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1 PDF hosted t the Rdboud Repository of the Rdboud University Nijmegen The following full text is publisher's version. For dditionl informtion bout this publiction click this link. Plese be dvised tht this informtion ws generted on nd my be subject to chnge.

2 ARTICLE Chlmydi trchomtis s Cuse of Neontl Conjunctivitis in Dutch Infnts Ingrid G. I. J. G. Rours, MD, MMed, Mrgret R. Hmmerschlg, MD b, Alewijn Ott, MD, PhD c, Tjeerd J. T. H. N. De Fber, MD d, Henri A. Verbrugh, MD c, Ronld de Groot, MD, Roel P. Verkooyen, PhD c Deprtment of Peditrics, Sophi Children s Hospitl, nd c Deprtment of Medicl Microbiology nd Infectious Diseses, Ersmus MC University Medicl Center, Rotterdm, Netherlnds; b Deprtment of Peditrics, Division of Infectious Diseses, Stte University of New York Downstte Medicl Center, Brooklyn, New York; d Deprtment of Ophthlmology, Rotterdm Eye Hospitl, Rotterdm, Netherlnds The uthors hve indicted they hve no finncil reltionships relevnt to this rticle to disclose. ABSTRACT BACKGROUND. Chlmydi trchomtis is the most common sexully trnsmitted pthogen in dults, which t delivery my be trnsmitted from mother to child nd cuse conjunctivitis nd pneumoni. In the Netherlnds, prentl chlmydil screening nd tretment of pregnnt women is not routine prctice. The contribution of C trchomtis to neontl ophthlmic disese hs not been studied in the Netherlnds nd remins uncler. METHODS. At the Sophi Children s Hospitl nd Rotterdm Eye Hospitl, 2 cohorts of infnts 3 months of ge presenting with conjunctivitis were studied, 1 retrospectively (July 1996 to July 2001) nd 1 prospectively (September 2001 to September 2002). Lbortory dignosis ws bsed on bcteril culture nd polymerse chin rection for C trchomtis. RESULTS. C trchomtis ws detected in 27 (64%) of 42 retrospectively studied infnts nd 14 (61%) of 23 prospectively studied infnts. Mucopurulent dischrge ws present in 35 (95%) of 37, swelling of the eyes in 27 (73%) of 37, conjunctivl erythem in 24 (65%) of 37, respirtory symptoms in 14 (38%) of 37, nd feeding problems in 5 (14%) of 37 infnts respectively. Before microbiologicl dignosis, generl prctitioners prescribed ntichlmydil ntibiotics loclly to 5 (12%) of 41 nd systemiclly to 4 (10%) of 41 infnts who tested positive for chlmydi, nd ophthlmologists prescribed to 21 (51%) of 41 nd 7 (17%) of 41, respectively. CONCLUSIONS. C trchomtis ws the mjor cuse of bcteril conjunctivitis in this popultion. Cliniclly, differentition from other pthogens ws not possible. Mny infnts who tested positive for chlmydi did not receive pproprite ntibiotic tretment. THE OCCURRENCE OF Chlmydi trchomtis infection in infnts is directly relted to the prevlence of mternl urogenitl infections nd verticl trnsmission rtes. 1 4 The overll risk for infnts born to women with untreted chlmydil infection is 50% to 75%, with infection occurring t 1 ntomic site. Conjunctivitis my occur in 20% to 50% of infected infnts, nsophryngitis in 70%, nd pneumoni in 5% to 20%. 5 C trchomtis hs become the most frequent identifible cuse of neontl conjunctivitis in mny countries. 6 9 The mjority of chlmydil peds doi: /peds Dr Rours is the principle investigtor nd first uthor nd ws responsible for sttistics; Dr Hmmerschlg is couthor nd dviser nd ws responsible for revision; Dr de Groot is co-uthor nd ws responsible for revision nd promotion; Dr de Fber is co-uthor nd ws responsible for revision nd logistics t the Rotterdm Eye Hospitl; Dr Verbrugh is co-uthor nd ws responsible for revision nd promotion; Dr Verkooyen is co-uthor nd ws responsible for revision nd co-promotion; nd Dr Ott is co-uthor nd ws responsible for revision nd sttistics. Key Words Chlmydi trchomtis, neontl conjunctivitis Abbrevitions REH Rotterdm Eye Hospitl SCH Sophi Children s Hospitl GP generl prctitioner