791

years, range 13;-30 years). All patients were severely iron

overloaded, had multiple endocrine abnormalities, and variableseverity of cardiomyopathy. The dose of desferrioxamine was60 mg/kg per 24 h continuously for 2 months.To assess reliability, ease of handling, and compliance, the

patients were given an anonymous questionnaire at the end of thetrial. The accuracy of the delivery time was to within 1 h per 24 h.The system was cosmetically preferred by all patients because oflightness and silent running, which gave complete freedom topursue daily activities compared with the conventional pump.Compliance was 100%, largely due to the unobtrusiveness of thepump and the lack of preparation needed before use. A furtheradvantage is the lack of handling by the patient, which reduces therisk of contamination from skin bacteria.Because this system is new, the cost is high, around 200 per

week per patient. We feel that the cost is justified by the excellentclinical results from long-term use of intravenous desferrioxamineand the increased compliance with the use of this system. We nowuse it for all patients requiring continuous desferrioxamine infusion.

We thank Unicare Medical Services and Baxter for helping with this study.

Department of Haematology,Whittington Hospital,London N19 5NF, UK

A. FIELDINGB. WONKE

1 Wonke B, Hoffbrand AV, Aldouri MA, Ward SE. Cardiac complications mhomozygous B thalassaemia. Prog Clin Biol Res 1989; 309: 51-56.

2. Marcus R, Davies S, Bantock H, Underwood S, Walton S, Huehns E.Desfernoxamme to improve cardiac function in iron overloaded patients withthalassaemia major. Lancet 1984, i: 392-93

3. Zurlo MG, De Stefano PD, Borgna-Pignatti C, et al. Survival and causes of death inthalassemia major. Lancet 1989; ii: 27-30.

Vaginal chlorhexidine disinfection duringlabour

SIR,-The data presented by Dr Burman and colleagues (July11, p 65) do not, in our view, support the assertions implicit in thetitle of their study. They demonstrate a significant reduction inadmission of full-term infants to special-care neonatal units whenmothers were treated with vaginal chlorhexidine, and an increasedrate of admission to special-care neonatal units if the mother was acarrier of group B streptococci, but they do not show an associationbetween the morbidity prevented by chlorhexidine and group Bstreptococci.The reduction in admission rate for infants bom to group B

streptococci carrier mothers was from 5-4% (22/409) to 2-8%(11/388) and the reduction in admission rate for infants born tonon-carrier mothers was from 2-4% (43/1794) to 1-9% (34/1793).An association between prevented neonatal morbidity and maternalcarrier status for group B streptococci can be supported only if thedifference between these two reduction rates is significant (such anassociation, however, may also be incidental because there are otherorganisms acquired in a similar pattern, such as mycoplasma andureaplasma, which could also be responsible). No data, however, areprovided about the significance of the difference between these tworeduction rates. With a x2-test, this difference is not significant(xî == 0,954, p= 0.33).We believe that vaginally applied chlorhexidine probably has a

limited role in the prevention of group B streptococcal sepsisbecause theoretically more than half of early-onset infections areapparent at birth’ and therefore presumably develop before the firstbolus of chlorhexidine is applied. It is therefore not surprising thatone of the two reported cases was in the chlorhexidine group.Furthermore, we question the severity of the morbidity (which

Burman et al used as the secondary end-point) prevented bychlorhiexdine application. These workers report an admission rateto special-care neonatal units that varies more than ten-fold betweendifferent centres, without further explanation. Since the studypopulation is otherwise fairly uniform, the differing admissioncriteria may be a confounding factor. The overall admission rate of25% for full-term healthy infants also suggests that morbidity wasnot severe.

No serious adverse effects of chlorhexidine were recorded but the

long-term effects of exposure to respiratory and other epithelial

surfaces have not been addressed. We are also concerned that when

extrapolated to preterm labour, the application of such largevolumes of chlorhexidine solution (60 ml every 6 h) throughoutlabour, particularly in the presence of prolonged rupture ofmembranes, will expose premature infants to potentially damagingamounts of chlorhexidine. The epidermal barrier in these infants isthought to be incompletely developed.2We believe that this study shows that vaginal application of

chlorhexidine may reduce minor neonatal morbidity but should notbe relied on to prevent group B streptococcal sepsis. Antimicrobialprophylaxis given to an appropriate target population has provenefficacious,3 and in the longer term, vaccination will probablyprevent most infections.’

Departments of Medical Microbiologyand Obstetrics,

Utrecht Academic Hospital,3508 GA, Utrecht, Netherlands,and Academic Medical Centre,3 Amsterdam

ROBERT FELDMANCARLA VAN OPPENARNOLD NOORDUYN

1. Boyer KM, Gadzala CA, Burd LI, et al. Selective intrapartum chemoprophylaxis ofneonatal group B streptococcal early-onset disease I, epidemiologic rationale.J Infect Dis 1983; 148: 795-801.

