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1.  Prevalence and Novel Mutations of Lysosomal Storage Disorders in United Arab Emirates 
JIMD Reports  2013;10:1-9.
Lysosomal storage disorders (LSD) are rare entities of recessive inheritance. The presence of a “founder” mutation in isolated communities with a high degree of consanguinity (e.g., tribes in the Middle East North Africa, MENA, region) is expected to lead to unusually high disease prevalence. The primary aim of this study was to estimate the prevalence of LSD and report their mutation spectrum in UAE. Between 1995 and 2010, 119 patients were diagnosed with LSD (65 Emiratis and 54 non-Emiratis). Genotyping was performed in 59 (50 %) patients (39 Emirati from 17 families and 20 non-Emiratis from 17 families). The prevalence of LSD in Emiratis was 26.9/100,000 live births. Sphingolipidoses were relatively common (9.8/100,000), with GM1-gangliosidosis being the most prevalent (4.7/100,000). Of the Mucopolysaccharidoses VI, IVA and IIIB were the predominant subtypes (5.5/100,000). Compared to Western countries, the prevalence of fucosidosis, Batten disease, and α-mannosidosis was 40-, sevenfold, and fourfold higher in UAE, respectively. The prevalence of Pompe disease (2.7/100,000) was similar to The Netherlands, but only the infantile subtype was found in UAE. Sixteen distinct LSD mutations were identified in 39 Emirati patients. Eight (50 %) mutations were reported only in Emirati, of which three were novel [c.1694G>T in the NAGLU gene, c.1336 C>T in the GLB1 gene, and homozygous deletions in the CLN3 gene]. Twenty-seven (42 %) patients were clustered in five of the 70 Emirati tribes. These findings highlight the need for tribal-based premarital testing and genetic counseling.
doi:10.1007/8904_2012_182
PMCID: PMC3755583  PMID: 23430803
2.  Mutation Spectrum and Birth Prevalence of Inborn Errors of Metabolism among Emiratis 
Objectives:
This study aimed to determine the mutation spectrum and prevalence of inborn errors of metabolism (IEM) among Emiratis.
Methods:
The reported mutation spectrum included all patients who were diagnosed with IEM (excluding those with lysosomal storage diseases [LSD]) at Tawam Hospital Metabolic Center in Abu Dhabi, United Arab Emirates, between January 1995 and May 2013. Disease prevalence (per 100,000 live births) was estimated from data available for 1995–2011.
Results:
In 189 patients, 57 distinct IEM were diagnosed, of which 20 (35%) entities were previously reported LSD (65 patients with 39 mutations), with a birth prevalence of 26.87/100,000. This study investigated the remaining 37 (65%) patients with other IEM (124 patients with 62 mutations). Mutation analysis was performed on 108 (87%) of the 124 patients. Five patients with biotinidase deficiency had compound heterozygous mutations, and two siblings with lysinuric protein intolerance had two homozygous mutations. The remaining 103 (95%) patients had homozygous mutations. As of this study, 29 (47%) of the mutations have been reported only in Emiratis. Two mutations were found in three tribes (biotinidase deficiency [BTD, c.1330G>C] and phenylketonuria [PAH, c.168+5G>C]). Two mutations were found in two tribes (isovaleric aciduria [IVD, c.1184G>A] and propionic aciduria [PCCB, c.990dupT]). The remaining 58 (94%) mutations were each found in individual tribes. The prevalence was 48.37/100,000. The most prevalent diseases (2.2–4.9/100,000) were biotinidase deficiency; tyrosinemia type 1; phenylketonuria; propionic aciduria; glutaric aciduria type 1; glycogen storage disease type Ia, and mitochondrial deoxyribonucleic acid depletion.
Conclusion:
The IEM birth prevalence (LSD and non-LSD) was 75.24/100,000. These results justify implementing prevention programmes that incorporate genetic counselling and screening.
PMCID: PMC3916276  PMID: 24516753
Metabolism, Inborn Errors; Mutations; Prevalence; Founder Effect; United Arab Emirates
3.  Spectrum of Paediatric Lysosomal Storage Disorders in Oman 
Objectives:
The aim of this study was to look at the spectrum of paediatric lysosomal disorders in Oman. Lysosomal storage disorders (LSDs) are a heterogeneous group of inherited metabolic diseases. Few studies on the birth prevalence and prevalence of LSDs have been reported from the Arabian Peninsula.
Methods:
We studied 86 children with LSDs diagnosed over a period of nine years, from June 1998 to May 2007. Detailed clinical data, including age of onset, sex, age and mode of first presentation, and presence of consanguinity were collected.
Results:
Our data showed the combined birth prevalence for all LSDs in Oman to be around 1 in 4,700 live births. Sphingolipidoses was the most common group of disorder encountered (47.7%), followed by neuronal ceroid lipofuscinoses (NCL) (23.2%) and mucopolysaccharidoses (MPS) (23.2%). The proportion of consanguineous marriages in our series was found to be 87.5%.
Conclusion:
Our data represent the birth prevalence and clinical spectrum of such disorders in Oman, one of the highly consanguineous societies in the Middle East.
