Outbreak of Paralytic Poliomyelitis in a Highly Immunized Population in Jordan

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1 862 Outbreak f Paralytic Plimyelitis in a Highly Immunized Ppulatin in Jrdan Mary R. Reichler, Adnan Abbas,* Sa'ad Kharabsheh, Azmi Mahafzah, James P. Alexander, Jr., Philip Rhdes, Samir Fauri, Haider Otum, Samir Blch, Mazen Abdel Majid, Mick Mulders, Rafi Aslanian, Harry F. Hull, Mark A. Pallansch, and Peter A. Patriarca* Pli Eradicatin Activity and Data Management Branch, Natinal Immunizatin Prgram, and Entervirus Branch, Natinal Center fr Infectius Diseases, Centers fr Disease Cntrl and Preventin, Atlanta, Gergia; Disease Preventin and Cntrl Directrate and Jrdan Vaccine Institute, Ministry fhealth, Department flabratry Medicine, Jrdan University Hspital, and Department fpediatrics, Al Bashir Hspital, Amman, Jrdan; Labratry f Virlgy, Natinal Institute fr Public Health and Envirnmental Prtectin (RIVM), Bilthven, Netherlands; Eliminatin and Eradicatin fdiseases, Eastern Mediterranean Reginal Office, Wrld Health Organizatin, Alexandria, Egypt; Glbal Prgramme fr Vaccines and Immunizatin, Wrld Health Organizatin, Geneva, Switzerland Between Nvember 1991 and March 1992, 37 cases f paralytic plimyelitis ccurred in Jrdan, where nne had been reprted since Of these, 17 (%) f 34 patients had received at least three dses f ral plivirus vaccine (OPV3). The first and 2 subsequent case-patients were children f Pakistani migrant wrkers, and the first 8 and a ttal f 27 (7%) case-patients resided in r near the Jrdan Valley. A serepidemilgic study f 987 children in all regins f Jrdan was perfrmed t assess OPV3 cverage and immune respnse t OPV. Althugh OPV3 cverage by 12 mnths f age was high (96%) in the general ppulatin, cverage was lwer amng Pakistani (21%), Beduin (63%), and Gypsy (9%) children (P <.1). Serprevalences fr plivirus type 3 were 71% in the Jrdan Valley versus 81% in ther regins after 3 dses f OPV (P <.6) and 77% in the Jrdan Valley versus 98% in ther regins after dses f OPV (P <.1). This utbreak demnstrates the imprtance f achieving high serimmunity t infectin in all gegraphic areas t prevent the reintrductin and spread f imprted strains f wild plivirus. Paralytic plimyelitis was rapidly eliminated frm industrialized cuntries and its incidence markedly reduced wrldwide nce high cverage with at least three dses f the live attenuated ral plivirusvaccine (OPV) was achieved [1, 2]. Despite high cverage with OPV, sme cuntries experience utbreaks f paralytic plimyelitis caused by imprted strains f wild plivirus several years after indigenus wild plivirus transmissin has ceased [3-]. Strategies t prevent the reintrductin and spread fwild plivirus in pli-free areas are essential t achieve the gal f glbal eradicatin f paralytic plimyelitis, planned fr the year 2. We reprt the results f ur investigatin f an unusual epidemic f paralytic plimyelitis in Jrdan, a cuntry with high OPV cverage and n reprted plimyelitis cases fr Presented in part: 32nd Interscience Cnference n Antimicrbial Agents and Chemtherapy, Anaheim, Califrnia, Octber 1992 (abstract 1723); 34th Interscience Cnference n Antimicrbial Agents and Chemtherapy, Orland, Flrida, Octber 1994 (abstracts J93 and J9). Infrmed cnsent was btained frm the parents f children enrlled in these studies. Reprints r crrespndence: Dr. Mary R. Reichler, Mailstp E-, NIP, CDC, 16 Cliftn Rd., Atlanta, GA * Present affiliatins: Department f Cmmunity Medicine, Jrdan University, Amman, Jrdan (A.A.); Center fr Bilgics Evaluatin and Research, Fd and Drug Administratin, Bethesda, Maryland (P.P.). The Jurnal f Infectius Diseases 1997; 17(8uppl 1): by The University f Chicag. All rights reserved /97/781-12$1. > 3 years. The epidemic ccurred during the winter (the lw seasn fr wild plivirus transmissin) and remained lcalized t ne regin f the cuntry fr