Biomedical subjects
Publications and source records attributed to H D Nothdurft.
In a survey among febrile European tourists in Kenya, only 68% were able to carry out immunochromatographic dipstick tests for detection of Plasmodium falciparum antigen correctly, and ten of 11 with malaria failed to diagnose themselves correctly. Rapid tests for self-diagnosis by tourists cannot be recommended without appropriate training before departure.
HISTORY AND ADMISSION FINDINGS: A 38-year-old patient, an experienced traveller to the tropics, fell ill with a flu-like infection, a fever of up to 38.6 degrees C and nausea on returning from an 8-week trip to southern Africa (Namibia, Zambia and Zimbabwe). Physical examination was unremarkable, except for slight physical debility. His father had died of liver cirrhosis of unknown aetiology, aged 68 years. INVESTIGATIONS: Laboratory tests revealed eosinophilia (12% on a count of 7,800 WBC/microliter, increased transaminase activities [SGPT 142 U/l, SGOT 50 U/l, gamma GT 32 U/l], slightly increased serum ferritin [1057 ng/dl], but normal serum iron and transferrin levels). Untreated stool contained Schistosoma mansoni eggs. Tests for a haemochromatosis gene and its type showed a homozygotic C282Y variant. Liver biopsy demonstrated chronic portal hepatitis with parenchymal transformation and marked haemosiderin deposits in liver epithelium. DIAGNOSIS, TREATMENT AND COURSE: The schistosomiasis was treated with praziquantel, 40 mg/kg by mouth on one day, divided in three doses, without complication. The haemochromatosis was treated symptomatically, at first by weekly bloodletting 500 ml while monitoring serum ferritin concentration. Life-long bloodletting at longish intervals is anticipated. CONCLUSIONS: The incidence of some infectious diseases has greatly risen as a result of an increase in tourism to distant lands. In particular, the diagnosis of frequent parasitic diseases should become part of the expertise in internal medicine. The combination of several diseases should be considered in the differential diagnosis.
The incidence of typhoid fever in emerging countries remains high, being estimated to be 500 per 100,000 head of population. Tourists from the industrialized countries can contract the infection in particular when travelling under conditions of poor hygiene in endemic regions. The risk of contracting typhoid appears to be highest on lengthy travels on the Indian subcontinent, while short visits to Latin America or Africa appreciably less often result in an infection. Currently, two vaccines are approved for use in Germany: a live oral vaccine containing the defective S. typhi mutant Ty 21a, and a parenteral inactivated vaccine prepared from the Vi capsid antigen of S. typhi. Both vaccines are well tolerated and provide similar levels of protection. The reported protection rate for the live vaccine varies in various studies between 33 and 67%; that of the inactivated vaccine between 55 and 75%. Medical advice prior to travel should weigh up such risk factors as age, duration of the journey, destination and the nature of the journey. While vaccination is particularly recommended for travelers with one or more risk factors, it should always be pointed out that an infection is nevertheless possible. In view of the fact that immunization against hepatitis A and typhoid fever are often indicated simultaneously, the development of a combination vaccine would be desirable.
HISTORY AND CLINICAL FINDINGS: A 57-year-old patient presented with malaise and severe persistent arthralgia of the left shoulder. He reported an acute illness with fever, generalized myalgia and arthralgias of the large joints which had started one month earlier during his flight back to Germany after a two weeks trip to the South Pacific. Physical examination showed extensive pain on palpation of the glenohumeral and acromioclavicular joints with impairment of active and passive mobility. Investigation of the cervical spine was normal. INVESTIGATIONS: Apart from elevated C-reactive protein and erythrocyte sedimentation rate levels, routine laboratory investigations were normal including negative immunodiagnostic tests for autoantibodies and various global infections that may be associated with arthritis. Immunofluorescence tests showed significant levels of specific IgM- and IgG-antibodies against Ross River virus (RRV) but not against other arboviruses endemic in the South Pacific and Australia (Dengue, West Nile, Chikungunya, Sindbis, Barmah Forest). This was confirmed by a positive RRV neutralisation test. Attempts at virus isolation and detection of viral RNA by PCR were not successful. TREATMENT AND COURSE: Symptomatic treatment with high doses of diclofenac quickly led to pain relief, and arthralgias receded within 10 days after begin of treatment. However, several bouts of arthralgia of the left shoulder and left knee occurred during a period of 4 months. CONCLUSIONS: Because of the current epidemiological situation in the South Pacific and Australia, infections by arboviruses like RRV should be considered in travellers returning from these areas with severe and persistent arthralgia of unknown origin, even in the absence of fever and other symptoms of acute infection.
