TataLaksanaTerkiniDemamTifoid

RHHNelwanCDK192/vol.39no.4,th.2012

DivisiPenyakitTropikdanInfeksiDepartemenIlmuPenyakitDalam,FKUI/RSCM
Jakarta

Sejakawalabadke20,insidensdemamtifoidmenurundiUSAdanEropadengan
ketersediaanairbersihdansistempembuanganyangbaikyangsampaisaatinibelum
dimilikiolehsebagianbesarnegaraberkembang.1Secarakeseluruhan,demamtifoid
diperkirakanmenyebabkan21,6jutakasusdengan216.500kematianpadatahun2000.
Insidensdemamtifoidtinggi(>100kasusper100.000populasipertahun)dicatatdiAsia
TengahdanSelatan,AsiaTenggara,dankemungkinanAfrikaSelatan;yangtergolong
sedang(10100kasusper100.000populasipertahun)diAsialainnya,Afrika,Amerika
Latin,danOceania(kecualiAustraliadanSelandiaBaru);sertayangtermasukrendah
(<10kasusper100.000populasipertahun)dibagiandunialainnya.1
DiIndonesia,insidensdemamtifoidbanyakdijumpaipadapopulasiyangberusia319
tahun.1Selainitu,demamtifoiddiIndonesiajugaberkaitandenganru

700600
500400300200100

mahtangga,yaituadanyaanggotakeluargadenganriwayatterkenademamtifoid,tidak
adanyasabununtukmencucitangan,menggunakanpiringyangsamauntukmakan,dan
tidaktersedianyatempatbuangairbesardalamrumah.5
Berikutinigambarmengenaiinsidensdemamtifoiddanusiarataratapasiendaristudi
mengenaidemamtifoiddi5negaraAsia,yangsalahsatunyaadalahIndonesia(lihat
gambar1).6

PemilihanantibiotiktergantungpadapolasensitivitasisolatSalmonellatyphisetempat.1
MunculnyagalurSalmonellatyphiyangresistenterhadapbanyakantibiotik(kelompok
MDR)dapatmengurangipilihanantibiotikyangakandiberikan.Terdapat2kategori
resistensiantibiotikyaituresistenterhadapantibiotikkelompokchloramphenicol,
ampicillin,dantrimethoprimsulfamethoxazole(kelompokMDR)danresistenterhadap
antibiotikfluoroquinolone.11Nalidixic
acidresistantSalmonellatyphi(NARST)merupakanpetandaberkurangnyasensitivitas
terhadapfluoroquinolone.11Terapiantibiotikyangdiberikanuntukdemamtifoidtanpa
komplikasiberdasarkanWHOtahun2003dapatdilihatpadatabel1.11
Antibiotikgolonganfluoroquinolone(ciprofloxacin,ofloxacin,danpefloxacin)
merupakanterapiyangefektifuntukdemamtifoidyangdisebabkanisolattidakresisten
terhadapfluoroquinolonedenganangkakesembuhanklinissebesar98%,waktu
penurunandemam4hari,danangkakekambuhandanfecalcarrierkurangdari2%.1
Fluoroquinolonememilikipenetrasikejaringanyangsangatbaik,dapatmembunuhS.
typhiintraselulerdidalammonosit/makrofag,sertamencapaikadaryangtinggidalam
kandungempedudibandingkanantibiotiklain.11
Berbagaistuditelahdilakukanuntukmenilaiefektivitasfluoroquinolonedansalahsatu
fluoroquinoloneyangsaatinitelahditelitidanmemilikiefektivitasyangbaikadalah
levofloxacin.Studikomparatif,acak,dantersamartunggaltelahdilakukanuntuk
levofloxacinterhadapobatstandarciprofloxacinuntukterapidemamtifoidtanpa
komplikasi.12Levofloxacindiberikandengandosis500mg,1kaliseharidan
ciprofloxacindiberikandengandosis500mg,2kaliseharimasingmasingselama7hari.
Kesimpulandaristudiiniadalahbahwapadasaatinilevofloxacinlebihbermanfaat
dibandingkanciprofloxacindalamhalwaktupenurunandemam,hasilmikrobiologi
dansecarabermaknamemilikiefeksampingyanglebihsedikitdibandingkan
ciprofloxacin.12