several mnths. Large utbreaks fparalytic plimyelitis are infrequent in highly immunized ppulatins, generally ccur during the summer mnths, and are usually assciated with rapid and wide gegraphic spread. In this reprt, we examine the relatinship f unimmunized subppulatins, reginal differences in immune respnse t vaccine, vaccinatin timing, and ther factrs t the risk f epidemic paralytic plimyelitis in a ppulatin with high verall vaccinatin cverage. Backgrund Children in Jrdan receive dses f OPV at 3, 4, -6, and 18 mnths f age. Estimated vaccinatin cverage with three dses f OPV (OPV3) by 1 year f age in Jrdan has been > 8% since 1986 and was estimated in 199 by cluster survey methdlgy t be 92%. Prir t the current utbreak, n cases f plimyelitis had been reprted in Jrdan since mid Althugh Jrdanians cmprise >9% fthe ttal ppulatin in all areas f Jrdan, there are a number f distinct subppulatins: (1) migratry Beduin tribes, fund thrughut Jrdan; (2) migratry agricultural wrkers frm Pakistan, residing in the suthern Jrdan Valley (Octber-April) and rural areas f Amman gvernrate (May-September); and (3) Gypsies, living in and near the Jrdan Valley (Octber-April) and in nrth- Dwnladed frm by guest n 27 December 218

2 JID 1997; 17 (Suppl 1) Pli Outbreak in Jrdan S63 em Jrdan (May-September). In additin, during the 1991 Gulf War..., nn-jrdanians sught temprary refuge in Jrdan and...3, Jrdanians living in Kuwait returned t Jrdan and were resettled thrughut the cuntry. Methds Case ascertainment. All hspitals and health centers in Jrdan were infrmed abut the utbreak:and instructed t reprt all cases facute flaccid paralysis (whether r nt acute plimyelitis was suspected) t the Jrdan Ministry fhealth. All cases were investigated by an expert team and cnfirmed r discarded accrding t standard Wrld Health Organizatin criteria [6]. Virlgy. Stl specimens frm 16 case-patients were prcessed at the Jrdan Vaccine Institute in Amman and the Natinal Institute fr Public Health and Envirnmental Prtectin in Bilthven, Netherlands. Enterviruses were islated and identified as pliviruses r nnpli enterviruses, and intratypic differentiatin was perfrmed n plivirus islates using previusly described techniques [7]. T determine the rigin f the type 1 wild pliviruses linked t the Jrdan utbreak, we perfrmed partial genmic sequencing f 8 f 9 utbreak strains and cmpared data frm these strains with a database cntaining nucletide sequences f >2 type 1 wild pliviruses islated between 197 and 1992 frm the Middle East, Africa, Asia, Nrth America, and Suth America, using previusly described techniques [3, 8-1]. Serepidemilgic studies. T evaluate the gegraphic extent f spread f wild plivirus during the utbreak and t determine the immune state f children in different regins f Jrdan, we btained sera frm the fllwing grups f children in the furth mnth f the utbreak (February 1992), prir t the first natinwide mass campaign: (1) 428 cntrl children frm 12 twns in the Jrdan Valley (the regin with the highest paralytic attack rate), including children frm 6 twns with and 6 twns withut detected cases; (2) 43 cntrl children frm Safi (lcated in the Gre Valley [4 kilmeters suth f the Jrdan Valley], where n cases were detected); (3) 23 cntrl children frm the 8 gvernrates in Jrdan (Amman, n = 71; Irbid, n = 43; Zarka, n = 39; Balka, n = 14; Mafraq, n = 11; Karak, n = 9; Tafila, n = 9; and Ma'an, n = 7), excluding Jrdan Valley districts; (4) 12 Pakistani (n = 62), Beduin (n = 18), and Gypsy (n = 22) children living in r near the Jrdan Valley; and () 17 case-patients ~21 days after paralysis nset (11 wh had received three r mre dses f OPV [fully immunized] and 6 wh had received n OPV dses [unimmunized] r ne t tw OPV dses [partially immunized] at least 21 days prir t paralysis nset) (figure 1). Since expsure t wild plivirus type 1 had already ccurred in parts f Jrdan, we