Miltefosine: issues to be addressed in the future.

Future issues that need to be addressed for miltefosine are efficacy against non-Indian visceral leishmaniasis, efficacy in HIV-coinfected patients, efficacy against the many forms of cutaneous and mucosal disease, effectiveness under clinical practice conditions, generation of drug resistance and the need to provide a second antileishmanial agent to protect against this disastrous event, and the ability to maintain reproductive contraceptive practices under routine clinical conditions.

A combined medical and surgical approach to hydatid disease: 12 years' experience at the Hospital for Tropical Diseases, London.

BACKGROUND: There is no consensus as to the most appropriate treatment for the varied and often complicated presentations of hydatid disease in Britain. We looked at our own results over a 12-year period to see if a consistent and logical plan had emerged. PATIENTS AND METHODS: 70 patients presenting between 1986 and 1998 were analysed retrospectively, with regard to their presentation, diagnosis, treatment and outcome, with particular reference to the use of chemotherapy, and to the difficulties of post-treatment assessment by serology and imaging. RESULTS: 37 patients had been treated previously. 35 had hepatic cysts and 26 multiple cysts. 4 patients were treated by surgery alone, 44 by chemotherapy and surgery, and 14 by chemotherapy alone. The combined use of albendazole and praziquantel pre-operatively reduced significantly the number of cysts that contained viable protoscolices: 1/25 versus 5/8 that received albendazole alone (P = 0.00013). During the 12-year period, it became our policy to aim for 3 months drug treatment (albendazole throughout with praziquantel for 2 weeks), re-assess and proceed either to surgery or to continue with chemotherapy. CONCLUSIONS: It is possible to construct an algorithm for the management of patients with hydatid disease by chemotherapy and surgery, but the assessment of results by indirect techniques remains difficult.

Subacute pulmonary granulomatous schistosomiasis: high resolution CT appearances--another cause of the halo sign.

A case of probable acute granulomatous pulmonary schistosomiasis is described with multiple focal opacities on chest radiography and widespread, but predominantly peribronchovascular, nodules with ground-glass halos on high resolution CT (HRCT). The HRCT appearances in early schistosomiasis have not been described previously. Although the features are not diagnostic and may be seen in other conditions, in the appropriate clinical context they may suggest pulmonary involvement in schistosomiasis. The features of pulmonary schistosomiasis in the different stages of infection are discussed. Pulmonary involvement should be suspected in patients with even minor respiratory symptoms when there is a history of exposure to fresh water in endemic areas.

Malaria at Christmas: risks of prophylaxis versus risks of malaria.

PIP: A large increase in the number of falciparum malaria cases imported into the UK was reported to the malaria reference laboratory in the first quarter of 1998. Contributory factors were unusually heavy rains in east Africa and a reduction in the use of the most effective antimalarial drug, mefloquine. There was also an increase in the number of cases of severe malaria in the UK. During December 1997 and January 1998, the Hospital for Tropical Diseases, London, treated 5 patients for severe malaria and gave advice on 20 more patients with malaria who had been admitted to intensive care units throughout England. 4 of the severe cases treated at the hospital are reported. In 3 of those 4 cases, incorrect, misleading, or inadequate advice was given by health care professionals. Media coverage of the adverse effects of antimalarial drugs has contributed to confusion about prophylactic regimens among both health care professionals and the public. The incidence of falciparum malaria among travellers who do not take prophylactic drugs is about 0.6% in east Africa and 3.5% in west Africa over a 2-week travel period. Travellers need to take measures to avoid being bitten by mosquitoes and should be taught to promptly seek medical help if they develop a fever while abroad or after they return. Moreover, using any one of the recommended prophylactic regimens is better than not using a potent regimen or no prophylaxis at all. Mefloquine is 90% protective against malaria in sub-Saharan Africa. While the efficacy of proguanil and chloroquine in 1987 was about 70% in west Africa and 50% in east Africa, those levels are now probably lower. The side effects of antimalarial drugs are discussed.^ieng

Efficacy and safety of liposomal amphotericin B (AmBisome) for visceral leishmaniasis in endemic developing countries.

