demam tifoid.docx

Tata Laksana Terkini Demam TifoidRHH Nelwan CDK-192/ vol. 39 no. 4, th. 2012

Divisi Penyakit Tropik dan Infeksi Departemen Ilmu Penyakit Dalam, FKUI/RSCM-Jakarta

Sejak awal abad ke 20, insidens demam tifoid menurun di USA dan Eropa dengan ketersediaan air bersih dan sistem pembuangan yang baik yang sampai saat ini belum dimili- ki oleh sebagian besar negara berkembang.1 Secara keseluruhan, demam tifoid diperkira- kan menyebabkan 21,6 juta kasus dengan 216.500 kematian pada tahun 2000. Insidens demam tifoid tinggi (>100 kasus per 100.000 populasi per tahun) dicatat di Asia Tengah dan Selatan, Asia Tenggara, dan kemungkinan Afrika Selatan; yang tergolong sedang (10-100 kasus per 100.000 populasi per tahun) di Asia lainnya, Afrika, Amerika Latin, dan Oceania (kecuali Australia dan Selandia Baru); serta yang termasuk rendah (<10 kasus per 100.000 populasi per tahun) di bagian dunia lainnya.1

Di Indonesia, insidens demam tifoid banyak dijumpai pada populasi yang berusia 3-19 tahun.1 Selain itu, demam tifoid di Indonesia juga berkaitan dengan ru-

700 600

500 400 300 200 100

mah tangga, yaitu adanya anggota keluarga dengan riwayat terkena demam tifoid, tidak adanya sabun untuk mencuci tangan, meng- gunakan piring yang sama untuk makan, dan tidak tersedianya tempat buang air besar dalam rumah.5

Berikut ini gambar mengenai insidens demam tifoid dan usia rata-rata pasien dari studi mengenai demam tifoid di 5 negara Asia, yang salah satunya adalah Indonesia (lihat gambar 1).6

Pemilihan antibiotik tergantung pada pola sensitivitas isolat Salmonella typhi setempat.1 Munculnya galur Salmonella typhi yang resisten terhadap banyak antibiotik (kelompok MDR) dapat mengurangi pilihan antibiotik yang akan diberikan. Terdapat 2 kategori resistensi antibiotik yaitu resisten terhadap antibiotik kelompok chloramphenicol, ampicillin, dan trimethoprim- sulfamethoxazole (kelompok MDR) dan resisten terhadap antibiotik fluoroquinolone.11 Nalidixic

acid resistant Salmonella typhi (NARST ) merupakan petanda berkurangnya sensitivitas terhadap fluoroquinolone.11 Terapi antibiotik yang diberikan untuk demam tifoid tanpa komplikasi berdasarkan WHO tahun 2003 dapat dilihat pada tabel 1.11

Antibiotik golongan fluoroquinolone (ciprofloxacin, ofloxacin, dan pefloxacin) merupakan terapi yang efektif untuk demam tifoid yang disebabkan isolat tidak resisten terhadap fluoroquinolone dengan angka kesembuhan klinis sebesar 98%, waktu penurunan demam 4 hari, dan angka kekambuhan dan fecal carrier kurang dari 2%.1

Fluoroquinolone memiliki penetrasi ke jaringan yang sangat baik, dapat membunuh S. typhi intraseluler di dalam monosit/makrofag, serta mencapai kadar yang tinggi dalam kandung empedu dibandingkan antibiotik lain.11

Berbagai studi telah dilakukan untuk menilai efektivitas fluoroquinolone dan salah satu

fluoroquinolone yang saat ini telah diteliti dan memiliki efektivitas yang baik adalah levofloxacin. Studi komparatif, acak, dan tersamar tunggal telah dilakukan untuk levofloxacin terhadap obat standar ciprofloxacin untuk terapi demam tifoid tanpa komplikasi.12 Levofloxacin diberikan dengan dosis 500 mg, 1 kali sehari dan ciprofloxacin diberikan dengan dosis 500 mg, 2 kali sehari masing-masing selama 7 hari. Kesimpulan dari studi ini adalah bahwa pada saat ini levofloxacin lebih bermanfaat dibandingkan ciprofloxacin dalam hal waktu penurunan demam, hasil mikrobiologi dan secara bermakna memiliki efek samping yang lebih sedikit dibandingkan ciprofloxacin.12