Selainitu,pernahjugadilakukanstuditerbukadilingkunganFKUImengenaiefikasi
dankeamananlevofloxacinpadaterapidemamtifoidtanpakomplikasi.13Levofloxacin
diberikandengandosis500mg,1kalisehariselama7hari.Efikasiklinisyangdijumpai
padastudiiniadalah100%denganefeksampingyangminimal.Daristudiinijuga
terdapattabelperbandinganrataratawaktupenurunandemamdiantaraberbagaijenis
fluoroquinoloneyangberedardiIndonesiadimanapenurunandemampada
levofloxacinpalingcepat,yaitu2,4hari.13
Sebuahmetaanalisisyangdipublikasikanpadatahun2009menyimpulkanbahwapada
demamenterikdewasa,fluoroquinolonelebihbaikdibandingkanchloramphenicoluntuk
mencegahkekambuhan.14
Namun,fluoroquinolonetidakdiberikanpadaanakanakkarenadapatmengakibatkan
gangguanpertumbuhandankerusakansendi.1,2,11
Chloramphenicolsudahsejaklamadigunakandanmenjaditerapistandarpadademamti
foidnamunkekurangandarichloramphenicoladalahangkakekambuhanyangtinggi(5
7%),angkaterjadinyacarrierjugatinggi,dantoksispadasumsumtulang.11,15
Azithromycindancefiximememilikiangkakesembuhanklinislebihdari90%dengan
waktupenurunandemam57hari,durasipemberiannyalama(14hari)danangka
kekambuhansertafecalcarrierterjadipadakurangdari4%.1
Pasiendenganmuntahyangmenetap,diareberat,distensiabdomen,ataukesadaran
menurunmemerlukanrawatinapdanpasien
dengangejalaklinistersebutditerapisebagaipasiendemamtifoidyangberat.1Terapi
antibiotikyangdiberikanpadademamtifoidberatmenurutWHOtahun2003dapat
dilihatditabel2.11Walaupunditabeliniterteracefotaximeuntukterapidemamtifoid
tetapisayangnyadiIndonesiasampaisaatinitidakterdapatlaporankeberhasilanterapi
demamtifoiddengancefotaxime.
Selainpemberianantibiotik,penderitaperluistirahattotalsertaterapisuportif.Yang
diberikanantaralaincairanuntukmengkoreksiketidakseimbangancairandanelektrolit
danantipiretik.1,2NutrisiyangadekuatmelaluiTPNdilanjutkandengandietmakanan
yanglembutdanmudahdicernasecepatkeadaanmengizinkan.1,2
Tabel1AntibiotikyangdiberikanpadademamtifoidtanpakomplikasimenurutWHO2003
Tabel2AntibiotikyangdiberikanpadademamtifoidberatmenurutWHO2003

RINGKASAN
Demamtifoidmasihmenjadimasalahkesehatanyangpentingdinegarayangsedang
berkembangdiAsia,termasukIndonesia.JugadiAfrikaSelatandanAmerikaLatin.
Diagnosisdemamtifoidditegakkanberdasarkangambaranklinisdanpemeriksaan
tambahandarilaboratorium.
Terapiyangdiberikanadalahistirahat,dietlunak,danantimikroba.Padasaatini,

antimikrobadenganwaktupenurunandemamcepat,pemberianpraktis1kalisehari
selama7hari,danefeksampingminimaladalahlevofloxacin.
Diagnosisdemamtifoidyangditegakkansecaradinidandisertaipemberianterapiyang
tepatmencegahterjadinyakomplikasi,kekambuhan,pembawakuman(carrier),dan
kemungkinankematian.
Strategipencegahandiarahkanpadaketersediaanairbersih,menghindarimakananyang
terkontaminasi,higieneperorangan,sanitasiyangbaik,danpemberianvaksinsesuai
kebutuhan.
REVIEW10.1111/j.14690691.2011.03552.x

Treatmentoftyphoidfeverinthe21stcentury:promises
andshortcomings
T.Butler
DepartmentofMicrobiologyandImmunology,RossUniversitySchoolofMedicine,North
Brunswick,NJ,USA

Abstract
Emergenceofmultidrugresistanceanddecreasedciprofloxacinsusceptibility(DCS)in
SalmonellaentericaserovarTyphiinSouthAsiahaverenderedolderdrugs,includingampicillin,
chloramphenicol,trimethoprimsulphamethoxazole,ciprofloxacin,andofloxacin,ineffectiveor
suboptimalfortyphoidfever.Ideally,treatmentshouldbesafeandavailableforadultsand
childreninshortenedcoursesof5days,causedefervescencewithin1week,renderbloodand
stoolculturessterile,andpreventrelapse.Inthisreviewof20prospectiveclinicaltrialsthat
enrolledmorethan1600cultureprovenpatients,azithromycinmeetsthesecriteriabetterthan
otherdrugs.Amongfluoroquinolones,whicharemoreeffectivethancephalosporins,gatifloxacin
appearstobemoreeffectivethanciprofloxacinandofloxacinforpatientsinfectedwithbacteria
showingDCS.Ceftriaxonecontinuestobeusefulasabackupchoice,andchloramphenicol,
despiteitstoxicityforbonemarrowandhistoryofplasmidmediatedresistance,ismakinga
comebackindevelopingcountriesthatshowtheirbacteriatobesusceptibletoit.
Keywords:Entericfever,Salmonella,Salmonellaenterica,serovarParatyphiA,serovarTyphi,
Typhi,typhoidfeverArticlepublishedonline:25April2011ClinMicrobiolInfect2011;17:959963

