Presymptomatic Diagnosis of Spinal Muscular Atrophy Through Newborn Screening.

OBJECTIVE: To demonstrate the feasibility of presymptomatic diagnosis of spinal muscular atrophy (SMA) through newborn screening (NBS). STUDY DESIGN: We performed a screening trial to assess all newborns who underwent routine newborn metabolic screening at the National Taiwan University Hospital newborn screening center between November 2014 and September 2016. A real-time polymerase chain reaction (RT-PCR) genotyping assay for the SMN1/SMN2 intron 7 c.888+100A/G polymorphism was performed to detect homozygous SMN1 deletion using dried blood spot (DBS) samples. Then the exon 7 c.840C>T mutation and SMN2 copy number were determined by both droplet digital PCR (ddPCR) using the original screening DBS and multiplex ligation-dependent probe amplification (MLPA) using a whole blood sample. RESULTS: Of the 120 267 newborns, 15 tested positive according to the RT-PCR assay. The DBS ddPCR assay excluded 8 false-positives, and the other 7 patients were confirmed by the MLPA assay. Inclusion of the second-tier DBS ddPCR screening assay resulted in a positive prediction value of 100%. The incidence of SMA was 1 in 17 181 (95% CI, 1 in 8323 to 1 in 35 468). Two of the 3 patients with 2 copies of SMN2 and all 4 patients with 3 or 4 copies of SMN2 were asymptomatic at the time of diagnosis. Five of the 8 false-positives were caused by intragenic recombination between SMN1 and SMN2. CONCLUSION: Newborn screening can detect patients affected by SMA before symptom onset and enable early therapeutic intervention. A combination of a RT-PCR and a second-tier ddPCR can accurately diagnose SMA from DBS samples with no false-positives. TRIAL REGISTRATION: ClinicalTrials.gov NCT02123186.

Incidence of severe combined immunodeficiency through newborn screening in a Chinese population.

BACKGROUND/PURPOSE: In order to know the true incidence of severe combined immunodeficiency (SCID) in a Chinese population, we conducted and implemented SCID newborn screening in Taiwan. METHODS: Between May 1, 2010 and December 31, 2011, the National Taiwan University Hospital Newborn Screening Center screened all newborns for T-cell lymphopenia by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were subjected to complete blood cell counts and flow cytometry. RESULTS: A total of 106,391 newborns were screened using the TREC assay over a period of 19 months. Five newborns were immediately referred for confirmatory tests, including two SCID patients and two patients with persistent T-cell lymphopenia; a third SCID patient was found 2 months after the study period. All three SCID cases received stem cell transplantation at the age of 2-5 months. We also identified five cases of 22q11.2 microdeletion syndrome. During this period, two SCID patients from among the unscreened newborns were reported, and they died at ages 3 months and 4 months, respectively. CONCLUSION: Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.

Application of mass spectrometry in newborn screening: about both small molecular diseases and lysosomal storage diseases.

Many genetic diseases, especially the inborn errors of metabolism, have very low incidences, so developing a newborn screening test for each disease is not practical. This obstacle was overcome by employing the tandem mass spectrometry (MS/MS) technology. In the analysis, the samples can be injected directly into the flowing system without passing through a column, and both acylcarnitine and amino acid profiles can be obtained at the same time. MS/MS newborn screening has been shown to improve the outcome of patients affected by a number of inborn errors of metabolism. Recently, MS/MS analytical methods were developed for second-tier tests of newborn screening; new substrates have also been developed to measure the activity of lysosomal enzymes so lysosomal storage diseases can be diagnosed by MS/MS method now.

Polymorphisms of COMT Val158Met and DAT1 3'-UTR VNTR in illicit drug use and drug-related psychiatric disorders.

To investigate the involvement of COMT Val158Met and DAT1 3'-UTR VNTR genotypes in the pathogenesis of illicit drug use and drug-induced psychotic disorders (DIP), 187 substance users and 386 normal controls were recruited from Northern Taiwan. Substance users and normal controls significantly differed in allele frequencies of COMT Val158Met (p = 0.039) but not in allele frequencies of DAT1 3'-UTR VNTR (p = 0.879). However, neither allele frequencies of COMT Val158Met nor allele frequencies of DAT1 3'-UTR VNTR were associated with DIP. The findings should be confirmed in further studies of a larger sample size and a more homogenous patient group.

Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.

Pompe disease is caused by autosomal recessive mutations in the acid alpha-glucosidase (GAA) gene, which encodes GAA. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease-induced pluripotent stem cells (PomD-iPSCs) from two patients with different GAA mutations and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to recombinant human GAA reversed the major pathologic phenotypes. Furthermore, l-carnitine treatment reduced defective cellular respiration in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria-related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for the development of novel therapeutic strategies for Pompe disease.

Newborn screening for citrin deficiency and carnitine uptake defect using second-tier molecular tests.

BACKGROUND: Tandem mass spectrometry (MS/MS) analysis is a powerful tool for newborn screening, and many rare inborn errors of metabolism are currently screened using MS/MS. However, the sensitivity of MS/MS screening for several inborn errors, including citrin deficiency (screened by citrulline level) and carnitine uptake defect (CUD, screened by free carnitine level), is not satisfactory. This study was conducted to determine whether a second-tier molecular test could improve the sensitivity of citrin deficiency and CUD detection without increasing the false-positive rate. METHODS: Three mutations in the SLC25A13 gene (for citrin deficiency) and one mutation in the SLC22A5 gene (for CUD) were analyzed in newborns who demonstrated an inconclusive primary screening result (with levels between the screening and diagnostic cutoffs). RESULTS: The results revealed that 314 of 46 699 newborns received a second-tier test for citrin deficiency, and two patients were identified; 206 of 30 237 newborns received a second-tier testing for CUD, and one patient was identified. No patients were identified using the diagnostic cutoffs. Although the incidences for citrin deficiency (1:23 350) and CUD (1:30 000) detected by screening are still lower than the incidences calculated from the mutation carrier rates, the second-tier molecular test increases the sensitivity of newborn screening for citrin deficiency and CUD without increasing the false-positive rate. CONCLUSIONS: Utilizing a molecular second-tier test for citrin deficiency and carnitine transporter deficiency is feasible.

Lyso-globotriaosylsphingosine (lyso-Gb3) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation.

Lyso-globotriaosylsphingosine (lyso-Gb3) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb3 is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb3 levels from dried blood spots (DBS) from male newborns with the Fabry disease later-onset phenotype, IVS4+919G>A mutation, and their family members. The lyso-Gb3 levels were below the detection limit in normal control newborns and were slightly higher in adults. In males of all ages with the IVS4+919G>A mutation, lyso-Gb3 levels were elevated and were higher than in age-matched controls. The elevation of lyso-Gb3 levels in males with the IVS4+919G>A mutation was only slightly elevated compared with patients with the classical Fabry phenotype. The measurement of lyso-Gb3 levels is useful in the diagnosis of Fabry disease, including the later-onset phenotype. The DBS lyso-Gb3 level was not elevated in IVS4+919G>A heterozygotes, and is not useful for their diagnosis. Since lyso-Gb3 levels are elevated from birth in Fabry disease males, "an elevated lyso-Gb3 level" may be of little values for deciding when to begin enzyme replacement therapy.

Risk factors for HIV, viral hepatitis, and syphilis among heroin users in northern Taiwan.

A total of 125 heroin users were recruited from a detention center and two psychiatric hospitals in northern Taiwan during 2006 in order to investigate the prevalence and correlates of blood-borne infections among heroin users. The seroprevalence rates of the human immunodeficiency virus (HIV), hepatitis C virus (HCV), HBV, HDV, and syphilis were 15.2%, 74.4%, 15.2%, 6.4%, and 8%, respectively. Injection risk behaviors were associated with HIV, HCV, and syphilis infections, but not with HBV infections. Meanwhile, HCV and HBV infections were correlated with the duration of heroin use and age of the subjects, respectively. The results of this study suggest that a comprehensive public health program is needed to prevent transmission of these blood-borne infections. The study's limitations are noted.

Fabry disease: incidence of the common later-onset α-galactosidase A IVS4+919G→A mutation in Taiwanese newborns--superiority of DNA-based to enzyme-based newborn screening for common mutations.

