910

and oliguric with black urine. Haemoglobin was 68 g/dl. The next day, his temperature was 38°C and he was anuric with no sign of complicated malaria. He was transferred here; blood smears were negative. All drugs were discontinued. Haemodialysis was necessary over 15 days, and he was discharged on day 20. Blackwater fever is a life-threatening, acute, intravascular haemolysis with dramatic onset and an often fatal outcome.2 It disappeared from 1950, when quinine was no longer used as chemoprophylaxis. The mechanism of this exaggerated haemolytic response in the absence of hyperparasitaemia remains to be determined, but may involve immune lysis of quinine-sensitised erythrocytes. Quinine may also cause severe haemolysis in patients with the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) deficiency, closely mimicking blackwater fever. Parasite-related IgM antibodies or autoantibodies can also destroy erythrocytes in chronically parasitised individuals,3but such an acute haemolysis is never observed. Neither of our patients had severe or complicated malaria. In case 1, the main diagnostic hypothesis was severe G6PD deficiency, with halofantrine being responsible for the acute haemolytic crisis. No data are available to support this hypothesis.4 Unfortunately, the patient could not be screened for G6PD deficiency after recovery. Blackwater fever could be excluded, since halofantrine had been given for the first time and quinine was continued. In case 2, halofantrine seemed to have behaved like quinine in blackwater fever. Halofantrine is a phenanthrene-methanol compound with structural similarity to quinine, both being aryl-methanols. If confirmed, these data (especially case 2) suggest a potential risk from the frequent and irregular use of halofantrine as presumptive treatment for acute febrile illness by people in endemic areas, because this may reproduce the conditions for blackwater fever.

PATIENTS’ CHARACTERISTICS

icteric,

Intensive Care Unit for Infectious Diseases and Infectious and Parasitologic Diseases Department, Bichat-Claude Bernard Hospital, 75877 Paris, France

FRANCOIS VACHON ISABELLE FAJAC BERTRAND GACHOT JEAN-PIERRE COULAUD GUY CHARMOT

I

Total C

I

LDL-C

LJ. Quinine and the mystery of blackwater fever. Acta Leidensia 1987;

55: 181-96 2. World Health Organisation. Severe and complicated malaria. Trans R Soc Trop Med Hyg 1990; 84 (suppl 2): 1-65 3. Lefrançois G, Bouvet E, Le Bras J, Vroklans M, Simonneau M, Vachon F. Anti-erythrocyte autoimmunisation during chronic falciparum malaria. Lancet 1981; ii: 661-64. 4. Horton RJ, Pan SW. Halofantrine, an overview of efficacy and safety Parasitol Today 1989; (special issue): 65-79.

Depressive symptoms in hypercholesterolaemic patients treated with pravastatin four with SiR,—We report patients primary hypercholesterolaemia who developed serious depressive symptoms during treatment with pravastatin. This 3-hydroxy-3methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor is said to be superior to lovastatin and simvastatin because of its hydrophilicity and liver selectivity.’ Side-effects with other HMGCoA reductase inhibitors, such as ophthalmological complications, myopathy, and sleep disturbances, should thus be prevented. In-vitro pravastatin had no effect on the concentration of prostaglandin Dz, an endogenous sleep-promoting factor, whereas lovastatin and simvastatin inhibited prostaglandin synthetase. In contrast, in clinical and sleep electroencephalographic studies, simvastatin and pravastatin had no differences on sleep quality.2 Insomnia

was

the main disturbance in the central

nervous

system.

Depressive syndromes have not been described. We have seen four women (table) with primary hypercholesterolaemia (aged 44-66, mean total cholesterol 311 [SD 69] mg/dl, mean low-density-lipoprotein [LDL] cholesterol 225 [71] mg/dl) who developed depressive symptoms during 12 weeks of pravastatin treatment, 10 mg in the evening. Their total and LDL cholesterol were lowered to 267 (41) and to 186 (70) mg/dl, respectively. In three patients, depressive symptoms were mild, and

HDL-C

I

C= cholesterol, HDL=high-densrty lipoprotein, TG=tnglycendes m parentheses after 4 weeks of pravastatm treatment

*Numbers

reversible when the treatment was changed to cholestyramine and intensive dietary regimen. One patient (aged 66), who had been additionally treated with enalapril because of hypertension, had increasing psychiatric problems, including the likelihood of suicide. Pravastatin was stopped after 8 weeks, and the patient improved without antidepressive therapy within 2 weeks. Despite an intensive lipid-lowering diet and cholestyramine, cholesterol increased, and, because of high vascular risk (family history, hypertension), lovastatin 20 mg in the evening was started in June, 1992. Lipid indices improved, and the patient did not report any depressive symptoms at the weekly follow-ups, now 3 months after starting an

]ov:;J>;nnin -

Department of Internal Medicine, University of Innsbruck, 6020 Innsbruck, Austria

MONIKA LECHLEITNER FRITZ HOPPICHLER GÜNTHER KONWALINKA JOSEF R. PATSCH HERBERT BRAUNSTEINER

1. Tsujita Y, Kuroda M, Shimada Y, et al. CS-514, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzymeA reductase tissue selective inhibition of sterol synthesis and hypolipidemic effect on various animal species. Biochim Biophys Acta 1986; 877: 50-60. 2. Eckernnas SA, et al. Clinical and sleep EEG study of two structurally different HMG-CoA reductase inhibitors. 9th international symposium on atherosclerosis, Rosemont, Illinois, USA, October, 1991.

Vibrio cholerae O1 1. Bruce-Chwatt

I

septicaemia

has not been associated with We report a case of septicaemia from during the recent outbreak of cholera in Karachi,

SIR,7--Vibrio cholerae 01

bacieraemia/septicaemia. Vibrio cholerae 01 Pakistan.

An 8-month-old, admitted with

previously healthy girl from a Karachi slum, a 3 day history of passage of 10-15 loose, non-mucoid, non-bloody stools with vomiting. She was severely dehydrated, unresponsive, and in shock; temperature was 36°C. White blood cells (WBC) were raised (27-2 x 109/1), with 88% neutrophils, 11 % lymphocytes. Electrolyte abnormalities indicated secretory diarrhoea. Stool microscopy showed over 20 WBC per high-power field; no ova or parasites were seen. The child’s temperature worsened to 38’6°C, and intravenous cefotaxime 150 mg and amikacin 30 mg, 6 and 8 hourly, respectively, were started. She was rehydrated and her electrolyte imbalance was corrected. The patient responded well and her was

temperature became normal about 24 h later. Blood culture showed curved gram-negative rods; the stool cultures became positive for vibrio. Both organisms were identified by agglutination with specific antisera (Wellcome Diagnostics) and confirmed by API 20-E system as V cholerae 01, serotype Inaba, biotype Eltor. The further course was uneventful, and the child was discharged on the fifth day. Of the ten species of vibrio known to be pathogenic in man, seven cause septicaemia.1,2 All are non-cholera vibrios. Isolation of V cholerae 01from blood in our case allows the addition of one more to the list of septicaemia-causing vibrios. Most of the previous cases of vibrio septicaemia were in patients with compromised immune status. Factors associated with V vulnificus septicaemia are heavy alcohol consumption, liver disease, haemopoietic disorder, and chronic renal disease. Defective leucocyte mobilisation may be common in all these disorders.3The same probably holds true for infections with other vibrios. Because of these associated factors, vibrio septicaemia, although rare, has a different clinical spectrum and a worse prognosis than does