Azithromycinshouldbeusedmore,bothindevelopingcountrieswithahighprevalence
ofinfectioncausedbybacteriawithDCSandinreturnedtravellersinindustrialized
countries.Otherthanthehighercost,itoutperformsotherdrugswithregardtocure
rates,speedofdefervescenceagainstinfectionscausedbybacteriawithDCS,and
preventionoffaecalcarriageandrelapse.ResistanceofS.Typhitoazithromycinhas
notemerged,butculturedstrainsneedtobetestedforsusceptibility,becauseonecaseof
resistantS.ParatyphiAinfectiontreatedwiththisantibioticresultedinclinicalfailure
[30].AgainstinfectionscausedbybacteriawithDCS,itistheonlyeffectivedrugthat
canbeusedinshort,5daycourses[4,8].Ceftriaxoneinshortenedcoursesof5or7days
hassignificantrelapserates[8,28],but,asabackup,thisantibioticcanachieveclinical
curewithgoodreliability.Althoughchloramphenicolcontinuestobeusedincountries
withoutresistancetoit,thisolddrugallowsrelapses[16,31]andexposespatientsto
serioustoxicity.

Pilihan Terapi Empiris Demam

Tifoid pada Anak: Kloramfenikol
atau Seftriakson?
SondangSidabutar,HindraIrawanSatari
DepartemenIlmuKesehatanAnak,RSDrCiptoMangunkusumo,Fakultas
KedokteranUniversitasIndonesia,Jakarta

erdasarkanhasilpenelusuranliteraturyangada,studiterkinilebih
menganjurkanpemberianseftriaksondibandingkankloramfenikol
untukpasiendemamtifoidyangdirawatdirumahsakit.Beberapastudi
menunjukkanbuktiluaranyanglebihbaiktentangpenggunaan
seftriaksonsebagaiterapiempirispadademamtifoid.Kriteriayang
sebaiknyadipenuhiolehantibiotikempirisantaralaincarapemberian
Sari Pediatri, Vol.11,No.6,April2010

437
SondangSidabutardkk:Pilihanterapiempirisdemamtifoidpadaanak:kloramfenikol
atauseftriakson?

mudahbagianak,tidakmudahresisten,efeksampingminimal,dan
telahterbuktiefikasisecaraklinis.19Padakasuskami,usiapasien
sesuaidenganpredileksiusiatersering,danterdapatriwayatjajanyang
merupakansumberpenularanpenyakit.Perjalananpenyakitpasien
telahmemasukiminggukeduademam,danterdapatgangguan
gastrointestinalyangmenyebabkanasupantidakadekuatdananak
terlihatlemas.Padapasiendenganperjalananklinisyangtelah
memasukiminggukeduadengangejalagastrointestinalyangnyata,
terapiperoraltidakideal.

Lamademamturun(timeoffeverdefervescence)merupakansalahsatu
parameterkeberhasilanpengobatan.Demamyangtetaptinggi
menunjukkankemungkinankomplikasi,fokusinfeksilain,resistensiS.
typhi,atausalahdiagnosis.19Berdasarkanhasilujiresistensibakteri
terhadapberbagaiantibiotik,tidakditemukanadanyaMDRSTdari
isolatyangdiperiksasejaktahun20032007dilaboratorium
MikrobiologiFakultasKedokteranUniversitasIndonesia.20Demam
tifoidanakdenganMDRSTsecaraklinisakanmenunjukkanrespon
yanglambatterhadapterapi(lebihdari4872jam),lebihsering
mengalamikomplikasi,dankemungkinanmenjadifatallebihbesar.
AntibiotikterpilihuntukMDRSTadalahsiprofloksasindanseftriakson.
Pemberiansiprofloksasinpadaanakusia<18tahunmasih
diperdebatkankarenaadanyapotensiartropati,sehinggaseftriakson
lebihdirekomendasikan.8,5Pasienkamimemilikikepatuhanminum
obatyangbaik,tidakditemukanfokusinfeksilain,dandosisantibiotik
kloramfenikolyangdiberikantelahsesuai.Secarainvitro,S.typhi
menunjukkansensitivitasterhadapkloramfenikol,namunresponsyang
ditunjukkanpasientidaksesuai.Riwayatpemakaianantibiotikperoral
selamarawatjalandanresponsyanglambatterhadapkloramfenikoldi
rumahsakit,menunjukkankemungkinanadanyaresistensi,sehingga
antibiotikseharusnyadapatdigantilebihawal.1
Perbedaanyangmendasarpadakeduaantibiotikiniadalahlama
demamturunlebihcepatsehinggalamaterapilebihsingkat,efek
sampinglebihringan,danangkakekambuhanyanglebihrendahpada
penggunaanseftriaksondibandingkankloramfenikol.Durasiterapi
seftriaksonbervariasiantara310haridenganwaktudemamturun
ratarataempathari,danamandiberikanpadaanakdengandosisantara
50100mg/kg/hari.12,13,15,16Efeksampingyangmungkinditemukan
karenapemberiankloramfenikol
438
adalahsupresisumsumtulang.13,15Hargaseftriaksonlebihmahal
dibandingkloramfenikol,namunlamarawatyanglebihpendeksangat
mengurangibiayapengobatan.l4,18,19Pasienmengalamiefeksamping