measured antibdy t plivirus type 3 t assess immune respnse t OPV at the time f the utbreak. T examine the immune state f children in different regins fjrdan fllwing tw natinwide mass campaigns, we btained sera 6 weeks after the secnd campaign (May 1992) frm 198 cntrl children frm all 8 gvernrates in Jrdan, all f whm had received bth mass campaign dses f OPV. T determine the immune state f children in different regins f Jrdan at baseline (in the absence f wild plivirus circulatin), we btained sera in December 1993 and January 1994 frm the fllwing grups f children brn after the utbreak: (1) 74 cntrl children frm 2 twns in the Jrdan Valley (38 frm Abu-Obeideh and 36 frm Almashara); (2) 4 cntrl children frm Safi; (3) 4 cntrl children frm Amman gvernrate; and (4) 4 cntrl children frm Zarka gvernrate (figure 1). All cntrl children frm twns in the Jrdan Valley and Safi were a cnvenience sample selected accrding t a histry (dcumented by vaccinatin card) f having received three r mre dses f OPV at least 21 days prir t serum cllectin and age mnths at the time f serum cllectin. All cntrl children frm Jrdan gvernrates were a cluster survey sample selected accrding t a histry (dcumented by vaccinatin card) f having received three OPV dses thrugh the rutine prgram at least 3 days prir t serum cllectin and age 7-12 mnths at the time f serum cllectin. Pakistani, Beduin, and Gypsy cntrl children represented all children 7-36 mnths f age in these subppulatins that culd be identified in r near the Jrdan Valley at the time the survey was cnducted. All 987 sera frm case-patients and cntrl children enrlled in the serepidemilgic studies were tested in triplicate with a mdified micrneutralizatin technique at the Centers fr Disease Cntrl and Preventin (CDC), in dilutins ranging frm 1/8 t [7]. Immunizatin cverage studies. Written, standardized questinnaires prviding immunizatin infrmatin (dcumented by vaccinatin card) were cmpleted at the time sera were cllected fr all 987 children enrlled in the serepidemilgic studies. Evaluatin fthe cld chain. During the utbreak (January and February 1992), 11 vaccinatin sites (the central stre at the Jrdan Vaccine Institute in Amman and 1 peripheral sites in the JrdanValley) were visited t bserve vaccine strage, handling, and administratin techniques and t review cld-chain maintenance recrds. Vaccine efficacy. Using a standard frmula [11], we estimated the efficacy f three r mre dses f OPV administeredthrughthe rutineprgram amng childrenin Jrdan at the time f the utbreak. Statistical analysis. Statistically significant differences in type-specific antibdy titers and vaccinatin timing amng the varius grups f children were assessed with a nnparametric test (Wilcxn rank sum test) using SAS (Cary, NC) sftware. Results Outbreak. Between Nvember 1991 and March 1992, 37 cases f paralytic plimyelitis ccurred in Jrdan (figure 2). Of these patients, 33 (89%) were <36 mnths f age (range, 1-18) and 17 (%) had received at least three dses fopv; (14%) case-patients died. Type 1 wild plivirus was islated frm 9 (6%) f 16 case-patient stl specimens. The first 8 and a ttal f 27 (7%) cases ccurred in the Jrdan Valley (n = 18) r neighbring districts (n = 9) (figure 2). Paralytic attack rates were 13/1 in the Jrdan Valley and./1 utside the Jrdan Valley. Althugh 33 (92%) case-patients were Jrdanian, the first and 2 subsequent case-patients were children f Pakistani migrantwrkers. In the Jrdan Valley, paralytic attack rates were 1111 amng Jrdanians and 86/1 amng Pakistanis. Dwnladed frm by guest n 27 December 218