Selain itu, pernah juga dilakukan studi terbu- ka di lingkungan FKUI mengenai efikasi

dan keamanan levofloxacin pada terapi demam tifoid tanpa komplikasi.13 Levofloxacin diberikan dengan dosis 500 mg, 1 kali sehari selama 7 hari. Efikasi klinis yang dijumpai pada studi ini adalah 100% dengan efek samping yang minimal. Dari studi ini juga terdapat tabel perbandingan rata-rata waktu penurunan demam di antara berbagai jenis fluoroquinolone yang beredar di Indonesia di mana penurunan demam pada levofloxacin paling cepat, yaitu 2,4 hari.13

Sebuah meta-analisis yang dipublikasikan pada tahun 2009 menyimpulkan bahwa pada demam enterik dewasa, fluoroquinolone lebih baik dibandingkan chloramphenicol untuk mencegah kekambuhan.14

Namun, fluoroquinolone tidak diberikan pada anak-anak karena dapat mengakibatkan gangguan pertumbuhan dan kerusakan sendi.1,2,11

Chloramphenicol sudah sejak lama digunakan dan menjadi terapi standar pada demam tifoid namun kekurangan dari chloramphenicol adalah angka kekambuhan yang tinggi (5-7%), angka terjadinya carrier juga tinggi, dan toksis pada sumsum tulang.11,15

Azithromycin dan cefixime memiliki angka kesembuhan klinis lebih dari 90% dengan waktu penurunan demam 5-7 hari, durasi pemberi- annya lama (14 hari) dan angka kekambuhan serta fecal carrier terjadi pada kurang dari 4%.1

Pasien dengan muntah yang menetap, di- are berat, distensi abdomen, atau kesadaran menurun memerlukan rawat inap dan pasien

dengan gejala klinis tersebut diterapi sebagai pasien demam tifoid yang berat.1 Terapi antibiotik yang diberikan pada demam tifoid berat menurut WHO tahun 2003 dapat dilihat di tabel 2.11 Walaupun di tabel ini tertera cefotaxime untuk terapi demam tifoid tetapi sayangnya di Indonesia sampai saat ini tidak terdapat laporan keberhasilan terapi demam tifoid dengan cefotaxime.

Selain pemberian antibiotik, penderita perlu istirahat total serta terapi suportif. Yang diberikan antara lain cairan untuk mengkoreksi ketidakseimbangan cairan dan elektrolit dan antipiretik.1,2 Nutrisi yang adekuat melalui TPN dilanjutkan dengan diet makanan yang lembut dan mudah dicerna secepat keadaan mengizinkan.1,2

Tabel 1 Antibiotik yang diberikan pada demam tifoid tanpa komplikasi menurut WHO 2003Tabel 2 Antibiotik yang diberikan pada demam tifoid berat menurut WHO 2003

RINGKASAN

• Demam tifoid masih menjadi masalah kesehatan yang penting di negara yang sedang berkembang di Asia, termasuk Indonesia. Juga di Afrika Selatan dan Amerika Latin.

• Diagnosis demam tifoid ditegakkan berdasarkan gambaran klinis dan pemeriksaan tambahan dari laboratorium.

• Terapi yang diberikan adalah istirahat, diet lunak, dan antimikroba. Pada saat ini,

antimikroba dengan waktu penurunan demam cepat, pemberian praktis 1 kali sehari selama 7 hari, dan efek samping minimal adalah levofloxacin.

• Diagnosis demam tifoid yang ditegakkan secara dini dan disertai pemberian terapi yang tepat mencegah terjadinya komplikasi, kekambuhan, pembawa kuman (carrier), dan kemungkinan kematian.

• Strategi pencegahan diarahkan pada ketersediaan air bersih, menghindari makanan yang terkontaminasi, higiene perorangan, sanitasi yang baik, dan pemberian vaksin sesuai kebutuhan.

