1427

Prevalence of Leishmania infection among AIDS patients SIR,-Over

150

cases

of visceral leishmaniasis

(VL) and HIV

co-infection have been reported world wide, most of them in Spain. It is estimated that 50% of VL in adults is associated with HIV and that 1-3% of AIDS patients acquire VL in Southwest Europe.1 Surveys of skin-test reactivity indicate that transmission of Leishmania infantum is more common than might be thought from the incidence of disease. Furthermore, the frequency of coinfection of HIV and L infantum infection suggests that some percentage

(undetermined) of the population is infected as carriers. If they become immunodepressed, for any reason, typical VL can appear. We screened HIV-positive individuals for L infantum using bone-marrow culture in NNN medium. Indications for obtaining bone marrow were splenomegaly and/or fever of unknown origin for 2 weeks and/or leucopenia, non-specific signs shared by both VL and HIV infection. 19 (17%) of 111 aspirates were positive. This high percentage illustrates the importance of considering Leishmania as a complication of HIV infection in endemic areas and underlines its opportunistic behaviour. Three different L infantum zymodemes have been isolated on bone-marrow biopsy from HIV-positive individuals so far, including the dermatotropic ones, as might be expected given the anergic condition of these patients with inversion of the CD4/CD8 ratio. Analysis by molecular karyotyping of eight Leishmania stocks isolated from AIDS patients in Madrid revealed a high degree of chromosomal size polymorphism,2 which is a characteristic of L infantum. This fmding could argue against a common source of infection in this high-risk group. Our observations do not, however, rule out the possibility of Leishmania transmission by blood. When we fed 53 Phlebotomus perniciosus sandflies with 1 ml blood from a co-infected patient, 26% of them became infected.3 A sandfly normally ingests about 1 ttl of blood, an amount less than that transported in shared syringes. L infantum has also been detected in immunocompromised patients not infected with HIV (18% of 91 cases ofVL diagnosed between 1984 and 1991). All these fmdings suggest that a considerable proportion of the "normal" population may be infected in endemic areas. The prevalence of latent asymptomatic infection with L infantum may have important implications for blood banks, iatrogenic immunosuppressive therapy, and transplant programmes. Centro Nacionale de Microbiologia, Instituto de Salud Carlos III,

28220-Matadahonda, Madrid, Spain Hospital

Ramón y

J. ALVAR B. GUTIERREZ-SOLAR R. MOLINA

R. LOPEZ-VELEZ A. GARCIA-CAMACHO

Cajal,

Madrid Centro de Investigaciones Clínicas, Institituo de Salud Carlos III

Hospital Provincial "G Marañon, Madrid

Hospital

Son Dureta, Palma de Mallorca

P. MARTINEZ

F. LAGUNA E. CERCENADO

A. GALMES

World Health Organisation. AIDS, leishmaniasis dangers of clash highlighted. TDR News 1991; 36: 1. 2. Jiménez MI, Gutierrez-Solar B, Bemto A, et al. Cutaneous Leishmania infantum zymodemes isolated from bone marrow in AIDS patients. Res Rev Parasitol 1991; 51: 91-94. 3. Molina R, López-Vélez R, Gutiérrez-Solar B, Jiménez MI, Alvar J. Leishmania 1.

infantum isolation from an AIDS patient blood using sandflies. Trans R Soc Trop Med Hyg (in press).

