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The genetic subtypes of HIV-1 in the Sudan epidemic have not been characterized. Here we report the partial sequencing and analysis of 30 strains collected from HIV-1-positive patients and blood donors in Khartoum in 1998 and 1999. From analysis of partial pol and env sequences, it was determined that 50% were subtype D and 30% were subtype C. Of interest, some subtype D clustered with those from East Africa whereas others joined subtype D from West Africa. Subtype A, subtype B, and three unique recombinants were also found, some partially unclassifiable. One unclassified strain matched another reported previously from the Democratic Republic of Congo. Sudan borders nine other African countries, and has suffered more than 20 years of civil strife with large population displacements. The intermixing of HIV-1 subtypes previously separated in Africa may be occurring there, with the potential to generate novel new strains by recombination.

Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic component. An association between RA and the human leukocyte antigen (HLA) complex has long been observed in many different populations, and most studies have focused on a direct role for the HLA-DRB1 "shared epitope" in disease susceptibility. We have performed an extensive haplotype analysis, using 54 markers distributed across the entire HLA complex, in a set of 469 multicase families with RA. The results show that, in addition to associations with the DRB1 alleles, at least two additional genetic effects are present within the major histocompatibility complex. One of these lies within a 497-kb region in the central portion of the HLA complex, an interval that excludes DRB1. This genetic risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03 (8.1) haplotype. Additional risk genes may also be present in the HLA class I region in a subset of DRB1*0404 haplotypes. These data emphasize the importance of defining haplotypes when trying to understand the HLA associations with disease, and they clearly demonstrate that such associations with RA are complex and cannot be completely explained by the DRB1 locus.

Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion. DRB1 and DQB1 typing of founders showed that the three haplotypes contained DRB1*1501/ DQB1*0602, DRB1*0801/ DQB1*0402, and DRB1*0301/DQB1*0201 alleles, respectively. By visualizing ancestral recombinants, we narrowed the disease-associated haplotypes containing DRB1*1501 and DRB1*0801 to an approximately 500-kb region. We conclude that HLA class II haplotypes containing DRB1 and DQB1 alleles are strong risk factors for human SLE.

In recent years, we have witnessed an explosion in our understanding of the biology of SLE through the study of lupus-prone mice and the identification and subsequent narrowing of the genomic intervals likely responsible for SLE in human beings. The data from these efforts support the hypothesis that multiple genes contribute to disease susceptibility. Clearly, there is no single locus operating in all families multiplex for SLE, and the degree of ethnic and genetic heterogeneity seems to be quite significant. In this respect, the genetics of SLE resemble those of many other complex genetic diseases. The list of candidate genes and pathways (see Table 1) implicated in the pathogenesis of SLE is expanding at a rapid rate. Understanding how alterations in these genes and pathways lead to the lupus phenotype is the primary objective of future genetic studies in SLE.

We analyzed the genetic diversity of HIV-1 strains circulating in the Czech Republic. Phylogenetic analysis of the env and gag gene sequence fragments from 39 isolates revealed that the majority of these strains (32 of 39, 82%) were of subtype B; other genetic subtypes identified were A, C, F, and recombinant circulating form CRF01_AE. The isolates that did not cluster with subtype B originated almost exclusively from a heterosexual route of transmission. The molecular epidemiological data are suggestive of multiple entry of HIV-1 infection into the Czech Republic and show that the genetic pattern of the HIV-1 strains circulating in this country corresponds to that found in other European countries.

Genetic predisposition plays a crucial role in susceptibility to systemic lupus erythematosus (SLE) in both human patients and animal models. Recent progress in experimental systems and human linkage analysis is providing key insights into the genetic basis for susceptibility and elucidating the manner in which genetic interactions mediate severe disease pathogenesis. Genes in multiple pathways appear to participate in specific elements of the disease, and epistatic interactions among these genes play an important role in both aggravating and suppressing disease development.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.