REVIEW 10.1111/j.1469-0691.2011.03552.x

Treatment of typhoid fever in the 21st century: promises

and shortcomings

T. Butler

Department of Microbiology and Immunology, Ross University School of Medicine, North Brunswick, NJ, USA

Abstract

Emergence of multidrug resistance and decreased ciprofloxacin susceptibility (DCS) in Salmonella enterica serovar Typhi in South Asia have rendered older drugs, including ampicillin, chloramphenicol, trimethoprim–sulphamethoxazole, ciprofloxacin, and ofloxacin, ineffective or suboptimal for typhoid fever. Ideally, treatment should be safe and available for adults and children in shortened courses of 5 days, cause defervescence within 1 week, render blood and stool cultures sterile, and prevent relapse. In this review of 20 prospective clinical trials that enrolled more than 1600 culture-proven patients, azithromycin meets these criteria better than other drugs. Among fluoroquinolones, which are more effective than cephalosporins, gatifloxacin appears to be more effective than ciprofloxacin and ofloxacin for patients infected with bacteria showing DCS. Ceftriaxone continues to be useful as a back-up choice, and chloramphenicol, despite its toxicity for bone marrow and history of plasmid-mediated resistance, is making a comeback in developing countries that show their bacteria to be susceptible to it.

Keywords: Enteric fever, Salmonella, Salmonella enterica, serovar Paratyphi A, serovar Typhi, Typhi, typhoid fever Article published online: 25 April 2011Clin Microbiol Infect 2011; 17: 959–963

Azithromycin should be used more, both in developing countries with a high prevalence of infection caused by bacteria with DCS and in returned travellers in industrialized countries. Other than the higher cost, it outperforms other drugs with regard to cure rates, speed of defervescence against infections caused by bacteria with DCS, and prevention of faecal carriage and relapse. Resistance of S. Typhi to azithromycin has not emerged, but cultured strains need to be tested for susceptibility, because one case of resistant S. Paratyphi A infection treated with this antibiotic resulted in clinical failure [30]. Against infections caused by bacteria with DCS, it is the only effective drug that can be used in short, 5-day courses [4,8]. Ceftriaxone in shortened courses of 5 or 7 days has significant relapse rates [8,28], but, as a back-up, this antibiotic can achieve clinical cure with good reliability. Although chloramphenicol continues to be used in countries without resistance to it, this old drug allows relapses [16,31] and exposes patients to serious toxicity.

Pilihan Terapi Empiris

Demam Tifoid pada Anak: Kloramfenikol atau Seftriakson?Sondang Sidabutar, Hindra Irawan Satari

Departemen Ilmu Kesehatan Anak, RS Dr Cipto Mangunkusumo, Fakultas Kedokteran Universitas Indonesia, Jakarta

erdasarkan hasil penelusuran literatur yang ada, studi terkini lebih menganjurkan pemberian seftriakson dibandingkan kloramfenikol untuk pasien demam tifoid yang dirawat di rumah sakit. Beberapa studi menunjukkan bukti luaran yang lebih baik tentang penggunaan seftriakson sebagai terapi empiris pada demam tifoid. Kriteria yang sebaiknya dipenuhi oleh antibiotik empiris antara lain cara pemberian

Sari Pediatri, Vol. 11, No. 6, April 2010

437

Sondang Sidabutar dkk: Pilihan terapi empiris demam tifoid pada anak: kloramfenikol atau seftriakson?

mudah bagi anak, tidak mudah resisten, efek samping minimal, dan telah terbukti efikasi secara klinis.19 Pada kasus kami, usia pasien sesuai dengan predileksi usia tersering, dan terdapat riwayat jajan yang merupakan sumber penularan penyakit. Perjalanan penyakit pasien telah memasuki minggu kedua demam, dan terdapat gangguan gastrointestinal yang menyebabkan asupan tidak adekuat dan anak terlihat lemas. Pada pasien dengan perjalanan klinis yang telah memasuki minggu kedua dengan gejala gastrointestinal yang nyata, terapi peroral tidak ideal.

