Krugman's Infectious Diseases of Children 11th edition (September 18, 200 !

by Anne Gershon (Editor), Peter Hotez (Editor), Samuel Katz (Editor) By Mosby By Ok oKe!

Chapter " # $%$&'(S ()*CK+&,! &'D '%*'&$&) $%$&'(S

Catherine ,ilfert -eter .ote/ Clostridium tetani "rodu#es a "otent, soluble e$oto$in that is res"onsible %or the #lini#al mani%estations o% tetanus& 'etanus, or (lo#k)a*,+ is an a#ute to$emia #hara#terized by toni# s"asms o% ,oluntary mus#les and a hi-h %atality rate& C. tetani in%e#tion usually o##urs at a break in the skin, *hi#h may be tri,ial or unre#o-nized, but the in%e#tion also #an #om"li#ate burns, "uer"eral in%e#tions, and in%e#tions o% the umbili#al stum" (tetanus neonatorum) and #an o##ur a%ter #ertain sur-i#al o"erations, in *hi#h the sour#e o% in%e#tion may be #ontaminated sutures, dressin-s, or "laster& 'he illness be-ins *ith toni# s"asms o% the skeletal mus#les and is %ollo*ed by "aro$ysmal #ontra#tions& 'he mus#le sti%%ness in,ol,es the )a* (lo#k)a*) and ne#k %irst and later be#omes -eneralized& .n the /nited States, %e*er than 01 #ases ha,e been re"orted annually %or the "ast 2 years& Ho*e,er, in de,elo"in#ountries tetanus is a leadin- #ause o% death in #hildhood& 'he 3orld Health Or-anization estimates that in 4555 there *ere 677,111 deaths %rom tetanus, most o% *hi#h o##urred durin- the neonatal "eriod (neonatal tetanus 89':)& 9' is one o% the *orld;s leadin- killers o% in%ants& More than one<hal% o% the deaths resultin- %rom 9' o##ur in South Asia&

%$I*)*01
'he tetanus ba#illus is a lon-, thin (= to 2 >m ? 6 to @ >m), motile, -ram<"ositi,e anaerobi# rod& Older #ultures o% these or-anisms and smears %rom *ounds %reAuently stain as -ram<ne-ati,e mi#robes, and this result may be #on%usin- to the uninitiated& 'hese or-anisms may de,elo" a terminal s"ore that does not take the Gram stain and -i,es the ba#terium a drumsti#k a""earan#e& 'he s"ores are ,ery resistant to heat and the usual antise"ti#s, and they may "ersist in tissues %or many months in a ,iable, althou-h dormant, state& /nder anaerobi# #onditions the or-anisms are easily isolated on blood a-ar or in #ooked meat broth& 'he or-anism does not %erment #arbohydrates, does not usually liAue%y -elatin, and "rodu#es little #han-e in litmus milk& 'he ba#illi are *idely distributed in soilB street dustB and the %e#es o% some horses, shee", #attle, do-s, #ats, rats, -uinea "i-s, and #hi#kens& ConseAuently, manure<#ontainin- soil may be hi-hly in%e#tious& .n a-ri#ultural areas a si-ni%i#ant number o% normal human adults may harbor the or-anisms, and a-ri#ultural *orkers ha,e a hi-her in#iden#e o% in%e#tion& 'he s"ores ha,e also been %ound in #ontaminated heroin& 'etanus ba#illi "rodu#e a "otent neuroto$in that is one o% the most to$i# substan#es kno*nB the mouse D 21 o% hi-hly "uri%ied "re"arations is bet*een 1&4 and 4 n-Ek- ( S#hia,o et al&, 4552 )& 'etanus neuroto$in deri,es its "oten#y by ,irtue o% its absolute s"e#i%i#ity %or neuronal #ells and its tar-et intra#ellular #atalyti# a#ti,ity& .t

resembles other #lostridial neuroto$ins in that the mole#ule is synthesized as a sin-le ina#ti,e "oly"e"tide #hain o% 421 k a *ithout a leader seAuen#eF Gelease o% the neuroto$in o##urs as a #onseAuen#e o% ba#terial lysis in the host& E$"osure and #lea,a-e o% a "rotease<sensiti,e loo" *ithin the mole#ule -enerates an a#ti,e heterodimer #om"osed o% a 411<k a hea,y #hain and a 21<k a li-ht #hain )oined by a disul%ide bond& 9e* e,iden#e su--ests that the li-ht #hain is #atalyti#ally a#ti,e as a zin# metallo"rotease& On#e inside the host tar-et #ell the metallo"rotease de-rades s"e#i%i# "rotein #om"onents o% the host neuroe$o#ytosis a""aratus& 'he ma)or "rotease substrates are membrane "roteins o% syna"ti# ,esi#les, in#ludinsyna"tobre,in (also #alled HAMP), S9AP<=2, and synta$in&
"2"

