The clinical spectrum of Exophiala jeanselmei, with a case report and in vitro antifungal susceptibility of the species.

Exophiala jeanselmei is clinically redefined as a rare agent of subcutaneous lesions of traumatic origin, eventually causing eumycetoma. Mycetoma is a localized, chronic, suppurative subcutaneous infection of tissue and contiguous bone after a traumatic inoculation of the causative organism. In advanced stages of the infection, one finds tumefaction, abscess formation and draining sinuses. The species has been described as being common in the environment, but molecular methods have only confirmed its occurrence in clinical samples. Current diagnostics of E. jeanselmei is based on sequence data of the Internal Transcribed Spacer (ITS) region of ribosomal DNA (rDNA), which sufficiently reflects the taxonomy of this group. The first purpose of this study was the re-identification of all clinical (n=11) and environmental strains (n=6) maintained under the name E. jeanselmei, and to establish clinical preference of the species in its restricted sense. Given the high incidence of eumycetoma in endemic areas, the second goal of this investigation was the evaluation of in vitro susceptibility of E.jeanselmei to eight conventional and new generations of antifungal drugs to improve antifungal therapy in patients. As an example, we describe a case of black grain mycetoma in a 43-year-old Thai male with several draining sinuses involving the left foot. The disease required extensive surgical excision coupled with intense antifungal chemotherapy to achieve cure. In vitro studies demonstrated that posaconazole and itraconazole had the highest antifungal activity against E. jeanselmei and E. oligosperma for which high MICs were found for caspofungin. However, their clinical effectiveness in the treatment of Exophiala infections remains to be determined.

Evaluation of two staging systems for HIV infection for use in developing countries.

OBJECTIVE: To evaluate the clinical axis of the World Health Organization (WHO) clinical staging system and the modified WHO staging system proposed by Montaner et al. using the lymphocyte strata > 1500, 1500-1000 and < 1000 cells x 10(6)/l. DESIGN: Cross-sectional study. PATIENTS: Four hundred and fifteen consecutive patients with HIV infection attending three HIV reference centres in Belgium. METHODS: Absolute CD4 lymphocyte counts were compared between stages within the two staging systems. RESULTS: Median CD4 lymphocyte counts decreased with increasing stage of disease in both staging systems. Differences in median CD4 lymphocyte counts between stages of each staging system were statistically significant (Kruskal-Wallis one-way analysis of variance, P < 0.001). The WHO clinical stage 1 and the modified WHO stage I had positive predictive values of 56 and 58%, respectively, for identifying patients with CD4 lymphocyte levels > 500 cells x 10(6)/l. The WHO clinical stage 4 and the modified WHO stage IV had positive predictive values of 79 and 80%, respectively, for identifying patients with CD4 lymphocyte levels < 200 cells x 10(6)/l. CONCLUSIONS: The WHO clinical staging system or a modified version of this system using lymphocytes stratification may be a good alternative in developing countries to the CD4 lymphocyte count-based HIV staging system used in the developed world. Cohort studies in developing countries are needed to assess their prognostic value.

PIP: In 1990, Belgium, physicians enrolled 415 consecutive patients attending HIV reference centers in Antwerp, Brussels, and Ghent in a cross-sectional study designed to evaluate the clinical axis of the WHO staging system with and without the lymphocyte stratification proposed by Montaner el al. (that is, modified WHO staging system) (1500, 1500- 1000, and 1000 cells x 1 million/l). They filled in a standardized questionnaire with all criteria of the WHO staging system. Laboratory personnel used standard hematology and flow cytometry techniques to determine absolute and CD4 lymphocyte counts. 80% of the patients were Caucasians. 46% of all patients were homosexual and 42% were heterosexual; 79.2% were men. Median CD4 lymphocyte counts fell in both staging systems as the stage of HIV infection increased. There were significant differences in median CD4 counts between stages of each staging system (p .001). The modified WHO staging system's stage I was more sensitive at identifying patients with CD4 lymphocyte counts of more than 500 cells x 1 million/l than the WHO clinical stage 1 (83% sensitivity vs. 48% sensitivity). The positive predictive value of WHO clinical stage 4 and of the modified WHO staging system's stage IV for identifying people with CD4 lymphocyte counts of less than 200 cells x 1 million/l was quite high (79% and 80%, respectively). The researchers suggested that clinicians use stages 4 and IV as end-points is clinical trials in developing countries. Clinicians completing the questionnaire knew the patients' earlier CD4 lymphocyte count, which may have introduced a bias in the study. For example, they may have more thoroughly examined patients with low CD4 lymphocyte counts than those with normal counts. Nevertheless, the study's results indicated that either one of these systems may be a good alternative in developing countries to the technical equipment-dependent CD4 lymphocyte count-based HIV staging system used in developed countries. Cohort studies in developing countries would evaluate their prognostic value.