Background: While children represent the largest population group enrolled in Medicaid managed care, little is known about the pediatric performance measures used by state Medicaid agencies., Objective: To identify Medicaid managed care requirements for using Health Plan Employer Data and Information Set and other performance measures for children (defined as those aged 0-21 years in this study)., Design: A structured telephone survey of pediatric performance measures., Participants: Survey respondents were state Medicaid officials responsible for managed care quality oversight in 39 states., Main Outcome Measures: Percentage of states in 1998 with effectiveness-of-care measures on health promotion and disease prevention, early detection and screening, and acute and chronic illness; with use measures on preventive care, ambulatory care, pharmacy, inpatient hospital care, and mental health and chemical dependency services; and with access measures on primary care, low-birth-weight neonates delivered at appropriate facilities, and dental care., Results: In 1998, state Medicaid agencies placed most of their emphasis on monitoring preventive care for children, with immunization rates being the primary focus. Far less attention was directed at assessing the treatment of acute illness. Although more than half of states monitored the treatment of chronic childhood conditions, they focused exclusively on asthma and selected mental health diagnoses., Conclusions: States are still in the initial phases of designing and implementing quality oversight systems for Medicaid-insured children. Additional quality reporting requirements are clearly needed to assess the treatment of acute and chronic illness among children along with more age-specific reporting requirements.

Hepatitis A virus (HAV) cause an acute inflammation of the liver. Varicella-zoster virus (VZV) cause chickenpox (varicella) and herpes zoster. Effective vaccines against hepatitis A and varicella are available for children, adolescents and adults. In order to implement an appropriate vaccination policy, a baseline to assess the potential benefits and sections of the population who would benefit most are required. We investigated seroprevalence of hepatitis A virus and varicella zoster antibodies in a Javanese community. A total of 1,103 subjects were studied. The 600 subjects aged 4 to 9 years were sampled between 23 October and 2 November, 1995. The other subjects were sampled between 12 October and 1 November, 1996. The overall prevalence of anti-HAV in cohort was 28.7%. Anti-HAV seroprevalence rates were below 30% until the age of 15 and below 40% until the age of 25. The anti-varicella seroprevalence showed only in two thirds of seropositive population at the age of 15. The results of the study have implications for vaccination strategies for both hepatitis A and varicella zoster.

A multicenter cross-sectional survey was conducted comparing a commercially available chlamydial optical immunoassay (OIA) to the chlamydial ligase chain reaction (LCR). Endocervical samples from 415 outpatients visiting clinics from three hospitals in South Kalimantan, Indonesia, were evaluated. Relative to the LCR, the overall sensitivity and specificity of the OIA were 31.6 and 98.9%, respectively. The sensitivity of the OIA varied among the three hospital laboratories, ranging from 20 to 50%. The OIA performance was slightly lower on samples from patients attending dermatovenereology clinics than on samples from nondermatovenereology clinic patients. The results indicate that the OIA did not perform well compared to LCR.

A prospective study on dengue (DEN) viruses was initiated in October 1995 in Gondokusuman kecamatan, Yogyakarta, Indonesia. This report presents data from the first year of the study. The studied cohort included all children 4-9 years of age living in the kecamatan. Blood samples for serology were collected from 1,837 children in October 1995 and again in October 1996. Blood samples for virus isolation and serology were collected from cohort children who were seen in municipal health clinics with febrile syndromes or admitted to hospitals with a provisional diagnosis of dengue hemorrhagic fever. Dengue serotype antibody prevalence and 1995-1996 infection rates were calculated using a single dilution (1:60) 70% plaque reduction endpoint neutralization test. Prevalence of dengue antibody at the beginning of the study was DEN 1 = 12%, DEN 2 = 16%, DEN 3 = 2%, DEN 4 = 4%, and two or more dengue infections = 22%. Total dengue antibody prevalence increased from 38% in 4-year-old children to 69% in 9-year-old children. During the observation period, primary dengue infection rates were DEN 1 = 4.8%, DEN 2 = 7.7%, DEN 3 = 4.2%, and DEN 4 = 3.4%, while two or more dengue infections occurred in 6.7% of the study population. The secondary dengue infection rate was 19.0%. From febrile cases, all four dengue viruses were isolated with DEN 3 predominating. Seven children were hospitalized, including one fatal case with a hospital diagnosis of dengue shock syndrome. Based upon presence of antibody in the initial cohort bleeding and the serologic response both weeks and several months following illness, all had secondary dengue infections. Neutralizing antibody patterns in the initial cohort bleeding and in late convalescent serum samples permitted recognition of dengue infection sequence in five patients: DEN 2-DEN 1 (3), DEN 2-DEN 4 (1), DEN 1-DEN 3 (1), and none in the sequence DEN 1-DEN 2. In the total cohort 6.5% of the observed secondary infections were of the sequence DEN 2-DEN 1, while 4.9% were DEN 1-DEN 2, a highly pathogenic sequence in previous studies. Reduced pathogenic expression of secondary DEN 2 with enhanced pathogenic expression of secondary DEN 1 infections was an unexpected finding. Further studies will be required to understand the respective contributions to pathogenicity of antibody from initial dengue infections versus the biological attributes of the second infecting dengue viruses.