Lama demam turun (time of fever defervescence) merupakan salah satu

parameter keberhasilan pengobatan. Demam yang tetap tinggi menunjukkan kemungkinan komplikasi, fokus infeksi lain, resistensi S. typhi, atau salah diagnosis.19 Berdasarkan hasil uji resistensi bakteri terhadap berbagai antibiotik, tidak ditemukan adanya MDRST dari isolat yang diperiksa sejak tahun 2003-2007 di laboratorium Mikrobiologi Fakultas Kedokteran Universitas Indonesia.20 Demam tifoid anak dengan MDRST secara klinis akan menunjukkan respon yang lambat terhadap terapi (lebih dari 48-72 jam), lebih sering mengalami komplikasi, dan kemungkinan menjadi fatal lebih besar. Antibiotik terpilih untuk MDRST adalah siprofloksasin dan seftriakson. Pemberian siprofloksasin pada anak usia <18 tahun masih diperdebatkan karena adanya potensi artropati, sehingga seftriakson lebih direkomendasikan.8,5 Pasien kami memiliki kepatuhan minum obat yang baik, tidak ditemukan fokus infeksi lain, dan dosis antibiotik kloramfenikol yang diberikan telah sesuai. Secara invitro, S. typhi menunjukkan sensitivitas terhadap kloramfenikol, namun respons yang ditunjukkan pasien tidak sesuai. Riwayat pemakaian antibiotik peroral selama rawat jalan dan respons yang lambat terhadap kloramfenikol di rumah sakit, menunjukkan kemungkinan adanya resistensi, sehingga antibiotik seharusnya dapat diganti lebih awal.1

Perbedaan yang mendasar pada kedua antibiotik ini adalah lama demam turun lebih cepat sehingga lama terapi lebih singkat, efek samping lebih ringan, dan angka kekambuhan yang lebih rendah pada penggunaan seftriakson dibandingkan kloramfenikol. Durasi terapi seftriakson bervariasi antara 3 -10 hari dengan waktu demam turun rata-rata empat hari, dan aman diberikan pada anak dengan dosis antara 50-100 mg/kg/hari.12,13,15,16 Efek samping yang mungkin ditemukan karena pemberian kloramfenikol

438

adalah supresi sumsum tulang.13,15 Harga seftriakson lebih mahal dibanding kloramfenikol, namun lama rawat yang lebih pendek sangat mengurangi biaya pengobatan.l4,18,19 Pasien mengalami efek samping kloramfenikol berupa supresi sumsum tulang. Setelah pemberian seftriakson dengan dosis 80mg/kg berat badan/hari dengan maksimal dosis 2 g/hari, demam turun setelah hari ketiga terapi. Seftriakson

dilanjutkan sampai lima hari pengobatan, terbukti memberikan respon klinis yang baik.

Kesimpulan

Antibiotik empiris yang tepat sangat bermakna menurunkan morbiditas dan mortalitas. Pemberian seftriakson sebagai terapi empiris pada pasien demam tifoid secara bermakna dapat mengurangi lama pengobatan dibandingkan dengan pemberian jangka panjang kloramfenikol. Hal lain yang menguntungkan adalah efek samping dan angka kekambuhan yang lebih rendah, serta lama demam turun yang lebih cepat. Pengetahuan dan penilaian klinis yang baik diperlukan dalam memilih terapi empiris yang tepat terutama bila fasilitas uji resistensi tidak memadai. Seftriakson terbukti dapat dijadikan sebagai antibiotik pilihan utama pada kasus MDRST.

Guidelines for the diagnosis, management, and prevention of typhoid fever [2010]

Ministry of Health Fiji IslandsDRAFT – for endorsement4 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.

6 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

FijiThe 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, 5, 6

It has the lowest clinical failure rate, results in

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 casesTable 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 AnakNovie Homenta Rampengan

Sari Pediatri 2013;14(5):271-6.

Pilihan obat antibiotik lini pertama pengobatan demam tifoid pada anak di negara berkembang didasarkan pada faktor efikasi, ketersediaan, dan biaya. Berdasarkan ketiga faktor tersebut, kloramfenikol masih menjadi obat pilihan pertama pengobatan demam tifoid pada anak.