kloramfenikolberupasupresisumsumtulang.Setelahpemberian
seftriaksondengandosis80mg/kgberatbadan/haridenganmaksimal
dosis2g/hari,demamturunsetelahhariketigaterapi.Seftriakson
dilanjutkansampailimaharipengobatan,terbuktimemberikanrespon
klinisyangbaik.

Kesimpulan
Antibiotikempirisyangtepatsangatbermaknamenurunkanmorbiditas
danmortalitas.Pemberianseftriaksonsebagaiterapiempirispada
pasiendemamtifoidsecarabermaknadapatmengurangilama
pengobatandibandingkandenganpemberianjangkapanjang
kloramfenikol.Hallainyangmenguntungkanadalahefeksampingdan
angkakekambuhanyanglebihrendah,sertalamademamturunyang
lebihcepat.Pengetahuandanpenilaianklinisyangbaikdiperlukan
dalammemilihterapiempirisyangtepatterutamabilafasilitasuji
resistensitidakmemadai.Seftriaksonterbuktidapatdijadikansebagai
antibiotikpilihanutamapadakasusMDRST.

Guidelines for the diagnosis,

management, and prevention of
typhoid fever [2010]
Ministry of Health Fiji Islands
DRAFTforendorsement
4

Heymann D. Control of Communicable Diseases Manual, 19th Edition. WHO and

American Public Health Association. Washington DC, 2008.
5

Parry. Typhoid fever. N Engl J Med, 2002; 347: 1770-82.

WHO. The diagnosis, treatment and prevention of typhoid fever. Geneva, 2003.
Ordering code: WHO/V&B/03.07
7

US-CDC Weight for Age Tables, Children, Ages 2 to 20 Years. Available at

http://www.cdc.gov/growthcharts/html_charts/wtage.htm

Fiji
The majority of patients with typhoid fever can be managed at home under medical
supervision until they no longer have symptoms. Very sick patients should be managed in
the hospital for supportive care, close monitoring of complications, and, if necessary, IV
antibiotics.
Ciprofloxacin is the most effective treatment for typhoid fever.4,
clinical failure rate, results in

5, 6

It has the lowest

a faster recovery, has the lowest relapse rate, and the lowest carrier rate. In response to an
outbreak of typhoid fever in 2010, the Minister for Health approved ciprofloxacin as the
drug of choice for treatment of typhoid fever in all age groups, except in pregnant
women, for inpatients as well as outpatients. For pregnant women, amoxicillin or a

3rd generation cephalosporin is preferable.

Duration of ciprofloxacin treatment is 5 days or until the patient is free of symptoms,
whichever is longer (Table 1). For simplified dosing based on average weight for age 7
see Table 2. To prevent development of antibiotic resistance, ciprofloxacin should only be
used for patients with confirmed or suspected typhoid fever. It should not be used for
treatment of mild diarrhoea without fever or blood. Regardless of which antibiotic is
prescribed, patients must be explained the importance of finishing the entire course of
treatment, even when they feel better. Every effort should be made to make sure that the
patient takes the entire course. Ideally, the treatment should be directly observed (DOT).

Severe cases
Table 3 lists the recommended treatment of severe cases of typhoid fever. The third
generation cephalosporins (e.g. ceftriaxone) and azithromycin are as effective as
ciprofloxacin. However, these are more expensive and should be reserved for treatment
of severe patients and/or patients who don't respond to ciprofloxacin treatment. Patients
with intestinal perforation need intensive care as well as surgical intervention. Early
intervention is crucial as morbidity/mortality rates increase with delayed surgery after
perforation.

Table 3: Treatment of severe and drug resistant typhoid fever cases

Based on WHO guideline for diagnosis, treatment and prevention of typhoid fever 2003.

High-dose corticosteroid treatment, in combination with antibiotic treatment and

supportive care, reduces mortality in critically ill patients.

Antibiotik Terapi Demam Tifoid

Tanpa Komplikasi pada Anak
NovieHomentaRampengan
Sari Pediatri 2013;14(5):2716.