PMCID: PMC3413619  PMID: 22912921
Lysosomal storage disorders; Oman; Prevalence; Arabs
4.  Incidence and patterns of inborn errors of metabolism in the Eastern Province of Saudi Arabia, 1983-2008 
Annals of Saudi Medicine  2010;30(4):271-277.
BACKGROUND AND OBJECTIVES:
Individual inborn errors of metabolism (IEM) are rare disorders, but may not be that uncommon in our patient population. We report the incidence of IEM in a defined cohort of births at the Saudi Aramco medical facilities in the Eastern Province of Saudi Arabia over 25 years.
METHODS:
The records of all patients diagnosed with IEM from 1 January 1983 to 31 December 2008 were reviewed and categorized according to accumulated or deficient metabolites into small-molecule disorders (aminoacidemia, organic acidopathies [OA], urea cycle defects, fatty acid oxidation, and carbohydrate metabolic disorders) and other disorders, including glycogen and lysosomal storage disorders (LSDs), and organelle disorders.
RESULTS:
During the study period, 165 530 Saudi Arabian infants were born at Saudi Aramco and 248 were diagnosed with an IEM, corresponding to a cumulative incidence of 150 cases per 100 000 live births. Small-molecule disorders were diagnosed in 134/248 patients (54%). OA were the most common (48/248 patients; 19%), and methylmalonic aciduria was the most frequently observed OA (13/48 patients; 27%). LSDs were diagnosed in 74/248 patients (30%), and mucopolysaccharidosis was the most frequently observed LSD (28/74; 38%).
CONCLUSION:
We believe that our data underestimate the true incidence of IEM in the region. Regional and national newborn screening programs will provide a better estimation of the incidence of IEM. We recommend a centralized newborn screening program that employs tandem mass spectrometry.
doi:10.4103/0256-4947.65254
PMCID: PMC2931777  PMID: 20622343
5.  The Live-Birth Prevalence of Mucopolysaccharidoses in Estonia 
Previous studies on the prevalence of mucopolysaccharidoses (MPS) in different populations have shown considerable variations. There are, however, few data with regard to the prevalence of MPSs in Fenno–Ugric populations or in north-eastern Europe, except for a report about Scandinavian countries. A retrospective epidemiological study of MPSs in Estonia was undertaken, and live-birth prevalence of MPS patients born between 1985 and 2006 was estimated. The live-birth prevalence for all MPS subtypes was found to be 4.05 per 100,000 live births, which is consistent with most other European studies. MPS II had the highest calculated incidence, with 2.16 per 100,000 live births (4.2 per 100,000 male live births), forming 53% of all diagnosed MPS cases, and was twice as high as in other studied European populations. The second most common subtype was MPS IIIA, with a live-birth prevalence of 1.62 in 100,000 live births. With 0.27 out of 100,000 live births, MPS VI had the third-highest live-birth prevalence. No cases of MPS I were diagnosed in Estonia, making the prevalence of MPS I in Estonia much lower than in other European populations. MPSs are the third most frequent inborn error of metabolism in Estonia after phenylketonuria and galactosemia.
doi:10.1089/gtmb.2011.0307
PMCID: PMC3422553  PMID: 22480138
6.  Newborn Screening for Lysosomal Storage Disorders in Hungary 
JIMD Reports  2012;6:117-125.
Even though lysosomal storage disorders (LSDs) are considered to be orphan diseases, they pose a highly relevant cause for morbidity and mortality as their cumulative prevalence is estimated to be 1:4,000. This is especially important as treatment in form of enzyme replacement therapy, substrate reduction therapy or stem cell transplantation is amenable for some LSDs. It is plausible that an early start of treatment might improve the overall prognosis and, even more important, prevent irreversible damage of key organs. To get a more precise insight into the real frequency of some LSDs in the general population, we screened 40,024 samples from the Hungarian newborn screening (NBS) program in Szeged for Fabry disease (FD), Gaucher disease (GD), Pompe disease (PD), and Niemann-Pick A/B (NPB) disease using tandem mass spectrometry. Altogether, 663 samples (1.66%) were submitted for retesting. Genetic confirmation was carried out for 120 samples with abnormal screening results after retesting, which identified three cases of GD, three cases of FD, nine cases of PD, and two cases with NPB. In some cases, we detected up to now unknown mutations – one in NPB and seven in PD – which raise questions about the clinical consequences of a NBS in the sense of late-onset manifestations. Overall, we conclude that screening for LSDs by tandem MS/MS followed by a genetic workup in identified patients is a robust, easy, valid, and feasible technology in newborn screening programs. Furthermore, early diagnosis of LSDs gives a chance to early treatment, but needs more clinical long-term data especially regarding the consequence of private mutations.
doi:10.1007/8904_2012_130
PMCID: PMC3565645  PMID: 23430949
7.  Gene Therapy for Lysosomal Storage Diseases (LSDs) in Large Animal Models 
Ilar Journal  2009;50(2):112-121.
