were Asia (42%), Africa (33%), and Latin America (14%). Travellers to Sub-Saharan Africa (high risk for malaria) and to South/South-east Asia (high risk for DF/DHF) had the highest relative risk for thrombocytopenia. CONCLUSION: Platelet count among returned travellers is an essential screening parameter, as thrombocytopenia is highly correlated with important infectious diseases, particularly with malaria and DF/DHF.

Skin disorders among travellers returning from tropical and non-tropical countries consulting a travel medicine clinic.

OBJECTIVE: To evaluate the causes and risks for imported skin disorders among travellers. METHODS: Data of 34,162 travellers returning from tropical and non-tropical countries and presenting at the outpatient travel medicine clinic of the University of Munich, Germany, between 1999 and 2009 were analyzed for this study. Of these, 12.2% were diagnosed with skin disorders. RESULTS: Main destinations visited were Asia (40%), Africa (27%) and Latin America (21%). Tourism in the form of adventure travel/backpacking (47%) and package holidays (23%) was the most common purpose of travel. The leading causes of skin disorders were arthropodal (23%), bacterial (22%), helminthic (11%), protozoan (6%), viral (6%), allergic (5%) and fungal (4%). The 10 most frequently diagnosed specific skin diseases associated with specific destinations were insect bites (17%, Southern Europe), cutaneous larva migrans (8%, Asia and Latin America), cutaneous leishmaniasis (2.4%, Mediterranean Region/Middle East), dengue fever (1.5%, Asia), rickettsioses (1.3%, Southern Africa), myiasis (0.8%, Central America), filarioses (0.7%, Africa), tick bites (0.6%, Central/Eastern Europe), schistosomiasis (0.6%, Africa) and tungiasis (0.6%, Africa). Travellers in sub-Saharan Africa had the highest relative risk of acquiring skin disorders. CONCLUSION: As more than 20% of all skin disorders among returned travellers were caused by arthropods and about 50% by infectious pathogens, pre-travel consultations should include specific prophylaxis and consider the most important risk factor for the travel destination.

Epidemiological, clinical, and diagnostic data on intestinal infections with Entamoeba histolytica and Entamoeba dispar among returning travelers.

BACKGROUND: Among travelers returning from the tropics, Entamoeba spp. are among the most frequently detected intestinal parasites, mainly the presumable apathogenic E. dispar and the pathogenic E. histolytica. METHODS: Among 5,378 travelers seeking diagnosis and treatment for intestinal infections at the travel clinic of the University of Munich between 2005 and 2009, 103 laboratory-confirmed amebiasis cases were detected. The study compares the results of various diagnostic tests among these patients, analyzes data on co-infections and clinical symptoms, and determines the risk for acquiring amebiasis. RESULTS: Initial screening tests (stool microscopy, coproantigen enzyme-linked immunosorbent assay [ELISA]) were positive in 82.5 and 93.9%, respectively. Fecal samples from patients with positive screening test results were subjected to polymerase chain reaction (PCR), which detected E. histolytica in 9.7% and E. dispar in 88.3% of the cases. The majority of E. histolytica cases and more than half of the E. dispar cases had intestinal symptoms typical for amebiasis. In 53.4% of the cases, intestinal co-infections were found, mostly Blastocystis hominis (39.8%), Giardia lamblia (10.7%), Campylobacter spp. (4.9%), and Salmonella typhi (2.9%). The risk for travelers to be infected with E. histolytica or E. dispar was highest for destinations in West Africa, East Africa, and South and South-East Asia. CONCLUSION: Stool microscopy and coproantigen ELISA are appropriate screening tests for intestinal Entamoeba infections among travelers, but intestinal co-infections are common. PCR is highly recommended as the diagnostic method of choice for the differentiation of Entamoeba spp. The presumable apathogenic E. dispar seems to provoke intestinal symptoms.

[Gastroenteritis with fever, headache and rash after travelling in India]. / Gastroenteritis mit Fieber, Zephalgie und Exanthem nach Indienreise.

A 63-year-old patient presented to our emergency unit two days after returning from India suffering from watery diarrhea, nausea, fever and headache. On admission we found a maculopapular rash on his trunk and forehead. Laboratory findings revealed a leuko-thrombopenia and elevated levels of CRP and procalcitonin. We started treatment with ciprofloxacin. After 48 hours of treatment the diarrhea subsided, whereas the rush on his trunk increased. Under the suspicion of rickettsial fever we started doxycycline 200 mg/d. Because of an incipient pneumonia we added ceftriaxon. The patient improved rapidly and the laboratory abnormalities resolved. Serological investigations revealed a significant increase of specific antibodies against Rickettsia typhi. In conclusion, headache with fever and maculopapular rash after traveling to endemic countries should rise suspicion for murine typhus.