Pilihanobatantibiotiklinipertamapengobatandemamtifoidpadaanak
dinegaraberkembangdidasarkanpadafaktorefikasi,ketersediaan,dan
biaya.Berdasarkanketigafaktortersebut,kloramfenikolmasihmenjadi
obatpilihanpertamapengobatandemamtifoidpadaanak.
Selamakurunwaktu4tahun(20082012),jumlahkasusdemamtifoid
yangdirawatdiRSCMJakartayangmendapatpengobatan
kloramfenikol13orang,klinismembaikpadaharisakitke6yaitu
23,1%.Berdasarkanpolakumandanujikepekaanterhadapantibiotik
diRSCMpadatahun20092010,hasilbiakanS.typhipositifpada8
spesimen,dengansensitifitaskloramfenikollebihdari75%.17
Azitromisinadalahantibiotikgolonganmakrolidpertamayang
termasukdalamkelasazalide.MenurutWHO,pemberianazitromisin
dengandosis10mg/kgBBselama7hariterbuktiefektifpadaterapi
demam
tifoidtanpakomplikasipadaanakdandewasadenganlamaturunpanas
yangserupadenganyangdilaporkanpadapemberiankloramfenikol.18
Penelitianinvitromenunjukkanazitromisinlebihpotenterhadap

Salmonellaspp.dibandingkandenganobatlinipertamadanmakrolid
lain.BelumterdapatlaporantentangresistensiS.typhiterhadap
azitromisin.Studiterbarumenunjukkanazitromisinefektifsecaraklinis
danbakteriologisdalammengobatidemamtifoidbahkanyang
disebabkanolehstrainMDR.19
Azitromisindankloramfenikolberbedadalamhalcarapemberian,
farmakokinetik,prinsipterapi,danefeksamping.Azitromisindiberikan
sekalisehari,sedangkankloramfenikoldiberikanempatkalisehari.
Keduaantibiotikberpenetrasikedalamselsecaraefektif,danhal
tersebutmenerangkanaktivitasterapeutikobatterhadappatogenyang
beradadiintraselularsepertiS.typhi.20
Sefiksimmerupakanantibiotikgolongansefalosporingenerasiketiga
oral,mempunyaiaktifitasantimikrobaterhadapkumanGrampositif
maupunnegatiftermasukEnterobacteriaceae.Sefiksimmempunyai
efikasidantoleransiyangbaikuntukpengobatandemamtifoidanak.21
Meskipunkloramfenikolsampaisaatinimasihmerupakanobatpilihan
linipertama(firstdrugofchoice)untukpengobatandemamtifoidpada
anak,obatlinikeduasepertiazitromisindansefiksimdapat
dipertimbangkandalamterapidemamtifoidtanpakomplikasipada
anakterutamapadakasusdengankepatuhan(compliance)minumobat
diragukanatauapabilakloramfenikoltidakdapatdiberikan(misalnya
jumlahleukosit<2.000/ul,adanyahipersensitifterhadapkloramfenikol,
MDRS.typhi).20
Penelitiankamimempunyaibeberapaketerbatasan.Kamitidak
melakukanpemeriksaanbiakandarahsebagaibakuemasdiagnosis
demamtifoidsertatidakdapatmemperlihatkanpolakumandan
kepekaanantibiotiksecarainvitro.Selainitu,karenapenelitian
retrospektif,kamitidakdapatmelakukankontroldanpenyeragaman
terhadaplamarawatdirumahsakitpadatiapkelompokantibiotik.
Lamarawatdirumahsakittidakselaluberhubungandenganderajat
penyakit.Akantetapidapatberhubungandenganvariabellainyang
tidakberkaitandenganpenyakitnya,sepertiadanyapenyakitlain,
anoreksiarelatif,ataupasienyangtidaktaatdalamminumobat.

Dibutuhkanpenelitianlanjutandengansubjekyanglebihbesar,
pemeriksaanlaboratoriummikrobiologi,

MANAGEMENT OF ENTERIC FEVER

IN 2012
Falguni S. Parikh, Mumbai

ziThromycin
Nine prospective clinical trials have been done. Drug was received by a total 453
patients including children. Azithromycin was used in dose of 500mg 1 gm /day
for 5-7 days.
No relapses were recorded in 267 patients treated with azithromycin followed up
for 1 month after therapy where as relapses were recorded in 16 of 276 patients
(5.8%) treated with ceftriaxone, ofloxacin or gatifloxacin.
Bacteriological responses were very good with only 1.5% patients whose blood
was recultured after treatment showed salmonella.
Azithromycin is capable of achieving very high intracellular concentrations and its
ability to achieve intracellular concentrations 50-100 times greater than serum
levels explains its efficacy against salmonella species. It has half life of 2-3 days.
Raised MICS of azithromycin have been reported in S. and paratyphi A. Recently
azithromycin resistance and treatment failure in patient with S. paratyphi A
infection has been reported.
fluoroquinolones
Quinolones including ciprofloxacin and ofloxacin were drugs of choice for most
cases of enteric fever. However reports of resistance to fluoroquinolones in the
form of nalidixic acid resistance which correlates with decreased ciprofloxacin
susceptibility (DCS) was reported in 1990s. In Asian countries this gave rise to
them being rendered ineffective therapy. Gatifloxacin gave good results in 2 trials
that used 7 day courses, had low MIC (minimum inhibitory concentration) for
bacterial strains with DCS and is suggested to be more effective than older