Selama kurun waktu 4 tahun (2008-2012), jumlah kasus demam tifoid yang dirawat di RSCM Jakarta yang mendapat pengobatan kloramfenikol 13 orang, klinis membaik pada hari sakit ke-6 yaitu 23,1%. Berdasarkan pola kuman dan uji kepekaan terhadap antibiotik di RSCM pada tahun 2009-2010, hasil biakan S. typhi positif pada 8 spesimen, dengan sensitifitas kloramfenikol lebih dari 75%.17

Azitromisin adalah antibiotik golongan makrolid pertama yang termasuk dalam kelas azalide. Menurut WHO, pemberian azitromisin dengan dosis 10 mg/ kgBB selama 7 hari terbukti efektif pada terapi demam

tifoid tanpa komplikasi pada anak dan dewasa dengan lama turun panas yang serupa dengan yang dilaporkan pada pemberian kloramfenikol.18 Penelitian invitro menunjukkan azitromisin lebih poten terhadap Salmonella spp. dibandingkan dengan obat lini pertama dan makrolid lain. Belum terdapat laporan tentang resistensi S. typhi terhadap azitromisin. Studi terbaru menunjukkan azitromisin efektif secara klinis dan bakteriologis dalam mengobati demam tifoid bahkan yang

disebabkan oleh strain MDR.19

Azitromisin dan kloramfenikol berbeda dalam hal cara pemberian, farmakokinetik, prinsip terapi, dan efek samping. Azitromisin diberikan sekali sehari, sedangkan kloramfenikol diberikan empat kali sehari. Kedua antibiotik berpenetrasi ke dalam sel secara efektif, dan hal tersebut menerangkan aktivitas terapeutik obat terhadap patogen yang berada di intraselular seperti S. typhi.20

Sefiksim merupakan antibiotik golongan sefalosporin generasi ketiga oral, mempunyai aktifitas antimikroba terhadap kuman Gram positif maupun negatif termasuk Enterobacteriaceae. Sefiksim mempunyai efikasi dan toleransi yang baik untuk pengobatan demam tifoid anak.21

Meskipun kloramfenikol sampai saat ini masih merupakan obat pilihan lini pertama (first drug of choice) untuk pengobatan demam tifoid pada anak, obat lini kedua seperti azitromisin dan sefiksim dapat dipertimbangkan dalam terapi demam tifoid tanpa komplikasi pada anak terutama pada kasus dengan kepatuhan (compliance) minum obat diragukan atau apabila kloramfenikol tidak dapat diberikan (misalnya jumlah leukosit <2.000/ul, adanya hipersensitif terhadap kloramfenikol, MDR S. typhi).20

Penelitian kami mempunyai beberapa keterbatasan. Kami tidak melakukan pemeriksaan biakan darah sebagai baku emas diagnosis demam tifoid serta tidak dapat memperlihatkan pola kuman dan kepekaan antibiotik secara invitro. Selain itu, karena penelitian retrospektif, kami tidak dapat melakukan kontrol dan penyeragaman terhadap lama rawat di rumah sakit pada tiap kelompok antibiotik. Lama rawat di rumah sakit tidak selalu berhubungan dengan derajat penyakit. Akan tetapi dapat berhubungan dengan variabel lain yang tidak berkaitan dengan penyakitnya, seperti adanya penyakit lain, anoreksia relatif, atau pasien yang tidak taat dalam minum obat. Dibutuhkan penelitian lanjutan dengan subjek yang lebih besar, pemeriksaan laboratorium mikrobiologi,

MANAGEMENT OF ENTERIC FEVER IN 2012Falguni 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.

ASCITES — An Under-reported Finding in Enteric Fever?

Altered liver function is a notable feature of typhoid fever, but they are usually transient and resolve by 2 -3 weeks(2), similar to this series. Though there are many reports of peritonitis in typhoid fever only a couple of case reports on peritoneal fluid collection without any evidence of perforation are available in international literature. Chiu, et al.(3) reported an incidence of 4% of ascites or pleural effusion among 71 children with typhoid fever.

Judet, et al.(4) reported two cases of peritoneal effusion in patients with typhoid fever and suggested that typhoid fever should be considered when ultrasono- graphy shows an isolated peritoneal effusion in a febrile child.

The cause of ascites is not clear . Burdzinska, et al.(5) described polyserositis in course of typhoid fever .The exudative nature of the fluid in our cases also points to a generalised inflammation of peritoneal serous layer. Albumin was not low enough to be a likely cause .