PCR polymerse chin rection Accepted for publiction Jun 25, 2007 Address correspondence to Ingrid G. I. J. G. Rours, MD, MMed, Deprtment of Peditrics, Ersmus Medicl Centre, Sophi Children s Hospitl, Dr Molewterplein 60, 3015 GJ Rotterdm, Netherlnds. E-mil: rours123@ plnet.nl PEDIATRICS (ISSN Numbers: Print, ; Online, ). Copyright 2008 by the Americn Acdemy of Peditrics conjunctivitis cses hel spontneously during the first few months of life. However, untreted persistent infections cn led to cute discomfort nd distress for both infnt nd mother, s well s to chronic eye disese. Simultneous silent infection of the respirtory trct my cuse cute or chronic respirtory disese. 3,10,11 Screening of pregnnt women for C trchomtis infection ws recommended by the Centers for Disese Control nd Prevention more thn decde go. 12,13 In 2004 the Dutch Ntionl Helth Council dvised ginst routine chlmydil screening of Dutch pregnnt women, becuse locl dt with respect to chlmydil infection in pregnnt PEDIATRICS Volume 121, Number 2, Februry 2008 e321

3 women nd the contribution of C trchomtis to neontl disese (pregnncy outcome, conjunctivitis, nd respirtory trct infection) provided insufficient evidence to support screening. 14,15 Recently we reported prevlence of C trchomtis infection in pregnnt women of 6.4%. 16 Most of these infections hd been missed in routine cre, suggesting tht C trchomtis trnsmission to infnts my often remin unnoticed. The min objective of this study ws to estblish whether C trchomtis ws cuse of neontl conjunctivitis in infnts referred to hospitl-bsed cre in Rotterdm, the second lrgest city in the Netherlnds. In ddition, we evluted the clinicl presenttion of nd prescribed tretment for chlmydil conjunctivitis compred with other infections. MATERIALS AND METHODS Study Popultion We conducted our study t the Rotterdm Eye Hospitl (REH) nd Sophi Children s Hospitl (SCH) of the Ersmus University Medicl Centre (Rotterdm, Netherlnds). Rotterdm hs multiethnic popultion. Chlmydil screening is not stndrd prctice in pregnnt women in the study re; testing is done on clinicl suspicion. Neontl oculr prophylxis ginst chlmydi or gonorrhoe is not routinely provided. Most newborns with conjunctivitis re treted t mother nd child helth clinics or by generl prctitioners (GPs). Infnts with persistent conjunctivitis re referred to the REH or SCH depending on the prents or referring GP s choice. We studied infnts retrospectively between July 1996 nd July 2001 nd prospectively between September 2001 nd September Infnts 3 months of ge presenting to the REH or SCH with bcteril (mostly persistent) conjunctivitis were eligible for the study. We defined bcteril conjunctivitis s hving conjunctivl erythem, swelling of the eyelids, nd/or mucopurulent dischrge. In the retrospective study, infnts who were dignosed by ophthlmologists with virl conjunctivitis (conjunctivl erythem only) nd who were neither microbiologiclly tested nor treted with ntibiotics nd improved spontneously were excluded from the study. Similrly, infnts with dcryostenosis (nsolcriml duct obstruction) were excluded from the study. Infnts dignosed with chlmydil conjunctivitis in the REH were referred to the SCH for further investigtion nd systemic tretment. Infnts dignosed with C trchomtis conjunctivitis in our prospective study were treted systemiclly with erythromycin suspension (ethylsuccinte), 50 mg/kg per dy, in 3 to 4 orl doses for 10 to 14 dys nd were invited for single follow-up visit. Prents were sked to return to the clinic if the infnt hd respirtory symptoms. Prents themselves were referred to the sexully trnsmitted disese clinic for investigtion nd tretment. Microbiologicl Dignosis Eye swbs were tken for routine bcteril culture, including gonococcl culture, nd chlmydil nd gonococcl polymerse chin rection (PCR) (Cobs Amplicor, Roche