3 S64 Reichler et al. JID 1997; 17 (Suppl 1) LakeTiberias Gulf f Aqaba Figure 1. Gre Valley Bdies f water e Jrdan Valley and Gre Valley Study sites 2 Km " I I I I i, 2 Miles Map f Jrdan shwing all 8 Jrdan gvernrates and serepidemilgic study sites in Jrdan Valley and Gre Valley. A dr-t-dr vaccinatin campaign targeting all children < years f age with OPV was cnducted in the Jrdan Valley between 29 January and 6 February 1992; estimated vaccinatin cverage was 9%. Since cases cntinued t ccur in February, tw natinwide mass vaccinatin campaigns were cnducted, the first frm 24 February t 2 March and the secnd frm 6 t 13 April; estimated cverage fr bth natinwide campaigns was >9%. Althugh 4 cases ccurred in the 3-week perid fllwing the first natinwide vaccinatin campaign, nne ccurred fllwing the secnd campaign (figure 2). N further labratry-cnfirmed cases f plimyelitis have been reprted in Jrdan thrugh mid Virlgy. Type 1 wild plivirus was islated frm 9 (6%) f 16 case-patient stl specimens. All 8 utbreak islates analyzed by partial genmic sequencing were clsely related t ne anther (98% similarity f the VP1I2A regin), suggesting a recent cmmn rigin. The Jrdan islates were gentypically distinct frm prir wild type 1 pliviruses frm Israel (1988, 7% similarity) and mst ther cuntries in the Middle East but matched islates frm the utbreak in Oman (9% similarity) and a 1992 islate frm Pakistan (98% similarity) [9, 1]. Gegraphic extent fspread fwild plivirus during the utbreak. Vaccinated and unvaccinated case-patients, cntrl children frm twns in the Jrdan Valley with and withut cases, Pakistani cntrl children, and Beduin cntrl children wh had bld samples drawn during the utbreak all had similar type 1 neutralizing antibdy prfiles, suggesting that widespread expsure t wild plivirustype 1 ccurred in the JrdanValley during the utbreak (figure 3). Althugh serprevalences t plivirus type 1 were similar fr Jrdan Valley cntrls and nn-jrdan Valley gvernratecntrls wh had bld samples drawn during the utbreak(94% and 97%, respectively),titerswere significantly higher amng Jrdan Valley cntrls (gemetric mean titers f 898 vs. 616 [P <.], respectively), suggesting that expsure t wild plivirus was greater inside than utside the Jrdan Valley (figure 3). Dwnladed frm by guest n 27 December 218

4 JID 1997;17 (Supp11) Pli Outbreak in Jrdan S , N=37 - (I) <V (I) «S U- ~ <V. E:::J Z DOutside Jrdan Valley ffiilll Near Jrdan Valley In Jrdan Valley Oct Nv Dec Jan Feb Time (Weeks) - ~ r-- - r-- I I I I March April 1992 Figure 2. Cases f paralytic plimyelitis in Jrdan by gegraphic regin and week f nset. Of 37 cases, first 8 and ttal f 27 (7%) ccurred in Jrdan Valley (N; n = 18) r neighbring districts (n = 9). Arrws indicate timing f 4 mass vaccinatin campaigns, 2 limited t Jrdan Valley and 2 cnducted natinwide. Whereas cases cntinued t ccur fllwing first Jrdan Valley mass vaccinatin campaign, very few cases ccurred fllwing first natinwide campaign. Figure 4 presents the neutralizing antibdy prfiles fr children in selected twns inside and utside the Jrdan Valley wh had bld samples drawn during (figure 4A) versus after (figure 4B) the utbreak. Titers were significantly lwer in Jrdan Valley cntrls wh were brn and had bld samples drawn after the utbreak than in thse wh had bld samples drawn during the utbreak. Titers were als cnsistently lwer amng cntrls utside the Jrdan Valley wh were brn and had bld samples drawn after the utbreak cmpared with thse wh had bld samples drawn during the utbreak, suggesting that wild plivirus type 1 had already spread t at least sme areas utside the Jrdan Valley prir t the first natinwide mass campaign. Immune state f children in different regins f Jrdan. As illustrated in figure, the immune respnse t OPV was cnsistently lwer amng cntrl children in the Jrdan Valley than amng thse in ther regins f Jrdan. Serprevalence rates after three dses f OPV fr plivirus type 3 were 71% in the Jrdan Valley versus 81% (range, 64%-1%) amng gvernrate cntrls in ther regins (P <.6). Serprevalence rates after five dses f OPV fr plivirus type 3 were 77% in the Jrdan Valley versus 98% (range, 92%-1%) in ther regins (P <.1). Regins with higher