Fabry disease is a panethnic, X-linked, inborn error of glycosphingolipid metabolism resulting from mutations in the α-galactosidase A gene (GLA) that lead to the deficient activity of the lysosomal enzyme, α-galactosidase A (α-Gal A). Affected males with no α-Gal A activity have the early-onset classic phenotype, whereas those with residual activity present with the later-onset subtype. Recently, we reported that newborn enzyme-based screening using dried blood spots (DBS) in Taiwan revealed a high incidence of newborn males who had the GLA c.936+919G→A (IVS4+919G→A) mutation. This lesion causes cryptic splicing, markedly reducing the amount of wild-type GLA mRNA, and has been found in males with the later-onset Fabry phenotype, manifesting as cardiac, renal and/or cerebrovascular disease. To more accurately determine the incidence of the IVS4+919G→A mutation, 20,063 consecutive newborns were screened by a deoxyribonucleic acid (DNA)-based assay. Of the 10,499 males, 12 (1/875) and 24 of the 9,564 females (1/399) had the mutation. On the basis of these frequencies, the previous newborn enzyme-based DBS screening (cutoff: <30% of the normal mean) only identified 67% and 17% of mutation-positive males and females, respectively. The mean DBS α-Gal A activities in the mutation-positive males and females were 23% (1.54 U) and 55% (3.63 U) of normal mean male/female values, respectively. These studies confirm the high incidence of the IVS4+919G→A mutation in the Taiwanese population and indicate that its detectability by enzyme-based DBS screening is unreliable, especially in females. These studies emphasize the superiority of DNA-based newborn screening for common mutations, particularly for X-linked diseases.

Algorithm for Pompe disease newborn screening: results from the Taiwan screening program.

BACKGROUND: Pompe disease is caused by a deficiency in acid α-glucosidase (GAA) and results in progressive, debilitating, and often life-threatening symptoms. Newborn screening has led to the early diagnosis of Pompe disease, but the best algorithm for screening has not yet been established. MATERIALS AND METHODS: GAA and neutral α-glucosidase (NAG) activities in dried blood spots (DBSs) were assayed using 4-methylumbelliferyl-ß-d-glucopyranoside as the substrate. We also measure α-galactosidase A (GLA) activity in DBSs for comparison. A total of 473,738 newborns were screened for Pompe disease, and the data were analyzed retrospectively to determine the best screening algorithm. RESULTS: The fluorescence assay used in the screening possessed good reproducibility, but the NAG/GAA ratio was superior in separating the true-positive from the false-positive cases. An NAG/GAA cutoff ratio≥60 produces a positive predictive value (PPV) of 63.4%, and in our sample, only two cases of later-onset Pompe disease would have been missed. The GLA/GAA ratio is not as effective as the NAG/GAA ratio. CONCLUSION: A suitable control enzyme can improve the performance of newborn screening. Newborn screening for Pompe disease can be performed using the NAG/GAA ratio as a cutoff even in the presence of GAA partial deficiency.

Factors associated with drug-related psychiatric disorders and suicide attempts among illicit drug users in Taiwan.

Illicit drug users, entering a detention center and two psychiatric hospitals in Northern Taiwan, were interviewed for lifetime drug-use-related psychiatric disorders and suicide attempts. Among 197 participants, 17.3%, 16.8%, and 14.2% had a drug-induced psychotic disorder (DIP), a drug-induced mood disorder (DIM), and a history of suicide attempts, respectively. Continuous use of methamphetamine and joblessness were associated with DIP and DIM, accordingly. Polysubstance use was collectively correlated with DIP and DIM. Female gender and history of having any mood disorder were predictors of suicide. These results provide useful clues for detecting drug-related psychiatric disorders and suicide among illicit drug users. The study's limitations are noted.

Elevation of urinary globotriaosylceramide (GL3) in infants with Fabry disease.