Moleculr Dignostics, Plesnton, CA). Specimens were obtined by swbbing the conjunctiv of the everted lower eyelid using sterile Dcron swb. Bcteriologic cultures were processed ccording to stndrd procedures for erobic bcteri in clinicl microbiology lbortory. Chlmydil nd gonococcl PCRs were performed ccording to the mnufcturer s instructions. Tretment Antibiotics tht were prescribed nd considered to be effective ginst C trchomtis were erythromycin, zithromycin, clrithromycin, tetrcycline nd doxycycline, nd chlormphenicol. Dt Collection We collected retrospective dt through systemtic review of medicl chrts. We used stndrdized questionnire nd lbortory investigtions to collect prospective dt. Recorded vribles included the following: ge t presenttion, gender, complints (conjunctivl erythem, swelling of the eyelids, mucopurulent dischrge, unilterl/bilterl involvement, nd respirtory or feeding problems), physicl exmintion, dignostic tests, dignosis, nd therpy by GPs nd ophthlmologists before microbiologicl dignosis. Sttisticl Anlysis We used SPSS (SPSS Inc, Chicgo, IL) for our nlyses. We used uncorrected 2 tests to compre ctegoricl vribles. We clculted risk rtios (with 95% confidence intervls) to exmine fctors ssocited with dignosis of chlmydi conjunctivitis. RESULTS Demogrphics Retrospectively, 64 infnts with conjunctivitis were identified; 36 (56%) were boys. The medin ge ws 2 weeks, with rnge of 0 to 13 weeks. Prospectively, 23 infnts were enrolled; 12 (52%) were boys. The medin ge ws 1 week, with rnge of 0 to 7 weeks. Dignostic Tests Five of 64 retrospectively studied infnts were cliniclly dignosed with bcteril conjunctivitis without performing lbortory test. The remining 59 infnts hd bcteril culture done, including gonococcl culture; 42 infnts lso hd chlmydil PCR, nd 17 infnts hd gonococcl PCR. With inclusion of ll of the tests, 50 (85%) of 59 tested infnts hd positive result. All 23 of the prospectively studied infnts hd bcteril nd gonococcl cultures done, s well s chlmydil nd gonococcl PCR. Nineteen infnts (83%) hd pthogen detected. Tble 1 shows the frequency of isolted species. Detection of C trchomtis ws significntly higher thn of other pthogens (P.001), with similr rtes in retrospectively nd prospectively studied infnts: 27 (64%) of 42 nd 14 (61%) of 23, respectively. Three infnts in the retrospective cohort with Hemophilus influenze hd second pthogen dignosed. e322 ROURS et l

4 TABLE 1 Identified Pthogens Among Infnts <3 Months of Age With Conjunctivitis Pthogens Detected by Test Method Retrospective Cohort Prospective Cohort Totl Infnts P RR (95% CI) Bcteril culture, n Stphylococcus ureus, n (%) 11 (19) 0 (0) 11 (13) H influenze, n (%) 5 (8) 2 (9) 7 (9) Streptococcus pneumonie, n (%) 4 (7) 0 (0) 4 (5) N gonorrhoee, n (%) 2 (3) 0 (0) 2 (2) Other pthogens, n (%) 4 (7) b 3 (13) c 7 (9) Cultures with pthogens, n (%) d 24 (41) 5 (22) 29 (35) PCR N gonorrhoee, n (%) 1 (6) 0 (0) 1 (3) PCR C trchomtis, n (%) 27 (64) 14 (61) 41 (63) ( ) RR indictes risk rtio; CI, confidence intervl. The P vlue is for the difference in the yield between the nonchlmydi pthogen culture (29 of 82) nd C trchomtis PCR (41 of 65). RR reflects the higher likelihood of finding chlmydi thn nother pthogen in these infnts. b Other pthogens included Morxell ctrrhlis, Escherichi coli, Stenotrophomons mltophili, nd hemolytic streptococcus. c Other pthogens included 2 M ctrrhlis nd 1 N meningitidis. d Three coinfections included H influenze, twice with N gonorrhoee nd once with S pneumonie. Clinicl Presenttion We exmined the ge of 69 infnts with microbiologiclly confirmed conjunctivitis. Of these infnts, 41 hd chlmydil conjunctivitis nd 28 hd nother infection (Tble 2). Infnts with chlmydil conjunctivitis were 2.3 times (95% confidence intervl: times) more likely thn those with other infections to