3. Chiu CH, Tsai JR, Ou JT, Lin TY. Typhoid fever in children : A fourteen year experience. Acta Pediatr Taiwan 2000; 41: 28-32.

4. Judet O, Rouveix E, V erderi D, Bismuth V . A classical but unknown cause of peritoneal effusion disclosed by echography. Typhoid fever. J Radiol 1989; 70: 419-421.

5. Burdzinska J, Nowakowski TK , Pellar J. Polyserositis in the course of typhoid fever. Przegl Epidemiol 1966; 20: 211-215.

6. Shai Ashkenazi, Thomas G. Cleary. In: Salmonella Infections . Behrman, Kliegman Arvin, editors, Nelson Textbook of Pediatrics, 15th edition, W.B. Saunders Company, USA, pp 788-790.

7. Jagadish K, Patwari AK, Sarin S, Prakash C Srivastava, Anand VK. Hepatic mani-

Preventive Education against HIV/ AIDS in the Schools of

Iran

With reference to the informative editorial by Dr. M.K.C. Nair entitled: “Adolescent Sexual and Reproductive Health”(1), we present a summary of our recent country study of preventive education against HIV/ AIDS in the schools in Iran(2). Like India(1) the cultural and social mores of Iran complicate discussion of sexual activity, especially among the youth and unmarried(2,3). To deal with this as an obstacle in the preventive education, peer education programs have been started in guidance schools and high schools all over the country and thousands of students are being trained every year to educate their peers on HIV/AIDS(2). Consultants and health workers in guidance schools and high schools will educate the selected students for efficient peer education. These trained students will also attend the campaigns held by the Ministry of Education. We have

INDIAN PEDIA TRICS

Correspondence to:

Dr. Rajiv Sinha,

festations in typhoid fever. Indian Pediatr 1994; 31: 807-8.

3. Chiu CH, Tsai JR, Ou JT, Lin TY. Typhoid fever in children : A fourteen year experience. Acta Pediatr Taiwan 2000; 41: 28-32.

Typhoid glomerulonephritis pediatric infectious disease 5 (2013) 175e177

Case Report

A case report of acute glomerulonephritis associated with typhoid fever

Rajendra Karambelkar*, Geeta Karambelkar, Pravin Babhalgaonkar Consultant Pediatrician, Pune, Maharashtra, India

Despite high number of cases of typhoid fever worldwide and its various known complications 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.Reports dating back more than three decades have placed overall incidence of renal involvement in typhoid fever at 2e3%. However, in most cases mild proteinuria is the only manifestation.3 Various other forms of renal involvement include hemolytic-uremic syndrome, pyelonephritis, nephrotic syndrome, cystitis, interstitial nephritis and acute renal failure. However, acute GN during typhoid fever is uncommon.4,5 After the series of 15 children of typhoid GN reported by Buka and Coovadia2 in 1980 very few cases have been reported in the literature later on.6

In the present case the clinical presentation of fever >10 days duration, abdominal symptoms, edema, oliguria, hypertension, hematuria, and >5 fold rise in Widal titers a diagnosis of typhoid fever associated with GN was made.1 A positive antibody tests by immunochromatographic assay confirmed the diagnosis of typhoid fever.7 A normal ASO titer and serum C3 levels ruled out the possibility of acute post- streptococcal glomerulonephritis.

Acute GN due to/associated with typhoid fever develops during the course of infection as early as the first week.8 In the present case evidence of GN was apparent in the second week of illness. There is no latent period between the infection and the manifestations of GN caused by/associated with typhoid fever and thus typhoid GN is not a post-infectious phenome- non. Almost all the cases of typhoid GN reported so far were actually during an active stage of the disease where Salmo- nella organisms were either isolated or patients had a positive serology and a continuous febrile state while signs of GN were noted.2,6,8,9 In contrast, in acute post-streptococcal GN, there is a latent period between the streptococcal infection and signs and symptoms of GN.10 Of the 15 cases reported by Buka and Coovadia (1980)2 serum C3 levels were reported to be low in 13 and normal in 2 cases as also in a case reported by Do T nmez and Bas‚ demir9 but normal C3 levels have also been reported in GN due to/associated with typhoid fever8,10 as was observed in this case.

