1355

characterise thick film use.4 Your editorial also disregards the fact that peripheral clinics cannot do thick film diagnosiss (QBC enables them to do so) and the fact that this inability all too often leads to indiscriminate dispensing of antimalarialss,6 at much expense. Malaria experts decry the lack of new diagnostic methodss and new antimalarials. Where is the motivation to industry to help to meet these needs when

technology is so unscientifically evaluated? How does one adequately assess the enhanced sensitivity of a new method when it is expected to be compared to an inherently less sensitive reference method? QBC "false positives" have subsequently, with prolonged re-reading of the thick film (or by culture), often proven to be true positives.’2 7,11 With its QBC system it is the "impoverished reality of the malarious tropics" that Beckton Dickinson aims to serve. Becton Dickinson Tropical Disease

a

promising

new

(p 0-01, paired t-test). This finding prompted us to examine p-blocker studies for evidence of an effect of gender. However, only one of the major studies cited in Yusuf and colleagues1 meta-analysis of late intervention provided mortality figures for men and women separately-namely, the BHAT study, which shows a nonsignificant trend for a larger effect for women.7 Some support for this observation comes from the ISIS-1 study on acute =

administration of &bgr;-blockers:8 Diagnostics,

JOSEPH B. PERRONE

Franklin Lakes, New Jersey 07417, USA

CAROLINE POPPER

1. Rickman LS, Long GW, Oberst R, et al. Rapid diagnosis of malaria by acidine orange staining of centrifuged parasites. Lancet 1989; i: 68-71. 2. Pornsinlapatip J, Namsiripongpun V, Wilde H, Hanvanich M, Chutivongse S. Detection ofplasmodia in acridine orange stained capillary tubes (the QBC system). SE Asian J Trop Med Publ Health 1990; 21: 534-40. 3. Rapheron G, Overdraogo J. Application to epidemiological studies of a new and rapid diagnostic test for malaria that utilizes acridine orange: the QBC(R) test (quantitative buffy coat) from Becton Dickinson. Med D’Afrique Noir 1991; 38: 14-17. 4. Kaewsonthi S. Internal and external costs of malaria surveillance in Thailand. (TDR 6). UNDP/World Bank/WHO, 1989: 37-39. 5. WHO Expert Committee on Malaria. Tech Rep Ser WHO 1986; no 735. 6. Olivar M, Develoux M, Abari A, Loutan L. Presumptive diagnosis of malaria results m a significant risk of mistreatment of children in urban Sahel. Trans R Soc Trop Hyg 1991; 85: 729-30. 7. Spielman A, Perrone JB, Teklahaimanot A, Balcha F, Wardlaw SC, Levme RA. Malaria diagnosis by direct observation of centrifuged samples of blood. Am J Trop Med Hyg 1988; 42: 337-42. 8. Parzy D, Raphenon G, Martet G, et al. Quantitative buffy coat (QBC test), monofluo kit falciparum: comparative value in the rapid diagnosis of malaria. Méd Trop 1990; 50: 97-101.

Do women benefit

more

than

men

from

SiR,—Treatment with p-blockers after myocardial infarction (MI) leads to a reduction in deaths.1 Appropriate use of long-term will lead

to a

&bgr;-blocker Vascular mortality* Male 217/6189 Female 96/1848 *Dunng treatment penod (days 0-7)

Control

(3’5%) (5’2%)

225/6132 f7% 140/1858 r7%

the result for the men was not significant, but in women there was a highly significant beneficial effect (p 0-004 by x2-test). In a log-linear interaction model the effect of gender on mortality reduction was statistically significant (p=001). In both studies, however, the mortality rate on placebo was higher for women than for men; the apparently better results for women are thus not necessarily a gender effect, but could also be related to a larger effect in high-risk patients. These observations suggest that the introduction of post-MI P-blockade affects national vital statistics favourably, and that the treatment is especially beneficial for women.