2. Aggett PJ, et al. Percutaneous absorption of chlorhexidine m neonatal cord care. ArchDis Child 1981, 56: 878-80

3. Boyer KM, Gotoff SP. Prevention of early-onset neonatal group B streptococcaldisease with selective intrapartum chemoprophylaxis. N Engl J Med 1986; 314:1665-69.

4. Baker CJ. Immunization to prevent group B streptococcal disease: victories andvexation. J Infect Dis 1990, 161: 917-21

** This letter has been shown to Dr Burman and Dr Tullus, whosereply follows.-ED. L.

SIR,--Our study showed a statistically significant reduction ofthe admission rate of infants born to mothers who received vaginalflushing with chlorhexidine during labour. This reduction wasattributable to a lower frequency of minor neonatal morbidity.However, minor ailments were more than 10-fold more frequentthan invasive infection, and the mean length of stay of these infantswas at least as long as for those with other diagnoses. The reductionof the admission rate was surprisingly large and therefore bothethically and financially important.Even though the size of the study was considerable, it was not

large enough to measure any impact of chlorhexidine on invasivegroup B streptococcal infections. We also agree with Feldman et althat some of the early onset infections may start beforechlorhexidine is given and thus will not be preventable.Surprisingly, the impact of chlorhexidine in our study seemed to besimilar whether the prophylaxis was started before (36% feweradmissions) or after (31 %) rupture of the membranes. We did notprovide this information because the subgroups were too small forstatistical analysis.We agree, as we said in our report, with Feldman’s view that the

reduced admission rate for infants born to mothers who were

negative for group B streptococcal carriage suggested a possible roleof other vaginal organisms such as ureaplasma and mycoplasma. Infact, less common neonatal morbidity caused by vaginal group Astreptococci, chlamydia, listeria, gonococci, and Herpes simplexmight also be prevented by use of chlorhexidine. Furthermore, arecent Norwegian study to which we referred indicated an impacton puerperal infections (endometritis, urinary tract infection,post-caesarean section wound infection).

Invasive group B streptococcal infection continues to be

important clinically. No type of prophylaxis has so far proved totallysuccessful. Antimicrobial prophylaxis during labour in at-risk

populations has proved effective, but half of invasive group Bstreptococcal infections arise outside that group. Ampicillinprophylaxis to large cohorts of mothers and babies might also beecologically hazardous, and might cause serious allergic reactions insome mothers. This approach is also expensive because, apart fromthe cost of the drug, it requires vaginal cultures to be taken of allwomen, which have a predictive value for colonisation at delivery ofonly 67%, unless special enrichment broth and selective agar areused in combination.As we discuss in our report, the development of an effective

vaccine is another approach, although not without difficulties. The

792

subgroup of infants most susceptible to invasive infection-namely,those bom before 32 weeks’ gestation-will not benefit frommaternal IgG. There are also several group B streptococcalserotypes, the difficulty of non-responding mothers, and poorcommercial interest to be overcome.We believe that our proposed vaginal chlorhexidine disinfection

merits further investigation in even larger cohorts of children tostudy its impact on invasive neonatal and puerperal group Bstreptococcal disease and other low-frequency neonatal infections.In sharp contrast to its predecessor, hexachlorophene, the toxicityand percutaneous absorption of chlorhexidine is very low. Thisinexpensive approach may prevent various neonatal and puerperalproblems caused by vaginal microorganisms.National Bacteriological Laboratory,S-105 21 Stockholm, Sweden LARS G. BURMAN

Department of Paediatrics,St Goran’s Children’s,Stockholm KJELL TULLUS

SIR,-Colonisation of newborn babies with group B beta-haemolytic streptococci (GBS) before or during labour is associatedwith high neonatal morbidity and mortality.l Chlorhexidine is

bactericidal, being effective against gram-positive and some gram-negative microorganisms. It is effective in female carriers of GBS,protecting their offspring from colonisation and infection.2 DrBurman and colleagues report that with vaginal flushing withchlorhexidine diacetate (2 mg/ml), the admission rate for babiesbom to GBS-colonised mothers was reduced from 54 to 2-4%.

Between Oct 15,1990, and Jan 18, 1992, we compared the effectson neonatal morbidity of vaginal flushing with chlorhexidinediacetate (2 mg/ml) and our usual routine of chlorhexidine

gluconate obstetrical cream (10 mg/g). The total number ofdeliveries was 3236; after exclusion of premature and malformedinfants, elective caesarean sections, and subjects with obviousobstetric complications (ie, fractures, paralysis), this number was2853. Of the women with normal, full-term, vaginal deliveries 1467were randomised to vaginal flushing and 1386 to cream.

