[Frequent infectious diseases in migrants]. / Häufige Infektionskrankheiten bei Migranten.

The current influx of refugees and the high rate of immigration increase the rate and impact of infectious diseases in Europe. Infections can be detected at the initial examination of arriving refugees as a result of systematic screening or within the framework of general medical care. Diagnosis and treatment require special expertise and in some cases special precautions. The spectrum of infections is determined by the country of origin of migrants and the conditions experienced on fleeing to Germany. In this article the diagnostics and treatment of the most important infections are presented. As far as infections are concerned refugees and migrants do not represent a threat to the general population but instead have to be perceived as a highly vulnerable group.

Prevalence of hepatitis B virus infection among health care workers in a tertiary hospital in Tanzania.

BACKGROUND: Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania. METHODS: We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2%) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8%). RESULTS: The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0% (42/598). Chronic HBV infection was found in 7.4% of rHCW versus 5.6% of nrHCW (p-value = 0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3%. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5% and 20.2%, respectively. 4.8% of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1% of HCWs who received a full vaccination course had an anti-HBs titer >10 ml/U. An anti-HBs point-of-care test was 80.7% sensitive and 96.9% specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p < 0.0001 vs. nrHCW 1.385, p = 0.606) and among those HCW being employed more than 11 years (OR 2.51, p < 0.0001***). HCV prevalence was low (HCV antibodies 1.2% and HCV-RNA 0.3%). CONCLUSIONS: Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.

Suspected new wave of muscular sarcocystosis in travellers returning from Tioman Island, Malaysia, May 2014.

In May 2014, six patients presented in Germany with a Sarcocystis-associated febrile myositis syndrome after returning from Tioman Island, Malaysia. During two earlier waves of infections, in 2011 and 2012, about 100 travellers returning to various European countries from the island were affected. While the first two waves were associated with travel to Tioman Island mostly during the summer months, this current series of infections is associated with travel in early spring, possibly indicating an upcoming new epidemic.

[Coccidioidomycosis with manifestation on the tongue]. / Kokzidioidomykose mit Befall der Zunge.

Systemic mycoses are rare but important differential diagnoses in patients with imported infections. We report the case of a 51-year-old German traveller who acquired coccidioidomycosis during a holiday in Arizona, USA. The disease became apparent several months later primarily as a swelling of the tongue. Subsequent diagnostic investigations revealed infiltration of both lungs. The causal agent Coccidioides posadasii could be cultivated from transbronchial biopsy samples.

[Fever, leg swelling, coughing, and left upper quadrant pain in a 19-year-old woman]. / Fieber, Unterschenkelschwellung, Husten und linksseitige Oberbauchschmerzen bei einer 19-jährigen Patientin.

Persistent fever and unspecific general symptoms need a complete and thorough medical history and search for infection. We report on a case of brucellosis (Malta fever) with involvement of organs in a 19-year-old woman. She had previously lived on a farm in Portugal for several weeks, where she had consumed self-produced goat cheese. After a latency period of several months, unspecific general symptoms, fever, monarthritis, an increase of transaminases, and a newly diagnosed cardiac murmur became apparent. After the serologic and cultural proof of brucellosis, the patient underwent an antibiotic combination therapy. Within 20 days she was free of symptoms and could be released.

Prophylactic immunisation against traveller's diarrhoea caused by enterotoxin-forming strains of Escherichia coli and against cholera: does it make sense and for whom?

Traveller's diarrhoea (TD) constitutes the most common disease relevant to travel medicine with ETEC as the leading causative pathogen. Cholera is the most serious, but very rare form of TD. ETEC and cholera share pathogenic mechanisms by producing a toxin that has an 80% amino acid homology. A consensus of German-speaking experts sees the indication to use the whole cell/B subunit oral cholera vaccine (WC--BS) if cholera is a risk for aid workers or travellers with an anticipated threat of cholera who stay under poor hygienic conditions. The use of the vaccine should be considered in the indication to avoid ETEC TD for travellers with predisposing illness or medication or for travellers at risk to develop a serious course.

Skin and soft tissue infections in intercontinental travellers and the import of multi-resistant Staphylococcus aureus to Europe.