fluoroquinolones owing to better results of time-kill experiments but its use was
associated with more relapses than with azithromycin. In a recent paper in the
Lancet infectious disease from Nepal Gatifloxacin was compared to
chloramphenicol where it showed similar efficacy. However, on basis of its shorter
treatment duration, fewer adverse events and lower cost, authors recommend it as
preferred treatment of enteric fever.
cephalosporins
Trials of ceftriaxone show that fever defervescence takes longer and relapses occur
in patients treated for shorter duration. It is recommended for 14 days. This
antibiotic is safe and achieves good clinical cure.
chloramphenicol
The reduced use of chloramphenicol has increased sensitivity to chloramphenicol.
Reversal may be due to loss of plasmids encoding resistance to chloramphemicol.
It is making a comeback in developing countries.
prevenTion
The availability of full genome sequences for S. typhi and S. A confirms their
place as monomorphic human adapted pathogens vulnerable to control measures if
efforts for the same can be intensified.
Interventions to improve availability of safe water, food and basic sanitation
measures are underway in most countries. The identification and management of
S. carriers particularly those involved with food handling has proved to be
important strategy for control.
vaccines
While Ty 21a and Vi polysaccharide vaccines are effective, development of cheap,
safe vaccines with efficacy among infants which can provide protective immunity
after single does is required. The growing importance of S. A as a cause of enteric
fever is of great concern particularly due to lack of effective vaccine available.
CDC has issued special guidelines for typhoid vaccination in travelers to endemic
countries.
conclusions
Enteric fever continues to be important cause of illness with estimated global
burden of greater than 27 million cases per annum with a clinical relapse rate of
5% to 20%. In India there have been increasing reports of Salmonella enterica

serotype A causing enteric fever in addition to serotype. Typhoid vaccine does not
offer protection against paratyphi
Antimicrobial resistance has rendered many drugs particularly older
fluoroquinolones useless as therapy for typhoid. There is greater use of third
generation cephalosporins. Azithromycin and newer fluoroquinolone Gatifloxacin
have showed promise in the treatment of multidrug resistant typhoid. Safe water
supply and improvement in sanitation facility will go a long way in the control of
typhoid especially in developing countries.

ASCITESAnUnderreportedFindinginEntericFever?
Alteredliverfunctionisanotablefeatureoftyphoidfever,buttheyare
usuallytransientandresolveby23weeks(2),similartothisseries.
Thoughtherearemanyreportsofperitonitisintyphoidfeveronlya
coupleofcasereportsonperitonealfluidcollectionwithoutany
evidenceofperforationareavailableininternationalliterature.Chiu,et
al.(3)reportedanincidenceof4%ofascitesorpleuraleffusion
among71childrenwithtyphoidfever.
Judet,etal.(4)reportedtwocasesofperitonealeffusioninpatientswith
typhoidfeverandsuggestedthattyphoidfevershouldbeconsidered
whenultrasonographyshowsanisolatedperitonealeffusionina
febrilechild.
Thecauseofascitesisnotclear.Burdzinska,etal.(5)described
polyserositisincourseoftyphoidfever.Theexudativenatureofthe
fluidinourcasesalsopointstoageneralisedinflammationof
peritonealserouslayer.Albuminwasnotlowenoughtobealikely
cause.
3.

ChiuCH,TsaiJR,OuJT,LinTY.Typhoidfeverinchildren:Afourteenyear
experience.ActaPediatrTaiwan2000;41:2832.

4.

JudetO,RouveixE,VerderiD,BismuthV.Aclassicalbutunknowncauseofperi
tonealeffusiondisclosedbyechography.Typhoidfever.JRadiol1989;70:419421.

5.

BurdzinskaJ,NowakowskiTK,PellarJ.Polyserositisinthecourseoftyphoidfever.

PrzeglEpidemiol1966;20:211215.
6.

ShaiAshkenazi,ThomasG.Cleary.In:SalmonellaInfections.Behrman,Kliegman
Arvin,editors,NelsonTextbookofPediatrics,15thedition,W.B.SaundersCompany,
USA,pp788790.

7.

JagadishK,PatwariAK,SarinS,PrakashCSrivastava,AnandVK.Hepaticmani

PreventiveEducationagainstHIV/AIDSintheSchoolsof
Iran
WithreferencetotheinformativeeditorialbyDr.M.K.C.Nairentitled:
AdolescentSexualandReproductiveHealth(1),wepresenta
summaryofourrecentcountrystudyofpreventiveeducationagainst
HIV/AIDSintheschoolsinIran(2).LikeIndia(1)theculturaland
socialmoresofIrancomplicatediscussionofsexualactivity,especially
amongtheyouthandunmarried(2,3).Todealwiththisasanobstaclein
thepreventiveeducation,peereducationprogramshavebeenstartedin
guidanceschoolsandhighschoolsalloverthecountryandthousands
ofstudentsarebeingtrainedeveryyeartoeducatetheirpeerson
HIV/AIDS(2).Consultantsandhealthworkersinguidanceschoolsand
highschoolswilleducatetheselectedstudentsforefficientpeer
education.Thesetrainedstudentswillalsoattendthecampaignsheld
bytheMinistryofEducation.Wehave
INDIANPEDIATRICS

Correspondenceto:
Dr.RajivSinha,
festationsintyphoidfever.IndianPediatr1994;31:8078.
3.