present between 1 nd 6 weeks of ge thn within the first week of life. We were ble to exmine clinicl informtion in 37 infnts with chlmydil conjunctivitis (23 dignosed retrospectively nd 14 prospectively) nd 22 with nother pthogen (17 dignosed retrospectively nd 5 prospectively). Becuse there ws no significnt difference between the retrospective nd prospective study, nd the number of infnts in ech study ws smll, the overll results of totl of 37 evluble infnts who tested positive for chlmydi nd 22 infnts with nother pthogen re shown in Tble 2. Mucopurulent dischrge ws the presenting symptom for 35 (95%) of 37 infnts who tested positive for chlmydi, swelling of the eyelids for 27 (73%) of 37, nd conjunctivl erythem for 24 (65%) of 37 compred with 22 (100%) of 22, 11 (50%) of 22, nd 10 (45%) of 22, respectively, for infnts with other pthogens; 27 (73%) of 37 infnts who tested positive for chlmydi hd bilterl eye involvement compred with 17 (77%) of 22 of infnts with other pthogens. The presence of extrophthlmic symptoms did not differ between infnts with chlmydi nd those with nother pthogen (Tble 2). Feeding difficulties corresponded with respirtory complictions in infnts who tested positive for chlmydi. In the other group, these were seprte cses. Additionl symptoms in infnts who tested positive for chlmydi included rhinitis (12 of 37), cough (4 of 37), excessive mucous (3 of 37), nd wheezing or brething TABLE 2 Clinicl Presenttion of Neontl Conjunctivitis by Custive Pthogen Vrible C trchomtis, n (%) Other Pthogens, n (%) P RR (95% CI) Age t presenttion wk 4 (10) 9 (32) 1.0 (Reference) 1 to 6 wk 34 (83) 15 (54) 2.3 ( ) 6 wk 3 (7) 4 (14) 1.4 ( ) No. of symptoms symptom 8 (22) 9 (41) 1.0 (Reference) MP dischrge 7 (19) 9 (41) Redness 1 (3) 0 (0) 2 symptoms 9 (24) 5 (23) 1.4 ( ) MP dischrge swelling 6 (16) 3 (14) MP dischrge redness 2 (5) 2 (9) Redness swelling 1 (3) 0 (0) 3 symptoms 20 (54) 8 (36) 1.5 ( ) MP dischrge swelling redness Extrophthlmic symptoms Respirtory 14 (38) 6 (30) ( ) Feeding 5 (14) 2 (10) ( ) RR indictes risk rtio; CI, confidence intervl; MP, mucopurulent. The P vlue ws for the test of heterogeneity of ge or number of symptom ctegories; the P vlue of extrophthlmic symptoms ws for the difference between pthogen ctegories. PEDIATRICS Volume 121, Number 2, Februry 2008 e323

5 TABLE 3 Antibiotic Tretment Prescribed by GPs nd Ophthlmologists Antibiotic Tretment According to Dignosis GPs, n/n (%) Ophthlmologists, n/n (%) Any confirmed bcteril conjunctivitis Any ntibiotic 30/69 (43) 51/69 (74).001 Chlmydi conjunctivitis Any ntibiotic 20/41 (49) 31/41 (76).01 Antichlmydil ntibiotic 5/41 (12) 21/41 (51).0001 Systemic ntichlmydil ntibiotic 4/41 (10) 7/41 (17).33 The P vlue is for difference in tretment choice between GPs nd ophthlmologists. difficulty (2 of 37 infnts). In the group of infnts with other pthogens, 4 of 20 hd rhinitis; 1 hd cough, nd 1 hd wheezing nd crepittions. Therpy Both GPs nd ophthlmologists prescribed topicl ntibiotics s eye ointment, gel, or drops, including tetrcycline, minoglycosides with or without steroids (gentmicin, sofrmycin, or tobrmycin), fusidic cid, polymyxin/trimethoprim, ofloxcin, nd erythromycin. In ddition, GPs lso prescribed chlormphenicol. Both GPs nd ophthlmologists prescribed systemic tretment, including penicillin, clrithromycin, nd erythromycin. In ddition, GPs used cotrimoxzole nd ophthlmologists used moxicillin, ugmentin, flucloxcillin, nd cefotxime. Antibiotic tretment by dignosis s prescribed by GPs nd ophthlmologists is shown in Tble 3. Comprison of tretment in the retrospective nd prospective cohorts showed tht ophthlmologists gve empiric ntibiotics to 17 (63%) of 27 infnts who tested positive for chlmydi in the retrospective versus 14 (100%) of 14 in the prospective study (P.01), ntichlmydil ntibiotics to 14 (52%) of 27 