Staphylococcus aureus is emerging globally. Treatment of infections is complicated by increasing antibiotic resistance. We collected clinical data and swabs of returnees with skin and soft tissue infections (SSTI) at 13 travel-clinics in Europe (www.staphtrav.eu). Sixty-two percent (196/318) SSTI patients had S. aureus-positive lesions, of which almost two-thirds (122/196) were Panton-Valentine leukocidin (PVL) positive. PVL was associated with disease severity, including hospitalization for SSTI (OR 5.2, 95% CI 1.5-18.2). In returnees with SSTI, longer travel and more intense population contact were risk factors for nasal colonization with PVL-positive S. aureus. Imported S. aureus frequently proved resistant to trimethoprim-sulfamethoxazole (21%), erythromycin (21%), tetracycline (20%), ciprofloxacin (13%), methicillin (12%) and clindamycin (8%). Place of exposure was significantly (p < 0.05) associated with predominant resistance phenotypes and spa genotypes: Latin America (methicillin; t008/CC24/304), Africa (tetracycline, trimethoprim-sulfamethoxazole; t084/CC84, t314/singleton, t355/CC355), South Asia (trimethoprim-sulfamethoxazole, ciprofloxacin; t021/CC21/318), South-East Asia (clindamycin; t159/CC272). USA300-like isolates accounted for 30% of all methicillin-resistant S. aureus imported to Europe and were predominantly (71%) acquired in Latin America. Multi-resistance to non-ß-lactams were present in 24% of imports and associated with travel to South Asia (ORcrude 5.3, 95% CI 2.4-11.8), even after adjusting for confounding by genotype (ORadjusted 3.8, 95% 1.5-9.5). Choosing randomly from compounds recommended for the empiric treatment of severe S. aureus SSTI, 15% of cases would have received ineffective antimicrobial therapy. These findings call for the development of regionally stratified guidance on the antibiotic management of severe imported S. aureus disease and put the infected and colonized traveller at the centre of interventions against the global spread of multi-resistant S. aureus.

New drugs for the treatment of human African trypanosomiasis: research and development.

Chemotherapy of human African trypanosomiasis is problematic because of the high frequency of severe adverse events, the long duration and high cost of treatment, and an increasing number of treatment-refractory cases. New cost-efficient, easy-to-use drugs are urgently needed. Whereas basic research on potential drug targets is anchored in academia, the complex, highly regulated and very expensive process of preclinical and clinical drug development is almost exclusively in the hands of pharmaceutical companies. Jennifer Keiser, August Stich and Christian Burri here review, from the angle of industrial drug research and development, the past ten years of research activities at different stages of the development of trypanocidal drugs, and assess future prospects. The absence of compounds in clinical development Phases I-III indicates no new drugs will become available in the next few years.

Insecticide-impregnated bed nets reduce malaria transmission in rural Zanzibar.

There has been concern that impregnated bed nets are an insufficiently powerful method to control malaria in areas with very high perennial transmission, as in the humid lowland parts of tropical Africa. We carried out a 'cross-over' trial among children under 5 years of age in 2 villages in rural Zanzibar. In 1989, one village was supplied with newly permethrin-impregnated bed nets whereas the other served as unprotected control. In 1992, when those nets had lost their insecticidal activity and were badly torn, the village which had previously been the control was given newly impregnated bed nets. Each time, reinfection with Plasmodium falciparum was measured after initially clearing the parasites by administering a therapeutic dose of sulfadoxine/pyrimethamine. The introduction of bed nets led to a 74-78% reduction in the weekly rate of reinfection with malaria parasites, in all age groups. The nets apparently also affected perceived clinical symptoms, haemoglobin levels, and the mosquito sporozoite rate.

Antitrypanosomal naphthylisoquinoline alkaloids and related compounds.

In view of the need to develop new drugs against human African trypanosomiasis, a series of naturally occurring naphthylisoquinoline alkaloids, axially chiral acetogenic products derived from tropical plants, have been investigated for their activity against Trypanosoma brucei brucei TC 221. Likewise compounds corresponding to the two molecular portions, the naphthalene and the isoquinoline parts were tested, as well as molecules related to the central biaryl core of the alkaloids. Among all compounds tested, the natural, genuine alkaloids themselves, in particular dioncophylline B with its biaryl system and a moderate number of free hydroxy functions, showed the highest activities. Our results demonstrate that naphthylisoquinoline alkaloids constitute an interesting novel class of antitrypanosomal compounds worth further optimization.

[What is effective in traveler's diarrhea? Current recommendations on prevention, therapy and after care]. / Was hilft gegen Reisediarrhö? Aktuelle Empfehlungen zu Prophylaxe, Therapie und Nachsorge.

Traveller's diarrhea is almost always due to an infection with intestinal bacteria, viruses or parasites. The leading agents are the ubiquitous enterotoxic E. coli bacteria. Prophylaxis is achieved primarily by the strict avoidance of fecally contaminated food and drink--advice which, however, is often ignored. Chemoprophylactic measures include the use of probiotics, in particular Saccharomyces boulardii, with antibiotics being given only in special cases. Treatment consists mainly in the replacement of lost fluids and electrolytes in the form of oral rehydration solutions. Second-line treatment includes probiotics and antimotility agents such as loperamide. Antibiotics (quinolones) should be reserved for severe febrile forms of the condition.