ChiuCH,TsaiJR,OuJT,LinTY.Typhoidfeverinchildren:Afourteenyear
experience.ActaPediatrTaiwan2000;41:2832.

Typhoid glomerulonephritis

CaseReport

pediatricinfectiousdisease5(2013)175e177

Acasereportofacuteglomerulonephritis
associatedwithtyphoidfever
RajendraKarambelkar*,GeetaKarambelkar,Pravin
BabhalgaonkarConsultantPediatrician,Pune,Maharashtra,India
Despite high number of cases of typhoid fever worldwide and its
various known compli- cations involving renal system, acute
glomerulonephritis as a clinical presentation of typhoid fever at the
onset or as a complication later on is uncommon. The severity of acute
glomerulonephritis due to typhoid fever is variable; generally, it
resolves completely with treatment of typhoid fever but occasionally it
may be fatal. We present this case of acute glomerulonephritis
associated with typhoid fever in a 4-year-old boy who presented with
high fever, abdominal symptoms, edema, oliguria, hypertension and
hematuria and who recovered completely with treatment.
Reportsdatingbackmorethanthreedecadeshaveplacedoverallincidenceofrenalinvolvement
intyphoidfeverat2e3%.However,inmostcasesmildproteinuriaistheonlymanifestation.3
Variousotherformsofrenalinvolvementincludehemolyticuremicsyndrome,pyelonephritis,
nephroticsyndrome,cystitis,interstitialnephritisandacuterenalfailure.However,acuteGN
duringtyphoidfeverisuncommon.4,5Aftertheseriesof15childrenoftyphoidGNreported
byBukaandCoovadia2in1980veryfewcaseshavebeenreportedintheliteraturelateron.6
Inthepresentcasetheclinicalpresentationoffever>10daysduration,abdominalsymptoms,
edema,oliguria,hypertension,hematuria,and>5foldriseinWidaltitersadiagnosisoftyphoid
feverassociatedwithGNwasmade.1Apositiveantibodytestsbyimmunochromatographic
assayconfirmedthediagnosisoftyphoidfever.7AnormalASOtiterandserumC3levelsruled
outthepossibilityofacutepoststreptococcalglomerulonephritis.
AcuteGNdueto/associatedwithtyphoidfeverdevelopsduringthecourseofinfectionasearlyas
thefirstweek.8InthepresentcaseevidenceofGNwasapparentinthesecondweekofillness.
ThereisnolatentperiodbetweentheinfectionandthemanifestationsofGNcausedby/associated
withtyphoidfeverandthustyphoidGNisnotapostinfectiousphenomenon.Almostallthe
casesoftyphoidGNreportedsofarwereactuallyduringanactivestageofthediseasewhere
Salmonellaorganismswereeitherisolatedorpatientshadapositiveserologyandacontinuous
febrilestatewhilesignsofGNwerenoted.2,6,8,9Incontrast,inacutepoststreptococcalGN,
thereisalatentperiodbetweenthestreptococcalinfectionandsignsandsymptomsofGN.10Of
the15casesreportedbyBukaandCoovadia(1980)2serumC3levelswerereportedtobelowin
13andnormalin2casesasalsoinacasereportedbyDo nmezandBasdemir9butnormalC3
levelshavealsobeenreportedinGNdueto/associatedwithtyphoidfever8,10aswasobservedin
thiscase.
ThemechanismofglomerularinjuryintyphoidGNispossiblyimmunecomplexmediated;but
depositionofViantigenhasbeendocumentedinonlyfewcases.MesangialdepositionofIgA,
IgGandC3iscommon.5Histologicalexaminationofrenalbiopsymaybeconsiderednecessary

forconfirmationofGNandtoruleoutotherconditionscloselyresemblingGNespeciallylike
IgAnephropathy.However,inthepresentcasepatientshowedrapidresolutionofedema,
hematuriaandoliguria.Hishypertensionalsoresolvedcompletelyandtherewasnopersistent
microscopichematuriaat8weeksandhencepatientwasnotsubjectedtorenalbiopsy.His
followupat6monthscontinuestobenormaldecreasingthechanceofanybackgroundrenal
disease.
PrognosisisgenerallygoodinacuteGNdueto/associatedwithtyphoidfever.Deathshavebeen
reportedinsomecasesoftyphoidfeverwithacuteGN.However,inmajorityofcasesitresolves
completelyanddoesnotleadtoanylongtermsequele.2