-&$.*0%'%SIS
'he "ortal o% entry is usually the site o% a minor "un#ture *ound or s#rat#h, and the or-anism #an "roli%erate only i% the o$idation<redu#tion (Eh) "otential is lo*er than that o% normal li,in- tissues& ee" "un#ture *ounds, burns, and #rush or other in)uries that "romote %a,orable #onditions %or the -ro*th o% anaerobi# or-anisms may be %ollo*ed by tetanus& O##asionally, no a""arent "ortal o% entry #an be %ound& /nder these #ir#umstan#es the site o% in%e#tion may ha,e been the alimentary tra#t& 3hen #onditions are %a,orable, the ba#illi multi"ly at the site o% "rimary ino#ulation and "rodu#e to$in& 'o$in then tra,els #entri"etally in the a$o"lasm o% the al"ha motor %ibers and a##umulates in the motor neurons in the membrane<bound endo"lasmi# reti#ulum& .n 451=, Marie and Mora$ "ro"osed this route o% a##ess o% to$in to the #entral ner,ous system, as did Meyer and Gansome in 4516 & .t *as sho*n e$"erimentally that to$in *as not lethal i% the lo#al motor ner,es *ere se,ered& 'o$in is neutralizable *hen it is %ree and is only "artially neutralizable *hen it is on the #ell sur%a#e& Pino#ytosis, internalizin- the to$in, renders it nonneutralizable& 'hus, %i$ation o% to$in to ner,es and its internalization result in irre,ersible e%%e#ts& Clea,a-e o% host neuronal #ell membrane "roteins by the #atalyti#ally a#ti,e neuroto$in results in a "ersistent and sustained blo#kade o% neuroe$o#ytosis& 'he neuronal blo#kade then results in the un#ontrolled s"read o% im"ulses, hy"erre%le$ia, and #onstant mus#le #ontra#tion& 'he stron-est mus#les, usually e$tensors, e$ert the -reatest e%%e#ts& 'he to$in also a%%e#ts the sym"atheti# ner,ous system&

-&$.*)*01
'here are no s"e#i%i# "atholo-i# lesions #aused by the in%e#tious a-ent or to$in& Se#ondary e%%e#ts o% the mus#ular #ontra#tions may in#lude ,ertebral %ra#tures, "neumonia, and hemorrha-es into the mus#les&

C)I'IC&) 3&'I4%S$&$I*'S
'he in#ubation "eriod is ,ariable, *ith a usual ran-e o% 2 to 4I daysB ho*e,er, it may be as short as 4 day or as lon- as 6 or more *eeks& 'he a""earan#e o% the site o% in%e#tion, i% ob,ious, "ro,ides no #lue to the im"endin- to$emia& 'he disease be-ins insidiously, *ith "ro-ressi,ely in#reasin- sti%%ness o% the ,oluntary mus#lesB -enerally, the mus#les o% the )a* and ne#k are in,ol,ed %irst& 3ithin =I to I@ hours a%ter the onset o% the disease, ri-idity may be %ully de,elo"ed and may s"read

ra"idly to in,ol,e the trunk and e$tremities& 3ith s"asm o% the )a* mus#les, trismus (lo#k)a*) de,elo"s& 'he *rinklin- o% the %orehead and distortion o% the eyebro*s, and the an-les o% the mouth "rodu#e a "e#uliar %a#ial a""earan#e #alled risus sardonicus (sardoni# -rin)& 'he ne#k and ba#k be#ome sti%% and ar#hed (o"isthotonos)& 'he abdominal *all is boardlike, and the e$tremities are usually sti%% and e$tended& Pain%ul "aro$ysmal s"asms that "ersist %or a %e* se#onds or se,eral minutes may be "ro,oked by the most tri,ial kind o% ,isual, auditory, or #utaneous stimuli, su#h as bri-ht li-hts, sudden noises, and mo,ement o% the "atient& Gisus sardoni#us and o"isthotonos are most marked durin- these s"asms& .nitially the s"asms o##ur at in%reAuent inter,als, *ith #om"lete rela$ation bet*een atta#ks& Dater the s"asms o##ur more o%ten and are more "rolon-ed and more "ain%ul& .n,ol,ement o% the mus#les o% res"iration, laryn-eal obstru#tion #aused by laryn-os"asm, or a##umulation o% se#retions in the tra#heobron#hial tree may be %ollo*ed by res"iratory distress, as"hy$ia, #oma, and death& .n,ol,ement o% the bladder s"hin#ter leads to urinary retention& 'he mani%estations o% sym"atheti# ner,ous system in,ol,ement may in#lude labile hy"ertension, ta#hy#ardia, "eri"heral ,aso#onstri#tion, #ardia# arrhythmias, "ro%use s*eatin-, hy"er#a"nia, in#reased urinary e$#retion o% #ate#holamines, and late< a""earin- hy"otension& urin- the illness the "atient;s sensorium is usually #lear& 'he %e,er is -enerally lo* -rade or absent& Patients *ho re#o,er are usually a%ebrile& A%ter a "eriod o% *eeks the "aro$ysms de#rease in %reAuen#y and se,erity and -radually disa""ear& Generally, the trismus is the last sym"tom to subside& Patients *ith %atal disease are usually %ebrile, *ith death o##urrin- in most instan#es be%ore the tenth day o% illness& 'he s"inal %luid in "atients *ith tetanus is normal& 'he "eri"heral *hite blood #ell #ount may be normal or sli-htly ele,ated& Most "atients *ith tetanus sho* the -eneralized mani%estations des#ribed "re,iously& O##asionally, ho*e,er, -eneralized tetanus may be "re#eded by #e"hali# tetanus& .n this #ase the in#ubation "eriod is only 4 to = daysB it %ollo*s a head in)ury or otitis media, and the "atient has a "oor
"25