Reported are the results of a study to determine the efficacy and safety of liposomal amphotericin B (AmBisome) for treating visceral leishmaniasis (kala-azar) in several developing countries where the disease is endemic (Brazil, India, and Kenya). At each study site, sequential cohorts of 10 patients each were treated with AmBisome at a dose of 2 mg.kg-1.day-1 (2 MKD). The first cohort received regimen 1:2 MKD on days 1-6 and day 10 (total dose: 14 mg/kg). If the efficacy with this regimen was satisfactory, a second cohort received regimen 2:2 MKD on days 1-4 and 10 (total dose: 10 mg/kg); and a third cohort received regimen 3:2 MKD on days 1, 5, and 10 (total dose: 6 mg/kg). In India, regimens 1, 2, and 3 (which were studied concurrently) each cured 100% of 10 patients. In Kenya, regimen 1 cured all 10 patients, regimen 2 cured 90% of 10 patients, but regimen 3 cured only 20% of 5 patients. In Brazil, regimen 1 was only partially curative: 5 of 13 patients (62%). Therefore, 15 patients were administered regimen 4 (2 MKD for 10 consecutive days; total dose, 20 mg/kg) and 13 patients were cured (83%). These results suggest that for the treatment of kala-azar the following doses of AmBisome should be administered: in India and Kenya, 2 mg/kg on days 1-4 and day 10; and in Brazil, 2 mg/kg on days 1-10.

PIP: The efficacy and safety of liposomal amphotericin B (AmBisome) for the treatment of visceral leishmaniasis (kala-azar) were evaluated in a phase II clinical trial conducted in Brazil, India, and Kenya--countries where kala-azar is endemic. At each study site, sequential cohorts of 10 patients each received three different dosage regimens of AmBisome. The first cohort received 2 mg/kg/day (MKD) on days 1-6 and day 10 (total dose, 14 mg/kg). If the efficacy of this regimen was satisfactory, the second cohort received 2 MKD on days 1-4 and day 10 (total dose, 10 mg/kg) and a third cohort was administered 2 MKD on days 1, 5, and 10 (total dose, 6 mg/kg). In India, all three regimens (studied concurrently) cured 100% of the total of 30 patients. In Kenya, the first regimen cured all 10 patients (100%), the second cured 9 of 10 patients (90%), and the third cured only 1 of 5 patients (20%). In Brazil, since the first regimen cured only 5 of 13 patients (62%), the next 15 patients were given 2 MKD for 10 consecutive days (total dose, 20 mg/kg); this intensified regimen cured 13 of the 15 patients (83%). Adverse effects were minor, primarily fever and chills associated with infusion and irregular pulse. These findings suggest that leishmaniasis patients in India and Kenya should receive 2 mg/kg of AmBisome on days 1-4 and day 10, while those in Brazil should be given 2 mg/kg on days 1-10. AmBisome treatment is especially recommended for those for whom standard agents are likely to be ineffective, toxic, or difficult to administer.

Treatment of visceral leishmaniasis in children with liposomal amphotericin B.

We used liposomal amphotericin B as first-choice treatment of visceral leishmaniasis in 106 immunocompetent children who acquired the infection in a temperate region of southern Europe (Italy) where Leishmania infantum visceral leishmaniasis is endemic. The aim of the study was to identify the minimum total dose of liposomal amphotericin B needed to cure the infection in children and reduce the period of hospitalization. We conclude that the optimal regimen in immunocompetent children with L. infantum visceral leishmaniasis to be a total dose of 18 mg/kg of liposomal amphotericin B (3 mg/kg per day for 5 days, followed by 3 mg/kg administered as an outpatient regimen on day 10).

Disseminated infection due to Bipolaris australiensis in a young immunocompetent man: case report and review.

We report a case of disseminated infection due to Bipolaris australiensis in a 21-year-old immunocompetent Pakistani man. He presented with fever and jaundice. Examination revealed a mass in the right lung, mediastinal lymphadenopathy, a pericardial effusion, and abdominal masses obstructing and invading the common bile duct and right ureter. Histological examination and culture of a biopsy specimen of the hilar mass yielded the fungal pathogen B. australiensis. The patient was treated successfully with amphotericin B and itraconazole.

Ectopic cutaneous schistosomiasis: extragenital involvement with progressive upward spread.

The ectopic deposition of ova of Schistosoma haematobium within the dermis is very rare, even in countries where infection with this trematode is widespread. When it does occur, it usually affects the genital area. We report a patient who developed ectopic genital and extragenital cutaneous involvement 4 months after swimming in Lake Malawi. The lesions appeared sequentially and spread from the genitalia in a caudocephalic manner. Doppler imaging of the pelvic veins did not reveal any anomalous venous drainage to account for the distribution of these lesions.

Imported mucocutaneous leishmaniasis.