nd 7 (50%) of 14 infnts (P.9), nd systemic tretment to 6 (22%) of 27 nd 1 (7%) of 14 infnts, respectively (P.22). Follow-up At follow-up, no more conjunctivitis ws observed, nd no symptoms or signs of respirtory trct infection were present. DISCUSSION This study demonstrted tht C trchomtis ws the mjor cuse of neontl conjunctivitis in this popultion of infnts referred to peditric or eye hospitls in Rotterdm. On clinicl presenttion, no distinction could be mde between chlmydil conjunctivitis nd conjunctivitis cused by other pthogens. Empiric mngement to tret chlmydil conjunctivitis ws frequently inpproprite. The min limittion of this study ws tht we could only include infnts with conjunctivitis who were referred to specilist hospitls. Other limittions were the incomplete dignostic workup in the retrospective cohort nd missing dt on clinicl symptoms in few infnts. Also, the number of children in nlyses ws reltively smll, too smll to drw firm conclusions. P Although we cnnot show wht proportion of ll neontl conjunctivitis is cused by C trchomtis, we hve shown tht it is n importnt cuse of (persistent) conjunctivitis. Determining the incidence of chlmydil neontl conjunctivitis nd trnsmission rtes would require prospective study testing ll pregnnt women nd their newborns. The identifiction rte of pthogenic bcteri in our study ws 84%, which is higher thn in most reports In ddition, C trchomtis ws the orgnism isolted most often. This is likely to be relted to our study design nd to the Dutch referrl system, in which minly infnts with persistent conjunctivitis re referred to ophthlmologists. However, we my even hve underestimted the contribution of chlmydi to persistent neontl conjunctivitis, becuse we excluded the infnts with clinicl dignosis of virl conjunctivitis. Underdignosis of C trchomtis persistent conjunctivitis my lso be suggested by the reltively low observed number of 5 cses per yer in the retrospective study versus 14 in the prospective yer. However, the ltter increse my lso reflect n ctul increse of chlmydil infection in Dutch dults. 21 To put our results into context, we relted the findings from our prospective study to obstetric dt from the SCH in tht yer. There were 1648 deliveries in totl, of which 731 were in women 30 yers of ge. With n ntentl prevlence of 6.4%, women would be expected to hve C trchomtis infection. With n estimted trnsmission rte of 50% to 75% nd 20% to 50% of these developing conjunctivitis, 5 we would expect 9 to 24 infnts with chlmydil conjunctivitis, which corresponds with our findings. This my suggest tht ll of the infnts with conjunctivitis were detected. However, not ll of the studied infnts were born to women delivering t the SCH, but lso in other hospitls in Rotterdm or t home. The clinicl presenttion of chlmydil conjunctivitis hs been extensively described by others, nd our study shows similr results to previous reports. 3,4,9,22 24 Most infnts who tested positive for chlmydi presented between the ges of 1 nd 6 weeks (becuse of the slow reproductivity of the orgnism) nd with ll 3 of the symptoms (erythem, swelling, nd dischrge). Ophthlmologists more often prescribed ntibiotics tht were effective ginst chlmydil infection thn GPs. Still, only hlf of the infnts with chlmydil conjunctivitis received effective ntibiotics before microbiologicl dignosis, nd 20% received systemic tretment. In the prospective study, even fewer infnts received systemic tretment. This probbly reflects the greement mde with ophthlmologists to refer infnts to peditricin fter dignosis. We cnnot drw ny conclusions bout chlmydil conjunctivitis in primry helth cre from our study. Acute conjunctivitis my be correctly treted by GPs with topicl ntibiotics ccording to Helth Cre Insurnce Bord guidelines. However, chlmydi is probbly not being considered in the differentil dignosis by some GPs, becuse only 12% of infnts with chlmydi hd received ntibiotics tht were ctive ginst C trchomtis. e324 ROURS et l