paralytic attack rates were mre likely t have lwer serprevalence rates fr plivirus type 3 after three and five dses f OPV (figure ). In additin, the increase in serprevalence rates after five versus three dses f OPV fr plivirus type 3 was significantly smaller in the Jrdan Valley cmpared with ther regins (6% vs. 17%, respectively; P <.1). Immunizatin cverage studies. There was n assciatinbetween paralytic attack rate and OPV vaccinatin cverage, which ranged frm 96% t 1% by regin. Althugh survey children in the general ppulatin in the Jrdan Valley were selected n the basis f having received at least three dses f OPV, this is unlikely t represent a significant bias tward higher cverage estimates in this regin, since very few partially immunized r unimmunized children were identified during the survey. Figure 6 presents the timing f OPV receipt amng cntrls in the general ppulatin and Pakistani, Gypsy, and Beduin subppulatins in the Jrdan Valley. Althugh OPV3 cverage by 12 mnths f age was high amng children in the general ppulatin residing in the Jrdan Valley (96%), cverage was lwer amng Pakistani (21%), Beduin (63%), and Gypsy (9%) children (P <.1, cmparing general ppulatin and Pakistani children, general ppulatin and Beduin children, and general ppulatin and Gypsy children). Delays in cmpleting OPV3 ccurred in all grups in the Jrdan Valley surveyed: Only 71% f general ppulatin, 37% f Beduin, 3% fpakistani, and n Gypsy children had received OPV3 n schedule, by 6 mnths f age (figure 6). Althugh cverage at 12 mnths f age was similar fr children in the general ppulatin residing inside and utside the Jrdan Valley (96% vs. 1%, respectively), vaccinatin de- Dwnladed frm by guest n 27 December 218

5 S66 Reichler et al. lid 1997; 17 (Suppl 1) 7 Cases 6 (n=17) <8 8 Inside Jrdan Valley 1 twnswith cases (n=217) < >124 Inside Jrdan Valley 1 twns withut cases (n=211) < >124 II~Opv Titer 3 Pakistani 2 (n=62) <3PV < >124 Beduin (n=18) < >124 Outside Jrdan Valley (n=23) < >124 Figure 3. Serprevalence f neutralizing antibdy t plivirus type 1 amng case-patients and cntrls during utbreak ftype 1 paralytic plimyelitis in Jrdan. Vaccinated and unvaccinated case-patients, cntrl children inside and utside Jrdan Valley, and Pakistani and Beduin cntrl children wh had bld samples drawn during utbreak all had similar type 1 neutralizing antibdy prfiles. Dwnladed frm by guest n 27 December 218 lays were significantly greater amng children inside the Jrdan Valley (71% inside vs. 87% utside had received OPV3 by 6 mnths f age; P <.1) (data nt shwn). Regins in Jrdan with higher paralytic attack rates tended t have greater delays in cmpleting OPV3 (data nt shwn) Evaluatin fthe cld chain. N abnrmalities in vaccine strage r handling were nted in the central stre in Amman r in peripheral sites in the Jrdan Valley. Vaccine efficacy. Vaccine efficacy was estimated t be 96% verall in Jrdan, with separate estimates f 94% inside and 98% utside the Jrdan Valley. Discussin The plimyelitis utbreak in Jrdan ccurred fllwing imprtatin f wild plivirus int an area that had

6 JID 1997;17 (Suppll) Pli Outbreakin Jrdan Almashara A Almashara B (n=34) 1 1 (n=36) < >124 < > Abu Obeideh A Abu Obeideh B 2 (n=34) 2 (n=38) , CD ;; > c..., Amman A Amman B.- 2 < < ~ (n=71) (n=4) tn 2 2 ( , 1 C e... < > Zarka A Zarka B Z 1 (n=39) 1 (n=4) < < >124 < > Safi A 3 Safi B 2 (n=43) 2 (n=4) Dwnladed frm by guest n 27 December 218 < Titer < Figure 4. Serprevalence f neutralizing antibdy t plivirus type 1 amng cntrls frm selected twns inside and utside Jrdan Valley wh had bld samples drawn during (A) vs. thse wh were brn and had bld samples drawn after (B) utbreak f type 1 paralytic plimyelitis. Titers were cnsistently lwer amng cntrls inside and utside Jrdan Valley wh were brn and had bld samples drawn after utbreak cmpared with thse wh had bld samples drawn during utbreak.