Treatment failure of a single high dose of ivermectin for Mansonella perstans filariasis.

Infections with Mansonella perstans are common in certain parts of Africa and South America. There is no standard treatment at present. We evaluated the effect of a single high dose of ivermectin (600 micrograms/kg) on microfilaraemia in 7 consecutive patients. No decrease in microfilarial counts could be demonstrated after a follow-up period of 7-56 d.

Systemic anaplastic large cell lymphoma presenting with cutaneous manifestations in a young man: a case report.

Skin lesions can be a sign of internal disease. When they are associated with persisting systemic signs, the possibility of an internal malignancy should always be considered. We describe a 25-year-old man who presented with weight loss, fatigue, subpyrexia, xerostomia and skin rash of 6 months duration. Physical examination showed a dry red skin, most prominent in the face, the palms of the hands and the soles of the feet. Laboratory investigations revealed signs of inflammation and a high level of antinuclear antibodies. Retroperitoneal lymph nodes were visualized on a CT scan of the abdomen. CT-guided biopsy of an abdominal lymph node revealed the presence of an anaplastic large cell lymphoma (ALCL), ALK-positive. A biopsy of the skin showed non-specific signs of inflammation.The patient underwent 8 cycles of chemotherapy according to the CHOP protocol. A complete remission was obtained. Non-Hodgkin lymphoma can indeed be associated with skin lesions. They result from direct invasion by malignant cells or are of paraneoplastic origin, as was the case in this patient.

A traveler with neurobrucellosis.

An Indian traveler developed fever and neurological symptoms after a visit to East Africa. He was treated with suramin, melarsoprol and prednisolone for presumed East African trypanosomiasis. His condition deteriorated and cerebral lesions developed. Neurobrucellosis was diagnosed. Combination antibiotic therapy led to gradual clinical improvement and regression of the brain lesions. Misdiagnosis of East African trypanosomiasis followed by treatment with potentially lethal medication should be avoided by not relying on insufficient evidence during the diagnostic process.

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.

Haemoglobin K-Woolwich as cause of falsely elevated HbA1.

Falsely elevated levels for haemoglobin A1 can be found with the haemoglobinopathies. A case is reported where falsely high levels for haemoglobin A1 were caused by the asymptomatic presence of haemoglobin K-Woolwich.

Development of hyperreactive malarious splenomegaly in an 8 year-old Caucasian boy, 18 months after residence in Africa.

Hyperreactive malarial splenomegaly (the former tropical splenomegaly syndrome) refers to a combination of splenomegaly, high antimalarial antibodies and high serum IgM content, a condition resulting from an aberrant immunological response to malaria. It has rarely been described in expatriates. We report the case of an 8 year-old Dutch boy who developed this syndrome 18 months after returning from Zaire. Treatment with mefloquine resulted in gradual improvement of all laboratory abnormalities. The spleen did not decrease in size, but became normal for age as height increased.

Eosinophilic myositis resulting from sarcocystosis.

Muscle sarcocystosis is a parasitic infection acquired by ingestion of sporocysts of Sarcocystis species. A case is described where symptoms of fever, chronic myositis and eosinophilia were present. Diagnosis was made via muscle biopsy. Improvement and cure coincided with treatment with cotrimoxazole. A limited review of human muscle sarcocystosis and an outline of the gaps in the knowledge of this infection is presented.

Clinical training for tropical doctors in the nineties.

Together with economic causes, the declining belief in the relevance of clinical skills, the omission of the hospital from the health system, and the erroneous generalisation of a complaint centred approach enhanced the decline in clinical medicine in several developing countries over the last decades. Despite a growing interest and important efforts in continuous education, basic training remains generally knowledge-directed. Clinical training should start from a realistic job description, and aim at acquiring skills instead of knowledge. Basics of clinical epidemiology can help refine clinical logic both at the health centre and the hospital level. the district hospital should be awarded a key role in pre-graduate and continuous clinical training. Awaiting a revival of the economy in most tropical countries, and especially in tropical Africa, an effective way for improving clinical practice is to invest in training, at all levels, with an emphasis on continuous medical training.

[Sleeping sickness as an import pathology following a stay in Zaire]. / Slaapziekte als importpathologie na verblijf in Zaïre.

