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Metacyclic Leishmania promastigotes (PM), transmitted by sand-fly bite, are likely to interact initially with cells of the dendritic cell (DC) lineage(s) in the epidermis or dermis. Epidermal Langerhans cells internalize L. major amastigotes (AM) and transport them to draining lymph nodes (Moll, H., Fuchs, H., Blank, C. and Röllinghoff, M., Eur. J. Immunol. 1993. 23: 1595) but little is known about the interaction of DC with PM. The present study demonstrates that DC are able to internalize PM and that the fate of the parasites within DC differs from that within macrophages (Mphi). DC took up small numbers of PM which did not differentiate into AM but appeared to be degraded; Mphi internalized large numbers of PM into parasitophorous vacuoles where they differentiated into AM. In response to direct stimulation with PM, DC from both C3H ("resistant" to L. major infection) and BALB/c ("susceptible") up-regulated production of IL-12 p40. In contrast, IL-12 production by Mphi was not detected. DC exposed to either metacyclic PM or PM culture supernatants were also able to stimulate proliferative responses in lymph node T cells from naive mice. These data indicate that DC have the capacity to promote protective Th1 immune responses in Leishmania infection and suggest that DC exposed to PM may be useful in immunotherapy and vaccination.

This article summarises the clinical features of visceral, cutaneous and mucocutaneous leishmaniasis, and leishmaniasis in HIV-coinfected patients. The characteristics and clinical use of pentavalent antimonials and the traditional drugs used in all forms of leishmaniasis are described. There have been important developments in therapy, such as aminosidine (paromomycin) conventional amphotericin B and lipid-associated amphotericin B. In most cases of leishmaniasis there is a range of treatment options which is determined by the geographical and clinical features. This review is intended to assist the clinician in choosing treatment and in using unfamiliar drugs with safety and efficacy.

Amoebic liver abscesses (ALA) are characteristically large lesions at presentation, but their development in man has not previously been described. We present a case of an ALA that over the course of 2 days developed from an undetectable lesion to a 5 cm diameter lesion. This clinical history suggests that the pathogenesis of ALAs may pursue an acute rather than a chronic course.

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).

The increasing prevalence of tuberculosis (TB) and human immunodeficiency virus (HIV), particularly in Africa and Asia, led us to investigate the prevalence of HIV infection in immigrants with pulmonary TB at the time of arrival in the UK. We performed anonymous HIV testing of stored sera from 39/65 immigrants referred to our unit between January 1991 and December 1994, who had culture-positive pulmonary TB. None of the 39 patients tested was positive for either HIV-1 or HIV-2, and the characteristics of the 26 patients for whom no serum was available were similar to those of the tested group. Despite the need to consider concomitant HIV infection in any patient with TB, particularly those from an area of HIV endemnicity, the present data do not suggest that recently arrived refugees, asylum seekers, immigrants or long-term visitors to the UK constitute a group in whom dual infection of HIV and Mycobacterium tuberculosis is common.

To assess differences between Africans and expatriates, we reviewed records of 100 patients with loiasis presenting to The Hospital for Tropical Diseases, London. Fifty-one were black Africans, and 49 were white expatriates. A history of Calabar swellings was more common amongst expatriates (P = 0.0001, OR 8.1), whilst eyeworm was reported more frequently in Africans (P = 0.0038, OR 4.2). Higher eosinophil levels (P < 0.0001) and filarial antibody levels, whether measured by immunofluorescence (P = 0.047) or ELISA (P < 0.0001) were present in the expatriates. Africans were more likely to have microfilaraemia (P < 0.0025, OR 7.3), and among microfilaraemic patients, Africans had denser microfilaraemia (P = 0.012). The sensitivity of microfilaremia as a screening test for loiasis was 75% in Africans and 29% in expatriates. The sensitivities of filarial antibody tests in Africans and expatriates were 81% and 100% for IFAT, and 28% and 93% for ELISA. Following treatment, 63% of patients were considered cured, 25% were lost to follow-up and 12% had a documented relapse. The differences between the two groups of patients could be caused by differences in the chronicity of loiasis, but other explanations are also discussed.