Origins of

HIV

SIR,-Mr Kyle’s viewpoint (March 7, p 600) and the letters in The Lancet of April 4 should generate much-needed discussion on the possibility that HIV’s origin lies in poliovaccines, an idea we proposed in 19891 and again at the International Congress of Virology in Berlin, in August, 1990. We have in our colony a healthy vervet monkey (Cercopithecus pygerythrus) which tests seropositive

for major HIV-1 antigens by western blot. To use this animal’s tissue for human vaccine production would be unethical. Yet this could have happened many times since monkey kidney tissue was first used in poliovaccine production in the 1950s. Such cultures could support the growth of retroviruses. HIV can infect certain CD4- cells, and there is evidence that some mouse and simian fibroblast cultures bear the CD4 antigen, the major HIV receptor. The simultaneous appearance in man within the past 30 years of both HIV-1and HIV-2, which are distantly related in evolutionary terms, suggests contamination since closer relatives to the human strains exist in non-human primates. There is circumstantial evidence for a possible poliovirus vaccine origin of AIDS, and to ignore this possibility would be wrong ethically and scientifically. Department of Virology, Medical University of Southern Africa, Medunsa 0204, South Africa

G. LECATSAS

Department of Microbiology, University of the Witwatersrand

J. J. ALEXANDER

1. Lecatsas G, Alexander JJ. Safe testing of poliovirus vaccine and the infection in man. S Afr Med J 1989; 76: 451.

Cardiac

origin of HIV

arrhythmia and Leber’s hereditary optic neuropathy

SIR,-Cardiac arrhythmias are reportedly associated with Leber’s hereditary optic neuropathy (LHON). This is a mitochondrial disorder causing subacute blindness, usually in young males. Leber’s original report described palpitations in some patients and necropsy-proven cardiomyopathy was reported in one patient by Wilson.1 Reported electrocardiographic changes were non-specific2 until Nikoskelainen et al suggested that pre-excitation syndrome (PR interval < 120 ms and/or delta waves) was unusually 4 common in LHON pedigrees In Zeviani and colleagues’ report on a maternally inherited myopathy and cardiomyopathy related to a point mutation in the mitochondrial genome, the pedigree contained a 30-year-old man who died with cardiomyopathy and Wolff-Parkinson-White (WPW) pre-excitation syndrome. To investigate the frequency of WPW pre-excitation syndrome in LHON we did electrocardiography on 25 blind and 88 visually unaffected maternal relatives in three Tasmanian pedigrees with mitochondrial point mutations (details from S. P. C. B.). WPW syndrome, defined as a delta wave and PR interval < 120 ms, was found in one 55-year-old mother. One of her sons became blind at age 20 years; the mother was symptom-free but her 18-year-old daughter described a 6-month history of recurrent syncope. In this young woman, Holter monitoring revealed frequent multifocal ventricular ectopics that decreased in frequency when she was put on metoprolol 50 mg twice daily. Clinical examination, resting electrocardiography, left and right heart catheterisation, cardiac electrophysiological study, and right-ventricular biopsy were normal. She discontinued metoprolol, and 18 months later was found dead in bed. At necropsy the heart weighed 410 g, all chambers were dilated, the basal thickness of the left ventricle was 12 mm and right ventricle 5 mm, with notable endocardial pallor. There was no mural thrombus, coronary atherosclerosis, myocardial scarring, or mottling. Histologically the left-ventricular endocardium was thickened with myocardial fibre hypertrophy. Detailed histological examination of the sinoatrial node, atrioventricular node and His-Purkinje system was normal. WPW syndrome was no more common in these pedigrees than one would expect in the general population. Three symptomless siblings of the young woman with cardiomyopathy have PR intervals < 120 ms but no delta waves. Familial pre-excitation is increasingly being recognised, inheritance appears to be autosomal dominant, and there is an increased risk of sudden death. We cannot be sure that our patient’s death was related to abnormal but the cardiac mitochondria normal myocardial electrophysiological study and cardiomyopathy found at necropsy are inconsistent with the usual form of familial pre-excitation. Any mitochondrial abnormalities at electronmicroscopy were uninterpretable because of post-mortem autolysis. Syncope due to

1428

atrioventricular block may be the presenting feature of another mitochondrial disorder, Kearns-Sayre syndrome, in which myocardial ultrastructural abnormalities have been demonstrated.6 In LHON young males are at increased risk of sudden blindness and this report raises the possibility that maternal relatives may also be at risk of arrhythmia and sudden death. Departments of Medicine and Pathology, Royal Hobart Hospital, Tasmania, Australia,

