Vibrio cholerae 01 septicaemia

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

911

Survival from vibrio septicaemia tends to be low with non-eventful recoveries documented for septicaemia with V cholerae 01, V metschnikovii, and V cincinnatiensis.4-<> Also, vibrios causing septicaemia are more often associated with wound infections than with gastroenteritis. Our patient presented with signs of severe cholera and developed high temperature about 72 h after the onset of diarrhoea. No apparent cause of immunosuppression before onset could be detected.

gastroenteritis.

Department of Microbiology, Aga Khan University,

B. JAMIL A. AHMED A. W. STURM

PO Box 3500, Karachi 74800, Pakistan

1. Moms JG Jr, Black RE. Cholera and other vibrioses in the United States. N Engl

J

Med 1985; 312: 343-50. 2. Lowery PW, McFarland LM, Threefoot HK. Vibrio hollisae septicemia after consumption of catfish. J Infect Dis 1986; 154: 730-31. 3. Johnston JM, Becker SF, McFarland LM Vibrio vulnificus: man and the sea. JAMA 1985; 253: 2850-53. 4. Platia EV, Vosti KL. Noncholera Vibrio septicemia. West J Med 1980; 132: 354-57. 5. Jean-Jacques W, Rajashekaraiah KR, Farmer JJ III, Morris JG, Kallick CA. Vibrio metschnikovii bacteremia in a patient with cholecystitis. J Clin Microbiol 1981; 14: 711-12. 6. Bode RB, Brayton PR, Colwel RR, Russo FM, Bullock WE. A new Vibrio species, Vibrio cincinnatiensis, causing meningitis successful treatment in an adult. Ann Intern Med 1986; 104: 55-56.

Risk of

pneumonia after hospital treatment for pneumonia

SIR,-Dr Hedlund and colleagues (Aug 15,

p 396) report that admitted with an index diagnosis of pneumonia have a five-fold higher risk of subsequent readmission for pneumonia than patients admitted for non-respiratory infections. They also report a higher subsequent death rate in the patients initially presenting with pneumonia, and suggest that pneumococcal vaccination should be offered to all patients over 50 presenting with pneumonia. I found this paper strangely flawed. Hedlund et al do not tell us how many patients presented with pneumonia due to underlying causes such as chronic obstructive pulmonary disease, bronchial carcinoma, or conditions caused by smoking. Since patients with these and similar conditions inevitably present more commonly with pneumonia, and have a lower life expectancy than healthy controls, the two groups are probably not appropriately matched, and the findings are entirely predictable. Nor is their second point about pneumococcal vaccination borne out by their data. Although they cite Streptococcus pneumoniae as being the leading cause of pneumonia in elderly people, they give no indication of the frequency of organisms found in their series, and, in particular, the organisms most commonly associated with a fatal outcome. A large number of patients who die from pneumonia might be helped by pneumococcal vaccination; it is equally possible from their data, however, that other organisms are involved, or that the patients most likely to die from pneumonia have previously been exposed to pneumococcus, and thus have developed their own

patients

-

immunity. Lastly, if pneumococcal vaccination really is of benefit in the over 50s, why wait until patients have presented to hospital before providing prophylaxis-in many instances too late? A more relevant prospective trial might be pneumococcal vaccination in high-risk groups in the community, such as heavy smokers, before they present to hospital. Department of Nephrology, Guy’s Hospital, London SE1 9RT, UK