We studied evidence of Bartonella henselae and Bartonella clarridgeiae infection in 54 cats living in Jakarta, Indonesia. By using an indirect immunofluorescence assay, we found immunoglobulin G antibody to B. henselae in 40 of 74 cats (54%). The blood of 14 feral cats was cultured on rabbit blood agar plates for 28 days. Bartonella-like colonies were identified as B. henselae or B. clarridgeiae by using restriction fragment length polymorphism analysis and direct sequencing of the PCR amplicons. Of the cats sampled in the study, 6 of 14 (43%; all feral) were culture positive for B. henselae; 3 of 14 (21%; 2 feral and 1 pet) culture positive for B. clarridgeiae. This is the first report that documents B. henselae and B. clarridgeiae infections in Indonesian cats.

During the months of September 1993 through February 1994, an outbreak of hemorrhagic fever occurred in the city of Jayapura, the provincial capital of Irian Jaya, Indonesia. Seventy-two patients (age range = 1-41 years) with suspected dengue hemorrhagic fever (DHF) were enrolled into the outbreak investigation conducted during October-November 1993. The pediatric patient population consisted of 36 individuals ages 1-12 years of age with a similar male to female ratio. From clinical histories obtained from the children diagnosed with DHF (n = 23), the predominant complaints were fever (100%), headache (96.7%), vomiting (47.8%), abdominal pain (39.1%), back/bone pain (39.1%), cough (39.1%), sore throat (21.7%), convulsions (17.4%), and eye pain (13.0%). Clinical findings of the same pediatric patients included a positive tourniquet test result (100%), thrombocytopenia (100%), hemoconcentration (100%), skin petechiae (43.5%), epistaxis (39.1%), and maculopapular rash (26%). All four of the children diagnosed with DHF grade IV had hepatomegaly, pleural effusion, ascites, cold perspiration, and confusion. Serologic data demonstrated that a majority (46 of 70, 68.7%) of the individuals assessed did not have significant levels of IgM specific for dengue viruses at the time of their admission. However, the nine successful dengue virus isolations were only from these serononreactive cases (19.6%). From the other patients assessed, 11.4% had a primary (or first exposure) serologic response to dengue virus antigen (predominantly IgM); 17.1% had a secondary (or subsequent exposure) serologic response to the same dengue antigens (predominantly IgG response) and 5.7% (four adults) had indeterminate serologic data that could not differentiate between reactivity to dengue or Japanese encephalitis virus antigen preparations. Virus culture of blood samples produced nine dengue virus isolates: DEN- 1 (2), DEN-2 (1), and DEN-3 (6). Japanese encephalitis and influenza viruses were not isolated from blood and pharyngeal specimens, respectively, from any of the patients. Thus, this first reported outbreak of DHF in Irian Jaya, Indonesia was found to be attributed to dengue viruses types 1, 2, and 3.

To examine the genetic and antigenic characteristics of HIV-1 in Indonesia, samples from 19 HIV-positive volunteers were studied. By a combination of PCR typing and DNA sequence analysis, 12 of the 19 volunteers were determined to be infected with HIV-1 clade B and seven with clade E. Six of the seven Indonesian clade E isolates were from volunteers associated with the Indonesian Military during a peacekeeping mission in Cambodia. Infectivity reduction neutralization assays showed that the Indonesian E viruses were effectively neutralized by Thailand clade E HIV-1 antisera but not by U.S. clade B antisera. The Indonesian clade B virus tested was neutralized by U.S. clade B antisera and not by the Thailand E antisera. Using a previously described serologic typing ELISA based on clade B and E V3 peptides, genetic clade was accurately determined in eight of eight sera tested. This is the first report of the genetic and antigenic analysis of HIV-1 isolates from Indonesia. The data indicate that at least two genetic and antigenic HIV-1 clades (clade E and B) circulate in Indonesia.