Again,

=

Department of Internal Medicine, County Central Hospital, 4700 Næstved, Denmark

KJELD S. KRISTENSEN ASBJØRN HØEGHOLM

S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomised trials. Prog Cardiovasc Dis 1985, 27: 335-71. 2. Thomas L. On the science and technology of medicine. Dœdalus 1977; 106: 35-46. 3. The Norwegian multicenter study group. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. N Engl J Med 1981; 1. Yusuf

post-MI &bgr;-blockade? P-blockade

p-blockers could possibly be detected by separation of the mortality for the two countries. The figure shows age-standardised ischaemic heart disease mortality rates for 1978-87 (World Health Organisation data). Although there is no difference for men, Swedish women show a significantly lower mortality than Danish women, coincident with the introduction of 0-blockade, in 1982

curves

1-2% decrease in total heart disease

mortality,l but new therapeutic cardiological interventions are only seldom discernible in vital statisticsZ With the publication of the Norwegian Multicentre Study Group’s report3 widespread use of post-MI p-blockade was recommended. In Sweden this resulted in up to 60% of patients receiving p-blockade (Johan Herlitz, personal communication). In Denmark, &bgr;-blockers have never been established as standard post-MI treatment; surveys have shown that only 16% of the country’s coronary care units use it routinelyand that about 90% of Danish cardiologists give it to less than half their MI patients.s As Sweden and Denmark are much the same with respect to socioeconomic and demographic data as well as trend in mortality from ischaemic heart disease6 a beneficial effect of Sweden’s use of

304: 801-07. 4. Madsen EB, Nielsen PE. Behandlingen af akut myokardieinfarkt i Danmark. Ugeskr Lœger 1987; 149: 2585-89. 5. Kjøller E, Rasmussen C, Reckling JC. Beta-blokker efter akut myokardieinfarkt? Ugeskr Lœger 1987; 149: 3397-99. 6. World Health Statistics Annual. Geneva: World Health Organisation, 1987. 7. Beta-blocker heart attack trial research group. A randomised trial of propranolol in patients with acute myocardial infarction I: mortality results. JAMA 1982; 247: 1707-14. 8. ISIS-1 collaborative group. Randomised trial of intravenous atenolol among 16 027 cases of suspected myocardial infarction: ISIS-1. Lancet 1986; ii: 57-66.

Diphtheria, pertussis, and tetanus vaccination SiR,—Dr Booy and colleagues (Feb 29, p 507) express concern the long-term protection afforded by diphtheria-pertussistetanus (DPT) vaccination at monthly intervals, beginning at 2 months of age, on the basis of a comparison between two cohorts of infants vaccinated according to the old 3,5,99 and new 2,3,4 month over

schedules.

Different

batches

of DPT

and

different

Hib

(Haemophilus influenzae type b) conjugate vaccines were used in the cohorts, which may have contributed to the differences in the immune responses. In addition, maternal antibodies were not measured in the group vaccinated under the 3,5,99 month schedule. The possibility of random variation in maternal antibody cannot be ruled out in the fairly small samples. Although results of ELISA assays generally correlate well with those of in-vivo neutralisation assays, the protective concentration of antitoxin for diphtheria and tetanus of 0-01 neutralising units per ml cannot be assumed to apply to ELISA assays since the correlation between the two assays is poor at concentrations below O’l1 IU/ml.For pertussis, antibody titre after vaccination did not differ between the new and the old schedule, nor are there reliable immunological correlates of protection. two

Death rates from ischaemic heart disease age-standardised population. Index

100=average

(?DK= Damsh

men;

death rate 1978-80.$DK= Danish (?S = Swedish men;= Swedish women.

to

women;

1356

Titres of diphtheria and tetanus antitoxins 2 weeks after completing the primary series of DPT vaccines are lower when the first dose is applied at 3 months rather than at a later age, or when

intervals between doses of 1 rather than 2 months

are

used.