The rapidity and efficacy of a short course of liposomal amphotericin B was evaluated in 29 children affected by visceral leishmaniasis (Leishmania infantum). Their overall health status was assessed using the prognostic inflammatory and nutritional index (PINI), and their haematological status by the reticulocyte count and haemoglobin blood levels. All these quantities were measured on day 0, and 3 and 10 d after starting therapy. A significant decrease of inflammatory signs, associated with an improved reticulocyte count, was recorded after 3 d of therapy. A significant increase of haemoglobin levels was also observed 10 d after the start of treatment. The early reduction of inflammatory signs and the improvement of bone marrow function in most patients confirmed the validity of amphotericin B therapy. The PINI score is helpful in assessing the severity of visceral leishmaniasis and the follow-up of its treatment.

Visceral leishmaniasis (VL) in patients coinfected with human immunodeficiency virus (HIV) is often atypical, and characteristically relapses after treatment. We treated 10 HIV infected patients (9 men) with parasitologically confirmed VL with liposomal amphotericin B ("AmBisome': L-AMB) at a dose of 4 mg/kg/day on days 1, 2, 3, 4, 5, 10, 17, 24, 31, and 38. Patients were hospitalized for the first 5 days, and were monitored during, and 1 week and 1, 3 and 6 months after, L-AMB therapy. There were no serious adverse events, and L-AMB was well tolerated. 9/10 patients completed therapy, one patient defaulted at day 24. Clinical improvement was seen in all nine patients and the bone marrow aspirate was cleared of visible/culturable parasites in 8/9 patients. During follow-up, one patient defaulted. The seven remaining patients relapsed at 2, 3, 3, 5, 5, 6 and 7 months. Re-treatment with a variety of antileishmanial drugs was unsatisfactory. The time from first diagnosis of VL to death in six patients was 5-40 months (mean 18.8 months). Only one patient remained alive 26 months after treatment. L-AMB is safe and provides a good initial clinical response. Intermittent dosing enables a short period of hospitalization. However, relapse is probably inevitable.

A rapid, simple diagnostic polymerase chain reaction (PCR) method for the diagnosis of dengue fever was developed using a pair of consensus oligonucleotide primers and validated with laboratory-derived strains of dengue serotypes 1-4 and other common flaviviruses. A cluster of 13 patients with clinical dengue fever admitted to a single infectious diseases unit over a period of 3 months allowed evaluation of this technology. The PCR was positive in all 11 acute dengue cases and negative in 2 convalescent cases and 10 febrile patients recently returned from the tropics in whom an alternative diagnosis was established. In some of the acute cases, viraemia was detected before the development of a diagnostic antibody response (indirect immunoglobulin (Ig) G enzyme-linked immunosorbent assay (ELISA) and capture IgM ELISA). In patients from whom sequential sera were taken, defervescence and recovery from thrombocytopenia coincided with the disappearance of dengue ribonucleic acid from the blood. Nucleotide sequencing of the PCR products was undertaken in 2 cases (from India and Guyana) and the results showed a close match with previously reported serotype 2 sequencies, suggesting a potential for use of this region of the genome in epidemiological studies.

The rationale for exchange transfusion (ET) in severe Plasmodium falciparum malaria is to lower the parasite burden rapidly, to replenish unparasitized cells and to correct severe anaemia. In addition, parasite antigens or 'toxins' may be removed. Despite reports of successful ET in the treatment of malaria since 1974, it remains controversial and its role and technique have been poorly defined. We present a mathematical model of ET which relates volume of exchange to reduction in parasitaemia and change in haemoglobin concentration. This model fits published and unpublished clinical data well, and should facilitate standardization of ET in future.