"ro-nosis ( Ba-ratuni, 452= )& 'his %orm o% tetanus is #hara#terized by in,ol,ement o% ,arious #ranial ner,es, es"e#ially the se,enth, but the third, %ourth, ninth, tenth, and t*el%th may be a%%e#ted also& Ce"hali# tetanus #an o##ur *ithout subseAuent -eneralized disease& 'eonatal $etanus 'he onset o% 9' usually be-ins *hen the ne*born in%ant is 6 to 41 days old (2&0 J =&@ days in a re#ent re,ie* o% 76 #ases o% 9' in 'urkey 8 !aramis and 'as, =111 :) and is mani%ested by di%%i#ulty in su#kin- and by e$#essi,e #ryin-& Soon the )a* be#omes too sti%% %or the in%ant to su#k, and s*allo*in- be#omes di%%i#ult& Shortly therea%ter, sti%%ness o% the body a""ears, and intermittent )erkin- s"asms may be-in& Hariable de-rees o% trismusB sustained, toni#, or ri-id states o% mus#le #ontra#tionB and s"asms or #on,ulsions o##ur& 'he s"asms o##ur s"ontaneously or in res"onse to stimuli *ith ,ariable %reAuen#y& ee"<tendon re%le$ a#ti,ity may be in#reased, or the dee" tendons may sho* no res"onse durin- testin- be#ause o% #onstant -eneralized sti%%ness& O"isthotonos may be absent or so e$treme that the head almost tou#hes the heels& 'he #ry ,aries %rom a re"eated, short, mildly hoarse #ry to a stran-led<soundin- ,oi#eless noise& 'he "atient;s #olor may be normal, #yanoti#, or

"ale %rom hy"o$ia and im"endin- sho#k& Se,ere s"asms may be %ollo*ed by %la##idity, ano$ia, and e$haustion& Case 1 A 46<day<old male in%ant *as brou-ht to Children;s Hos"ital o% Dos An-eles *ith res"iratory arrest& 'he in%ant *as born at another hos"ital to a -ra,ida 2, "ara 2 mother& On the se#ond day o% li%e, the "atient le%t the other hos"ital& On the tenth day the umbili#al stum" %ell o%% and "urulent draina-e *as obser,ed at the site& On the thirteenth day the in%ant had trismus, *as irritable, and re%used %eedin-s& On the mornin- o% the %ourteenth day, the day o% admission to Children;s Hos"ital, the in%ant *as %ebrile, his body *as ri-id, his res"irations *ere noisy, and he *as droolin-& He had %reAuent s"asms o% the e$tremities and the body tri--ered by e$ternal stimuli& 'he mouth *as lo#ked in an o"en "osition& Ges"irations *ere shallo*, and an ins"iratory rattle *as heard that *as su--esti,e o% laryn-os"asm& Gram<"ositi,e rods and s"ores *ere "resent in "us %rom the umbili#us& 'reatment in#luded human tetanus antito$in ('A')B sur-i#al dKbridement o% the umbili#al stum"B tra#heostomyB redu#tion o% en,ironmental stimuliB and the use o% diaze"am (Halium), me"robamate, "henobarbital, thorazines, and antibioti#s (see belo*)& 'he in%ant re#ei,ed %eedin-s by -a,a-e, and the bladder *as em"tied by CredK;s method& 'he "atient;s #ondition im"ro,ed steadily& S"asms de#reased in %reAuen#y and sto""ed alto-ether a%ter I *eeks& 'he use o% medi#ations *as also dis#ontinued and the "atient *as dis#har-ed a%ter I@ days in the hos"ital& Case 2 A 40<year<old *hite %emale *as admitted to uke /ni,ersity Medi#al Center ( /MC) in Mar#h 4554 be#ause o% )a* ti-htness, ton-ue rollin-, and ne#k sti%%ness o% 4 day;s duration& A""ro$imately 6 *eeks be%ore admission a rusty %ishhook had been #au-ht in her s#al"& She had re#ei,ed no immunizations %or the "ast 41 years& 'he re%errin- "hysi#ian had re#o-nized trismus, o"isthotonos, and risus sardoni#us& He had administered tetanus immune -lobulin, intubated her, and had her trans"orted to /MC& Her tem"erature *as 60&4L C (57L M)B "ulse, 62B res"irations, 40B and blood "ressure, 4=2E01& She *as sedated and "aralyzed *ith "an#uronium (Pa,ulon)& She reAuired res"irator<assisted ,entilation %or 41 days, and she re#ei,ed "arenteral antibioti#s, tetanus immune -lobulin, and tetanus to$oid& 9o ba#terial "atho-ens *ere identi%ied, and there *as no *ound to #ulture& She re#o,ered #om"letely and *as dis#har-ed 47 days a%ter admission&