Lysosomal storage diseases (LSDs) are inherited metabolic disorders caused by deficient activity of a single lysosomal enzyme or other defects resulting in deficient catabolism of large substrates in lysosomes. There are more than 40 forms of inherited LSDs known to occur in humans, with an aggregate incidence estimated at 1 in 7,000 live births. Clinical signs result from the inability of lysosomes to degrade large substrates; because most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems. Thus LSDs are associated with high morbidity and mortality and represent a significant burden on patients, their families, the health care system, and society. Because lysosomal enzymes are trafficked by a mannose 6-phosphate receptor mechanism, normal enzyme provided to deficient cells can be localized to the lysosome to reduce and prevent storage. However, many LSDs remain untreatable, and gene therapy holds the promise for effective therapy. Other therapies for some LSDs do exist, or are under evaluation, including heterologous bone marrow or cord blood transplantation (BMT), enzyme replacement therapy (ERT), and substrate reduction therapy (SRT), but these treatments are associated with significant concerns, including high morbidity and mortality (BMT), limited positive outcomes (BMT), incomplete response to therapy (BMT, ERT, and SRT), life-long therapy (ERT, SRT), and cost (BMT, ERT, SRT). Gene therapy represents a potential alternative, albeit with its own attendant concerns, including levels and persistence of expression and insertional mutagenesis resulting in neoplasia. Naturally occurring animal homologues of LSDs have been described in all common domestic animals (and in some that are less common) and these animal models play a critical role in evaluating the efficacy and safety of therapy.
PMCID: PMC3340575  PMID: 19293456
cat model; dog model; fucosidosis; glycogen storage; lysosomal storage disease; mannosidosis; mucopolysaccharidosis
8.  Age biases in a large HIV and sexual behaviour-related internet survey among MSM 
BMC Public Health  2013;13:826.
Background
Behavioural data from MSM are usually collected in non-representative convenience samples, increasingly on the internet. Epidemiological data from such samples might be useful for comparisons between countries, but are subject to unknown participation biases.
Methods
Self-reported HIV diagnoses from participants of the European MSM Internet Survey (EMIS) living in the Czech Republic, Germany, the Netherlands, Portugal, Sweden and the United Kingdom were compared with surveillance data, for both the overall diagnosed prevalence and for new diagnoses made in 2009. Country level prevalence and new diagnoses rates per 100 MSM were calculated based on an assumed MSM population size of 3% of the adult male population. Survey-surveillance discrepancies (SSD) for survey participation, diagnosed HIV prevalence and new HIV diagnoses were determined as ratios of proportions. Results are calculated and presented by 5-year age groups for MSM aged 15–64.
Results
Surveillance derived estimates of diagnosed HIV prevalence among MSM aged 15–64 ranged from 0.63% in the Czech Republic to 4.93% in the Netherlands. New HIV diagnoses rates ranged between 0.10 per 100 MSM in the Czech Republic and 0.48 per 100 in the Netherlands. Self-reported rates from EMIS were consistently higher, with prevalence ranging from 2.68% in the Czech Republic to 12.72% in the Netherlands, and new HIV diagnoses rates from 0.36 per 100 in Sweden to 1.44 per 100 in the Netherlands. Across age groups, the survey surveillance discrepancies (SSD) for new HIV diagnoses were between 1.93 in UK and 5.95 in the Czech Republic, and for diagnosed prevalence between 1.80 in Germany and 4.26 in the Czech Republic.
Internet samples of MSM were skewed towards younger age groups when compared to an age distribution of the general adult male population. Survey-surveillance discrepancies (SSD) for EMIS participation were inverse u-shaped across the age range. The two HIV-related SSD were u- or j-shaped with higher values for the very young and for older MSM. The highest discrepancies between survey and surveillance data regarding HIV-prevalence were observed in the oldest age group in Sweden and the youngest age group in Portugal.
Conclusion
Internet samples are biased towards a lower median age because younger men are over-represented on MSM dating websites and therefore may be more likely to be recruited into surveys. Men diagnosed with HIV were over-represented in the internet survey, and increasingly so in the older age groups. A similar effect was observed in the age groups younger than 25 years. Self-reported peak prevalence and peak HIV diagnoses rates are often shifted to higher age groups in internet samples compared to surveillance data. Adjustment for age-effects on online accessibility should be considered when linking data from internet surveys with surveillance data.
doi:10.1186/1471-2458-13-826
PMCID: PMC3847490  PMID: 24020518
MSM; Internet samples; HIV prevalence; Survey-surveillance discrepancies; Participation bias
9.  Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders 
The British Journal of Radiology  2013;87(1033):20130467.
Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders.
doi:10.1259/bjr.20130467
PMCID: PMC3898971  PMID: 24234586
10.  Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders 
Background
With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling.
Methods
We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls.
Results
We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys.
Conclusion
We report the assessment of a next–generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis.
doi:10.1186/1750-1172-9-59
PMCID: PMC4024120  PMID: 24767253
In-solution enrichment; Targeted resequencing; Lysosomal storage disorders; Diagnostic odysseys
11.  Observational, retrospective study of a large cohort of patients with Niemann-Pick disease type C in the Czech Republic: a surprisingly stable diagnostic rate spanning almost 40 years 
Background
Niemann-Pick disease type C (NPC) is a rare, fatal neurovisceral disorder with autosomal recessive inheritance, and featuring striking clinical variability dependent on the age at onset of neurological symptoms. We report data from a large cohort of 56 Czech patients with NPC diagnosed over a period of 37 years.
