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AD-A234 210 PORT DOCUMENTATION PAGE la. REPORT SECURITY CLASSIFICATION lb. RESTRICTIVE MARKINGS UNCL 2a. SECURITY CLASSIFICATION AUTHORITY 3. DISTRIBUTION/AVAILABILITY OF REPORT Approved for public release; 2b. DECLASSIFICATION /D OWNGRADING SCHEDULE d is t r ibut ion is un li m it ed 4. PERFORMING ORGANIZATION REPORT NUMBER(S) S. MONITORING ORGANIZATION REPORT NUMBER(S) NMRI 91-10 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Naval Medical Research (Ifap plicable) Naval Medical Command Institute 6c. AgDRESS (try, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) 8901 Wisconsin Avenue Department of the Navy Bethesda, MD 20889-5055 Washington, DC 20372-5120 8a. NAME OF FUNDING /SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION Naval Med i ca I (If applicable) Research & Development Commanj 8c ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERS 8901 Wisconsin Avenue PROGRAM PROJECT TASK jWORK UNIT Bethesda, MD 20889-5044 ELEMENT NO. NO. NO. ACCESSION NO. N.A. 11. TITLE (include Security Cassification) Acute sporadic hepatitis in Sudanese children 12. PERSONAL AUTHOR(S) Hyams KC, Hussain MA, Al-Arabi MA, Atallab NA, El-Tigani A, McCarthy MC 13a. TYPE OF REPORT 13b. TIME COVERED 114. DATE OF REPORT (Year, Month, Day) S1.P AGE CO UN T journal article FROM TO 1991 4 16. SUPPLEMENTARY NOTATION Reprinted from: Journal of Medical Virology 1991 Vol.33 pp. 73-76 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP Epstein-Barr Virus, Jaundice, Enteric Transmission 19. ABSTRACT (Continue on reverse if necessary and identify by block number) " -i. Ck" 20. DISTRIBUTION/AVAILABILITY OF ABST " I2 1. ABSTRACT SECURITY CLSSIFTION EUNCLASSIFIEDIUNLIMITED 0 SAME AS RPT oDTIC USERS I Unlassi fied 22a. NAME OF RESPONSIBLE INDIVIDUAL 122b. TELEPHONE (Include Area Code) I2 2c. OFFICE SYMBOL I Phyllis Blum, Librarian (3'0i) 295-2188 MRL/NlrI DO FORM 1473,84 MAR 83 APR edition may be used until exhausted. SECURITY CLASSIFICATION OF THIS PAGE All other editions are obsolete. UNCLASS I F IED i Journal of Medical Virology 33:73-76 (1991) Acute Sporadic Hepatitis in Sudanese Children K.C. Hyams, M.A.M. Hussain, M.A. AI-Arabi, N. AI-Huda Atallah, A. EI-Tigani, and M.C. McCarthy U.S. Naval Medical Research Unit No. 3. Cairo, Egypt (K.C.H., M.C.M.u: Department of Pediatrics,K hartoum Un lersity Teaching Hospital M.A.M.H.. N.A.-H.A.) and Department of Virology, Central Public Health Laboratory, tA.E.-T.', Khartoum, Sudan: Department of Gastrocnterology, Omdurman Hospital, Omdurman, Sudan (M.A.A.-A.) Eighty consecutive cases of acute viral hepatitis PATIENTS AND METHODS and 80 controls selected from a public pediatric The study was conducted at the Pediatric Outpatient clinic were entered into a study of acute sporadic Clinic of the Khartoum University Teaching Hospital, hepatitis in Khartoum, Sudan. Study subjects Khartoum, Sudan. Children 14 years of age or younger were 14 years of age or younger and were presenting with acute clinicaljaundice ofnot more than mainly from a low socioeconomic level. Non-A, 1 month's duration were consecutively entered into the non-B hepatitis was diagnosed by exclusion in sLudy as cases. A control group of subjects was selected 35 (43.8%) patients, hepatitis A in 27 (33.8%), at the same time from patients presenting to the acute hepatitis B in 8 (10.0%), possible Epstein- pediatric clinic with medical complaints but without Barr virus (EBV) hepatitis in 1 patient; and dual evidence of liver pathology. One control subject was hepatitis A and B infection in 1 patient. Eight matched with each case by sex, age(within lyearofthe acute cases were positive for HBsAg but nega- case), and admission date (within 1 week of case tive for anti-HBc IgM and anti-HAV IgM. Delta admission). It was not possible to follow patients after hepatitis was not identified