Vol32No.4December2001SEREPORT

TYPHOIDGLOMERULONEPHRITISINACHILD:
ARARECOMPLICATIONOFTYPHOIDFEVER
ChitsanuPancharoen,JuraiWongsawat,SuwanneePhancharoen,UsaThisyakorn
DepartmentofPediatrics,FacultyofMedicine,ChulalongkornUniversity,Bangkok
10330,Thailand
ThepathogenesisoftyphoidGNisprobablycausedbydirectinvasionofS.typhiand
theprocessisimmunemediated.Thisissupportedbyapreviousstudyonrenalbiopsies
ofthreetyphoidpatientswhohadnoclinicalmanifestationsofGN(Sitprijaetal.1974).
TherenalpathologydemonstratedimmunecomplexGN,withdepositionofimmunoglo
bulinsandC,,andsalmonellaViantigenintheglomerularcapillarywall.Renalbiopsy
wasnotperformedinourcasebecausethisprocedurewouldnothavebenefitedourpa
tient,ascommentedinalettertotheeditor(LoGerfo,1974).
Insummary,clinicalGNisararecomplicationoftyphoidfeverwhereassubclinicalGN
maybefrequentandoverlooked.'Thepatientspresentwithclinicalfeaturesofty

CaseReport

Typhoidglomerulonephritisand

intestinalperforationinaNigerian
child
Pediatric Nephrology Unit, 1Department of Pediatrics, University of
Nigeria Teaching Hospital, Ituku Ozalla, Departments of 2Surgery,
Pediatric Surgery Unit, and 3Pediatrics, Enugu State University
Teaching Hospital, Enugu State, Nigeria

Typhoidglomerulonephritisisararecomplicationaffecting24%of
typhoidpatientsinendemicareasandinsubjectstravellingfrom
endemicregions.[1,3]Inadditiontotheclinicalsymptomsoftyphoid
fever,patientswithrenalcomplicationspresentwithedema,macroor
microhematuria,azotemiaandproteinuriawithorwithout
hypertension.[2,6]Thisissimilartothepresentationinourpatient.As
inourpatient,moststudiesreportdevelopmentofcomplicationsof
typhoidinfectioninthe3rdweekofinfectioninuntreatedandmulti
antimicrobialresistantcasesoftyphoidinfectioninchildren.[1,4,5]
Reportsfromothercentershavedocumentedglomerularinvolvements
tohaveabenigncoursewithcompleterecoveryoccurringwithinfew
weeks.[6,7]Theindexpatientpresentedwithsimilarglomerular
involvementswithfullresolutionofsymptomsbytheendof3rdweek
ofhospitaladmission.
Intestinalcomplicationssuchasintestinalperforationand
gastrointestinalhemorrhagearenotedtobemorecommonthanextra
intestinalcomplicationlikenephritisinpatientswithtyphoidinfection.
[1]Ourpatientpresentedwithsymptomsofacuteglomerulonephritis
withgeneralizededemaandasciteswithabdominaldistensionwhich
delayedthesuspicionofpossiblylongexistingintestinalperforation
untilthe5thdayofadmission.
ThoughWidalagglutinationtestmaybeusedfortheconfirmationof
thisdisease,ithasseverallimitations,leavingbloodcultureasthegold
standardinthediagnosis.[8]TheWidaltestdoneintheperipheral
hospitalhowedasignificanttiterbutbloodcultureandother

investigationscouldnotbedoneduetofinancialconstraintsofthecare
giver,whichfurtherdelayedthediagnosisandsurgicalintervention.
Theexploratorylaparotomyfindingsinourpatient,thepatternof
responsetoantimicrobialtherapywithprolongedhospitalizationand
completerecoveryofthepatientaresimilartoreportfromthiscenter.
[5]
AsOboegbulametal.,[9]havereportedthattyphoidisendemicin
SouthEastNigeriawiththerisingnumberofcasesinacertainperiod
oftheyear,thiscasereportdemonstratedtyphoidascauseof
glomerulonephritisinanendemictyphoidarealikeEnugu,SouthEast
Nigeriawithcomorbidityofothercomplicationsliketyphoidintestinal
perforation.

Conclusion
Atypicalpresentationoftyphoidfeverwillresultindelayeddiagnosis
andtreatment.Ahighindexofsuspicionisnecessarytoidentifyallco
existingintestinalandextraintestinalcomplicationsinordertoreduce
themorbidityandmortalityfromthedisease.Ameticulousapproachis
alsorequiredespeciallyinaresourcelimitedsetting.
Odetunde OI, Ezenwosu OU, Odetunde OA, Azubuike JC. Typhoid glomerulonephritis and intestinal
perforation in a Nigerian child. Niger J Clin Pract 2014;17:655-7.