7 S68 Reichler et al. JID 1997;17 (Suppll) :.p > 'en a. l- 4 (I) 3 C:~ ~ - /~...- <, '------r---r ~ lj~ ''3-~ ~flj. ~~*'3-3 dses f OPV dses f OPV (I) l- c 9 ~ LO v 7 c: l- :Q 6 :E 4 3 s ::: Figure. Prprtin f children with neutralizing antibdies t plivirus type 3 after 3 and dses f ral plivirus vaccine (OPY) and attack rates fparalytic plimyelitis by regin in Jrdan. Serprevalence rates after 3 dses f OPY fr plivirus type 3 were 71% in Jrdan Valley vs. 81% (range, 64%-1%) amng cntrls in ther regins (P <.6). Serprevalence rates after dses f OPV fr plivirus type 3 were 77% in Jrdan Valley vs. 98% (range, 92%-1%) in ther regins (P <.1). Statistical cmparisns were made with Wilcxn rank sum tests using SAS (Cary, NC) sftware. been pli-free fr several years. A gradual build-up fsusceptibles likely ccurs even in a highly immunized ppulatin nce endemic wild plivirus transmissin has ceased. Despite this, utbreaks rarely ccur if high levels f vaccinatin cverage are maintained. Our investigatin identified several factrs that greatly increased the number f susceptibles in the Jrdan Valley, thus cntributing t the utbreak. While cverage with at least three dses f OPV was very high amng children in the general ppulatin in all areas f Jrdan at the time fthe utbreak, there were 3 separate migratry subppulatins in the Jrdan Valley whse vaccinatin levels were cnsiderably lwer: children f Pakistani migrant wrkers, Gypsies, and Beduins. The initial case in the utbreak ccurred in a Pakistani child, and the attack rate in this subppulatin was 8-fld higher than amng children in the general ppulatin in the Jrdan Valley. The ptential fr wild plivirus transmissin t be sustained within pckets f unvaccinated children with subsequent spread t fully vaccinated children is well established [12, 13]. Thus, the intrductin and spread f wild plivirus by unimmunized migratry grups likely cntributed t infectin in the highly immunized general ppulatin in Jrdan. Althugh cverage with at least three dses f OPV by 12 mnths f age was high, fewer than three-quarters f children in the general ppulatin in the Jrdan Valley had received these dses n schedule, by 6 mnths f age. Furthermre, even greater delays in receipt f OPV dses ccurred fr Pakistani, Gypsy, and Beduin children. Thus, delays in cmpleting the OPV schedule amng children in the Jrdan Valley substantially increased the pl f unvaccinated children susceptible t plivirus infectin, likely increasing transmissin. Achieving high cverage with at least three dses f OPV in a timely fashin is imprtant t prvide sufficient ppulatin immunity t stp transmissin if reintrductin f wild plivirus ccurs. Reginal differences in antibdy respnses t OPV were present in Jrdan at the time f the utbreak despite high cverage with three dses f OPV in all regins. In the Jrdan Valley, serprevalence rates t plivirus type 3 after three and five dses f OPV were significantly lwer than in ther regins f the cuntry. Thus, subptimal immune respnse t as many as five dses f OPV amng children in the general ppulatin in the Jrdan Valley prduced a gap in immunity that als cntributed t spread f an imprted wild plivirus strain during the utbreak. Reginal variatin in immune respnse t OPV has als been nted in Oman, where utbreaks due t imprted strains fwild plivirus have been a recurrent prblem [3, 14]. Althugh risk factrs fr subptimal immune respnse t OPV culd nt be evaluated in the current study, factrs assciated with lw serprevalence in ther studies include residence in trpical and subtrpical areas; lw sciecnmic status; and diarrhea, nnpli entervirus infectin, r ther enteric Dwnladed frm by guest n 27 December 218

8 JID 1997;17 (Suppl 1) Pli Outbreakin Jrdan S69 1, Figure 6. Cumulative cverage with at least 3 dses f ral plivirus vaccine (OPV3) by mnth f age amng cntrls in general ppulatin and Pakistani, Gypsy, and Beduin subppulatins in Jrdan Valley. Althugh OPV3 cverage by 12 mnths f age was high amng Jrdanian children, cverage was lwer amng Pakistani, Beduin, and gypsy children. Delays in cmpleting OPV3 ccurred in all grups surveyed. Q! 6 ~ e ~ 4 infectins at the time OPV is administered [1-18]. At the time f the Jrdan utbreak, the sciecnmic status amng residents f the Jrdan Valley was generally cnsiderably lwer than in mst ther areas f Jrdan. Crwding and pr sanitatin, assciated with rapid spread f plivirus and ther