Chikungunya fever in two German tourists returning from the Maldives, September, 2009.

This report describes the first isolation and molecular characterisation of a chikungunya virus from two German tourists who became ill after a visit to the Maldives in September 2009. The virus contained the E1 A226V mutation, shown to be responsible for an adaptation to the Asian tiger mosquito Aedes albopictus. The E1 coding sequence was identical to chikungunya virus isolates from Sri Lanka and showed three nt-mismatches to the only available E1 nt sequence from the Maldives.

Excision of pre-ulcerative forms of Buruli ulcer disease: a curative treatment?

BACKGROUND: Previous investigations have revealed that Mycobacterium ulcerans is extensively distributed spatially throughout ulcerative lesions, including in the margins of excised tissue. In contrast, bacilli in pre-ulcerative lesions are assumed to be concentrated in the center of the lesion. In order to assess the extent to which the surgical excision of pre-ulcerative lesions is capable of removing all infected tissue, we subjected the excision margins of pre-ulcerative lesions to laboratory analysis. PATIENTS AND METHODS: Eleven patients with laboratory-confirmed pre-ulcerative lesions were included in the study. The diameter of the lesion and excised tissue and the "surgical distance" between the border of the lesion and excision margin were measured. The entire excision margin was cut into segments and subjected to IS2404 PCR. RESULTS: The results from the PCR analysis on the samples of excision margins were highly significantly associated with the surgical distance (p < 0.001). The margin samples of nodules were significantly more often PCR positive than the plaques (p = 0.025). The size of the lesion and the size of the excised tissue did not significantly influence the PCR results. Statistically, a surgical distance of more than 9 mm was found to reduce the risk of remaining infected tissue to less than 10%, that of 13 mm to reduce the risk to less than 5%, and that of 25 mm to reduce the risk to nearly 0%. CONCLUSION: The results of this study show that in preulcerative Buruli ulcer disease, bacilli may extend beyond the actual size of the lesion and that there is a strong correlation between the presence of M. ulcerans in the margin samples and the surgical distance. Excision with a surgical distance of 25 mm avoided the risk of remaining mycobacteria in this study. However, no recurrences occurred in the patients with M. ulcerans-positive excision margins. The need of postoperative antimycobacterial treatment in these patients remains to be determined.

[Spectrum of diseases occurring in refugees and asylum seekers: data from three different medical institutions in the Munich area from 2014 and 2015]. / Erkrankungen bei Flüchtlingen und Asylbewerbern: Daten von drei verschiedenen medizinischen Einrichtungen im Raum München aus den Jahren 2014 und 2015.

BACKGROUND: In 2014 the number of refugees and asylum seekers in Germany rose steeply. Therefore, the provision of sufficient medical care for this special group of people became a major topic. Up to now, data on the spectrum of illnesses in this group in Germany is scarce. PATIENTS AND METHODS: Anonymized data of 548 ill refugees and asylum seekers were retrospectively evaluated. Cases from three different institutions and time periods were collected and summarized: 329 outpatients from the general medical clinic of REFUDOCS (RD, January to beginning of March 2015), 175 inpatients from the 1. medical department of the municipal hospital Schwabing (KS, June 2014 to February 2015) and 44 outpatients from the department of infectious diseases and tropical medicine of the Ludwig-Maximilians-University, Munich (AITM, 2014). RESULTS: Health problems seen at the RD general medical clinic mostly matched the usual spectrum seen by general practitioners. Respiratory illnesses especially by unspecific viral infections (152 visits), followed by neuropsychiatric (68), and gastrointestinal illnesses (56), as well as musculoskeletal (52) and skin problems (45), were common. Infectious diseases or diseases typical or specific for the tropics were mostly treated in the specialized centers. Cases of pulmonary and extrapulmonary tuberculosis (53), malaria (53), scabies, pneumonia, and schistosomiasis were prevalent. CONCLUSION: The results of this exemplary study mostly show the occurrence of illnesses in refugees and asylum seekers that are well known to German general practitioners and pediatricians. However, depending on the country of origin infectious / tropical diseases like tuberculosis, malaria, or relapsing fever have to be considered. Rapid diagnosis of these illnesses is warranted to prevent severe cases or further spreading of contagious diseases.

Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis.