6 Our results my suggest the need to institute eye prophylxis for ophthlmi neontorum, which is not prcticed in the Netherlnds. However, we do not wnt to dvocte the ppliction of neontl eye prophylxis, becuse prophylxis does not prevent ll chlmydil neontl conjunctivitis, nd the bsence of conjunctivitis s n indictor of chlmydil infection my dely the proper dignosis of (silent) chlmydil infection t other sites. Another motivtion ginst the decision to strt routine eye prophylxis is tht this my led to overtretment of newborns in country with esy ccess to medicl cre. We would rther like to use our findings to indicte the need for proper (systemic) ntibiotic tretment of newborns who test positive for chlmydi nd screening of pregnnt women. Chlmydil screening for pregnnt women is not stndrd prctice in the study re or in the rest of the Netherlnds. Testing is only done when cliniclly wrrnted. In the prospective yer of the study, only 1% of 1648 deliveries were tested for C trchomtis, of which 4 tested positive. These figures my lso reflect the underestimtion of chlmydil infection in pregnnt women. The vlue of screening my wrrnt dditionl discussion. 16 To prevent 1 cse of chlmydil conjunctivitis, 31 to 78 pregnnt women need to be screened. Assuming specificity of 99.8%, 16 this could result in 0.06 to 0.16 flse-positive mothers nd 2 to 5 truly positive mothers (nd their prtners); furthermore, this could result in the prevention of 1.4 to 2.5 nsophryngitis cses nd 0.2 to 1.0 pneumoni cses. Previously we described the costs of chlmydi screening of pregnnt women by different DNA-isoltion methods in individul nd pooled urine smples. 16 The cost per chlmydi cse detected when using the Cobs Amplicor on individul urine smples ws 275 nd when using combined method of isoltion with the MgNA Pure bcteril DNA-isoltion kit (Roche Moleculr Dignostics, Plesnton, CA), nd subsequent mplifiction nd detection by Cobs Amplicor on pooled urine smples, s we did, ws 108. In the bsence of chlmydil screening progrm, we urge clinicins to hve higher index of suspicion for neontl nd mternl chlmydil infection. Furthermore, we recommend tht, in res where prentl chlmydil screening nd tretment of pregnnt women is not routine prctice, infnts with signs of conjunctivitis tht persist for 72 hours while pplying frequent norml sline eye irrigtion should hve full microbiologicl evlution including Neisseri gonorrhoee nd C trchomtis. While witing lbortory results, empiric tretment in this popultion should include erythromycin eye drops or ointment to both eyes. We recommend tht confirmed chlmydil conjunctivitis should be treted systemiclly with erythromycin suspension or lterntively zithromycin. 13,25 Current ntionl tretment guidelines for neontl chlmydil conjunctivitis re from the Helth Cre Insurnce Bord nd recommend tetrcycline eye drops (with or without orl erythromycin or tetrcycline). 26 The current Centers for Disese Control nd Prevention recommendtion, however, is to tret ll neontl chlmydil conjunctivitis systemiclly with 14-dy course of erythromycin suspension. 13 Systemic tretment hs been demonstrted to be more effective thn topicl tretment, nd infnts with conjunctivitis re often infected t other sites s well. 27 CONCLUSIONS The high rte of isoltion of C trchomtis in infnts with persistent conjunctivitis confirms the importnce of this infection in the Netherlnds. GPs nd ophthlmologists need to consider chlmydi in the differentil dignosis of neontl conjunctivitis nd use pproprite ntibiotics. Trgeted screening for C trchomtis prentlly to prevent infection nd relted complictions in both mother nd infnts should gin be considered in those countries where it is not routine prctice. ACKNOWLEDGMENTS We thnk Mrtin Bronner (REH) nd Connie Groenendijk nd Mirjm vn Veen (SCH) for ssisting with the logistics between centers. REFERENCES 1. Bell TA, Stmm WE, Kuo CC, Wng SP, Holmes KK, Gryston JT. Risk of perintl trnsmission of Chlmydi trchomtis by mode of delivery. J Infect. 