Thirty-one patients with visceral leishmaniasis (VL) caused by Leishmania infantum received liposomal amphotericin B (AmBisome) in a multi-centre study. Ten immunocompetent patients (six children) received 1-1.38 mg/kg/day for 21 days, and ten (nine children) received 3 mg/kg/day for 10 days. All were cured without significant adverse events and without relapse during 12-24 months of follow-up. Eleven immunocompromised adults, including seven co-infected with HIV (four with AIDS) received 100 mg (1.38-1.85 mg/kg) daily for 21 days. All were initially considered cured, but eight relapsed clinically and parasitologically at 3-22 months. Liposomal amphotericin B is a new, safe and effective drug for the treatment of VL.

We report 11 patients with leishmaniasis from different endemic areas, treated in the UK with intravenous aminosidine alone or in combination with other drugs. Clinical and parasitological cures were achieved in all 7 patients from the Mediterranean zone who had visceral disease, with one relapse. Two of 4 patients with cutaneous or mucosal disease were cured; the other 2, from Iraq and Iran, did not respond. Toxic effects were high-tone deafness in 2 patients, one of whom had pre-existing renal impairment, and transient, mild elevation of serum creatinine in 3. Aminosidine is an effective, tolerable and relatively non-toxic alternative to existing antileishmanial drugs for the treatment of visceral leishmaniasis. Further studies will be needed to assess its place in cutaneous and mucosal disease.

The treatment of visceral leishmaniasis (VL) may be complicated by drug toxicity or intolerance, and by drug resistance. Amphotericin B (AmB) is effective, but its use is limited by toxicity: renal impairment, anaemia, fever, malaise, and hypokalaemia are common. Liposomes have been proposed as an effective way to target drugs at macrophages, which are the cells infected in visceral leishmaniasis. In animals AmB incorporated into liposomes is highly effective against experimental leishmaniasis, with low toxicity. This report is of the successful treatment of a patient with multiply drug-resistant visceral leishmaniasis with a commercially prepared formulation of liposomal amphotericin B (L-AmB) ('AmBisome', Vestar, San Dimas, California, USA). We also report, for comparison, a patient treated with conventional AmB, and preliminary studies in mice comparing the two agents.

Ultrasound (U/S) imaging of liver was used in a prospective study of 62 consecutive patients with oesophageal varices in the central hospitals in Harare; 50 had haematemesis. U/S changes of Symmers's periportal fibrosis (PPF) were graded from mild (grade 1) to gross (grade 4). 46 patients (74%) had U/S features of PPF: 7 were grade 1, 7 grade 2, 29 grade 3, and 3 grade 4. Patients with PPF were more likely to have bled (P less than 0.05) and were less likely to have ascites (P less than 0.05) than those without PPF. Spleen or liver size or grade of varices did not correlate with the U/S grade of PPF. Rectal snips were positive for schistosome ova in 19 of 28 cases with PPF and 2 of 7 cases without PPF. Patients with PPF were more likely than those without PPF (P less than 0.005) or controls (P less than 0.0001) to have spent their childhood in an area of Zimbabwe with a high prevalence of Schistosoma mansoni. Schistosomal PPF appears to be a common cause of portal hypertension in Zimbabwe. It is strongly associated with childhood spent in areas of high S. mansoni prevalence.

A case is reported of a 32-year-old traveller with loiasis, schistosomiasis and African trypanosomiasis. The patient had been working in oil exploration in Nigeria and Gabon and presented with Calabar swellings and carpal tunnel syndrome. Serology for all 3 diseases was positive but microfilariae of Loa loa and ova of schistosomiasis were not found. Treatment with diethylcarbamazine and praziquantel was given for loiasis and schistosomiasis respectively. Trypanosomes were isolated from a lymph node aspirate only after repetition of the procedure 2 months later and the patient was treated with suramin. He developed a drug induced nephritis and was then treated successfully with alpha-difluoromethylornithine. There is a discussion of the difficulties encountered making these diagnoses in Europeans particularly where there are atypical clinical features. The risks of rural work in West Africa are noted and the importance of considering all parasitic diseases relevant to the travel/occupational history is emphasised.