DI&0'*SIS
'he de,elo"ment o% trismus, risus sardoni#us, -eneralized toni# ri-idity, and s"asms in a "atient *ith a #lear sensorium and a re#ent history o% trauma is hi-hly su--esti,e o% a dia-nosis o% tetanus& 'he re#o,ery o% C. tetani %rom the *ound #on%irms the dia-nosisB ho*e,er, in most instan#es the or-anism is not dete#ted&

DI44%6%'$I&) DI&0'*SIS
Side 6eaction to -henothia/ines Amon- the e$tra"yramidal neurolo-i# syndromes that may a##om"any the use o% some "henothiazine dru-s are a#ute dystoni# rea#tions, *ith %a#ial -rima#in-,

torti#ollis, and mus#le ri-idity& 'hey disa""ear *ith dis#ontinuation o% the dru-& $etan7 .n "atients *ith tetany, trismus is usually absent, but #ar"o"edal s"asms and laryn-os"asm may be "resent& Do* blood #al#ium #ontent #on%irms the dia-nosis& -eritonsillar &bscess Peritonsillar abs#ess, a %ebrile "ain%ul #ondition, usually is a##om"anied by trismus& Ho*e,er, there are no -eneralized mus#ular s"asms& %ncephalitis Patients *ith ,iral and "ostin%e#tious en#e"halitides rarely ha,e trismus, do not ha,e #lear minds as a rule, and usually ha,e abnormal s"inal %luid %indin-s&
"28

6abies Continuous toni# seizures are not "resent in "atients *ith rabiesB the seizures are usually intermittent and #loni#& 'rismus is rarely obser,ed& Str7chnine -oisoning Gela$ation bet*een #on,ulsions is usually #om"lete in "atients *ith stry#hnine "oisonin-& 3hen trismus o##urs, it o##urs late&

C*3-)IC&$I*'S
'he inter%eren#e *ith "ulmonary ,entilation by laryn-os"asm, res"iratory mus#le s"asm, or a##umulation o% se#retions may be %ollo*ed by "neumonia and atele#tasis& Hertebral #om"ression %ra#tures and la#erations o% the ton-ue may %ollo* a seizure&

-6*0'*SIS
'etanus remains a ,ery serious disease& 'he de#lines in in#iden#e ( Mi-ure 60N4 ) and mortality rate o% tetanus o,er the "ast t*o de#ades ha,e been "arallel, resultinin minor #han-es in the #ase %atality rate& .n "atients *ho sur,i,e, re#o,ery is #om"lete O*ithout seAuelae i% su""orti,e measures ha,e "ro,ided adeAuate ,entilation& 'he "ro-nosis is si-ni%i#antly a%%e#ted by the %ollo*in- %a#tors& &ge 'he hi-hest mortality rate is %ound amon- "atients in the e$tremes o% li%e& Mor neonates the #ase %atality rate is 00P, and %or "ersons 21 years o% a-e or older it is 71P& .n #ontrast, %or "atients 41 to 45 years old, the #ase %atality rate is 41P to =1P& Incubation -eriod 'he median in#ubation "eriod o% %atal and non%atal tetanus #ases *ith kno*n *ounds *as 0&= and 7&0 days, res"e#ti,ely, in 450@ and 4505& Christie (4505) belie,es that a more reliable -uide to the "ro-nosis is the len-th o% the "eriod o% onset, de%ined as the inter,al bet*een the %irst e,iden#e o% trismus and the %irst -eneralized #on,ulsion& .% this "eriod is shorter than I@ hours, the atta#k "robably *ill be se,ereB i% the inter,al is lon-er, the illness *ill be milder& 9e,ertheless, the #ourse o% tetanus #annot be "redi#ted until the se,erity and %reAuen#y o% the #on,ulsions ha,e been made #lear& .t is easy to be misled in the %irst day or t*o& Mortality in 9' is also hi-her i% the in#ubation "eriod is less than I days& 4e8er .n mild or moderately se,ere #ases o% tetanus, %e,er is not a #ommon %indin-& .n "atients *ith in,ol,ement o% the brain stem, %e,er or hy"er"yre$ia is o%ten "resent& A%ebrile "atients ha,e a better #han#e o% re#o,ery& 'his is also true in 9'& %9tent of In8ol8ement

.n "atients *ith lo#al tetanus the sym"toms are #on%ined to the *ound area, and the "ro-nosis
4igure "#1 'etanus by year in the /nited States, 4522 to 45@5& (From MMWR Morb Mortal Wkly Rep 1990;38 !1."
"2:

is usually -ood& Generalized in,ol,ement, ho*e,er, is %ollo*ed by a more serious out#ome& 'etanus %ollo*in- "enetratin- in)ury has a hi-her mortality than in%e#tion %ollo*in- abrasions& Mortality is lo*er in oto-eni# tetanus& 'he mani%estations o% tetanus that #orrelate si-ni%i#antly *ith a "oorer "ro-nosis are #on,ulsion and s"asms ( Patel and Mehta, 4555 )& &ntito9in $herap7 .n -eneral, antito$in thera"y does not si-ni%i#antly a%%e#t the "ro-nosis& 'o$in usually has been %i$ed and is not a,ailable %or neutralization& Ho*e,er, antito$in may modi%y the disease i% it is -i,en durin- the in#ubation "eriod or ,ery early in the #ourse o% the illness&