Methods
An observational, retrospective analysis of historic and current clinical and laboratory information was performed among all NPC patients originating from the area of the contemporary Czech Republic and diagnosed between 1975 and 2012. All patients with ≥1 positive diagnostic test and relevant clinical information were included. Data on diagnostic methods (histopathological and/or ultrastructural; biochemical; genetic), clinical status and general information on treatment were collated. Data were examined in accordance with international guidelines for the management of NPC.
Results
Between 1975 and 1985 diagnoses were based exclusively on specific histopathological findings, often at autopsy. Bone marrow smear (BMS) analyses have proved to be a very specific indicator for NPC and have become an important part of our diagnostic algorithm. Filipin staining and cholesterol esterification assays became the definitive diagnostic tests after 1985 and were applied in 24 of our patients. Since 2005, more and more patients have been assessed using NPC1/NPC2 gene sequencing. Twelve patients were diagnosed with neonatal/early-infantile onset NPC, 13 with the late-infantile onset form, 20 with the juvenile onset form, and nine with the adolescent/adult onset form. Two diagnosed patients remained neurologically asymptomatic at study completion. Nineteen patients were siblings. Causal NPC1 mutations were determined in 38 patients; two identical NPC2 mutations were identified in one patient. In total, 30 different mutations were identified, 14 of which have been confirmed as novel. The frequency of individual mutated NPC1 alleles in our cohort differs compared with previous published data: the most frequent mutant NPC1 allele was p.R1186H (n = 13), followed by p.P1007A (n = 8), p.S954L (n = 8) and p.I1061T (n = 4).
Conclusions
These data demonstrate the evolution of the diagnostic process in NPC over the last four decades. We estimate the contemporary birth prevalence of NPC in the Czech Republic at 0.93 per 100,000.
doi:10.1186/s13023-014-0140-6
PMCID: PMC4193985  PMID: 25236789
Niemann-Pick disease type C (NPC); Bone marrow smear (BMS); Cholesterol; Filipin; NPC1; NPC2; Diagnosis
12.  Relative acidic compartment volume as a lysosomal storage disorder–associated biomarker 
The Journal of Clinical Investigation  2014;124(3):1320-1328.
Lysosomal storage disorders (LSDs) occur at a frequency of 1 in every 5,000 live births and are a common cause of pediatric neurodegenerative disease. The relatively small number of patients with LSDs and lack of validated biomarkers are substantial challenges for clinical trial design. Here, we evaluated the use of a commercially available fluorescent probe, Lysotracker, that can be used to measure the relative acidic compartment volume of circulating B cells as a potentially universal biomarker for LSDs. We validated this metric in a mouse model of the LSD Niemann-Pick type C1 disease (NPC1) and in a prospective 5-year international study of NPC patients. Pediatric NPC subjects had elevated acidic compartment volume that correlated with age-adjusted clinical severity and was reduced in response to therapy with miglustat, a European Medicines Agency–approved drug that has been shown to reduce NPC1-associated neuropathology. Measurement of relative acidic compartment volume was also useful for monitoring therapeutic responses of an NPC2 patient after bone marrow transplantation. Furthermore, this metric identified a potential adverse event in NPC1 patients receiving i.v. cyclodextrin therapy. Our data indicate that relative acidic compartment volume may be a useful biomarker to aid diagnosis, clinical monitoring, and evaluation of therapeutic responses in patients with lysosomal disorders.
doi:10.1172/JCI72835
PMCID: PMC3934186  PMID: 24487591
13.  Impact of co-existent lumbar spine disorders on clinical outcomes and physician charges associated with total hip arthroplasty 
The Spine Journal  2012;12(5):363-369.
Background Context
Despite the common prevalence of lumbar spine and degenerative hip disorders, there are few descriptions of patients with coexisting hip and lumbar spine disorders. The independent economic burden of each disorder is substantial but the financial burden when the disorders are coexisting is unknown.
Purpose
The purpose of this study is to determine the prevalence of coexisting hip and lumbar spine disorders (LSD) in a large cohort of patients with hip osteoarthritis treated with total hip arthroplasty (THA) and determine the impact on pain and functional THA outcomes and physician charges.
Study Design/Setting
This is a retrospective study performed at a tertiary university.
Patient Sample
3206 patients who underwent total hip replacement from 1996-2008.
Outcome Measures
Self-report measures: Visual Analog Scale. Functional measures: modified Harris Hip Score (mHHS), UCLA hip questionnaire. Economic impact measures: physician medical charges.
Methods
International Classification of Diseases (ICD-9) billing codes related to LSDs were cross referenced with the 3206 patients who had undergone a THA to determine which patients were also evaluated by a spine specialist. Demographic, hip clinical outcomes and physician charges for patients with THA alone (THA alone) were compared to patients treated with THA and diagnosed with a LSD (THA + LSD).
Results
Of 3206 patients who underwent THA, 566 (18%) were also evaluated by a spine specialist. Of those with a LSD, 334 (59%) were women with an older average age (64.5+13.3yrs) compared to patients treated with THA alone (51%, 58.5+15.5 yrs, P=0.0001). Patients in the THA alone group as compared to the THA+ LSD group had greater improvement in the mHHS (P =0.0001), UCLA score (P =0.0001) and pain (P=0.0001). Patients in the THA+LSD group incurred on average $2,668 more in charges per episode of care as compared to patients in the THA alone group. (P<0.001) Patients in the THA+LSD group had more days per episode of care (P=0.001).