[Muscular sarcocystosis after travel to Malaysia: a case series from Germany]. / Muskuläre Sarkozystose nach Malaysiareise: eine Fallserie aus Deutschland.

BACKGROUND: Since 2011, about 100 travellers to the island of Tioman, Malaysia, have been diagnosed worldwide with suspected muscular sarcocystosis, a previously only sporadically observed parasitic disease. Source of infection and therapy remain unclear. Final diagnosis requires microscopic identification of cysts in muscle biopsies. The study objective was a systematic description of characteristic symptoms, laboratory investigations and treatment response. METHODS: Systematic case series. RESULTS: The 26 cases of 5 centers for tropical medicine in Germany showed a characteristic biphasic development: symptoms began in general 2 weeks after mid-holidays (min. 7.5, max. 22 days) with unspecific fever and headaches lasting for almost 1 week. After an asymptomatic period of 2 weeks, severe myalgia (6.5, scale 0-10) and fever developed and lasted for about 6 weeks (min. 7, max. 207 days), accompanied by creatin-phosphokinase(CK)-elevation (up to 3.5 times), and eosinophilia (2.9 times). One out of two muscle biopsies revealed a cyst typical for sarcocystosis. In 6 out of 7 patients an increase in Sarcocystis-specific antibody concentration could be demonstrated by ELISA. Treatment with systemic steroids and albendazole, or ivermectin resulted in significant symptomatic improvement in most of the patients. One patient was treated early with cotrimoxazole and subsequently did not develop a second phase of the disease. All patients had stayed in the North-West of the island Tioman. CONCLUSIONS: Muscular sarcocystosis develops in a biphasic pattern with initial fever and later prolonged myalgia, eosinophilia, and CK-elevation. Steroids achieve symptomatic relief in the late phase. Early cotrimoxazole-therapy could possibly prevent parasitic muscle invasion. In fever after travel to Malaysia differential diagnosis should include sarcocystosis. The source of infection appears to be located in North-West of Tioman. Further studies are needed, including addressing early diagnosis and treatment.

Evidence for an extraterrestrial impact 12,900 years ago that contributed to the megafaunal extinctions and the Younger Dryas cooling.

A carbon-rich black layer, dating to approximately 12.9 ka, has been previously identified at approximately 50 Clovis-age sites across North America and appears contemporaneous with the abrupt onset of Younger Dryas (YD) cooling. The in situ bones of extinct Pleistocene megafauna, along with Clovis tool assemblages, occur below this black layer but not within or above it. Causes for the extinctions, YD cooling, and termination of Clovis culture have long been controversial. In this paper, we provide evidence for an extraterrestrial (ET) impact event at approximately equal 12.9 ka, which we hypothesize caused abrupt environmental changes that contributed to YD cooling, major ecological reorganization, broad-scale extinctions, and rapid human behavioral shifts at the end of the Clovis Period. Clovis-age sites in North American are overlain by a thin, discrete layer with varying peak abundances of (i) magnetic grains with iridium, (ii) magnetic microspherules, (iii) charcoal, (iv) soot, (v) carbon spherules, (vi) glass-like carbon containing nanodiamonds, and (vii) fullerenes with ET helium, all of which are evidence for an ET impact and associated biomass burning at approximately 12.9 ka. This layer also extends throughout at least 15 Carolina Bays, which are unique, elliptical depressions, oriented to the northwest across the Atlantic Coastal Plain. We propose that one or more large, low-density ET objects exploded over northern North America, partially destabilizing the Laurentide Ice Sheet and triggering YD cooling. The shock wave, thermal pulse, and event-related environmental effects (e.g., extensive biomass burning and food limitations) contributed to end-Pleistocene megafaunal extinctions and adaptive shifts among PaleoAmericans in North America.

Comparison of different PCR protocols for the detection and diagnosis of Plasmodium falciparum.

An assessment of differing PCR protocols for the diagnosis of Plasmodium falciparum infection was performed on samples from an area of holoendemic malaria transmission in western Burkina Faso. The PCR protocols had generally high sensitivities (>92%) and specificities (>69%), but the negative predictive values (NPV) were moderate and differed widely among the PCR protocols tested. These PCR protocols that amplified either the P. falciparum pfcrt gene or the small subunit ribosomal DNA were the most reliable diagnostic tools. However, the moderate NPV imply that more than one PCR protocol should be used for diagnosis in holoendemic areas.

Human African trypanosomiasis: an emerging public health crisis.