%-ID%3I*)*0IC 4&C$*6S
'etanus is *orld*ide in distribution& Ge"orted #ases o% tetanus in the /nited States %rom 4522 to 45@5 are sho*n in Mi-ure 60N4& 'he s"ores are *idely disseminated in soil and in animal %e#es& 'etanus s"ores or to$in #an #ontaminate a ,ariety o% biolo-i# and sur-i#al "rodu#ts, su#h as ,a##ines, sera, and #at-ut& /nimmunized "ersons o% all a-es and both se$es are eAually sus#e"tible& .n s"ite o% the ubiAuity o% C. tetani, tetanus is a relati,ely rare o##urren#e, but 9' is still a serious "roblem in de,elo"in- #ountries, *here it is the #ause o% bet*een @P and 05P o% neonatal mortality& Southern Asia and sub<Saharan A%ri#a are es"e#ially a%%e#ted& .n .ndia, 9' is, a%ter se"ti#emia, the leadin- #ause o% neonatal mortality& More than 611,111 in%ants die annually %rom 9'& Community<based sur,eys ha,e identi%ied risk %a#tors %or 9', in#ludin- the omission o% maternal tetanus to$oid immunization durin- "re-nan#y, home deli,ery, unhy-ieni# #uttin- o% the umbili#al #ord, the a""li#ation o% an unhy-ieni# dressin- to the umbili#al stum" (in#ludin- -hee, a ty"e o% #lari%ied butter, "arti#ularly *hen it is heated *ith #o* dun- %uel 8 Bennet et al&, 4555 :), and a history o% 9' a%ter an earlier deli,ery ( Galazka and Gasse, 4552 )& 'hus the disease #an be "re,ented in ne*borns by immunizin- *omen either durin- or be%ore "re-nan#y and in#reasin- the "ro"ortion o% deli,eries that are attended by trained indi,iduals& .n %a#t, *ith a,ailable tools o% modern ase"ti# te#hniAue and a#ti,e immunization, tetanus is a disease that #ould be eliminated& 'he 3HO estimates that in 455= immunization and #lean deli,ery "ra#ti#es "re,ented 0@0,111 neonatal deaths %rom tetanus ( Galazka and Gasse, 4552 )& Many o% these e%%orts *ere a#hie,ed throu-h the E$"anded Pro-ramme on .mmunization&

I33('I$1
.t is estimated that 1&14 / o% antibody to C. tetani to$in in serum is "rote#ti,e in humans& Maternal .-G antibodies, i% "resent, are transmitted throu-h the "la#enta& 'his "assi,ely a#Auired immunity is, ho*e,er, o% short duration, be#ause maternal -lobulins are metabolized by the in%ant& 'he administration o% tetanus to$oid to in%ants, #hildren, and adults stimulates the "rodu#tion o% antibodies that "ro,ide "rote#tion a-ainst the e%%e#ts o% to$in& 'his "rote#ti,e le,el #an be maintained by "eriodi# booster in)e#tions& Elderly "atient *ho ha,e not re#ei,ed a re#ent booster may be at "arti#ularly hi-h risk %or tetanus& Patients re#o,erin- %rom tetanus should be

a#ti,ely immunized be#ause the e$tremely "otent to$in may not stimulate an antibody res"onse in the "atient&

$6%&$3%'$
Control of 3uscular Spasms 'he "atient should be admitted to a Auiet, darkened room *here all "ossible auditory, ,isual, ta#tile, or other stimuli are redu#ed to a minimum& 'he %irst "riority in the mana-ement o% mus#ular s"asms should be the administration o% a""ro"riate dru-s to redu#e the number and se,erity o% s"asms& iaze"am is a ,aluable dru- be#ause it e%%e#ti,ely #ontrols s"asms and hy"ertoni#ity *ithout de"ressin- the #orti#al #enters& 'he re#ommended dosa-e %or in%ants under = years o% a-e is @ m-Ek- o% body *ei-ht "er day -i,en in doses o% = to 6 me,ery 6 hours& Alternati,ely, %or in%ants an initial dose o% 1&4 to 1&= m-Ek-, intra,enously (.H), is used to relie,e an a#ute s"asm, %ollo*ed by a #ontinuous .H in%usion o% 42 to I1 m-Ek-Eday ( Gerdes, 4552 )& A%ter 2 to 7 days the dose #an be ta"ered by 2 to 41 m-Eday and then -i,en by the oro-astri# route& He#uronium *ith me#hani#al ,entilation may be reAuired to #ontrol s"asms ( Sin-hi et al&, =114 )& Phenobarbital and mor"hine may also be used as an ad)un#ti,e thera"y, *ith the understandin- that it be administered only in a #ontrolled, intensi,e settin- be#ause o% the risk o% a"nea&
""0