in any study subject. discharge from the hospital. A household case of jaundice and acquaintance The parents of nearly all study subjects were urban with an individual outside of the household with laborers from a low socioeconomic level and were living jaundice during the prior 6 months were associ- in Khartoum or Omdurman, Sudan. Informed consent ated with non-A, non-B hepatitis. There was no was obtained from the parents of all study participants. association between parenteral exposure and An epidemiologic questionnaire was completed for non-A, non-B hepatitis. These findings suggest each study subject. Along with basic demographic data, that enterically transmitted non-A, non-B hepa- the parents of study subjects were asked about exposure titis may be a major cause of acute sporadic to potential risk factors of hepatitis transmission dur- hepatitis in children in this area, as well as a ing the 6 months prior to the onset of symptoms. The cause of epidemic hepatitis. number of people actually living in a study subject's home and the number of major rooms in the home were KEY WORDS: Epstein-Barr virus, jaundice, en- recorded to determine whether crowding was a factor in teric transmission hepatitis transmission [Hyams et al., 19891. An acute serum sample was drawn from each study participant upon entry into the study. Sera were tested for the presence of serologic markers of acute hepatitis A (anti-HAV IgM) and hepatitis B (anti-HBc IgM) INTRODUCTION using commercial ELISA test kits (Abbott Laborato- The importance of non-A, non-B hepatitis as a cause ries, North Chicago, IL). HBsAg-positive and anti- of acute sporadic hepatitis in developing countries is HBc-IgM-positive samples were additionally tested for not well understood, although numerous outbreaks of anti-delta antibody, and HBsAg-negative samples were non-A. non-B hepatitis associated with contaminated tested for anti-HBs (Abbott). Sera samples were also drinkipg water have been reported [Byskov et al., 1989; tested for heterophile antibody (Trend Kit IM, V-Tech, Gust and Purcell, 1987: Kane et al., 1984; Khuroo, Inc., Pomona, CA) and anti-CMV IgM (Enzygnost, 1980: Wong et al., 1980: Zakaria et al., 1988 1.I n Sudan, Hoechst, Behringwerke AG, Marburg, Germany). Sera non-A, non-B hepatitis has been found to be a major were not tested with the newly developed hepatitis C cause of sporadic hepatitis in adults, and an outbreak of ELISA assay because it was not possible to follow study enterically transmitted non-A, non-B hepatitis has been described in a refugee camp [Al-Arabi et al., 1987; CDC. 1987aI. In the present study, the causes and risk Accepted for publication September 5. 1990. factors of acute sporadic hepatitis in Sudanese children Address reprint requests to Research Publications Branch. were investigated. NAMRU-3, New York, 09527-1600. 1991 WILEY-LISS, INC. 91 4 0 5 0t 74 Hyams et al. subjects for extended periods to detect seroconversion to Acute hepatitis A patients tended to be younger (mean, hepatitis C antibody JAlter et al., 19891. 4.1 ± 2.8 years) than other cases of hepatitis (mean, Along with serologic tests, serum samples were an- 7.1 ± 3.3 years). It is noteworthy that a higher percent- alyzed for aspartate aminotransferase (AST), alanine age of acute hepatitis cases (including hepatitis A and aminotransferase (ALT), and total serum bilirubin by non-A, non-B) reported the presence of running water standard methods. Only patients with AST and ALT (59() and electricity (66%) in their homes than did levels greater than two and one-half times the upper controls (33%/( and 44,-/, respectively). limit of normal were considered cases of acute hepatitis. Analysis of hepatitis non-A, non-B cases for potential Patients with evidence of surgical or toxic liver pathol- transmission risk factors indicated that a household ogy were excluded from