Objective: To evaluate cervical endometriosis as a source of abnormal glandular cells in cervicovaginal smears., Study Design: Histologically documented cases of cervical endometriosis with concurrent cervicovaginal smears were reviewed. The cytologic specimens were evaluated for the presence of glandular abnormalities., Results: There were eight cases of superficial endometriosis (five of which had concurrent tuboendometrioid glandular metaplasia) and two cases of deep endometriosis in this series. Five of the eight cases of superficial endometriosis had abnormal glandular cells in the smears; neither of two cases of deep endometriosis had glandular abnormalities. Four of the eight cases of superficial endometriosis had previously undergone conization for cervical intraepithelial neoplasia (CIN) (squamous intraepithelial lesion [SIL]) and were being monitored for recurrence. Of the five cases of atypical glandular cells of unknown significance (AGUS), one case had concurrent high grade CIN (SIL). Another case was originally misinterpreted as recurrent glandular dysplasia., Conclusion: Physicians monitoring patients after treatment for CIN need to be aware that endometriosis and tuboendometrioid metaplasia may be the source of atypical glandular cells and on occasion may be subject to misinterpretation.

Leptospiral antibody prevalence was 16% in residents of Baltimore. Seropositivity was associated with age, gender, race, and bird ownership, reduced the antibody risk associated with age and race from odds ratios (95% confidence interval) of 3.3 (2.0, 5.5) and 3.3 (1.1, 9.3), respectively, to the baseline level. These data establish the high prevalence of leptospiral antibody in Baltimore and suggest a protective role for cats in reducing the risk of human infection.

In a series of 1137 diagnostic breast biopsy specimens in a 2-year period, nearly half (n = 534) underwent specimen mammography. Calcifications were found in 48% of the specimen mammograms. In a quarter of the cases, calcification was a marker either for carcinoma or a significant precursor lesion. Moreover, in the majority of these malignancies, calcifications were markers of preinvasive carcinoma. In another quarter of cases, some form of proliferative ductal hyperplasia accounted for calcifications, and in the remainder, cysts and miscellaneous other conditions accounted for calcifications. The yield of malignancy was much lower in noncalcified specimens (12%). A nodular or asymmetric density proved to be a fibroadenoma in 30% of cases. However, the majority of cases had less well-defined changes, probably representing some form of lobular fibrosis. We found submission of a duplicate specimen mammogram with the breast biopsy specimen to pathology to be a significant adjunct to correlation. The abnormal area is marked on the mammogram by the radiologist for the pathologist. This is particularly helpful for localizing noncalcified stromal abnormalities. Calcifications are most easily and reliably isolated by serial slicing and performing another radiograph of the slices.

A clinical case of keratoconjunctivitis sicca prompted a study to determine normal values for the Schirmer tear test in rhesus monkeys. Normal values for rhesus monkeys were calculated to be 6 to 24 mm wetting/minute (mean = 15.1) and it was determined that neither sex nor ketamine had a statistically significant effect on these values.

Two cases of malignant eccrine spiradenoma of the hand are reported. This malignancy is potentially fatal and is believed to arise from preexisting, long-standing benign spiradenomas. These rare tumors should be considered in the hand surgeon's evaluation and management of any long-standing undiagnosed tumor of the hand. Benign spiradenomas should be excised completely and the patient followed carefully. Location and grade of established malignant tumors should dictate therapy.

Epidemiological studies have demonstrated the susceptibility of the owl monkey (Aotus trivirgatus) to hepatitis A virus, but have not shown an association between infection and histopathological or chemical evidence of liver disease. Therefore, 12 seronegative, colony-bred monkeys were inoculated intravenously with a fecal suspension containing either PA33 strain hepatitis A virus (a strain recovered from a naturally infected Aotus sp.) or HM-175 virus (recovered from a human). Viral antigen was detected by radioimmunoassay in the feces of six monkeys 6 to 17 days after inoculation with PA33 virus, and by 9 to 21 days serum aminotransferase activities were significantly elevated in each. Antibody to the virus developed in each monkey by 28 days after inoculation. Similar findings were noted in five of six monkeys inoculated with HM-175 virus, although the incubation period preceding aminotransferase elevations was somewhat longer (25 to 39 days). Liver biopsies obtained from the 11 infected monkeys demonstrated mild to moderate portal inflammation, as well as random areas of focal necrosis and inflammation extending outward from the portal region. These data confirm the susceptibility of Aotus sp. to hepatitis A virus and indicate that the infection of this primate provides a useful animal model of human hepatitis A.