S. P. C. BOWER I. HAWLEY D. A. MACKEY

and Johns Hopkins Center for Hereditary Eye Diseases, Baltimore, Maryland, USA

The use of CPII allowed very good and stable glucose control throughout pregnancy despite brittle diabetes and the device was well tolerated throughout pregnancy and during labour. This device facilitates the use of CPII, as we have shown before.’ Other workers2 have reported diabetic pregnancy managed by CPII with another device, but multiple local infections and thus transient bad control episodes were recorded. Our technique offers a chance for young women with very brittle diabetes who wish to have a baby. Services of Endocrinology and Nutritional Diseases, Gynaecology and Obstetrics, Urgent and General Surgery, and Endocrinology, Hôpitaux Universitaires de Strasbourg,

Hôpital Civil, 67091 Strasbourg, France 1. Wilson J. Leber’s hereditary optic atrophy, some clinical and aetiological considerations. Brain 1963; 234: 614-18. 2. Rose FC, Bowden AN, Bowden PM. The heart in Leber’s optic atrophy. Br J Ophthalmol 1970; 54: 388-292. 3. Nikoskelainen EK, Wanne O, Dahl M. Pre-excitation syndrome and Leber’s hereditary optic neuroretinopathy. Lancet 1985; 1: 969. 4. Zeviani M, Gellera C, Antozzi C, et al. Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNALeu(URR). Lancet 1991; 338: 143-47. 5. Vidaillet HJ, Pressley JC, Henke E, Harrell FE, German LD. Familial occurrence of accessory atrioventricular pathways (preexcitation syndrome). N Engl J Med 1987; 317: 65-69. 6. Charles R, Holt MB, Kay JM, Epstein EJ, Russell Rees J. Myocardial ultrastructure and the development of atrioventricular block in Kearns-Sayre syndrome. Circulation 1981; 63: 214-19.

Successful pregnancy in

severe

diabetes

SIR,-We report pregnancy and normal delivery in a 27-year-old diabetic patient being treated with intraperitoneal insulin infusion (CPII) by means of a programmable implantable Infusaid, model 1000, device. In September, 1989, this device was implanted as part of a safety and feasibility study. The patient had brittle diabetes (high frequency of moderate hypoglycaemic reactions complicated by transient hemiplegia) despite continuous subcutaneous insulin infusion (CSII). Diabetes duration was 21 years with no late complications. After implantation, hypoglycaemia frequency improved and neurological complications disappeared. Data before and after implantation were, respectively, HbAlc 63% vs 6% (normal 4-4%-6%); mean number of monthly hypoglycaemic episodes (blood sugar below 3-6 mmol/1) fell from 45 to 20-7; and blood glucose 24 h standard deviation changed from 4-55 to 2.05 mmol/l. In September, 1990, due to a technical problem, CPIIwas discontinued and a transient CSII regimen was used for 3 weeks; a moderate hypoglycaemic reaction complicated by hemiplegia took place after about 1 week of this regimen. In March, 1991, the patient unexpectedly became pregnant. HbAjc was 7-2% and she had no late complications. Because of her very brittle diabetes and history of neurological complications after hypoglycaemic events, we decided to pursue CPII with the implant for as long as possible. Throughout pregnancy, the patient was seen every 2 weeks to maintain optimum metabolic control and monitor the pump. During her pregnancy HbAlC decreased from 6-9% to 5-5%, blood sugar daily standard deviation varied between 2-94 and 4-05 mmol/1, and monthly frequency of hypoglycaemic events increased from 23 to 30, but no moderate or severe episodes were reported. She tolerated the pump well until 3 days before delivery, when she had some discomfort. Ultrasonography was done during every trimester. At the last examination labia majora hypertrophia or hypospadias were suspected. Other indices were normal. Labour was artificially induced at fetal maturation. At 37 weeks, the pump was filled with diluent and while fasting she received intravenous (iv) insulin and iv 10% glucose during labour. A boy (birthweight 3410 g, length 50 cm, Apgar score 10) was delivered by forceps. He had hypospadias. His blood glucose concentration was 15 mmol/1 and blood calcium 2-15 mmol/1. No late hypoglycaemia or metabolic complications were seen. Mother and baby were discharged 5 days after delivery. After pump rinsing due to slowdown in infusion, the pump was filled with insulin and the CPII regimen started again, without

complications.