A direct antigen-capture ELISA based on the detection of mycobacterial lipoarabinomannan (LAM) in unprocessed urine was evaluated for its usefulness in clinical practice. In Tanzania, 231 patients with suspected pulmonary tuberculosis (TB) and 103 healthy volunteers were screened with standard TB tests and with the new LAM-ELISA. Of 132 patients with confirmed pulmonary mycobacterial disease (positive sputum culture), 106 were positive using the LAM-ELISA (sensitivity 80.3%). In comparison, the sensitivity of acid-fast bacilli (AFB) sputum microscopy was 62.1% (82 of 132 confirmed cases). Of the 231 patients, 17 were both culture- and AFB-negative, but had typical radiographic signs of pulmonary mycobacterial infection and did not respond to antibiotic treatment. Of these 17 patients, 13 (76.5%) had positive LAM-ELISA test results. To define the specificity of the assay, urine samples from 103 healthy volunteers were also screened using LAM-ELISA. All but one had an optical density below the cut-off (specificity 99%). Of interest was a significant correlation between level of microscopic density of mycobacteria in sputum and LAM antigen concentration in urine (chi2=8.44). The LAM-ELISA is a field-adapted tool that can improve screening standards in countries with a high incidence of TB.

Prevalence of infection with dengue virus among international travelers.

BACKGROUND: Dengue has been recognized as a potential hazard to tourists. A prospective, controlled study in the outpatient clinic of a German infectious disease clinic was conducted to assess the prevalence of dengue virus infection among international travelers. METHODS: Serum samples from 130 patients with signs or recent history clinically compatible with dengue (fever, headache, muscle and joint pain, or rash), 95 matched controls with diarrhea, and 26 patients who never visited a country endemic for dengue were investigated. RESULTS: Nine (6.9%) of the 130 patients with compatible symptoms and 1 (1%) of the 95 controls with diarrhea developed rising antibody titers against dengue virus. Of these 10 patients with probable dengue infection, 6 had been to Thailand, 2 to Malaysia, and 1 each to Indonesia and Brazil. CONCLUSIONS: Infection with dengue virus appears to be a realistic threat to travelers to Southeast Asia. Symptoms commonly associated with dengue, such as fever, myalgia, arthralgia, and vomiting, can be helpful for diagnosis when present, but the absence of typical symptoms does not exclude infection.

Taenia solium metacestode preparation in rural areas of sub-Saharan Africa: a source for diagnosis and research on cysticercosis.

BACKGROUND: Taenia solium metacestodes/cysts obtained from pig carcasses constitute a primary source for diagnostic tools used for the detection of human cysticercosis. Data on T. solium cyst preparation in Africa is still scarce but required to establish independent reference laboratories. OBJECTIVES: The aim of the present study is a) to present the likely yield of T. solium cyst material by the use of two different preparation methods in the field and b) to investigate its suitability for immunodiagnosis of human cysticercosis. METHODS: In Zambia, Uganda and Tanzania 670 pigs were screened for T. solium infection. Cysts were prepared by 'shaking method' and 'washing method'. Generated crude antigens were applied in a standard western blot assay. RESULTS: 46 out of 670 pigs (6.9%) were found positive for T. solium (Zambia: 12/367, 3.3%; Uganda: 11/217, 5.1%; Tanzania 23/86, 26.7%). Mean values of 77.7 ml whole cysts, 61.8 ml scolices/membranes and 10.9 ml cyst fluid were obtained per pig. Suitability of collected material for the use as crude antigen and molecular diagnostic techniques was demonstrated. CONCLUSION: This study clearly shows that T. solium cyst preparation in African settings by simple field methods constitutes an effective way to obtain high quality material as source for diagnostic tools and research purposes.

Diagnostic significance of blood eosinophilia in returning travelers.

This study was conducted to investigate the predictive value of blood eosinophilia (total white blood cell count with > or =8% eosinophils) for the diagnosis of travel-related infections in 14,298 patients who returned from developing countries. The data show that blood eosinophilia in travelers returning from developing countries has only limited predictive value for the presence of travel-related infections. However, the likelihood of the presence of helminth infections increases considerably with the extent of eosinophilia.

Disequilibria in the distribution of rpoB alleles in rifampicin-resistant M. tuberculosis isolates from Germany and Sierra Leone.

The effectiveness of culture-independent resistance predictions by molecular techniques is dependent on the number and the frequency of accessible resistance-associated genomic mutations. We have characterized an rpoB gene region involved in rifampicin resistance in 49 Mycobacterium tuberculosis isolates resistant to rifampicin from Germany and Sierra Leone. The determined frequencies of mutations differed between both countries of origins as well as with respect to previously reported distributions of resistance mutations. It is concluded that at least for some isolates the acquisition of mutations leading to rifampicin resistance in clinical samples of M. tuberculosis is a non-random process which may lead to a geographical and temporal dependence of the sensitivities of molecular typing techniques for rifampicin resistance predictions.