Conclusions
Patients undergoing THA alone had greater improvement in function and pain relief with fewer medical charges as compared to patients undergoing a THA and treatment for a LSD. The prevalence of coexisting hip and spine disorders is likely higher than currently documented. Further study is needed in order to improve therapeutic recommendations and determine the potential for reduction in medical expenses associated with concurrent treatment of hip osteoarthritis and lumbar spine disorders.
doi:10.1016/j.spinee.2011.11.002
PMCID: PMC3340523  PMID: 22227176
hip; arthroplasty; lumbar spine; low back pain; osteoarthritis; hip-spine syndrome
14.  Selective Screening for Lysosomal Storage Diseases with Dried Blood Spots Collected on Filter Paper in 4,700 High-Risk Colombian Subjects 
JIMD Reports  2013;11:107-116.
Lysosomal storage disorders (LSDs) are a very heterogeneous group of hereditary disorders. The diagnostic process usually involves complex sampling, processing, testing, and validation procedures, performed by specialized laboratories only, which causes great limitations in reaching a diagnosis for patients affected by these diseases.
There are few studies about LSDs in Colombia. The diagnostic limitations often make medical practitioners disregard the possibility of these disorders while diagnosing their patients. The current study documents the results of a 7-year screening in high-risk patients, aimed to detect LSDs using dried blood spots (DBS) collected on filter paper, with a micromethodology that facilitates diagnosis even with a large number of samples.
The activities of α-galactosidase A, α glucosidase, α-l-iduronidase, arylsulfatase B, β-galactosidase, β-glucosidase, total hexosaminidase, iduronate sulfatase, and chitotriosidase were analyzed in high-risk patients for lysosomal disease. The catalytic activity was evaluated with fluorometric micromethods using artificial substrates marked with 4-methylumbelliferone.
The reference values for a control population were established for the enzymes listed above, and 242 patients were found to have an enzyme deficiency, guiding to the following diagnoses: Fabry disease (n = 31), Pompe disease (n = 16), Hurler Syndrome (n = 15), Maroteaux-Lamy Syndrome (n = 34), GM1 Gangliosidosis (n = 10), Morquio B (n = 1), Gaucher disease (n = 101), Sandhoff disease (n = 1), Mucolipidosis (n = 2), and Hunter Syndrome (n = 31). In conclusion, this protocol provides a comprehensive diagnostic approach which could be carried out in Colombia and made it available to medical services spread around the country, enabling the identification of a large number of patients affected by LSDs, which could potentially benefit from the therapeutic tools already available for many of these diseases.
doi:10.1007/8904_2013_229
PMCID: PMC3755556  PMID: 23609959
15.  Incidence and Clinical Characteristics of Childhood Glaucoma: A Population-Based Study 
Archives of ophthalmology  2010;128(4):478-482.
Objective
To describe the incidence and clinical characteristics of childhood glaucoma in a defined population of the United States.
Methods
The medical records of all patients (< 20 years) meeting diagnostic criteria for glaucoma or glaucoma suspect, as residents of Olmsted County, Minnesota, from January 1, 1965, through December 31, 2004 were reviewed.
Results
Thirty children were diagnosed with glaucoma during the 40-year study period. The age- and sex-adjusted incidence of childhood glaucoma was 2.29 (95% CI: 1.47–3.12) per 100,000 residents < 20 years of age, with the following types and incidences: 19 acquired (1.46/100,000; 95% CI: 0.80–2.12), 6 secondary (0.45/100,000; 95% CI: 0.08–0.82) and 5 with primary glaucoma (0.38/100,000; 95% CI: 0.05–0.72). The birth prevalence of primary congenital glaucoma during the 40-year period was 1 in 68,254 births or 1.46 per 100,000 births (95% CI: 0.03–8.16). Twenty-four glaucoma suspects were also identified, yielding an incidence of 1.9 per 100,000 patients < 20 years of age (95% CI: 1.14–2.66).
Conclusion
The incidence of childhood glaucoma in this population was 2.29 per 100,000 or 1 in 43,575 for patients <20 years of age. Acquired and secondary forms of glaucoma were the most common while congenital and juvenile glaucoma were rare.