However, geometric mean titres 1 year after completing the series much the same, irrespective of age at first dose or interval between doses.2 Diphtheria and tetanus antitoxin concentrations are maintained until the booster dose at school entry after accelerated vaccination schedules with completion of the primary series before 8 months of age, and antitoxin concentration at age 4 years does not differ between those who completed the series by age 6 months and those completing at 8-13 months.3Longer follow-up of children vaccinated at 2, 3, and 4 months of age is therefore needed before any conclusions can be drawn about persistence of immunity to school entry. The Public Health Laboratory Service is conducting a longitudinal study of the early and long-term antibody responses to the new schedules. The introduction of an accelerated vaccination schedule in the UK has been associated with improved coverage in the first year of life.3 In developing countries, 20-30% of pertussis cases occur before 6 months,S,6 and in developed countries, 50-67% of all deaths from pertussis took place in infants under 6 months of age in the prevaccine era.7 The World Health Organisation’s Expanded Programme on Immunisation (EPI)1 schedule provides guidelines on the minimum age for starting the series and the minimum intervals between doses, which simplifies training of health workers, helps to reduce missed opportunities, and increases coverage 8 Data from Booy and colleagues’ study cannot be extrapolated to countries in which there is great variation in the efficiency of transplacental transfer of maternal antibodies9 and in the extent of boosting from natural exposure to diphtheria and pertussis. The need for booster doses of DPT in developing countries should be considered in the context of competing demands on scarce resources. Any primary series of three doses of DPT is unlikely to confer lifelong protection. However, the EPI has appropriately directed resources to achieving high coverage with the primary series at the earliest age possible. Tetanus toxoid (TT) has been targeted to women to reduce deaths from neonatal tetanus which cause up to 70% of neonatal mortality in developing countries, and current recommendations are to provide 5 doses of TT to women of are

childbearing age.1o Communicable Disease Epidemiology Unit, School of Hygiene and Tropical Medicine, London WC1 E 7HT, UK

FELICITY T. CUTTS

PHLS Communicable Disease Surveillance Centre, London NW9

NORMAN BEGG

1. Halsey N, Galazka A. The efficacy of DPT and oral poliomyelitis immunisation schedules initiated from birth to 12 weeks of age. Bull WHO 1985; 63: 1151-69. 2. Brown GC, Volk VK, Gottshall RY, et al. Responses of infants to DTP-P vaccine used in nine injection schedules. Public Health Rep 1964; 79: 585-602. 3. Jones AE, Johns A, Magrath DI, Melville-Smith M, Sheffield F. Durability of immunity to diphtheria, tetanus and poliomyelitis after a three dose immunisation schedule completed in the first eight months of life. Vaccine 1989; 7: 300-02. 4. Ramsay MEB, Corbel MJ, Redhead K, Ashworth LAE, Begg NT. Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine. Br Med J 1991; 302: 1489-91. 5. Morley D, Woodland M, Martin W. Whooping cough m Nigerian children. Trop

Geogr Med 1966; 18: 169-82. 6. Zamora A, Chiozza A, Alonso A. Complicaciones de la coqueluche atraves de 500 casos observados en el Servicia de Clinica Epidemiologica de la Casa Cuna. Rev Assoc Med Argent 1962; 76: 121-27. 7. Sako W, Treuting WL, Witt DB, Nichamin SJ. Early immunisation against pertussis with alum-precipitated vaccine. JAMA 1945; 127: 379-84. 8. Cutts F, Soares A, Jecque AV, Cliff J, Kortbeek S, Colombo S. The use of evaluation to improve the Expanded Programme on Immunization in Mozambique. Bull WHO 1990; 68: 199-208. 9. Gendrel D, Richard-Lenobele D, Picaud C, Francoual C, Blot P. Placental transfer of tetanus antibodies and protection of the newborn. J Trop Pediatr 1990; 36: 279-82. 10. Expanded Programme on Immunization. Tetanus control. Wkly Epidem Rec 1987; 50: 380-83.