the study. case of jaundice and acquaintance with a case of Comparisons of proportions were done using the X' jaundice outside the household was more common in test with Yates' correction or the Fisher's exact test. cases of non-A, non-B hepatitis than in controls Mean values (reported as ± 1 SD) were analyzed using (Table 11). The occurrence during the prior 6 months of the Student's t test. parenteral risk factors of infection (transfusion, hospi- RESULTS talization, medical injection, dental care) were no more common in cases of hepatitis non-A, non-B than in Eighty cases and 80 controls were entered into the controls. When hepatitis A cases were evaluated, ac- study from January 1987 to May 1988. Sixty-seven quaintance with a case of jaundice outside the house- percent of cases were male. The mean age of cases hold was more common in hepatitis A cases than in (6.1 _ 3.4 years; range, 1-14 years) was similar to controls (Table 11). Too few patients had acute hepatitis control study subjects (6.3 ± 3.6 years; range, 1-14 B to make meaningful comparisons of risk factors. years). Cases had been ill with jaundice for a mean of There was no relation between the occurrence of risk 6.3 days (range, 1-25 days). factors of transmission and the age and sex of study Based on serologic test results (Table I, hepatitis A subjects. was diagnosed in 27 (33.8%) acute cases, hepatitis B in There was no significant difference between the 8 (10% patients positive for anti-HBc IgM, possible various types of hepatitis and presenting complaints or Epstein-Barr virus (EBV) hepatitis in 1 (1.317) patient physical findings. One acute hepatitis B case and two and dual hepatitis A and B infection in 1 patient. Eight HBsAg-positive/anti-HBC-IgM-negative cases were acute cases were positive for HBsAg but negative for known to have died. Higher AST, ALT, and total anti-HBc IgM and anti-HAV IgM, indicating reactiva- bilirubin levels were found in hepatitis non-A, non-B tion of chronic hepatitis B or chronic hepatitis B with cases compared with hepatitis A and hepatitis B, but superimposed non-A, non-B hepatitis. By exclusion, the differences were not statistically significant non-A, non-B hepatitis was diagnosed in 35 (43.8/,) (Table 111. patients. None of the cases or controls was positive for anti- cytomegalovirus IgM. No control study subject was positive for anti-HBc IgM or heterophile antibody, but Non-A, non-B hepatitis was found to be the most three controls were positive for anti-HAV IgM. HBsAg common cause of acute sporadic hepatitis in this pedi- was found in 7.5% of controls and in 27.51c of cases. One atric population living in an urban area of Sudan. In a control, one hepatitis B case, and five hepatitis non-A, previous study of adults in Omdurman, Sudan, non-A, non-B cases had a previous history of acute jaundice. non-B hepatitis was also found to be the most frequent The sex, number of people living at home, and the cause of acute hepatitis IAI-Arabi et al., 19871. The number of major rooms in the home were similar for additional finding in this study that hepatitis A was a controls and cases of hepatitis A, B, and non-A, non-B. major cause of acute hepatitis in children is consistent TABLE I. Number of Study Subjects With Positive Serologic Markers of Viral Hepatitis Infection Hepatitis class Control A Non-A, non-B Acute B Chronic B" Dual A/B EBV Marker (n = ho, (n = 27) (n -35) (n = 9) (n = 8) (n -1) (n = 1) Anti-IIAV IgM 3 27 0 0 0 1 0 Anti-HBc IgM () 0 0 8 0 1 0 HBsAg 6 8 0 6 8 0 0 Anti-delta 0 0 ( 0 Anti-H~s 5 2 5 3 0 0 0 tleterophile antibody 0 0 0 0 0 0 1 Anti-CMV IgM 0 ( 0 0 0 0 0 f'I1sAg-positivw, a nti-H P,(H-IgM-negative. Pediatric Hepatitis in Sudan 75 TABLE II. Number of Study Subjects With Risk Factors for Hepatitis Transmission Among Controls and Acute Hepatitis A, Non-A, Non-B, and Hepatitis B Cases Control Hepatitis A