doi:10.1001/archophthalmol.2010.41
PMCID: PMC2885872  PMID: 20385945
16.  HIV/AIDS among minority races and ethnicities in the United States, 1999-2003. 
BACKGROUND: During June 1981 to June 1982, 37% of more than 400 cases of AIDS reported to the CDC were in minority races and ethnicities. In 2003, 72% of the estimated 43,171 cases of AIDS diagnosed in the 50 states; District of Columbia; and U.S. dependencies, possessions and free nations were in minority races and ethnicities. METHODS: We analyzed HIV/AIDS data for 2000-2003 reported by the 32 states that have had confidential name-based reporting of HIV infection since 1999. For analysis of AIDS data, we used data for 1999-2003 reported by the 50 states and the District of Columbia. HIV/AIDS and AIDS data were statistically adjusted for reporting delays and redistribution of cases initially reported without risk factors. RESULTS: For all years, the numbers of HIV/AIDS and AIDS diagnoses were consistently higher among non-Hispanic blacks than among other races and ethnicities. In the 32 states with HIV reporting, the HIV/AIDS diagnosis rate in 2003 was 74 per 100,000 for blacks, 25 per 100,000 for Hispanics, 11 per 100,000 for American Indians/Alaska Natives, nine per 100,000 for whites, and seven per 100,000 for Asians/Pacific Islanders. The rates for persons living with HIV/AIDS at the end of 2003 were highest for blacks (765 per 100,000) and Hispanics (220 per 100,000). In the 50 states and the District of Columbia, AIDS diagnosis rates in 2003 were 58 per 100,000 for blacks, 20 per 100,000 for Hispanics, eight per 100,000 for American Indians/Alaska Natives, and four per 100,000 for Asians/Pacific Islanders. CONCLUSION: HIV/AIDS disproportionately affects minority races and ethnicities in the United States. To reduce rates of HIV/AIDS in these populations, effective and culturally appropriate prevention interventions must be developed and implemented.
PMCID: PMC2640648  PMID: 16080451
17.  Liver Storage Disease in Iran: A Ten Year Study of Liver Biopsies in Children Medical Center Hospital in Tehran-Iran 
Hepatitis Monthly  2011;11(8):652-655.
Background
Liver storage diseases are rare biochemical and inherited diseases that affect multiorgan systems.
Objectives
This study was performed to determine the rate of storage diseases and their types in liver pathology specimens of subjects who were referred to a tertiary pediatric center.
Patients and Methods
Two pathologists evaluated 2216 pathology specimens (stained with hematoxylin and eosin and periodic acid-Schiff) from subjects who were referred to the largest pediatric tertiary referral center in Iran between 1996 and 2007. Baseline data and clinical and laboratory manifestations were retrieved from the patients' files.
Results
We identified 117 patients who had storage diseases. A combination of clinical and laboratory findings was used to assess the final diagnosis. Glycogen storage disease (GSD) was observed in 85 of cases, compared with lysosomal storage diseases (LSD) in 31 patients and mucopolysaccharidoses in 1 case. LSD was more prevalent in those aged between 1 month and 1 year, whereas GSD was more frequent in those aged between 1 and 6 years. Most of the patients aged between 1 and 6 years. Most patients with LSD and GSD had unknown types of the disease. The most common known types in the LSD and GSD groups were Niemann-Pick disease and GSD type I respectively. The most common clinical and laboratory manifestation was hepatomegaly and abnormal liver enzymes, respectively.
Conclusions
Most of our patients with storage diseases had Gaucher disease. Hepatomegaly and elevated transaminase levels were the most striking finding. However, with regard to the limitations of our methodology, further studies that collect more accurate data are warranted.
doi:10.5812/kowsar.1735143X.718
PMCID: PMC3227485  PMID: 22140390
Epidemiology; Gaucher disease; Lysosomal storage diseases; Mucopolysaccharidoses; Glycogen storage disease
18.  Door-to-door survey of major neurological disorders (project) in Al Quseir City, Red Sea Governorate, Egypt 
A door-to-door survey, including every household, was conducted for all inhabitants of Al Quseir City (33,283), Red Sea Governorate, Egypt by three specialists of neurology as well as nine senior staff members of neurology and 15 female social workers to assess the epidemiology of major neurological disorders. Over six phases, from July 1, 2009 to January 31, 2012, screening of all eligible people in the population was carried out, by which case ascertainment of all major neurological disorders included in the study was done according to the accepted definitions and diagnostic criteria of the World Health Organization. The order of frequency of prevalence of the studied neurological disorders was dementia (3.83% for those aged > 60 years), migraine (2.8% for those aged > 8 years), stroke (6.2/1000 for those aged > 20 years), epilepsy (5.5/1000), Parkinson’s disease (452.1/100,000 for those aged > 40 years), cerebral palsy (3.6/1000 among children < 18 years), spinal cord disorders (63/100,000) dystonia (39.11/100,000), cerebellar ataxia (30.01/100,000), trigeminal neuralgia (28/100,000 for those aged > 37 years), chorea (21.03/100,000), athetosis (15/100,000), and multiple sclerosis (13.74/100,000). The incidence rates of stroke, epilepsy, and Bell’s palsy were 181/100,000, 48/100,000, and 98.9/100,000 per year, respectively.
doi:10.2147/NDT.S36956
PMCID: PMC3671800  PMID: 23745047
prevalence; incidence; neurological disorders
19.  Clarifying lysosomal storage diseases 
Trends in neurosciences  2011;34(8):401-410.