BACKGROUND: Fabry disease is caused by a deficiency of α-galactosidase A (α-Gal A), which results in the accumulation of globotriaosylceramide (GL3) and related glycosphingolipids in different organs. Urinary GL3 levels increase in symptomatic Fabry disease patients, but it is not clear whether urinary GL3 excretion also increases in young or pre-symptomatic patients. SUBJECTS AND METHODS: Eighty-nine newborns with leukocyte α-Gal A activities of less than 30% of the normal mean were discovered by newborn screening. Urine samples were collected on filter paper, and GL3 levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Five newborns with classic Fabry disease mutations all had elevated urinary GL3 levels (mean=5.2 mg/mmol creatinine (creat.), range=0.80-14.39, normal <0.6). Among the 84 newborns with later-onset mutations, 45 (54%) had a mild elevation of urinary GL3 levels (mean=1.1 mg/mmol creat., range=0.60-3.07, normal <0.6). The urinary GL3 levels decreased in all newborns over the course of a three-year follow-up period. However, four children with classic mutations and seven with IVS4+919G>A mutations still had elevated GL3 levels at the end of the study. CONCLUSION: Elevated urinary GL3 levels can be present at birth in Fabry disease patients, suggesting an early involvement of the kidneys in this disease. The increased urinary GL3 excretion in those with later-onset mutations supports a pathogenic role for these mutations.

Rapid progressive course of later-onset Pompe disease in Chinese patients.

BACKGROUND: Pompe disease presents with a wide variety of phenotypes ranging from a fatal disease in infancy (the infantile-onset form) to other milder later-onset forms. Currently, the clinical manifestations in Chinese patients with later-onset Pompe disease are still not well understood. METHODS: Fifteen Chinese patients who were clinically diagnosed with Pompe disease at later than one year of age at the National Taiwan University Hospital from 1993 to 2009 were included in this study. Confirmatory diagnosis included both biochemical and molecular tests. Patient outcomes after recombinant human acid α-glucosidase (GAA) therapy were also evaluated by assessing the percentage of predicted forced vital capacity in the upright position, hours of daily ventilator use, and the functional status change using Walton Gardner Medwin Scale. RESULTS: The median age at symptom onset was 15 (12-35)years, and the median age at diagnosis was 21 (10-38)years. At the time of diagnosis or shortly after, 8 patients (53%) required mechanical ventilation. A quadriceps muscle biopsy from a 13-year-old boy already showed extensive glycogen storage and muscle fiber destruction. Mutation analysis revealed that the two dual mutations in the GAA gene c.[1935C>A; 1726G>A] (p.[D645E; G576S]) and c.[2238G>C; 1726G>A] (p.[W746C; G576S]) represented 66.5% of the mutated chromosomes. Using mutagenesis, we showed that the p.G576S pseudodeficiency mutation significantly decreased the residual enzyme activity of p.W746C. Most patients responded poorly to recombinant human GAA. CONCLUSIONS: Chinese patients with later-onset Pompe disease often showed onset of symptoms in their second decade of life with rapid disease progression, which is probably due to a specific pattern of GAA gene mutation. Therefore, early diagnosis and early treatment would be necessary to improve the prognosis of these patients.

The Timely Needs for Infantile Onset Pompe Disease Newborn Screening-Practice in Taiwan.

Pompe disease Newborn screening (NBS) aims at diagnosing patients with infantile-onset Pompe disease (IOPD) early enough so a timely treatment can be instituted. Since 2015, the National Taiwan University NBS Center has changed the method for Pompe disease NBS from fluorometric assay to tandem mass assay. From 2016 to 2019, 14 newborns were reported as high-risk for Pompe disease at a median age of 9 days (range 6-13), and 18 were with a borderline risk at a median age of 13 days (9-28). None of the borderline risks were IOPD patients. Among the 14 at a high-risk of Pompe disease, four were found to have cardiomyopathy, and six were classified as potential late-onset Pompe disease. The four classic IOPD newborns, three of the four having at least one allele of the cross-reactive immunologic material (CRIM)-positive variant, started enzyme replacement therapy (ERT) at a median age of 9 days (8-14). Western Blot analysis and whole gene sequencing confirmed the CRIM-positive status in all cases. Here, we focus on the patient without the known CRIM-positive variant. Doing ERT before knowing the CRIM status created a dilemma in the decision and was discussed in detail. Our Pompe disease screening and diagnostic program successfully detected and treated patients with IOPD in time. However, the timely exclusion of a CRIM-negative status, which is rare in the Chinese population, is still a challenging task.

Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G>A (IVS4+919G>A).