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It has been proposed that polymorphisms of the Merozoite Surface Protein 1 and 2 (MSP1 and MSP2) and the Glutamate Rich Protein (GLURP) genes can be considered as genetic markers for the genotyping of field populations of Plasmodium falciparum. During a field study on in vivo drug resistance against chloroquine, sulphadoxine/pyrimethamine (S/P) and cotrimoxazole in West Uganda, sensitive and resistant isolates were collected from patients by fingerprick for genotyping. 59 (72.8%) of the 81 P. falciparum samples isolated at day 0 showed multiclonal infection with 2-7 clones. Among the isolates we investigated, presence of the allelic family MAD20 of MSP1 at day 0 was significantly (P = 0.0041) associated with decreased resistance to antimalarials. Use of this method in a field study on in vivo drug resistance demonstrates another potential application of genotyping as a tool for epidemiological investigations.
Circumsporozoite (CS) antibodies have been shown to be reliable indicators of malaria transmission in endemic areas. Their prevalence in travelers can indicate the degree of exposure to plasmodial infection. Two hundred sixty-two short-term travelers to Kenya were recruited to a prospective study to determine the incidence of CS antibody conversion. All travelers were receiving malaria chemoprophylaxis. Serum samples were drawn before departure and 4-6 weeks after their return to Germany. Sera from 310 volunteers who did not leave Germany served as controls. Serum specimens from 13 (4.96%) of the 262 travelers were found to be positive after return. None of the travelers developed symptoms of clinical malaria or antibodies against the blood stages of Plasmodium falciparum. All 310 control samples tested negative. These data demonstrate a considerable risk of malaria transmission for short-term travelers to East Africa.
Swift diagnosis of Plasmodium falciparum malaria in areas where the disease is not endemic is frequently complicated by the lack of experience on the side of involved laboratory personal. Diagnostic tools based on the dipstick principle for the detection of plasmodial histidine-rich protein 2 (HRP-2) and parasite-specific lactate dehydrogenase (pLDH), respectively, have become available for the qualitative detection of P. falciparum malaria. In order to evaluate two of the currently available assays, specimens from 231 patients were screened during a prospective multicenter study. Among the screened specimens, samples from 53 patients (22.9%) were positive for P. falciparum malaria by microscopy and/or PCR. While the test kit based on the detection of HRP-2 performed with a sensitivity of 92.5% and a specificity of 98.3%, the kit for the detection of pLDH showed a sensitivity of 88.5% and a specificity of 99.4%. Dipstick tests have the potential of enhancing speed and accuracy of the diagnosis of P. falciparum malaria, especially if nonspecialized laboratories are involved.
OBJECTIVE: To investigate the effectiveness of chemoprophylaxis and the determinants of malaria importation from Kenya. METHOD: In a population-based case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers returning from Kenya (controls) were interviewed. Data were analysed by multiple logistic regression. RESULTS: Mefloquine (OR = 0.055; 95% CI 0.019-0.16) and chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly protective against P. falciparum malaria, whereas other drugs were ineffective (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non-prophylaxis (11.2%) were the main reasons for malaria importation. Travelling alone or with friends, male sex, and travel duration over 4 weeks could be identified as additional risk factors. The main reason for inadequate chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal occurred frequently despite correct advice (58.1%). Diagnosis was often delayed unnecessarily (27.5%). CONCLUSION: Malaria importation from Kenya could be reduced substantially (34%) by eliminating inappropriate medical advice.
OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) dipstick test for detecting chloroquine (CQ) in urine in a malaria-endemic region of north-western Namibia. METHOD: Urine samples from 92 patients attending the outpatient department of Kamhaku Hospital with suspected malaria infection were tested for CQ with both the Dill-Glazko test and the ELISA dipstick test. Results were compared to the history of CQ intake as documented in the patients' health passes. RESULTS: The dipstick test proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 120 nmol/l. It showed high agreement with the history of CQ intake within the last 6 months. The specificity in a negative control group was 100%. The Dill-Glazko test was far less sensitive and specific with a lower detection limit of 150 micromol/l. CONCLUSION: The dipstick test can be used in pharmacological studies to evaluate the use of CQ, and as an inclusion criterion for in vivo and in vitro sensitivity tests, whereas the Dill-Glazko test is appropriate to test compliance during and a few days after CQ intake.
Most knowledge about the synthesis of human tumor necrosis factor (TNF)-alpha and its regulation derives from in vitro studies. The hypothesis that the syndrome of malaise, myalgia, and low fever observed after a vaccination with live attenuated yellow fever virus could be associated with increased synthesis of TNF was investigated. Plasma samples of 15 healthy subjects taken before and until day 2 (until day 11 in 5 of these subjects) after yellow fever vaccination, showed a significant increase of plasma TNF concentration on day 2 after vaccination and a second peak on day 7. Interleukin-1 receptor antagonist (IL-1ra) concentration was significantly elevated in all subjects on day 2 after vaccination. In a control group receiving non-live vaccinations, TNF and IL-1ra concentrations were unchanged. Thus, yellow fever vaccination represents a routine medical intervention that results in a reproducible increase in the plasma concentration of TNF and secondary cytokines. This may serve as a unique model for the study of the regulation of TNF synthesis in vivo.
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.
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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.
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PATIENTS AND METHODS: Travel and medical histories as well as clinical features of 62 German and 21 native patients with schistosomiasis who were presented to a German outpatient clinic for infectious and tropical diseases were investigated in order to identify the risk factor leading to infection in travellers and expatriates. RESULTS: All patients were able to remember the incidents which led to a likely exposure to cercariae of schistosoma spp. Fifty-nine German patients (95%) acquired infection in Africa, 2 (3%) in South America and one each (2% each) in the Euphrat and the Mekong River, respectively. All but 1 native patients acquired infection in Africa. The highest proportion of infection (45% in Germans and 37% in native patients) was imported from West Africa. Patients returning from this area had had either contact with tributaries of the Niger or with waters of the Volta River, notably the Lake Volta and/or its delta. The most sensitive method for detection of schistosomiasis appeared to be a combination of thorough travel history and serological testing (IHA, IFAT and ELISA) of all patients with possible infection. CONCLUSIONS: In the investigated group, most infections were acquired by travellers on a lengthy and adventurous journey or by expatriates venturing outside their normal areas of activity. Most patients knew that they travelled in an area endemic for schistosomiasis but were uninformed about the risks they took with their behaviour in a specific setting. Others simply could not avoid skin exposure to freshwater like backpacking tourists travelling in boats on the Niger or Congo River and native patients. Travellers to the tropics should therefore be informed thoroughly about the dangers of water-related diseases such as schistosomiasis.
The role of Blastocystis hominis as a pathogen for man has been controversially discussed, while travel history has been implicated as a risk factor of infection. Few controlled studies of the association between B. hominis and symptomatic diseases have been performed. Therefore, a case-control study among 795 German tourists returning from tropical countries was conducted. The prevalence of the organism among patients with and without symptoms was assessed. Blastocystis hominis was detected in 69 of 469 (14.7%) patients with diarrhoea and in 21 of 326 (5.7%) controls. However, other organisms causing diarrhoea were detected in 18 of the 69 (26.1%) symptomatic patients with B. hominis. Thus, 51 of 469 (10.8%) symptomatic patients had B. hominis in the absence of other pathogens in their stool, significantly more than in the asymptomatic group (5.2%; P = 0.005). Irrespective of the development of symptoms, the organism was most frequently acquired during journeys to the Indian subcontinent. The results of this study suggest that B. hominis is associated with development of diarrhoea in travellers to tropical destinations and that frequently concurrent infections with other organisms occur.