The mechanism of glomerular injury in typhoid GN is possibly immune complex mediated; but deposition of Vi antigen has been documented in only few cases. Mesangial deposition of IgA, IgG and C3 is common.5 Histological ex- amination of renal biopsy may be considered necessary for confirmation of GN and to rule out other conditions closely resembling GN especially like IgA nephropathy. However, in the present case patient showed rapid resolution of edema, hematuria and oliguria. His hypertension also resolved completely and there was no persistent microscopic hematuria at 8 weeks and hence patient was not subjected to renal biopsy. His follow up at 6 months continues to be normal decreasing the chance of any background renal disease.

Prognosis is generally good in acute GN due to/associated with typhoid fever. Deaths have been reported in some cases of typhoid fever with acute GN. However, in majority of cases it resolves completely and does not lead to any long-term sequele.2

Vol 32 No. 4 December 2001 SE REPORT

TYPHOID GLOMERULONEPHRITIS IN A CHILD: A RARE COMPLICA TION OF TYPHOID FEVER

Chitsanu Pancharoen, Jurai Wongsawat, Suwannee Phancharoen, Usa Thisyakorn

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

The pathogenesis of typhoid GN is prob- ably caused by direct invasion of S. typhi and the process is immune-mediated. This is sup- ported by a previous study on renal biopsies of three typhoid patients who had no clinical manifestations of GN (Sitprija et al. 1974). The renal pathology demonstrated immune complex GN, with deposition of immunoglo- bulins and C,, and salmonella Vi antigen in the glomerular capillary wall. Renal biopsy was not performed in our case because this procedure would not have benefited our patient, as commented in a letter to the editor (LoGerfo, 1974).

In summary, clinical GN is a rare complication of typhoid fever whereas subclinical GN may be frequent and overlooked. 'The patients present with clinical features of ty-

Case Report

Typhoid glomerulonephritis and intestinal perforation in a Nigerian childPediatric 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

Typhoid glomerulonephritis is a rare complication affecting 2‐4% of typhoid patients in endemic areas and in subjects travelling from endemic regions.[1,3] In addition to the clinical symptoms of typhoid fever, patients with renal complications present with edema, macro‐or micro‐hematuria, azotemia and proteinuria with or without

hypertension.[2,6] This is similar to the presentation in our patient. As in our patient, most studies report development of complications of typhoid infection in the 3rd week of infection in untreated and multi‐antimicrobial resistant cases of typhoid infection in children.[1,4,5] Reports from other centers have documented glomerular involvements to have a benign course with complete recovery occurring within few weeks.[6,7] The index patient presented with similar glomerular involvements with full resolution of symptoms by the end of 3rd week of hospital admission.

Intestinal complications such as intestinal perforation and gastrointestinal hemorrhage are noted to be more common than extra intestinal complication like nephritis in patients with typhoid infection.[1] Our patient presented with symptoms of acute glomerulonephritis with generalized edema and ascites with abdominal distension which delayed the suspicion of possibly long existing intestinal perforation until the 5th day of admission.

Though Widal agglutination test may be used for the confirmation of this disease, it has several limitations, leaving blood culture as the gold standard in the diagnosis.[8] The Widal test done in the peripheral hospital howed a significant titer but blood culture and other investigations could not be done due to financial constraints of the care giver, which further delayed the diagnosis and surgical intervention. The exploratory laparotomy findings in our patient, the pattern of response to antimicrobial therapy with prolonged hospitalization and complete recovery of the patient are similar to report from this center.[5]

As Oboegbulam et al.,[9] have reported that typhoid is endemic in South‐East Nigeria with the rising number of cases in a certain period of the year, this case report demonstrated typhoid as cause of glomerulonephritis in an endemic typhoid area like Enugu, South‐East Nigeria with co‐morbidity of other complications like typhoid intestinal perforation.

Conclusion

Atypical presentation of typhoid fever will result in delayed diagnosis and treatment. A high index of suspicion is necessary to identify all co‐existing intestinal and extra‐intestinal complications in order to reduce the morbidity and mortality from the disease. A meticulous approach is also required especially in a resource‐limited setting.

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.

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