enteric pathgens, were present in a number f areas in the Jrdan Valley. Furthermre, the Jrdan Valley is ne f nly tw areas in Jrdan with a subtrpical rather than an arid r temperate climate. Thus, many f the risk factrs fr subptimal immune respnse t OPV identified in ther settings were present in the Jrdan Valley at the time f the utbreak. The Jrdan utbreak was assciated with a 2-fld higher paralytic attack rate in the Jrdan Valley than in ther regins f the cuntry. Our investigatin findings suggest that at least three factrs-the presence f unimmunized subppulatins, delays in receipt f OPV, and lwer immune respnse t OPV in the Jrdan Valley cmpared with ther regins f the cuntry-likely cntributed t the high attack rate in that regin. In additin, the seasnal migratin fall three underimmunized subppulatins (Pakistanis, Beduins, and Gypsies) t the Jrdan Valley in the mnth prir t the utbreak may have been assciated with the initial intrductin and spread fwild plivirus in that regin. Furthermre, gegraphic and climatic factrs-a steep muntain range separating the Jrdan Valley frm ther areas f the cuntry and an unusually severe winter, with blizzards restricting travel t and frm the Jrdan Valley n three separate ccasins-likely played a rle in limiting the spread f wild plivirus during the utbreak. By cntrast, wild plivirus spread was mre limited and resulted in largely subclinical infectin in areas f the cuntry with high serprevalences fantibdies t pliviruses. In Safi,... 2 "' Age (mnths) Jrdanian Beduin Pakistani Gypsy a twn utside the Jrdan Valley where subptimal immune respnse t vaccine was als demnstrated, wild plivirus spread appeared t be mre extensive. Althugh the reasns fr largely subclinical infectin in mst areas utside the Jrdan Valley are unclear, ur findings suggest that high ppulatin serimmunity may have resulted in predminantly silent transmissin f wild plivirus utside the Jrdan Valley. A mass vaccinatin campaign limited t the Jrdan Valley and nearby areas during the third mnth f the utbreak did nt prevent wild plivirus spread t ther areas fthe cuntry. By cntrast, very few paralytic cases ccurred fllwing a natinwide mass vaccinatin campaign launched in the furth mnth f the utbreak, despite evidence that wild plivirus had already spread beynd the Jrdan Valley t ther areas f Jrdan. Since the natinwide campaign was launched late in the utbreak and at a time when cases had already begun t decline, its true impact is unclear. An alternative explanatin fr interruptin f wild plivirus transmissin during mnth f the Jrdan utbreak is that high preexisting serimmunity t infectin amng children in mst areas utside the Jrdan Valley limited the curse fthe utbreak. Thus, wild plivirus transmissin may have ceased as a result f exhaustin f the pl f susceptibles rather than as a result f the natinwide mass campaign. Gentypic studies prvide clear evidence that the utbreak strain was imprted [9, 1]. Clser hmlgy f the Jrdan strain with a Pakistan strain than with the Oman utbreak strain suggests that this represents a separate intrductin frm Pakistan rather than spread frm a fcus in the Middle East. Althugh a direct epidemilgic linkage culd nt be established, the gentypic findings, tgether with the ccurrence f Dwnladed frm by guest n 27 December 218

9 S7 Reichler et al. TID 1997;17 (Suppll) the first case in the utbreak amng Pakistani migrant wrkers, suggest that imprtatin may have ccurred directly int this cmmunity. In recent years, wild pliviruses imprted frm the India Pakistan subcntinent have been assciated with utbreaks in Oman [3], Malaysia [4], Netherlands [], and nw Jrdan. T prevent recurrent imprtatin, the best lng-term slutin is t eradicate wild plivirus reservirs in pli-endemic cuntries that are majr exprters f wild plivirus, including Pakistan and India. A nearly 8% reductin in reprted plimyelitis. cases in Pakistan fllwing natinal immunizatin days (NIDs) in 1994 [19, 2] and India's recent cmmitment t cnduct NIDs in 199 and 1996 prvide hpe that the risk f imprtatin will be reduced in the near future. The reintrductin and spread f wild plivirus in the Jrdan Valley and subsequently in ther areas f Jrdan demnstrates the imprtance fachieving high serimmunityt infectin in all gegraphic areas t prevent utbreaks caused by imprted strains f wild plivirus. Until glbal eradicatin f plimyelitis is