Lysosomal storage diseases (LSDs) are a class of metabolic disorders caused by mutations in proteins critical for lysosomal function. Such proteins include lysosomal enzymes, lysosomal integral membrane proteins, and proteins involved in the post-translational modification and trafficking of lysosomal proteins. There are many recognized forms of LSDs, and although individually rare, their combined prevalence is estimated to be 1 in 8000 births. Over two-thirds of LSDs involve central nervous system (CNS) dysfunction—progressive cognitive and motor decline—and these symptoms are often the most debilitating. Although the genetic basis for these disorders are clear and the biochemistry of the proteins well understood, the cellular mechanisms by which deficiencies in these proteins disrupts neuronal viability remain ambiguous. In this review, we provide an overview of the widespread cellular perturbations occurring in LSDs, how they may be linked, and interventions that may specifically or globally correct those defects.
doi:10.1016/j.tins.2011.05.006
PMCID: PMC3153126  PMID: 21723623
20.  Epidemiologic application of verbal autopsy to investigate the high occurrence of cancer along Huai River Basin, China 
Background
In 2004, the media repeatedly reported water pollution and "cancer villages" along the Huai River in China. Due to the lack of death records for more than 30 years, a retrospective survey of causes of death using verbal autopsy was carried out to investigate cancer rates in this area.
Methods
An epidemiologic study was designed to compare numbers of deaths and causes of death between the study areas with water pollution and the control areas without water pollution in S County and Y District in 2005. The study areas were selected based on the distribution of the Huai River and its tributaries. Verbal autopsy was used to assist cause of death (COD) diagnoses and to verify mortality rates. The standard mortality rates (SMRs) of cancer in the study area were compared with those in the control areas. In order to verify the difference between mortality rates due to cancers in the study and the control areas, patients who reported having cancer in the survey received a second diagnosis by national and provincial oncologists with pathological and laboratory examinations. Comparisons were made to determine if differential cancer prevalence rates in the study and control areas were similar to the difference in mortality due to cancer in these study and control areas. Mortality rates of cancers in study and control areas were also compared with national statistics for the rural population of China.
Results
Over five years, 3,301 deaths were identified, including 1,158 cancer deaths. The annual average SMRs of cancer in the study areas of S County and Y District were 277.8/100,000 and 223.6/100,000, respectively, which is three to four times higher than those in the control areas. In addition, a total of 626 cases of cancer in the study and control areas were confirmed. The prevalence rates of cancer were 545/100,000 and 128.1/100,000 per year in the study and control areas in S County, respectively, and 440.9/100,000 and 200/100,000 per year in the study and control areas in Y District, respectively. The mortality and prevalence rates of digestive cancers were higher in the study areas than the control areas. In 2000, the SMR for cancer in rural areas nationwide was 120.9/100,000, and in study areas in S County and Y District, the excess rates of deaths were 184/100,000 and 138.8/100,000, respectively.
Conclusions
The death rates of digestive cancers were much higher in the study areas of S County and Y District. The patterns for between-area differences in prevalence and mortality rates of cancer were similar. Verbal autopsy is shown to be a useful tool in retrospective mortality surveys in low-resource areas with limited access to health care.
doi:10.1186/1478-7954-9-37
PMCID: PMC3160930  PMID: 21816097
Verbal autopsy; cancer; mortality rate; prevalence rate; water pollution
21.  Burden of Lysosomal Storage Disorders in India: Experience of 387 Affected Children from a Single Diagnostic Facility 
JIMD Reports  2013;12:51-63.
Lysosomal storage disorders (LSDs) are considered to be a rare metabolic disease for the national health forum, clinicians, and scientists. This study aimed to know the prevalence of different LSDs, their geographical variation, and burden on the society. It included 1,110 children from January 2002 to December 2012, having coarse facial features, hepatomegaly or hepatosplenomegaly, skeletal dysplasia, neuroregression, leukodystrophy, developmental delay, cerebral-cerebellar atrophy, and abnormal ophthalmic findings. All subjects were screened for I-cell disease, glycolipid storage disorders (Niemann-Pick disease A/B, Gaucher), and mucopolysaccharide disorders followed by confirmatory lysosomal enzymes study from leucocytes and/or fibroblasts. Niemann-Pick disease-C (NPC) was confirmed by fibroblasts study using filipin stain. Various storage disorders were detected in 387 children (34.8 %) with highest prevalence of glycolipid storage disorders in 48 %, followed by mucopolysaccharide disorders in 22 % and defective sulfatide degradation in 14 % of the children. Less common defects were glycogen degradation defect and protein degradation defect in 5 % each, lysosomal trafficking protein defect in 4 %, and transport defect in 3 % of the patients. This study demonstrates higher incidence of Gaucher disease (16 %) followed by GM2 gangliosidosis that includes Tay-Sachs disease (10 %) and Sandhoff disease (7.8 %) and mucopolysaccharide disorders among all LSDs. Nearly 30 % of the affected children were born to consanguineous parents and this was higher (72 %) in children with Batten disease. Our study also demonstrates two common mutations c.1277_1278insTATC in 14.28 % (4/28) and c.964G>T (p.D322Y) in 10.7 % (3/28) for Tay-Sachs disease in addition to the earlier reported c.1385A>T (p.E462V) mutation in 21.42 % (6/28).
doi:10.1007/8904_2013_244
PMCID: PMC3897787  PMID: 23852624
22.  Amenable mortality as a performance indicator of Italian health-care services 
Background
Mortality amenable to health-care services (‘amenable mortality’) has been defined as “premature deaths that should not occur in the presence of timely and effective health care” and as “conditions for which effective clinical interventions exist.” We analyzed the regional variability in health-care services using amenable mortality as a performance indicator. Convergent validity was examined against other indicators, such as health expenditure, GDP per capita, life expectancy at birth, disability-free life expectancy at age 15, number of diagnostic and laboratory tests per 1,000 inhabitants, and the prevalence of cancer and cardiovascular diseases.