Flushing was started on arrival and repeated every 6 hours untildelivery, as in Burman’s study. In the women who did not receivechlorhexidine flushing, exploration was done with chlorhexidine-containing cream, when indicated clinically during labour.

All infants with clinical symptoms possibly associated withinfection (tachypnoea, grunting, hypotonia, excessive crying,irritability, hypothermia, or hyperthermia) were included in thestudy. 68 babies had hyperthermia, of whom 40 were bom tomothers who received chlorhexidine by flushing and 28 to mothersassigned to cream application (not significant, p = 0-2). 11-7% weretransferred to the neonatal intensive care unit, 4% of whom werefull-term infants. Septicaemia was diagnosed on the basis of positivebacterial culture, on clinical and serological signs, or, in some cases,the detection of GBS capsule antigen in the urine.3 The serologicalsigns included raised C-reactive protein persisting for more than 24hours, low platelet counts, and granulocytosis or granulocytopenia.The frequencies of verified infections (positive blood culture,

serology, and clinical signs) and of suspected infection (clinical andserological signs of infection), but with a negative blood culturewere:

There was a tendency towards a higher proportion of infants withverified septicaemia in the obstetrical cream group, but thedifference was not significant (p=02). The 2 infants with

septicaemia in the flushing group and 4 of the 6 in the cream grouphad GBS; in the remaining 2, the infectious agents were

Haemophilus influenzae and Enterococcusfaecalis, respectively.Disinfection with chlorhexidine before delivery may, clearly,

reduce the frequency of neonatal infections In our patients,neonatal septicaemia with GBS could be verified in 6 full-terminfants, representing 21 per 1000 deliveries. This incidence isreduced to 1-8 per 1000 when all deliveries are included, which

accords with data from other studies (1-3 per 1000 deliveries).1 Useof a chlorhexidine-containing exploration cream (which is routinein many obstetrics departments) on clinical indication seems to be asefficacious as flushing with chlorhexidine during labour to preventcolonisation. The introduction of chlorhexidine flushing thus offersno additional benefits in obstetrical procedures.

Departments of Paediatrics,and Obstetrics and Gynaecology,

Ullevaal Hospital,N-0407 Oslo, Norway

ROLF LINDEMANNTHORE HENRICHSENLEIF SVENNINGESENKRISTI HJELLE

1. Baker CJ, Edwards MS. Group B streptococcal infections. In Remington J, Klein JO,eds. Infectious diseases of the fetus and newborn infant. Philadelphia WBSaunders, 1990: 743-811.

2 Kvist Christensen K, Christensen P, Dykes AK, Kahlmeter G Chlorhexidine forprevention of neonatal colonization with group B streptococci III. Effect of vaginalwashing with Chlorhexidine before rupture of the membranes. Eur J Obstet GynecolReprod Biol 1985, 19: 231-36.

3. Thore M, Faxelius G, Hedin G, et al. The role of a commercial latex agglutination testin the diagnosis of Group B streptococcal infection in neonates. Acta PaediatrScand 1991; 80: 1667-72

Sensitivity of QBC malaria test

SiR,—Your April 25 editorial (p 1022) and the responses byProfessor Levine and Dr Perrone and their colleagues (May 30,p 1354) on the sensitivity of QBC malaria test warrant comment.Your editorial summarised the strength and weaknesses of theQBC. We do not think the technique has been "unscientificallyevaluated". What seems unscientific is the way QBC sensitivity wasdealt with (in the responses) by selectively citing papers thatreported high sensitivity of QBC irrespective of study design.The table shows sensitivities that are or approach 100% when

QBC is compared with Giemsa thin smear instead of Giemsa thicksmear (GTS) (table, 1A, 1B), when the number of GTS

microscopic fields read is small (2A), and in study groups of highparasite densities (lB, 2A, 2B, 3, 4). Lower sensitivities of QBC areseen when GTS is examined with an increased number of

microscopic fields (5A, 5B, 6) and in a study of low-densityparasitaemia (6). After gaining expertise from studies 2 and 3, thesame team of QBC readers did study 6, which had the lowest level ofparasitaemia and the most experienced group of GTS

microscopists.

CHARACTERISTICS OF FIELD STUDIES OF THE QBC MALARIA

SYSTEM

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-

i i i

*QBC additional=additional true positives detected by QBC, tGTS=g!emsa thicksmear, I-relatively low sensitivity may be partly explained by madequate opticalconfiguration