accmplished, supplementing rutine immunizatin with mass campaign dses fopv-which are believed t be mre immungenic than OPV delivered thrugh the rutine prgram [21, 22]-and achieving high OPV cverage in all cmmunity subppulatins in a timely fashin may be effective means f ensuring unifrmly high ppulatin serimmunity t infectin. Acknwledgments Weare indebted t Atef Batyneh fr encuragement and supprt; Nadjwa Khuri-Buls fr assistance in evaluating suspected plimyelitis cases; Ali Assad, Bassam Hijawi, and physicians frm the Health Directrates in the Jrdan Valley fr assistance in cnducting fieldwrk fr the serepidemilgic studies; Snia Russell and Barbara Rice fr graphics assistance; and Peter Bing fr helpful cmments n the manuscript. References 1. Paul JR. A histry f plimyelitis. New Haven: Yale University Press, Strebel PM, Sutter RW, Cchi SL, et al. Epidemilgy f plimyelitis in the United States ne decade after the last reprted case f indigenus wild virus-assciated disease. Clin Infect Dis 1992; 14: SutterRW, PatriarcaPA, Brgan S, et al. Outbreakf paralytic plimyelitis in Oman. Evidence fr widespread transmissin amng fully vaccinated children. Lancet 1991;338: Centers fr Disease Cntrl and Preventin. Prgress tward glbal eradicatin f plimyelitis, MMWR 1994;43: Ostvgel PM, van WijngaardenJK, van der Avrt HG, et al. Plimyelitis utbreak in an unvaccinated cmmunity in the Netherlands, Lancet 1994;344: Hull HF, Ward NA, Hull BP, Milstien JB, de Quadrs C. Paralytic plimyelitis: seasned strategies, disappearing disease. Lancet 1994; 343: Melnick JL, Wenner HA, Phillips CA. Enterviruses. In: Lennette EH, Schmidt NJ, eds. Diagnstic prcedure fr viral, rickettsial, and chlamydial infectins. Washingtn DC: American Public Health Assciatin, 1979: Ric-Hesse R, Pallansch MA, Nttay BK, Kew OM. Gegraphic distributin f wild plivirus type 1 gentypes. Virlgy 1987; 16: Mulders MN, Lipskaya GY, van der Avrt HGAM, Kpmans MPG, Kew OM, van Ln AM. Mlecular epidemilgy f wild plivirus type 1 in Eurpe, the Middle East, and the Indian subcntinent. J Infect Dis 199;171: Huvilainen A, Mulders M, Agbatwalla M, Pyry T, Stenvik M, Hvi T. Genetic divergence f plivirus strains islated in the Karachi regin f Pakistan. J Gen Virl 1996; 76: Orenstein WA, Bernier RH, Dnder TJ, et al. Field evaluatin f vaccine efficacy. Bull WHO 198;63: Wrld Health Organizatin. Expanded Prgramme n Immunizatin. Plimyelitis utbreak, Bulgaria. Wkly Epidemil Rec 1992;67: Strebel P, Aubert-Cmiescu A, ln-nedelcu N, et al. Paralytic plimyelitis in Rmania, : evidence fr a high risk f vaccine assciated disease and reintrductin f wild-virus infectin. Am J Epidemil 1994; 14: Sutter RW, Patriarca PA, Suleiman AJ, et al. Paralytic plimyelitis in Oman: assciatin between reginal differences in attack rate and variatins in antibdy respnses t ral plivirus vaccine. lnt J Epidemil 1993; 22: Jhn TJ, Jayabal P. Oral plivirus vaccinatin in the trpics. The pr sercnversin rates and the absence fviral interference. Am J Epidemil 1972;96: Pangi NS, Master JM, Dave KH. Efficacy f ral pli vaccine in infancy. Indian Pediatr 1977; 14: Mahmud AA, Imam IZ, Abuzid SS, Mished AME, Mitkis FA. The influence f bacillary dysentery n the efficacy f ral plivaccine in Egypt. Gazette Egyptian Paediatr Assc 1976;24: Lebarn C, Linkins R, Glass R, et al. Reductin in the immungenicity f ral plivirus vaccine (OPV) fllwing rtavirus infectin: preliminary evidence frm Brazil [abstract]. In: Prgram and abstracts f the 34th Interscience Cnference n Antimicrbial Agents and Chemtherapy (Orland). Washingtn, DC: American Sciety fr Micrbilgy, 1991: Wahdan MH, Aslanian R, Reichler MR, Gaafar M. Prgress tward plimyelitis eradicatin in the Eastern Mediterranean Regin f the Wrld Health Organizatin. J Infect Dis 1997(suppl 1); 17:S-. 2. Reichler MR, Aslanian R, Ldhi ZH, et al. Evaluatin f ral plivirus vaccine delivery during the 1994 natinal immunizatin days in Pakistan. J Infect Dis 1997(suppl 1); 17:S Reichler MR, Kharabsheh S, Rhdes P, et al. Increased immungenicity f ral plivirus vaccine administered in mass vaccinatin campaigns cmpared with the rutine vaccinatin prgram in Jrdan. J Infect Dis 1997(suppl 1); 17:S Richardsn G, Linkins R, Eames M, et al. Immungenicity fral plivirus vaccine administered in mass campaigns versus rutine immunizatin prgrams. Bull Wrld Health Organ 199;73: Dwnladed frm by guest n 27 December 218