CHLOROQUINE FOR DONATED BLOOD?

100 Intravenous cimetidine has been associated with atrial fibrillation and serious ventricular arrhythmias,l and asystole.2 We emphasise the need for caution with this drug, particularly where pre-existing bundle branch block may make identification and consequently 3 treatment of tachycardias difficult.

WILLIAM DICKEY MARK SYMINGTON

Lagan Valley Hospital, Lisburn BT28 1JP

Triatomidae previously implicated in the transmission of Chagas’ disease in Jalisco have been T barberi and T phyllosoma picturata. T phyllosoma intermedia, the vector responsible for this outbreak, appears to have been an opportunistic vector because of the patients’ temporary encroachment on its habitat. Studies are underway to determine if this triatomide is a regular domiciliary vector in the area.

University of Texas 1. McMahon B, Bakshi M, Walsh MJ. Cardiac arrythmias after intravenous cimetidine.

N Engl J Med 1981; 305: 832-33. J, Weetman AP, Dargie HJ, Krikler DM. Life-threatening arrhythmias intravenous cimetidine. Br Med J 1979; ii: 768.

2. Cohen

3. Editorial. "Looks like SVT". Lancet

Medical School at Houston, Houston, Texas 77030, USA

INGRID M. HERNANDEZ-MATHESON CHARLES D. ERICSSON

Universidad de Guadalajara, Guadalajara, Mexico

CARMEN DELGADILLO JAIME PATRICIA PAREDES CASILLAS MARIO PAREDES ESPINOZA

and

1986; ii: 612-13.

CM, Ponce EC, Recio R. Cinco nuevos casos de enfermedad de Chagas en Zacatecas y Jalisco de la Republica Mexicana. Rev Invest Salud Publ (Mex) 1967; 27: 29-36. 2. Velasco Castrejon O, Luna Valadez A, Garcia J, Maya J. Nuevo caso humano de enfermedad de Chagas en Jalisco, Mexico. Prensa Med Mex 1970; 35: 438-40. 3. Velasco Castrejon O, Tay J, Luna Valadez A. La enfermedad de Chagas en el estado de Jalisco, Republica Mexicana. Presentacion de 3 nuevos casos humanos. Rev Invest Salud Publ (Mex) 1974; 34: 107-13. 4. Tay J, Salazar Schettino PM, Velasco Cedano M, de Haro Arteaga I, Garcia Yanez Y, Gutierrez Quiroz M. Estudio epidemiologico de la enfermedad de Chagas en el estado de Jalisco, Republica Mexicana. Salud Publ Mex 1979; 21: 145-49. 5. Tay J, Ontiveros D, Ortega M, Torres J. Estado actual de los conocimientos sobre infeccion en vertebrados por la enfermedad de Chagas en Mexico. Bol Of Sanit Panam 1969; 67: 310-14. 6. Mazza S. Esquizotripanides: Manifestaciones eruptivas agudas en la enfermedad de Chagas (exantemas o reseolas). MEPRA 1941; 51: 1-31. 7. Basso G, Basso R, Bibiloni A. Investigaciones sobre la enfermedad de Chagas-Mazza. Buenos Aires: Editorial Universitaria de Buenos Aires, 1978. 1. Cuartero

NEW FOCUS OF CHAGAS’ DISEASE IN MEXICO

SIR,-Cuartero and colleagues described the first two cases of Chagas’ disease in the State of Jalisco, Mexico, in 1967.1 To date, an additional three patients with acute disease and 32 symptomless individuals with seroreactivity to Trypanosoma cruzi