PETER A. ANDREWS

**This letter has been shown to Dr Hedlund and colleagues, whose reply follows.-ED. L. SiR,—The first point that Dr Andrews raises is that.we did a scientific study in a field in which the result, according to clinical experience, was known or entirely predictable. We believe that clinical experience is sometimes mistaken and such knowledge should be tried and if possible verified by scientific studies. We emphasise that our investigation was not a case-control study but a cohort study, so the patients were not matched. Since the

frequency of pneumonia was age dependent, the results were adjusted for age. Our main finding was that patients who had previously been admitted for pneumonia were at high risk of a new pneumonia during the next three years after discharge. The occurrence of a pneumonia episode is quite possibly only a marker of underlying factors increasing the patient’s susceptibility to agents causing pneumonia. However, our point is that hospitalisation for pneumonia is a very simple way to identify a patient with a high risk of a new pneumonia. Predisposing factors are clearly of interest from a pathogenetic point of view. We are therefore now analysing this material for factors of importance for long-term outlook. However, in this group of 241 patients only 2 had lung cancer, and according to preliminary data the risk of recurrent pneumonia was not significantly increased among the 20% of patients who had chronic pulmonary diseases. With respect to the specific importance of pneumococcal vaccination in patients at high risk of pneumonia, there is overwhelming evidence, not least from the UK,’-4 for the importance of Streptococcus pneumoniae as a cause of morbidity and mortality in pneumonia in elderly patients. Furthermore, the immunity to S pneumoniae is type specific and, since there are 84 pneumococcal types with little cross-immunity, the occurrence of a pneumococcal pneumonia does not prevent further attacks of S pneumoniae pneumonia. Of course, other causal agents should be considered as a cause of pneumonia in elderly patients with pneumonia, but unfortunately other common bacterial pathogens cannot be covered by vaccines. Thus we believe that patients with a high risk of pneumonia should receive pneumococcal vaccination. Lastly, there is as yet no prospective blind study demonstrating that pneumococcal vaccination is of benefit in the over fifties and we have therefore initiated such a study. We chose, to avoid a large sample size, to investigate a group of patients among whom we know the incidence of pneumonia is high-namely, those who have had pneumonia. JONAS HEDLUND Department of Infectious Diseases, AKE ÖRTQVIST Karolinska Institute, Danderyd Hospital, S-182 88 Danderyd, Sweden,

MATS KALIN JOHAN GIESECKE

1. Macfarlane JT, Finch RG, Ward MJ, Macrae AD. Hospital study of adult community-acquired pneumonia. Lancet 1982; ii: 255-58. 2. Research Committee of the British Thoracic Society and the Public Health Laboratory Service. Community-acquired pneumonia m adults in British hospitals in 1982-1983: a survey of aetiology, mortality, prognostic factors and outcome. Q J Med 1987; 62: 195-220. 3. Woodhead MA, Macfarlane JT, McCracken JS, Rose DH, Finch RG. Prospective study of the aetiology and outcome of pneumonia m the community. Lancet 1987; ii 671-74.

P, Gladman J, Macfarlane JT, et al. A hospital study of communityacquired pneumonia m the elderly. Thorax 1990; 45: 254-58.

4. Venkatesan

Motorcyclists and wind noise SIR,-We report worrying preliminary results on noise and hearing in motorcyclists, who are exposed to high noise due to low frequency wind noise caused by turbulent airflow around the helmet;l,2 the motorbike’s noise does not exceed safe limits.3,4 We have examined 106 motorcyclists, including police and social riders and professional grand-prix racers, with a median age of 30 years, riding experience of i0 years, and no history of previous noise exposure or ear disease. Comparison with age-matched non-noiseexposed control values,s,6 indicated that a high proportion (49 subjects, 46%) had sensorineural hearing loss consistent with noise damage. Only 15% of these 106 riders regularly used earplugs. Furthermore, measuring sound attenuation effects of earplugs under crash helmets, we have found that any crash helmet will impair the performance of any earplug for the lower sound frequencies, especially around 500 Hz, where there is a mean performance reduction of 4-7 dB (95% CI 4-1-5-3). This is disturbing for two reasons: the protection afforded by earplugs is poorest for these low frequencies, and the maximum sound energy of wind noise is concentrated around 250-500 Hz.2 We have two recommendations. First, we should raise awareness of this problem among motorcyclists and increase the use of