Fabry disease (alpha-galactosidase A (alpha-Gal A, GLA) deficiency) is a panethnic inborn error of glycosphingolipid metabolism. Because optimal therapeutic outcomes depend on early intervention, a pilot program was designed to assess newborn screening for this disease in 171,977 consecutive Taiwanese newborns by measuring their dry blood spot (DBS) alpha-Gal A activities and beta-galactosidase/alpha-Gal A ratios. Of the 90,288 male screenees, 638 (0.7%) had DBS alpha-Gal A activity <30% of normal mean and/or activity ratios >10. A second DBS assay reduced these to 91 (0.1%). Of these, 11 (including twins) had <5% (Group-A), 64 had 5-30% (Group-B), and 11 had >30% (Group-C) of mean normal leukocyte alpha-Gal A activity. All 11 Group-A, 61 Group-B, and 1 Group-C males had GLA gene mutations. Surprisingly, 86% had the later-onset cryptic splice mutation c.936+919G>A (also called IVS4+919G>A). In contrast, screening 81,689 females detected two heterozygotes. The novel mutations were expressed in vitro, predicting their classical or later-onset phenotypes. Newborn screening identified a surprisingly high frequency of Taiwanese males with Fabry disease (approximately 1 in 1,250), 86% having the IVS4+919G>A mutation previously found in later-onset cardiac phenotype patients. Further studies of the IVS4 later-onset phenotype will determine its natural history and optimal timing for therapeutic intervention.

Prevalence of human immunodeficiency virus and its association with hepatitis B, C, and D virus infections among incarcerated male substance abusers in Taiwan.

Taiwan has been facing a rising epidemic of human immunodeficiency virus (HIV) infection since 2004. Injection drug users comprised 38.5% of accumulated HIV cases by 2007. This cross-sectional study investigated the seroprevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and HIV infection in 753 male substance users who were detained in a detoxification center in Taoyuan, Taiwan. The subjects were enrolled into the study consecutively between February and October, 2005. The seroprevalence rates of HIV antibodies, HCV antibodies, and HBV surface antigens among all subjects, and HDV antibodies among HBV carriers were 6.9% (95% confidence interval [CI]: 5.19-8.95), 30.5% (95% CI: 27.23-33.93), 16.9% (95% CI: 14.24-19.71) and 13.7% (95% CI: 8.19-21.04), respectively. Subjects in the heroin injection group had significantly higher rates of HIV infection, HCV infection and HDV superinfection (25.5%, 89.6%, and 38.7%) than those in the heroin non-injection group (0.9%, 24.5%, and 6.25%), the methamphetamine group (0.3%, 8.1%, and 6.7%), and the club drug group (1%, 3%, and 0%; P < 0.001). The odds of HCV, HIV, or HDV infection were 74.7, 63.8, and 11.1 higher, respectively, for heroin injection drug users than for non-injection drug users (P < 0.0001). Compared to HIV-negative individuals, the odds of being a heroin injector and the odds of HCV co-infections were 64-fold and 149-fold higher, respectively, in HIV-positive individuals. The impact of HBV, HCV, and HDV infection on the HIV epidemic in Taiwan should be monitored closely.

The Petersen-Lincoln estimator and its extension to estimate the size of a shared population.

The Petersen-Lincoln estimator has been used to estimate the size of a population in a single mark release experiment. However, the estimator is not valid when the capture sample and recapture sample are not independent. We provide an intuitive interpretation for "independence" between samples based on 2 x 2 categorical data formed by capture/non-capture in each of the two samples. From the interpretation, we review a general measure of "dependence" and quantify the correlation bias of the Petersen-Lincoln estimator when two types of dependences (local list dependence and heterogeneity of capture probability) exist. An important implication in the census undercount problem is that instead of using a post enumeration sample to assess the undercount of a census, one should conduct a prior enumeration sample to avoid correlation bias. We extend the Petersen-Lincoln method to the case of two populations. This new estimator of the size of the shared population is proposed and its variance is derived. We discuss a special case where the correlation bias of the proposed estimator due to dependence between samples vanishes. The proposed method is applied to a study of the relapse rate of illicit drug use in Taiwan.

Performance of the Four-Plex Tandem Mass Spectrometry Lysosomal Storage Disease Newborn Screening Test: The Necessity of Adding a 2nd Tier Test for Pompe Disease.