A 32-year-old Italian man developed fever and general malaise 3 weeks after arrival in Zaïre. Malaria was diagnosed by a thick blood film, but consequent treatment with quinine was unsuccessful. After repatriation, the diagnosis of early stage sleeping sickness was established. Treatment with eflornithine (Ornidyl) resulted in complete recovery.

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.

Atypical varicella zoster infection in persons with HIV infection.

Four patients with HIV infection and severe immunodeficiency are described who developed atypical varicella zoster lesions. Three of the patients presented with chronic varicella zoster lesions. In two of them such lesions were hyperkeratotic. All three patients had been treated initially with subtherapeutic doses of acyclovir. In one of the patients the lesions were clinically resistant to high dose acyclovir treatment and disappeared only when renal insufficiency developed during foscarnet-famcyclovir treatment. One patient developed a disseminated varicella zoster infection.

Mansonella perstans filariasis: failure of albendazole treatment.

Infections with Mansonella perstans are common in certain parts of Africa and South America. There is no standard treatment at present. We evaluated the effect of albendazole on microfilaremia in ten consecutive patients. No decrease in microfilarial counts could be demonstrated after a median follow-up period of 45 days. Albendazole was not shown to be useful for treatment of Mansonella perstans filariasis.

[Treatment of human trypanosomiasis caused by Trypanosoma brucei gambiense using alpha-difluoromethylornithine. Results in 7 patients]. / Traitement de la trypanosomiase humaine à Trypanosoma brucei gambiense par l'alpha-difluorométhylornithine. Résultats chez 7 patients.

Alpha-difluoromethylornithine (DFMO, eflornithine) is a specific irreversible inhibitor of ornithine decarboxylase, shown to be curative in various Trypanosoma species infections of animals. In the present open study, the efficiency of DFMO was assessed in 7 patients (4 Africans, 3 Europeans) with Trypanosoma brucei gambiense (Tbg) infection, 4 in the advanced stage and 3 in the early phase of the disease. Treatment with DFMO at initial dosages ranging 300-500 mg/kg/day administered IV (except 1 case) for 10-15 days, followed by 200-300 mg/kg/day per os for 28-69 days was associated with clearing of trypanosomes from blood within 1-4 days, a trend towards normalisation or full normalisation of all altered biological values characterizing the disease and disappearance of clinical symptoms. Side effects of DFMO, including loose stools (5 cases), anemia (3 cases) and decreased hearing (1 case), were mild and transient requiring no treatment or interruption of the drug, except in one case. Pharmacokinetic studies carried out in 4 patients, demonstrate penetration of the drug into CNS. In 6 cases, no evidence of relapse was found at 24 months posttreatment follow-up indicating that DFMO can be curative in early and late-stage of Tbg sleeping sickness. In 1 case, no relapse could be detected after a follow-up of 6 months. Further studies are needed to confirm our encouraging results and to determine the optimal regimens of DFMO for the cure of the early and late-stage of sleeping sickness.

Kabisa: an interactive computer-assisted training program for tropical diseases.

In Europe, tropical pathology is usually taught in special short courses, intended for those planning to practise in developing countries. The theoretical knowledge to be assimilated during this short period is considerable, and turning such newly acquired knowledge into competence is difficult. Kabisa is a computer-based training program for tropical diseases. Instead of concentrating on strictly tropical diseases, students are trained in recognizing diseases in patients presenting randomly in an imaginary reference hospital in a developing country. Databases are compiled by experts from experiences in various parts of Africa, Asia and tropical America. Seven languages and three levels of competence can be chosen by the student. Updating of all databases is possible by teachers who want to describe a particular setting. A 'consistency checker' verifies the internal consistency of a new configuration. The logical engine is based upon both a 'cluster' and a Bayesian logic, with built-in corrections for related disease characteristics. This correction allows calculated probabilities to stay closer to real probabilities, and avoids the 'probability overshoot' that is inherent to 'idiot Bayes' calculations. The program provides training in diagnostic skills in an imaginary second-line setting in a tropical country. It puts tropical and cosmopolitan diseases in perspective and combines applied clinical epidemiology and pattern recognition within varying sets of presenting symptoms. Students are guided in searching for the most relevant disease characteristics, in ranking disease probability, and in deciding when to stop investigating.

[Clinical aspects and treatment of bites by poisonous snakes]. / Kliniek en behandeling van beten door gifslangen.

Every year there are hundreds of snake bites in Europe, but the main problems occur in tropical areas. Symptoms such as hemorrhages, paralysis and local necrosis vary according to the snake species. Inappropriate first aid should be avoided. Antitoxin should be administered if there are signs of poisoning. It is never too late to give antitoxin. Antitoxin can have a number of potentially very dangerous side-effects.