SIR,-In criticising your Feb 29 editorial on pertussis (p 526), Dr Mulholland predicts that countries with high rates of infant vaccination will develop pools of susceptible young adults, as immunity wanes, and that outbreaks of pertussis among these adults would provide the source of infection in infants too young to be vaccinated. Your comprehensive review revealed no evidence of

substantial transmission among adults in any country, nor does Mulholland cite any; nor has this fear materialised in eastern European countries where the incidence of pertussis has fallen to very low levels after persistent use of compulsory vaccination starting at 3 months of age.1 Nevertheless, Mulholland’s particular concern about immunity to measles and pertussis, in countries with high vaccination rates, deserves elaboration. As with diphtheria and poliomyelitis, it is herd immunity on which elimination of these diseases depends, and this, in turn, depends on an optimum response of each child to vaccination. For measles, this means waiting until 15 months of

age.2 For

pertussis, three doses

at

3, 4, and 5 months constitute

a

popular and effective scheduler and concern about an earlier start has already been expressed.3,4 If your editorial can be faulted, it is for mentioning only the UK and developing countries where a start is now made before 3 months; other countries, such as the USA, Canada, and France, have for some years started at 2 months-with questionable wisdom. Dr Booy and colleagues’ findings add considerable weight to the case for delaying the start until 3 months. This is not only because of a suppressed immune response in the presence of residual maternal antibody, as they conclude; they also found a weaker response to diphtheria toxoid, even in the absence of maternal antitoxin, when the (three) monthly doses started at 2 months, and this suggests that immunological immaturity also affects the response before 3 months of age. Department of Medical Microbiology, Pertussis Reference Laboratory, University Medical School, Manchester M13 9PT, UK

NOEL W. PRESTON

Organisation. Fifth meeting of the European Advisory Group on the Expanded Programme on Immunisation. Copenhagen: WHO Regional Office for Europe, 1991: 5-6. (WHO report EUR/ICP/EPI 026). 2. Preston NW. Childhood immunisation in the new decade. Br Med J 1991; 302: 1. World Health

966-67. 3. Preston NW. Accelerated immunisation with diphtheria-tetanus-pertussis vaccine. Br MedJ 1991; 303: 248. 4. Preston NW. Assessing the response to pertussis vaccine. Br Med J 1991; 303: 1204.

Routine examination of children at risk of

autosomal dominant polycystic kidney disease SIR,-Ravine and colleagues’ found symptoms in 37% of children with autosomal dominant polycystic kidney disease (ADPKD). They investigated 321 children over the age of 15 years with a positive family history of ADPKD: 68 (21 %), undiagnosed up to that time, had kidney cysts revealed by ultrasonography. Clinical features (hypertension, impaired renal function, urinary tract infections) were observed in 25 (37%) of these children and were regarded as treatable complications of the disease. Similar results have been obtained by the Arbeitsgemeinschaft fiir Padiatrische Nephrologie (German study group on paediatric nephrology) investigating cystic kidney diseases in children. In this prospective study, we are analysing the clinical picture and course of the disease in 99 children with early manifestation of ADPKD out of 350 children with cystic kidney disorders. In 27 of these children the diagnosis was established only because of a positive family history. 8 of these children (30%) had clinical features when examined for the first time. The patient’s mean age at the time of

diagnosis was 8-5 years (range 7 months to 16 years). The following symptoms were observed: hypertension requiring antihypertensive treatment (4), significant bacteriuria (1), proteinuria (1), hypertension and proteinuria (1), and hypertension, raised creatinine, and proteinuria (1). Thus, 7 patients had a treatable complication of ADPKD even though they had been detected by chance; so far only a minority of those at risk are examined as a routine. ADPKD is a common autosomal dominant disorder. The genetic fitness of patients with ADPKD is not much reduced, and a large number of undiagnosed gene carriers at various ages exist, most of whom will not manifest clinical complications before adulthood. The findings of Ravine and colleagues’ and our observations raise the question--should regular clinical