Non-A, non-B Hepatitis B Risk factor ('X) (n = 80) (n = 27) (n = 35) (n = 8) Contact with jaundiced Family member 3 (4) 2 (7) 5 (14)** 3 (38) Non-household person 7 (9) 6 (22)* 9 (26)*** 2 (25) Parenteral risk factors Medical injection 26 (33) 7 (26) 2 (6) 4 (50) Transfusion 1 (1) 0 (0) 1 (3) 0 (0) Hospitalization 11 (14) 2 (7) 1 (3) 0 (0) Duntal care 0 '0) 0 0 (0) 1 (13) *P -0.13, hepatitis A compared with controls. **P = 0.05, hepatitis non-A, non-B compared with controls, ***P = 0.04, hepatitis non-A, non-B compared with controls. TABLE III. Comparison of Mean Values of Biochemical Tests Among Cases of Acute Hepatitis A, Non-A, Non-B, and Hepatitis B* Hepatitis A Non-A, non-B Hepatitis B Test (mean + SD) (n = 27) (n = 35) (n = 8) AST (IU/liter) 754.2 ± 663.9 955.0 ± 715.3 641.8 ± 459.1 ALT (IU/liter) 583.0 ± 397.9 733.2 ± 534.8 415.0 ± 223.8 Total serum bilirubin (mg/dl) 5.7 ± 4.6 7.2 + 5.0 6.3 ± 3.2 *P> 0.05, non-A, non-B hepatitis compared with hepatitis A and B for all tests. with previous studies of pediatric hepatitis [Dienstag adults [CDC, 1987a,b; Khuroo, 1980; Belabbes et al., et al., 19781. 1985]. Non-A, non-B hepatitis was not associated in this Delta hepatitis was not found to be a cause of acute study of pediatric hepatitis with parenteral exposure. hepatitis in this pediatric population, although it was The previous study of adult hepatitis in Sudan also diagnosed in 13% of adult hepatitis cases in a previous found no increase in parenteral risk factors among study IAl-Arabi et al., 1987]. Finding few acute cases of cases of non-A, non-B hepatitis [Al-Arabi et al., 19871. delta hepatitis in this population endemic for this These findings suggest that enterically transmitted infection could have resulted either from a low level of non-A, non-B hepatitis may be the most frequent cause transmission in children or from an unknown bias in of acute sporadic hepatitis in all age groups in this area, the selection of patients. There was no evidence, how- although the possibility of sexual transmission in ever, of sampling bias in this study except for a higher adults has yet to be studied. percentage of male cases compared with female cases, The association between non-A, non-B hepatitis and which may have resulted from differential utilization of acquaintance with another case of jaundice outside the health services, as previously noted [Al-Arabi et al., household is suggestive of shared exposure to a common 19871. source of infection, like contaminated water, as in epidemic non-A, non-B hepatitis. Because contact with ACKNOWLEDGMENTS a jaundiced household member was also associated This research was supported by the Naval Medical with non-A, non-B hepatitis, person-to-person trans- Research and Development Command, NMC, NCR, mission may be a factor as well JCDC, 1987bI. Bethesda, MD, Work Unit No. 61152N-MR00001001- Previous reports have indicated that both epidemic 3080. The opinions and assertions contained herein are and sporadic non-A, non-B hepatitis are common in the private ones of the authors and are not to be nearby countries, and an outbreak of non-A, non-B construed as official or reflecting the views of the hepatitis has been described in Sudan IBassily et al., Department of the Navy or the Sudanese Ministry of 1986; CDC, 1987a; Belabbes et al., 1985; Khuroo et al., Health. Informed consent was obtained from the par- 1983; Molinie et al., 1988; Nouasria et al., 1984; ents of study subjects, and guidelines for human exper- Shamma's, 1984; Zakaria et al., 19881. However, enter- imentation of the NAMRU-3 Committee for the Pro- ically transmitted non-A, non-B hepatitis has been tection of Human Subjects were followed. The authors noted to have a lower attack rate in children than in acknowledge the assistance of Dr. Sawsan Salih, Fatih 76 Hyams et al. 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