&ntito9in $herap7 A%ter adeAuate sedation has been a#hie,ed, human tetanus immune -lobulin ('.G) should be -i,en in a sin-le dose (6,111 to 0,111 /, intramus#ularly)& Do*er doses o% 211 / may be a""ro"riate %or 9'& Althou-h not a""ro,ed by the Mood and ruAdministration, intra,enous immune -lobulin (.H.G) #ontains antibodies to tetanus and #an be #onsidered i% '.G is not a,ailable& 'he standard dose o% .H.G %or other indi#ations is I11 to 211 m-Ek- ( Gerdes, 4552 )& .n some #ountries *here human immune -lobulin is una,ailable, eAuine 'A' should be -i,en i% the sensiti,ity rea#tions to horse serum are ne-ati,e& 'he antito$in is -i,en intra,enously and intramus#ularly, hal% the dose ,ia ea#h route& Mor neonates it may be ne#essary to delay a#ti,e immunization *ith tetanus to$oid %or I to 0 *eeks %ollo*in- the administration o% '.G& &ntimicrobial $herap7 Oral or intra,enous metronidazole (61 m-Ek- "er day, -i,en at 0<hour inter,als) is e%%e#ti,e in redu#in- the number o% ,e-etati,e %orms o% C. tetani& Parenteral "eni#illin G is an alternati,e dru-& Surgical $reatment A%ter the "atient has been sedated and has re#ei,ed antito$in, any *ound should be thorou-hly #leansed and dKbrided& E$tensi,e sur-i#al e$#ision is usually not indi#ated& Supporti8e $reatment Good medi#al and nursin- #are must minimize stimuli that may "re#i"itate a #on,ulsion& Pro#edures su#h as #atheterization or "la#ement o% ind*ellin- lines should be #arried out at a time *hen any sedati,e is e$ertin- its ma$imal e%%e#t& Su#h "ro#edures "re%erably are "er%ormed early in the #ourse o% #lini#al illness& .n addition, #are should be taken to anti#i"ate and "re,ent #om"li#ations su#h as as"iration "neumonia, lo*er<bo*el obstru#tion resultin- %rom %e#al im"a#tion, urinary retention, and

de#ubitus ul#ers& AdeAuate sedation may "re,ent a #om"ression %ra#ture o% the ,ertebra& Ges"iratory su""ort is essential, and intubation or tra#heostomy *ith res"irator ,entilation may be reAuired& Hi-h<Auality intensi,e #are durin- the %irst *eek (i&e&, early intubation, me#hani#al ,entilation, and neuromus#ular blo#kade 8"an#uronium or its eAui,alent:) is an essential #om"onent o% the mana-ement o% a neonate *ith tetanus& $racheostom7 'he #ombination o% hea,y sedation, di%%i#ulty in s*allo*in-, laryn-os"asm, and a##umulation o% se#retions leads to obstru#tion o% the air*ay& A relati,ely lo* mortality rate o% 41P *as re"orted by Edmondson and Mlo*ers (4575) , *ho treated 411 "atients *ith tetanus in an intensi,e #are unit& .ntubation #an be li%esa,in-&

-6%;%'$I;% 3%&S(6%S
&cti8e Immuni/ation Be#ause many #ases o% tetanus %ollo* minor abrasions and la#erations that are i-nored, #ontrol o% the disease #an best be a#hie,ed by a#ti,e immunization *ith to$oid be%ore e$"osure& All in%ants should be immunized routinely *ith tetanus to$oid that is in#or"orated *ith di"htheria to$oid and "ertussis ,a##ine& 'he usual basi# series o% the tri"le anti-en should #onsist o% %i,e doses o% tetanus and di"htheria to$oidN #ontainin- ,a##ine& 'he initial three doses are -i,en as 'aP administered at =<month inter,als be-innin- at a""ro$imately = months o% a-e& A %ourth dose is re#ommended 0 to 4= months a%ter the third dose, usually at 42 to 4@ months o% a-e& An additional dose o% 'aP is ne#essary be%ore s#hool entry, usually at I to 0 years o% a-e, unless the %ourth dose *as -i,en a%ter the %ourth birthday& 'aP #an be -i,en #on#urrently *ith other ,a##ines& Mor s"e#i%i# re#ommendations re-ardin#hildren *ho ha,e missed one or more ,a##inations or *ho ha,e started their ,a##inations at a time later than the ty"i#al s#hedule, the reader is ad,ised to #onsult the Ge"ort o% the Committee on .n%e#tious iseases o% the Ameri#an A#ademy o% Pediatri#s (Ged Book, =116)& .n%ant sur,i,ors o% 9' still reAuire a#ti,e immunization a-ainst tetanus& A%ter the initial immunization series is #om"leted, a booster dose o% tetanus to$oid (-i,en as d') should be -i,en at 44 to 4= years o% a-e and no later than by 40 years o% a-e, and e,ery 41 years therea%ter& .% more than 2 years ha,e ela"sed sin#e the last dose, a booster o% d' should be #onsidered %or "ersons *ho are -oin- to hi-h risk areas or on *ilderness e$"editions *here tetanus boosters may not be a,ailable& 'he 3HO has re#ently ado"ted the -oal o% eliminatin- 9' *orld*ide in de,elo"in#ountries
""1