acute

chronic disease manifestations have been reported We report the appearance of acute Chagas’ infection in an area of Jalisco in which no cases had been identified previously. These are the first cases to be reported in that state in 14 years. 5 males aged 15-53 years and 4 females aged 8-50 were admitted on the same day in the summer of 1986 to the Hospital Civil in Guadalajara, Jalisco, with a similar acute illness. 8 of the 9 patients had worked for one week in the town of Tuxcueca, about 35 km south of Guadalajara where they normally reside. They had slept in one room of an abandoned and dilapidated house made of mud brick with many cracks in the walls. All eight reported having been bitten at night by insects; the ninth person seems to have been exposed via bedding used by the family. The incubation period was 15-21 days with symptoms presenting 8-13 days before admission. All patients reported a history of fever, malaise, and myalgia for 1-2 weeks before admission. 8 patients had a headache. All were acutely ill. 2 had hypotension and bradycardia, and a third had hypotension without bradycardia. A 15-year-old boy had bradycardia, hypotension, an electrocardiogram compatible with myocarditis, and an echocardiogram suggesting mild intraventricular hyperkinesis. 7 of the 9 patients presented with a distinctive rash characterised by diffuse maculopapular eruption with irregular borders. The rash was reddish and violet; it was slightly painful to touch and was non-pruritic. Lesions extended over most of the torso and extremities but spared the hands and feet. 1 patient had a 2-3 cm cutaneous lesion on the cheek. The rash disappeared 7-17 days after admission. The rash is unusual because of its impressive appearance and the frequency of its occurrence. We suspect that the extensive rash was due to an immunological or allergic response to the high inoculum of multiple bites. The appearance of the rash 29-31 days after inoculation and its disappearance in less than 3 weeks fit in with observations made by Mazza6and Basso et al .7 No patient presented with the classical portal-of entry lesions, chagoma, or Romana sign. The haemoglobin level was normal in 3 patients, slightly reduced in 4, and very low in 2. Blood, urine, and throat cultures were negative. Chest X-rays were normal and chemical tests on blood and urinalysis were normal. Prothrombin times were prolonged in 6 patients, but thrombocytopenia and overt bleeding were absent. Chagas’ infection was confirmed by identification of T cruzi in fresh blood and Giemsa-stained thin peripheral blood films. Of 6 patients who consented to xenodiagnosis-in which vectors are examined for T cruzi after they have been allowed to bite a patient in whom Chagas’ disease is suspected-5 were positive. 6 of 7 were positive in mouse inoculation tests. Treatment was with benznidazole 5 mg/kg daily given by mouth for 18-21 days. Post-treatment blood smears and xenodiagnoses were negative for T cruzi in the 6 patients consenting to repeat xenodiagnosis. Triatoma phyllosoma inlt?171Wdia and a rat, captured at the house wherein the family contracted the infection, were parasitised with T cruzi.

or

YELLOW FEVER AND THE TRAVELLER

SIR,—Your Dec 6 editorial on yellow fever in Africa emphasises the seriousness of the disease, especially among those not normally living in endemic areas. This group includes travellers to countries such as Nigeria, where an epidemic is underway. We have been studying the background and travel experiences of those attending the yellow fever immunisation clinic in Glasgow. 15 out of 68 (22 %) business travellers received yellow fever immunisation for the first time less than 10 days before leaving for yellow fever zones, compared with 9 out of 113 (8 %) holidaymakers. 10 days is the time required before an international immunisation certificate becomes valid and it is only a minimum interval for protective immunity to be achieved. Clearly many travellers go to yellow fever zones without adequate protection because immunisation has been received too late. Business travellers, who may get only short notice of the need for travel, appear to be especially at risk. Businesses and their medical advisers should be aware of this danger and should encourage employees who are likely to travel to keep up to date their immunity to exotic infections. Department of Occupational Health, Southern General Hospital, Glasgow

E. R. WACLAWSKI

Department of Infectious Diseases, Ruchill Hospital, Glasgow G20 9NB

E. WALKER

CHLOROQUINE FOR DONATED BLOOD? common in the tropics. In areas with hyperendemic and holoendemic malaria (ie, much of Africa) many blood-donors are asymptomatically infected. It is very SiR,—Transfusion malaria is

expensive (and possibly ineffective) to screen blood smears on all donors, and it has been suggested that all blood recipients in these areas should receive antimalarial drugs. A simple and cheap alternative would be to add chloroquine to all blood donations. If chloroquine was added to the anticoagulant in the donation bag to give a final concentration of 20-50 mg/’l, the asexual stages of the parasite would be exposed to a chloroquine concentration about one hundred times higher than those achieved during treatment of malarial yet the total dose administered would be very small.

101 These concentrations would be effective resistant strains of Plasmodiumfalciparum.

even

for

chloroquine

Wellcome/Mahidol University/ Oxford Tropical Medicine Research Programme,

Hospital for Tropical Diseases, Bangkok 10400, Thailand

N. J. WHITE

1. Walker O, Dawodu AH, Adeyokunnu AA, Salako LA, Alvan G. Plasma chloroquine and desethylchloroquine concentrations in children during and after chloroquine treatment for malaria. Br J Clin Pharmacol 1983; 16: 701-05. 2 White NJ, Watt G, Bergquist Y, Njelesani E. Parenteral chloroquine in the treatment of falciparum malaria. J Infect Dis (in press).

BRAIN DAMAGE AFTER HIGH-ALTITUDE CLIMBS WITHOUT OXYGEN

SiR,—West’ has suggested that brain damage due to hypoxia might ensue after a climb without supplementary oxygenon the very high mountains of the Himalayas. We have studied cerebral function at extreme high altitude, using simple tests commonly applied in clinical evaluation of memory, language fluency, and idiomotor apraxia. We studied seven climbers (five men, two women) who ascended, without supplementary oxygen, Mount Satopanth (7075 m, base camp 5200 m). They were tested three times: before leaving Italy, at the base camp after the ascent, and 75 days after their return. To avoid possible bias due to altitudeinduced brain damage in the observer, the trials were tape recorded or drawings were used. The tests at base camp were done after 2 days of complete rest, to rule out the possibility of low performances due to physical exhaustion. The most interesting results are summarised in the table. MEMORY AND FLUENCY TESTS (MEAN VALUES) IN SEVEN CLIMBERS