1994;29(2): Schchter J, Sweet RL, Grossmn M, Lnders D, Robbie M, Bishop E. Experience with the routine use of erythromycin for chlmydil infections in pregnncy. N Engl J Med. 1986;314(5): Preece PM, Anderson JM, Thompson RG. Chlmydi trchomtis infection in infnts: prospective study. Arch Dis Child. 1989; 64(4): Alexnder ER, Hrrison HR. Role of Chlmydi trchomtis in perintl infection. Rev Infect Dis. 1983;5(4): Hmmerschlg MR. Chlmydil infections. J Peditr. 1989; 114(5): Lg M, Plummer FA, Nznze H, et l. Epidemiology of ophthlmi neontorum in Keny. Lncet. 1986;2(8516): Sergiw A, Prtt BC, Eren E, Sunon TC, Hrt CA. Ophthlmi neontorum in Bngkok: the significnce of Chlmydi trchomtis. Ann Trop Peditr. 1993;13(3): Sndstrom I. Etiology nd dignosis of neontl conjunctivitis. Act Peditr Scnd. 1987;76(2): Dnnevig L, Strume B, Melby K. Ophthlmi neontorum in northern Norwy. II. Microbiology with emphsis on Chlmydi trchomtis. Act Ophthlmol (Copenh). 1992;70(1): Mordhorst CH, Dwson C. Sequele of neontl inclusion conjunctivitis nd ssocited disese in prents. Am J Ophthlmol. 1971;71(4): Hrrison HR, English MG, Lee CK, Alexnder ER. Chlmydi trchomtis infnt pneumonitis: comprison with mtched controls nd other infnt pneumonitis. N Engl J Med. 1978; 298(13): Centers for Disese Control nd Prevention. Sexully trnsmitted diseses tretment guidelines [published correction ppers in MMWR Morb Mortl Wkly Rep. 1989;38(38):664]. MMWR Morb Mortl Wkly Rep. 1989;38(suppl 8): Centers for Disese Control nd Prevention. Sexully trnsmitted diseses tretment guidelines [published correction ppers in MMWR Recomm Rep. 2006;55(36):997]. MMWR Recomm Rep. 2006;55(RR-11): Bosch WJHMvd. Chlmydi Trchomtis. The Hgue, Netherlnds: Gezondheidsrd; 2003 PEDIATRICS Volume 121, Number 2, Februry 2008 e325

7 15. vn de Lr MJW. SOA en AIDS in Nederlnd. Bilthoven, Netherlnds: Rijksinstituut voor Volksgezondheid en Milieu; Rours GI, Verkooyen RP, Willemse HF, et l. Use of pooled urine smples nd utomted DNA isoltion to chieve improved sensitivity nd cost-effectiveness of lrge-scle testing for Chlmydi trchomtis in pregnnt women. J Clin Microbiol. 2005;43(9): Sndstrom KI, Bell TA, Chndler JW, et l. Microbil cuses of neontl conjunctivitis. J Peditr. 1984;105(5): Frnsen L, Vn den Berghe P, Mertens A, Vn Brussel K, Clr R, Piot P. Incidence nd bcteril etiology of neontl conjunctivitis. Eur J Peditr. 1987;146(2): Di Brtolomeo S, Mirt DH, Jner M, et l. Incidence of Chlmydi trchomtis nd other potentil pthogens in neontl conjunctivitis. Int J Infect Dis. 2001;5(3): Persson K, Ronnerstm R, Svnberg L, Pohl MA. Neontl chlmydil eye infection: n epidemiologicl nd clinicl study. Br J Ophthlmol. 1983;67(10): Kolder ME, Thiesbrummel HFJ, Peetm E. Yer Report STD Clinic Amsterdm, Netherlnds: Municipl Helth Services Amsterdm; Hmmerschlg MR. Neontl conjunctivitis. Peditr Ann. 1993; 22(6): Stenberg K, Mrdh PA. Chlmydil conjunctivitis in neontes nd dults: history, clinicl findings nd follow-up. Act Ophthlmol (Copenh). 1990;68(6): Hmmerschlg MR, Chndler JW, Alexnder ER, English M, Koutsky L. Longitudinl studies on chlmydil infections in the first yer of life. Peditr Infect Dis. 1982;1(6): Hmmerschlg MR, Gelling M, Roblin PM, Kutlin A, Jule JE. Tretment of neontl chlmydil conjunctivitis with zithromycin. Peditr Infect Dis J. 1998;17(11): Loenen AC. Frmcotherpeuticl Kompss. Amstelveen, Netherlnds: Helth Cre Insurnce Bord; Ptmsucon P, Rettig PJ, Fust KL, Kusmiesz HT, Nelson JD. Orl v topicl erythromycin therpies for chlmydil conjunctivitis. Am J Dis Child. 1982;136(9): e326 ROURS et l