Recent studies on the pharmacokinetics of parenteral chloroquine and quinine have resulted in safer regimens for the treatment of severe falciparum malaria. In this article we summarise these regimens, and discuss the emergence of chloroquine resistance and the implications for treatment.

A method of examining cytological material during fibreoptic bronchoscopy using a methylene blue (MB) stain was assessed in 164 consecutive fibreoptic bronchoscopies where cytology specimens were taken. The MB method provided an immediate positive diagnosis in 86% of bronchoscopically visible tumours. Subsequent histology provided a positive diagnosis in 69%, conventional brush cytology in 81% and trap cytology in 77%. The MB method produced no false positive diagnosis of malignancy and the tumour cell type identified by MB stain agreed with the histological cell type in 72% of cases. This technique is considered to be sufficiently specific to provide a method of controlling the quality of specimens taken at bronchoscopy, for further analysis in the laboratory.

The author spent an undergraduate elective period in Tunisia, and some of the features of a community health scheme in rural Cap Bon are described, such as the use of auxiliaries and standardized techniques.

Two cases of endocarditis caused by a group G streptococcus are reported and the literature on group G streptococcal endocarditis is reviewed. The onset of illness is usually acute and the portal of entry for the organism through the skin. The left side of the heart is mainly involved and in about 50% cases the endocarditis arises on a normal valve. Most patients develop complications, both embolic and cardiac, and the mortality is high (36%). We suggest that patients with proven group G streptococcal endocarditis should be treated with large doses of benzyl penicillin and with an aminoglycoside for not less than 4 weeks. Patients with complications should be referred to a cardiothoracic centre. We should be glad to know details of complications, treatment and outcome in other cases of group G streptococcal endocarditis.

We describe the construction of a simple device which may be used to connect a patient with a tracheostomy to standard lung function testing equipment. We compared the lung function of nine patients after laryngectomy with nine patients matched for similar degrees of airflow obstruction, and found that peak flow rate (as per cent predicted) was significantly lower than predicted FEV1 in the patients with tracheostomy. This suggests that the larynx may normally affect production of peak flow. We then compared the change in resistance over the normal tidal volume in the two groups, finding no significant difference, and obtained similar results from paired studies in two patients before and after laryngectomy. We conclude that, while the laryngeal aperture varies during tidal breathing, it plays no major part in the overall resistance changes which occur during a normal breath.

We bench-tested a commercially available instrument for measuring respiratory impedance (Siregnost FD5: Siemens) and found that resistance (R) and phase changes were accurately recorded in models. In a single human subject, total respiratory resistance (R(l)) was closely comparable to resistance measured by the Mead-Whittenberger technique. The derived continuous variable (R(os)) was similar to R at less than 4 cmH2O . litres-1 . sec, but underestimated R at higher values. Ros was highly correlated with airways resistance by body plethysmography (R(aw)), but with a low slope and high intercept (R(os) = 1.38 + 0.59 R(aw): r = 0.89). Because of turbulence, both in model larynxes and in normal subjects, R(os) tends to rise with increases in flow in either direction. R(os) also tends to fall as lung volume rises, and vice versa, reflecting cyclic changes in airway calibre. We devised indices of expiratory narrowing of airways from the maximum flow-volume loop, and the plethysmographic alveolar pressure-flow loop, and compared them with the slope of the relation between R(os) and lung volume during tidal breathing, in nine normal subjects and 16 patients with airflow obstruction. Twelve of the 16 patients, all with abnormal flow-volume loops, had high R(os)-volume slopes, demonstrating excessive expiratory narrowing even during tidal breathing. We found no patients with normal inspiratory R(os) together with an abnormal R(os)-volume slope. Thus unstressed inspiratory calibre was never dissociated from airways narrowing on expiration.