Direct amplification and differentiation of pathogenic and nonpathogenic Entamoeba histolytica DNA from stool specimens.

Discrimination of pathogenic and nonpathogenic Entamoeba histolytica is of great clinical importance. A simple and rapid DNA extraction method that can be used directly with stool specimens was developed without the need for prior cultivation of the parasites. The entire protocol can be performed at room temperature in a 1.5-ml microcentrifuge tube format. There is no DNA precipitation step. The subsequent nested polymerase chain reaction consists of an initial E. histolytica-specific amplification, followed by two separate amplifications using two primer pairs specific for pathogenic and nonpathogenic E. histolytica, respectively. Amplification products can be verified by restriction endonuclease digests. There is no need for hybridizations or the use of radionucleotides. One trophozoite per milligram of stool sample could be detected and differentiated in a 0.1-g specimen.

Long-term efficacy of primaquine in the treatment of vivax malaria in nonimmune travelers.

Fifty-six travelers presenting with vivax malaria to a German travel clinic were followed regularly for at least 18 months between 1984 and 1992 to investigate the long-term efficacy of primaquine in nonimmune patients without reinfection. All received a standard treatment of 15 mg of primaquine a day for 14 days following an initial total dose of 1,500 mg of chloroquine (base) given over a 48-hr period. None of the patients visited countries endemic for malaria during the period of observation. In seven patients (12.5%), relapses were confirmed microscopically by detection of malaria parasites in blood films. The frequency of relapses varied between one and four per patient and these occurred between 60 and 252 days after treatment. Four of these seven patients had acquired infection in Papua New Guinea or eastern Indonesia, while only five (10.2%) of the remaining 49 patients without relapses had traveled to these areas prior to referral (P < 0.01).

Assessing the incidence of infection with Plasmodium falciparum among international travelers.

Circumsporozoite (CS) antibodies, indicating plasmodial infection but not necessarily development of disease, have been shown to be reliable indicators of transmission in endemic areas. To estimate the actual rate of plasmodial infection, the prevalence of CS antibodies was investigated by an ELISA test system in a selected population of 2,131 travelers returning from areas endemic for malaria who presented to an outpatient clinic without any apparent symptom or clinical sign of malaria. Serum specimens from 104 of the investigated 2,131 patients (4.9%) were found to be positive (titer > or = 6.25 international ELISA units [IEU]). The geometric mean titer of antibody concentrations (IEU) in seropositive patients was 18.64 IEU (95% confidence interval [CI] = 13.15-24.13), while it was 2.1 IEU (95% CI = 1.8-2.4) in seronegative patients. A significantly above average risk for plasmodial infection could be found among travelers to East Africa (risk ratio [RR] = 4.5, P < 0.001), West Africa (RR = 4.5, P < 0.001), and Southern Africa (RR = 3.2, P = 0.015), while areas with a comparatively low risk included Central America (RR = 0.86, P < 0.001), the Indian subcontinent (RR = 0.45, P = 0.015), South America (RR = 0.49, P = 0.091), East Asia (RR = 0.68, P = 0.441), West Asia (RR = 0.24, P = 0.099), and Southeast Asia (RR = 0.69, P = 0.094). The results of this study emphasize the importance of adequate malaria chemoprophylaxis in nonimmune travelers to endemic areas. By use of the described method, estimates of the true infection rate of malaria in travelers can be derived for certain areas and the value of prophylactic measures can be demonstrated.

Geographic differences in the sensitivity of a polymerase chain reaction for the detection of Plasmodium falciparum infection.

The amplification of target DNA by highly specific probes using the polymerase chain reaction (PCR) provides a highly sensitive and specific method for the detection of malaria infection. The use the of PCR in settings with varying endemicity within one survey area has not been investigated intensively. Therefore, a cross-sectional study was conducted in the districts of Kabarole and Bundibugyo in western Uganda using material from three villages with different epidemiologic situations regarding malaria and DNA primers for a PCR that had shown satisfactory sensitivity and specificity in previous trials. The sensitivity of the PCR varied significantly (P < 0.001) in the three survey villages (between 63.2% and 83.9% for the primer pair K1-14-1 and between 37.9% and 69.9% for the primer pair MSP-1) and was highly linked to geographic differences and social exchanges of the inhabitants with other areas of the district. According to the results of this investigation, it is advisable not to use a single primer pair in epidemiologic field studies for the detection of falciparum malaria. The use of combined primer pairs and the frequent confirmation of the results by microscopy are recommended.