throu-h a strate-y o% administerin- at least t*o "ro"erly s"a#ed doses o% to$oid (-i,en as d' i% a,ailable) to *omen o% #hildbearin- a-e in hi-h<risk areas& 'y"i#ally, the t*o doses o% d' should be administered at least I *eeks a"art, and the se#ond dose should be -i,en at least = *eeks be%ore deli,ery& 'he strate-y relies on the stimulation o% maternal antibodies that *ill "assi,ely "rote#t ne*borns at birth& /n%ortunately, many lots o% to$oid "rodu#ed in de,elo"in- #ountries are o% inadeAuate "oten#yB %e*er than hal% o% the nations that "rodu#e to$oid ha,e a %un#tional national #ontrol authority to monitor ,a##ine "rodu#tion and Auality ( ietz et al&, 4550 )& .mmunization *ith tetanus to$oid or d' is not #ontraindi#ated durin- "re-nan#y& .n the e,ent o% an in)ury, administration o% an additional booster dose o% tetanus to$oid

may be indi#atedB a "rote#ti,e antito$in le,el is usually a#hie,ed *ithin 4 *eek& .t is #ommon "ra#ti#e to use d' instead o% tetanus to$oid alone in a #hild 7 years or older, so that adeAuate le,els o% di"htheria immunity are also maintained& Children youn-er than 7 years should re#ei,e 'aP (unless "ertussis ,a##ine is #ontraindi#ated)& A booster dose #an "ro,oke an adeAuate res"onse a%ter a 41<year la"se sin#e the last in)e#tion& .n se,ere, #rush, and hea,ily #ontaminated *ounds ("arti#ularly, #om"ound skull %ra#tures), human '.G (=21 /) should be -i,en intramus#ularly in #on)un#tion *ith the to$oid& 'his "ro#edure should "re,ent a "otential short<in#ubation "eriod disease& Patients re#o,erin- %rom tetanus may not be immuneB there%ore they should be a#ti,ely immunized *ith tetanus to$oid& Ge#ent studies su--est that there is minimal, i% any, risk o% indu#in- Guillain<BarrK syndrome %ollo*inadministration o% tetanus to$oid ( 'uttle et al&, 4557 )& -assi8e Immuni/ation Persons *ho ha,e not been a#ti,ely immunized should be "rote#ted *ith human '.G in the e,ent o% an in)ury& 3hen '.G is reAuired %or *ound "ro"hyla$is, it is -i,en intramus#ularly (=21 /)& 'he dose used %or "ro"hyla$is is di%%erent %rom the treatment dose& Care of a ,ound A *ound should be #leansed thorou-hly, %orei-n bodies and ne#roti# tissues should be remo,ed, and the area should be dKbrided *hen indi#ated& 3ounds #ontaininde,italized tissue and those resultin- %rom #rush and a,ulsion in)uries, as *ell as burns, are "arti#ularly "rone to #ontamination *ith C. tetani& <I<)I*06&-.1
Adams QM, Kenny Q , Gudol"h AQ& Modern mana-ement o% tetanus neonatorum& Pediatri#s 4575B0IFI7=& Armita-e P, Cli%%ord G& Pro-nosis in tetanusF use o% data %rom thera"euti# trials& Q .n%e#t is 457@B46@F4N @& Ba-ratuni D& Ce"hali# tetanusF *ith re"ort o% a #ase& BMQ 452=B4FI04& Bennett Q, Ma C, 'ra,erso H, et al& 9eonatal tetanus asso#iated *ith to"i#al umbili#al -hee& .nt Q E"idemiol 4555B=@F447=& Bizzini B& 'etanus to$in& Mi#robiol Ge, 4575BI6F==IN=I1& B)erre-aard P, Stein-lass G, Mutie M, et al& 9eonatal tetanus mortality in #oastal KenyaF a #ommunity sur,ey& .nt Q E"idemiol 4556B==F406N405& Brand A, A#am"ora , Gottlieb R , et al& AdeAua#y o% antitetanus "ro"hyla$is in si$ hos"ital emer-en#y rooms& 9 En-l Q Med 45@6B615F060N0I1& Brooks HB, Asanuma H& A#tion o% tetanus to$in in the #erebral #orte$& S#ien#e 450=B467F07I& Brooks HB, Curtis G, E##les QC& Mode o% a#tion o% tetanus to$in& 9ature 4522B472F4=1& Christie AB& .n%e#tious diseasesF e"idemiolo-y and #lini#al "ra#ti#e& BaltimoreF 3illiams S 3ilkins, 4505& Corradin G, 3atts C& Cellular immunolo-y o% tetanus to$oid& Curr 'o" Mi#robiol .mmunol 4552B452F77N @7& ietz H, Milstien QB, ,an Doon M, et al& Per%orman#e and "oten#y o% tetanus to$oidF im"li#ations %or eliminatin- neonatal tetanus& Bull 3orld Health Or- 4550B7IF045N0=@& Edmondson GS, Mlo*ers M3& .ntensi,e #are in tetanusF mana-ement, #om"li#ations, and mortality in 411 #ases& BMQ 4575B4F4I14& Edsall G& S"e#i%i# "ro"hyla$is o% tetanus& QAMA 4525B 474FI47& Edsall G& Passi,e immunization& Pediatri#s 4506B6=F255& Eidels D, Proia GD, Hart A& Membrane re#e"tors %or ba#terial to$ins& Mi#robiol Ge, 45@6BI7F250N0=1& Einterz EM, Bates ME& Carin- %or neonatal tetanus "atients in a rural "rimary #are settin- in 9i-eriaF a re,ie* o% =67 #ases& Q 'ro" Pediatr 4554B67F475N4@4& Galazka A, Gasse M& 'he "resent status o% tetanus and tetanus ,a##ination& Curr 'o" Mi#robiol .mmunol 4552B452F64N26&