N. JEANDIDIBR E. MIRANDA C. MATHELIN S. BOIVIN M. PINGET

Jeandidier N, Pmget M, Keipes M, Charton MN, Marescaux J, Réville PH. Long term treatment of type I diabetes in 28 patients using two different implantable programmable pumps Transplant Proc (in press). 2. Fonseca VA, Menon RK, O’Brien MS, Fernando ON, Stephen R, Dandona P. Diabetic pregnancy managed with intraperitoneal insulin. Diabet Med 1987; 4: 1.

74-76

Octreotide SiR,—Your April 4 editorial (p 837) points out the importance of octreotide in treatment of various pathological conditions. The ability of octreotide to suppress the exocrine pancreas suggests that it also has potential in the treatment of pancreatic fistulas. You fail to discuss this new indication of octreotide therapy. However, experience with use of octreotide in external pancreatic fistulas has great clinical importance, since we do not have an effective standardised method for conservative treatment of this condition. Published data about the effect of octreotide in pancreatic fistulas are

contradictory.1-3

We have done a prospective trial to assess the efficacy of octreotide in the management of high-output external pancreatic fistulas. A total of 11 male and 5 female patients (mean age 45-5 years, range 28-58) with postoperative external, high-output pancreatic fistulas were investigated. In 3 patients, a fistula developed after pancreatic injury at abdominal surgery, and in 3 others it did so after surgical removal of insulin-secreting islet cell tumours. In the remaining 10 patients, pancreatic fistulas arose after abdominal surgery for chronic pancreatitis or following its complications (pseudocysts). The output of the fistulas was constant before the administration of long-acting somatostatin and varied between 190 and 570 ml per day (mean 335 ml per day). Fistula-related infection could not be clearly demonstrated in any patient. The subjects had received total parenteral nutrition (TPN) since the appearance of fistulas, but the fistula output had not changed. Octreotide (Sandostatin) therapy was begun at a mean of 17 days (range 4-35 days) after appearance of the fistula. The patients received 0-1 mg octreotide subcutaneously every 12 h. On the first day of treatment, mean fistula output had fallen to 45% (range 31-74%) of pretreatment output. By day 3, it had decreased to 30% (range 0-74%) of the pretreatment value. The average length of treatment was 8 days (range 3-15). The fistula was closed in 14 of the 16 patients; surgical procedures were done in the two fistulas that did not heal. There was a significant negative correlation between fistula output and its amylase concentration 0-87, p < 0-01). An octreotide related side-effect could not be (r demonstrated in any patient. These results show that octreotide has a consistent, clear effect in decreasing fistula output, and indicate that it is equally successful in producing favourable changes in the secretion of pancreatic fistulas irrespective of aedologv. Z. TULASSAY Department of Medicine and Surgery, L. FLAUTNER Semmelweis University Medical School, 1083 Budapest, Hungary I. FEHÉRVÁRI =

-

1. Miller

BM, Traverso WL, Freeny PC, Abumrad NN. Failure of somatostatin or an analog to promote closure of end pancreatic fistulae. Int J Pancreatol 1989; 4: 65-72. 2. Lansden FT, Adams DB, Anderson MC. Treatment of external pancreatic fistulas with somatostatin. Am Surg 1989; 55: 695-98. 3. Prinz RA, Pickleman J, Hoffman JP. Treatment of pancreatic cutaneous fistulas with a somatostatin analog. Am J Surg 1988; 55: 36-42.