There is a dramatic resurgence of human African trypanosomiasis (HAT) in sub-Saharan Africa. T.b. gambiense is spreading epidemically in large areas of Central Africa, especially the Southern Sudan, Congo-Zaire, Angola, Uganda and the Central African Republic. Devastating epidemics of T.b. rhodesiense have occurred in south-eastern Uganda. The causes of the re-emergence of sleeping sickness as a public health problem include widespread civil disturbance and war, declining economies, reduced health financing and the dismantling of disease control programmes. Despite the inevitably fatal outcome without treatment, HAT is often given low priority by donors and national governments. The advances made in diagnosis, treatment and vector control have not been sufficiently implemented. To limit the human impact in some of the poorest communities in Africa, endemic countries will require external support to implement strategies for disease control. Donor agencies, NGOs and mission organisations could play an important role in supporting control efforts. National authorities will need to control and co-ordinate these efforts with assistance from WHO and the international community.

L-lactate dehydrogenase A4- and A3B isoforms are bona fide peroxisomal enzymes in rat liver. Evidence for involvement in intraperoxisomal NADH reoxidation.

The subcellular localization of l-lactate dehydrogenase (LDH) in rat hepatocytes has been studied by analytical subcellular fractionation combined with the immunodetection of LDH in isolated subcellular fractions and liver sections by immunoblotting and immunoelectron microscopy. The results clearly demonstrate the presence of LDH in the matrix of peroxisomes in addition to the cytosol. Both cytosolic and peroxisomal LDH subunits have the same molecular mass (35.0 kDa) and show comparable cross-reactivity with an anti-cytosolic LDH antibody. As revealed by activity staining or immunoblotting after isoelectric focussing, both intracellular compartments contain the same liver-specific LDH-isoforms (LDH-A4 > LDH-A3B) with the peroxisomes comprising relatively more LDH-A3B than the cytosol. Selective KCl extraction as well as resistance to proteinase K and immunoelectron microscopy revealed that at least 80% of the LDH activity measured in highly purified peroxisomal fractions is due to LDH as a bona fide peroxisomal matrix enzyme. In combination with the data of cell fractionation, this implies that at least 0.5% of the total LDH activity in hepatocytes is present in peroxisomes. Since no other enzymes of the glycolytic pathway (such as phosphoglucomutase, phosphoglucoisomerase, and glyceraldehyde-3-phosphate dehydrogenase) were found in highly purified peroxisomal fractions, it does not seem that LDH in peroxisomes participates in glycolysis. Instead, the marked elevation of LDH in peroxisomes of rats treated with the hypolipidemic drug bezafibrate, concomitantly to the induction of the peroxisomal beta-oxidation enzymes, strongly suggests that intraperoxisomal LDH may be involved in the reoxidation of NADH generated by the beta-oxidation pathway. The interaction of LDH and the peroxisomal palmitoyl-CoA beta-oxidation system could be verified in a modified beta-oxidation assay by adding increasing amounts of pyruvate to the standard assay mixture and recording the change of NADH production rates. A dose-dependent decrease of NADH produced was simulated with the lowest NADH value found at maximal LDH activity. The addition of oxamic acid, a specific inhibitor of LDH, to the system or inhibition of LDH by high pyruvate levels (up to 20 mm) restored the NADH values to control levels. A direct effect of pyruvate on palmitoyl-CoA oxidase and enoyl-CoA hydratase was excluded by measuring those enzymes individually in separate assays. An LDH-based shuttle across the peroxisomal membrane should provide an efficient system to regulate intraperoxisomal NAD+/NADH levels and maintain the flux of fatty acids through the peroxisomal beta-oxidation spiral.

[Old age as risk factor for complications of malaria in non-immune travellers]. / Höheres Lebensalter: Risikofaktor für einen schweren Verlauf der Malaria.

BACKGROUND: Malaria plays an important role as a dangerous imported infection in Europe. In addition, the number of elderly travellers is increasing. We examined the hypothesis, whether age can be considered as a risk factor for the development of complications in malaria. PATIENTS AND METHODS: We examined retrospectively 134 case records of patients of all age groups with a plasmodial infection. We analysed personal data, travel details and patient histories, the neurological status, respiratory function, as well as haematological, biochemical and parasitological parameters. RESULTS: There is significant evidence for a correlation between age and the frequency of complications in malaria like cerebral involvement, respiratory failure, renal failure, anaemia, and hyperparasitaemia. Out of 132 patients over 15 years of age, 49 (37.1 %) developed a severe course of malaria. In the age group of 60 years and above this percentage increased to 61.5 %. The age distribution in the group with severe malaria was significantly shifted towards the elderly (p = 0.016 in Mann-Whitney test). The duration of hospitalisation also increased with age from an average of five days for the group below 45 years to 21 days for the elderly of 60 years and above. CONCLUSION: Our findings suggest a higher risk for a severe course of malaria in the elderly. For this reason, extensive advice on the correct use of exposure- and chemoprophylaxis of malaria is especially important for travellers above the age of 60.