Gerdes QS& 'etanus neonatorum& .n Bur- M , .n-el%in-er QG, 3ald EG, Polin GA (eds)& Gellis S Ka-an;s Current Pediatri# 'hera"y, ed 42& Philadel"hiaF Saunders, 4552& Goyal GK, 9eo-y C9, Mathur GP& A #ontrolled trial o% antiserum in the treatment o% tetanus& Dan#et 4500B=F4674& Hlady 3G, Bennett QH, Samadi AG, et al& 9eonatal tetanus in rural Ban-ladeshF risk %a#tors and to$oid e%%i#a#y& Am Q Publi# Health 455=B@=F4602N4605& Kaeser HE, Sauer A& 'etanus to$inF a neuromus#ular blo#kin- a-ent& 9ature 4505B==6F@I=& Kerr QH, et al& .n,ol,ement o% the sym"atheti# ner,ous system in tetanusF studies on @= #ases& Dan#et 450@B=F=60& Kessimer QG, Habi- 3H, Harde-ree MC& Mono#lonal antibodies as "robes o% tetanus to$in stru#ture and %un#tion& .n%e#t .mmun 45@6BI=F5I=N5I@&
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Daird 3Q, Aronson 3, Sil,er GP, et al& Plasmid<asso#iated to$i-eni#ity in Clostridium tetani. Q .n%e#t is 45@1B4I=F0=6& De,ine D, Edsall G& 'etanus to$oidF *hat determines rea#tion "ronenessT Q .n%e#t is 45@4B4IIF670& Di#htenhan QB, Kellerman G , Gi#hards QM& 'etanus& A threat to elderly "atients& Post-rad Med 455=B42F25& Dooney QM, Edsall G, .s"en Q Qr, Chasen 3H& Persisten#e o% antito$in le,els a%ter tetanus to$oid ino#ulation in adults and e%%e#ts o% a booster dose a%ter inter,als& 9 En-l Q Med 4520B=2IF0& Marie A, Mora$ H& Ge#her#hes sur l;absor"tion de la to$ine tetaniAue& Ann .nst Pasteur 451=B40F@4@& M#Cra#ken GH Qr, o*ell D, Marshall M9& ouble<blind trial o% eAuine antito$in and human immune -lobulin in tetanus neonatorum& Dan#et 4574B4F44I0& Meyer H, Gansome M& /ntersu#hun-en uber den 'etanus& Ar#h E$" Pathol Pharmakol 4516BI5F605& Patel QC, Mehta BC& 'etanusF study o% @,057 #ases& .ndian Q Med S#i 4555B26F656& Pratt ED& Clini#al tetanusF a study o% 20 #ases, *ith s"e#ial re%eren#e to methods o% "re,ention and a "lan %or e,aluatin- treatment& QAMA 45I2B4=5F4=I6& Gubbo S , Suri QC& Passi,e immunization a-ainst tetanus *ith human immune -lobulin& BMQ 450=B=F75& Gubinstein HM& Studies on human tetanus antito$in& Am Q Hy- 450=B70F=70& S#hia,o G, Gossetto O, 'onello M, Monte#u##o C& .ntra#ellular tar-ets and metallo"rotease a#ti,ity o% tetanus and botulism neuroto$ins& Curr 'o" Mi#robiol .mmunol 4552B452F=27N=7I& Sin-hi S, Qain H, Subramanian C& Post<neonatal tetanusF issues in intensi,e #are mana-ement& .ndian Q Pediatr =114B0@F=07& Smolens Q, Ho-t A, Cra*%ord M9, Stokes Q Qr& 'he "ersisten#e in the human #ir#ulation o% horse and human tetanus antito$ins& Q Pediatr 4504B25F@55& Stan%ield QP, Gall , Braden PM& Sin-le dose<antenatal tetanus immunization& Dan#et 4576B4F=42& 'uttle Q, Chen G', Gantala H, Cherry Q , et al& 'he risk o% Guillain<BarrK syndrome a%ter tetanus<to$oidN #ontainin- ,a##ines in adults and #hildren in the /nited States& Am Q Publi# Health 4557B@7F4545& Heronesi G& Clini#al obser,ations on 74= #ases o% tetanus sub)e#t to %our di%%erent methods o% treatmentF 4@&= "er#ent mortality rate under a ne* method o% treatment& Am Q Med S#i 4520B=6=F0=5& 3orld Health Or-anization& 3orld e,elo"ment Ge"ort =111, Gene,a, =111, 3HO& !aramis A, 'as MA& 9eonatal tetanus in the southeast o% 'urkeyF risk %a#tors, and #lini#al and "ro-nosti# as"e#ts& Ge,ie* o% 76 #ases, 4551N4555& 'urk Q Pediatr =111BI=F=7=