Early diagnosis of lysosomal storage diseases (LSDs) through newborn screening (NBS) has been adapted widely. The National Taiwan University Hospital Newborn Screening Center launched the four-plex tandem mass spectrometry LSD newborn screening test in 2015. The test determined activities of acid α-glucosidase (GAA; Pompe), acid α-galactosidase (GLA; Fabry), acid ß-glucocerebrosidase (ABG; Gaucher), and acid α-l-iduronidase (IDUA; MPS-I) in dried blood spots (DBS). Through 2017, 64,148 newborns were screened for these four LSDs. The screening algorithm includes enzyme activity/ratio as the cutoffs for the first screening test and a second-tier test for Pompe disease screening. The second-tier Pompe disease screening test measured activity inhibition by acarbose. Twenty-nine newborns required a confirmatory test; six were confirmed to have Pompe disease, and nine were confirmed to have Fabry disease. The screen-positive rate for Pompe disease was 0.031%. Therefore, in Pompe disease newborn screening, a validated 2nd tier test is necessary to decrease false positives.

Prevalence of heroin and methamphetamine male users in the northern Taiwan, 1999-2002: capture-recapture estimates.

BACKGROUND: Illegal drug use and related problems have been emerging as an important public health issue in Taiwan. Via the capture-recapture approach, the present study aimed to offer insights into the size of heroin and methamphetamine male user population in the northern Taiwan during the period from 1999 to 2002. METHODS: Annual lists of male subjects were collated from both judiciary and medical systems in Taoyuan County, Taiwan. A total of 2809, 2486, 1661, and 1440 local male illegal drug users aged 15 to 54 years were identified in Taoyuan County from 1999 to 2002, respectively. RESULTS: An estimated number of 16192, 14532, 16844, and 11783 local male methamphetamine or heroin users were found in each of the four consecutive years in the region. From 1999 to 2002, the annual prevalence rate for heroin use was 0.27% (95% CI = 0.20%, 0.38%), 0.33% (95% CI = 0.25%, 0.44%), 0.63% (95% CI = 0.44%, 0.92%), and 0.72% (95% CI = 0.54%, 0.97%), respectively, suggesting a trend of significant increase (chi-square for linear trend = 1677.76, d.f. = 3, p < 0.0001). In contrast, a decreasing trend was found for methamphetamine (2.38%, 1.91%, 2.47%, and 1.24%), with a modest rebound in 2001. The prevalence rates of illegal drug use for male residents in Taoyuan County were approximately 2-3% during this period, and the scale of problem shows no sign of diminution. CONCLUSION: By taking advantage of existing datasets that were incomplete by each alone, the approach of capture-recapture model may be ultimately considered as a tool to estimate the scale of illegal drug use problems. The population of heroin-using males apparently is stably expanding in the northern part of Taiwan in the first years of 21st century.

Gender difference in the clinical and behavioral characteristics of human immunodeficiency virus-infected injection drug users in Taiwan.

BACKGROUND/PURPOSE: Injection drug users (IDUs) have become the major contributors to the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic in Taiwan, accounting for more than 60% of new cases in 2005. In Taiwan, gender difference in risk factors for HIV among IDUs has not been reported before. We studied the clinical and sociodemographic characteristics, sexual behaviors, drug use histories and criminal records of male and female HIV-infected IDUs. METHODS: A total of 100 male and 25 female HIV-infected inmates from two prisons were included. An individually structured interview was conducted with each inmate. Serostatus of hepatitis B virus (HBV) and hepatitis C virus (HCV) were tested. CD4+ T cell count and HIV viral load were also evaluated. RESULTS: The mean age of the HIV-infected inmates was 31.7 +/- 6.4 years. All inmates were co-infected with HCV and 20% were HBV carriers. The mean CD4+ T cell count was 498 cells/microL, and the mean viral load was 20,119 copies/mL. Heroin use history averaged 6.3 +/- 5.1 years, and 84.8% of patients had a previous criminal offense prior to current conviction. Female inmates were significantly younger, had more sexual partners, had more drug-using family members or sexual partners, shared injection paraphernalia more frequently, and started using methamphetamine and heroin at younger ages (p < 0.05). Male inmates tended to be single, had less parental support, had been more frequently convicted of non drug-related crimes, started using non-illicit substances more frequently at younger ages and had sex with prostitutes more frequently (p < 0.05). CONCLUSION: The results of this study suggest that drug injection risks and sexual behavior related risks are equally important in determining the risk of HIV infection among IDUs. Gender-specific approaches to prevention which reflect differences in gender-related patterns of risk are also needed.