In all cases memory performance decreased, either at base camp or, to a lesser degree, at sea level 75 days after the climb. Fluency tests revealed very few differences whenever they were done. Furthermore there was a learning effect, and this was noted by the climbers themselves. Idiomotor ability was unaffected by altitude. None of the differences found was statistically significant in this small series, but our findings suggest that deficits due to high altitude may prove to be detectable with simple tests even 75 days

after a climb. G. CAVALETTI R. MORONI P. GARAVAGLIA G. TREDICI

Istituto Anatomia Umana Normale, University of Milan, 20133 Milan, Italy, and Equipe Enervit 1. West JB. Do climbs to extreme altitude

cause

brain damage? Lancet 1986; ii: 387-88.

ANALGESICS, AGRANULOCYTOSIS, AND APLASTIC ANAEMIA

SiR,—The international study of the environmental causes of agranulocytosis and aplastic anaemia, to which attention was drawn in your editorial of Oct 18 (p 899), was a massive investigation in which information was obtained about exposure of more than 2000 patients (including 221 with agranulocytosis and 113 with aplastic anaemia) to a wide range of drugs and other environmental agents of potential aetiological significance. The full results will be published in a book and it was perhaps inevitable that the desire to have some of the results published quickly should result in so much abbreviation that misunderstanding was likely to arise. Since the honorary advisory committee responsible for approving the design of the study and for deciding when the results should be reported to the sponsors (Hoechst AG), to the medical profession, and to

licensing

authorities advised quick publication, we write, as members of that committee, in the hope that we can remove some of the misunderstanding that our advice has apparently caused.

The need for brevity prevented the inclusion of a detailed account of one of the most striking fmdings-namely, the difference in the estimated relative risk associated with the use of dipyrone in Budapest and Israel, which was close to 1, and that in Barcelona, Berlin, and Ulin which was over 20. Your editorial understandably suggested that this difference (which was statistically highly significant) might have arisen because of spuriously frequent reports of the use of dipyrone by the control patients in Israel and Budapest. This was our own suspicion when the unexpected results from Israel first became evident (the data for Budapest were obtained later) and we recommended that more data should be collected, that interviewers in Israel should be changed (despite the fact that all the interviewers in all areas had used the same protocol and received the same training), and that further steps should be taken by the principal investigators to ensure the uniformity of interviewing techniques in the different areas. The results continued, however, to show the same pattern, and our original hypothesis was abandoned. There remained the possibility that the use of dipyrone by the controls in Barcelona, Berlin, and Ulm was underestimated because of differential memory loss associated with the many dipyrone-containing preparations available in those regions (as was discussed in the paper) or that there are, as we now think to be most likely, real regional differences in the risk of agranulocytosis among dipyrone users. If there are real regional differences this should provide an important scientific lead. We were surprised, however, that the editorial should have misunderstood the observation that 18% of the patients with agranulocytosis in Israel and Budapest (the 18% refers to Israel and Budapest not to Israel only, as was implied) had used dipyrone and attributed 18 % of the cases in those regions to the use of dipyrone. Even in the abbreviated version of the report we would have hoped that it was clear that use of dipyrone did not imply that the drug caused the disease, any more than the use of paracetamol (acetaminophen) by 11 % of the affected patients meant that 11% were caused by that drug.- In interpreting these figures we have to take account of the experience of the control patients, 13 % of whom in Israel and Budapest had also used dipyrone and 5 % of whom had used paracetamol. The suggestion that the excess risks associated with the use of different drugs could have been estimated by using defined daily doses (DDDs) as the denominator is one that we had made ourselves. It was not, unfortunately, practicable at the time because the data then available were not thought to be adequately comparable. The results obtained from further research will, however, be published shortly by J.-R. Laporte and X. Came (personal communication). In the circumstances, the investigators used instead the standard epidemiological technique for calculating excess risks from the data in the study. A seven-day interval was selected because the mechanism underlying the production of agranulocytosis by dipyrone was believed to be immunological, and because it conformed to what was known about the pharmacokinetics of the drug. There are several other points on which we might comment (such as the suggestion that regional fatality rates had not been reported because they might be taken to reflect differences in the effectiveness of medical care) but the explanations will become clear when the full report is published. We should, however, like to add (which was not noted in the editorial) that neither dipyrone nor other pyrazalones were associated with aplastic anaemia and to emphasise our view, which seems to differ from that of your editorial, that any evaluation of the safety of a given analgesic must take into consideration not only its haematological side-effects but also all its other side-effects, and that the frequency of these should also be compared with those attributable to alternative analgesics of

equivalent efficacy. ICRF Cancer Epidemiology and Clinical Tnals Unit, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE

RICHARD DOLL

Department ofPharmacotherapeutics, University of Oslo, Oslo, Norway

PER KNUT M. LUNDE

Solothurn, Switzerland

SVEN MOESCHLIN