We report a case of mucocutaneous leishmaniasis in a otherwise fit Caucasian man who had traveled in an endemic area. Initial tissue microscopy failed to identify the causative organism, which was only determined by subsequent culture as Leishmania braziliensis. This case illustrates the variability in the presence of Leishman-Donovan (LD) bodies in histopathological studies and emphasizes the need for culture in suspected cases of leishmaniasis, particularly given the ability of certain Leishmania species such as L. braziliensis to cause recalcitrant and destructive infections of the nose and mouth.

Fever in the returning traveller.

Diagnosing the febrile returned traveller is a problem faced ever more frequently by the practising physician. This article aims to provide a structured approach to what may, at first, seem a complex issue.

Short-course treatment of visceral leishmaniasis with liposomal amphotericin B (AmBisome).

We evaluated liposomal amphotericin B (AmBisome; Vestar, San Dimas, CA) administered to 88 immunocompetent patients (56 children) with visceral leishmaniasis (VL) caused by Leishmania infantum. Thirteen patients received 4 mg/kg on days 1-5 and 10 (total dose, 24 mg/kg), and all were cured; 42 received 3 mg/kg on days 1-5 and 10 (18 mg/kg), and 41 were cured; 32 received 3 mg/kg on days 1-4 and 10 (15 mg/kg), and 29 were cured (amastigotes were not cleared from 1 child, and 2 relapsed). One adult was cured with a total dose of 12mg/kg. The four children who were not cured received 3 mg/kg for 10 days; none had further relapses. There were no significant adverse events. For VL due to L. infantum, we recommended a total dose of AmBisome of > or = 20 mg/kg, given in > or = 5 doses of 3-4 mg/kg over > or = 10 days.

Fever as the presenting complaint of travellers returning from the tropics.

We investigated prospectively the cause of fever in patients requiring hospitalization after returning from the tropics. All consecutive admissions (n = 195) with oral temperature > 37.0 degrees C at the time of admission were enrolled. Final diagnosis as recorded on the discharge summary by the attending physician and results of any relevant laboratory or radiological investigations were recorded on standard proforma. Malaria accounted for 42% of admissions; two patients had returned to Britain more than 6 months before presentation. The second largest group was assumed to have a non-specific viral infection (25%). Cosmopolitan infections (urinary tract infection, community-acquired pneumonia, streptococcal sore throat, etc.) accounted for 9%. Coincidental infections (schistosomiasis, filariasis, intestinal helminths) were found in 16%. Serology was positive for HIV infection in 3%. The most useful investigation was a malaria film, which was positive in 45% of cases in which it was performed. The combination of thrombocytopaenia (platelet count < 100 x 10(9)) and hyperbilirubinaemia (bilirubin > 18 IU/ml) were useful predictive markers of malaria: all 23 patients with both abnormalities had positive malaria films. Malaria must be excluded in any febrile patient returning from the tropics. In the absence of a positive malaria film, the combination of a low platelet count and raised bilirubin may suggest the need for an empirical course of therapy.

Laryngeal leishmaniasis.

A patient suffering from persistent hoarseness was eventually shown to have laryngeal leishmaniasis. The incubation period for the disease must have been at least 16 years, following infection in Southern Europe. Mucosal leishmaniasis is rare in the Eastern hemisphere, and laryngeal leishmaniasis has not previously been reported in the UK. Previous Mediterranean cases have run a similar chronic course and have caused diagnostic difficulty, in particular being mistaken for malignancy. Treatment with aminosidine was ineffective, but the patient responded to liposomal amphotericin.

Treatment of 'Old World' cutaneous leishmaniasis with aminosidine ointment: results of an open study in London.

Five preparations of ointment containing aminosidine were used to treat lesions of 'Old World' cutaneous leishmaniasis. A preparation containing 12-15% aminosidine with 10% urea in white soft paraffin was nontoxic. 23 of 27 patients treated healed in a mean of 6.7 weeks, the ointment being applied daily for up to 12 weeks.

Epidemic visceral leishmaniasis in Sudan: a randomized trial of aminosidine plus sodium stibogluconate versus sodium stibogluconate alone.

In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600. Patients (200) were randomized to receive sodium stibogluconate (Sbv) at 20 mg/kg/day for 30 days (groups S, n = 99) or Sbv at 20 mg/kg/day plus aminosidine at 15 mg/kg/day for 17 days (group AS, n = 101). Of 192 patients who had spleens or lymph nodes aspirated at entry, 134 (70%) were positive for parasites. During treatment, 7% in group S and 4% in group AS died. All 184 patients who completed treatment were clinically cured. At days 15-17, microscopy of aspirates showed that 57 (95%) of 60 in group AS were negative for parasites compared with 47 (81%) of 58 in group S (P = .018). At day 30, 57 (93.4%) of 61 group S aspirates were negative.