Methods
Amenable mortality rate was calculated as the average annual number of deaths in the population aged 0–74 years per 100,000 inhabitants, and it was then stratified by gender and region. Data were drawn from national mortality statistics for the period 2006–08.
Results
During the study period (2006–08), the age-standardized death rate (SDR) amenable to health-care services in Italy was 62.6 per 100,000 inhabitants: 66.0 per 100,000 for males and 59.1 per 100,000 for females. Significant regional variations ranged from 54.1 per 100,000 inhabitants in Alto Adige to 76.3 per 100,000 in Campania. Regional variability in SDR was examined separately for male and females. The variability proved to be statistically significant for both males and females (males: Q-test = 638.5, p < 0.001; females: Q-test = 700.1, p < 0.001). However, among men, we found a clear-cut divide in SDR values between Central and Southern Italy; among women, this divide was less pronounced. Amenable mortality was negatively correlated with life expectancy at birth for both genders (male: r = −0.64, p = 0.002; female: r = −0.88, p <0.001) and with disability-free life expectancy at age 15 (male: r = −0.70, p <0.001; female: r = −0.67, p <0.001). Amenable mortality displayed a statistically significant negative relationship with GDP per capita, the quantity of diagnostic and laboratory tests per 1,000 inhabitants, and the prevalence of cancer.
Conclusions
Amenable mortality shows a wide variation across Italian regions and an inverse relationship with life expectancy and GDP per capita, as expected.
doi:10.1186/1472-6963-12-310
PMCID: PMC3506466  PMID: 22963259
Amenable mortality; Health-care services performance; Socioeconomic status; Gender
23.  Intimate Partner Femicide in South Africa in 1999 and 2009 
PLoS Medicine  2013;10(4):e1001412.
Naeemah Abrahams and colleagues compare the incidence of female homicide in women aged over 14 years in South Africa in 1999 and 2009 and analyze the fatal violent attacks perpetrated by intimate partners.
Background
Death is the most extreme consequence of intimate partner violence. Female homicide studies with data on the perpetrator–victim relationship can provide insights. We compare the results of two South African national studies of female homicide with similar sampling done 10 y apart.
Methods and Findings
We conducted a retrospective national survey using a weighted cluster design of a proportionate random sample of 38 mortuaries to identify homicides committed in 2009. We abstracted victim data from mortuary and autopsy reports, and perpetrator data from police interviews. We compared homicides of women 14 y and older in 2009 with previously published data collected with the same methodology for homicides committed in 1999.
The study found that the rate of female homicide per 100,000 female population in 2009 was 12.9 (95% confidence interval [CI]: 9.3, 16.5), compared to 24.7 (95% CI: 17.7, 31.6) in 1999. The incidence rate ratio of 0.54 (95% CI: 0.20, 0.84) reflects a significantly lower rate in 2009. The rate of intimate partner femicide was 5.6/100,000 in 2009 versus 8.8/100,000 in 1999, with an incidence rate ratio of 0.63 (95% CI: 0.24, 1.02), indicating no difference between rates. Logistic regression analysis of homicide characteristics showed that the odds ratio of suspected rape among non-intimate femicides in 2009 compared to 1999 was 2.61 (95% CI: 1.23, 4.08) and among intimate partner femicides it was 0.84 (95% CI: 0.50, 1.42). The OR of homicide by gunshot was 0.54 (95% CI: 0.30, 0.99) in 2009 versus 1999. There was a significant drop in convictions of perpetrators of non-intimate femicide in 2009 versus 1999 (OR = 0.32 [95% CI: 0.19, 0.53]). Limitations of the study include the relatively small sample size and having only two time points.
Conclusions
Female homicide in South Africa was lower in 2009 than 1999, but intimate partner femicide and suspected rape homicide rates were not statistically different. The cause of the difference is unknown. The findings suggest that South Africa needs greater efforts nationally to implement evidence-based violence prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Violence against women (often referred to as gender-based violence) is common, serious, and takes many forms, including physical, sexual, and emotional abuse, and has profound implications for every aspect of women's lives. One of the most common forms of violence is perpetrated by a husband or male partner (often referred to as intimate partner violence), and as it usually happens in private, is often ignored or goes unreported. According to the World Health Organization, population surveys indicate that 10%–69% of women have been abused by an intimate partner. This form of violence is so prevalent because in many countries and cultures, violence against a female partner is often not perceived as a crime but rather as a private family matter.
Why Was This Study Done?
The extreme consequence of violence against women is death, and given the seriousness of the widespread problem of violence against women, there have been many international and national efforts to raise awareness of the issue and to implement policies to reduce such violence. In order for these policies to be most effective, countries implementing strategies to prevent intimate partner violence should also have the capacity to monitor the results of such strategies, but unfortunately, these data are not routinely available. Tracking changes in fatal intimate partner violence (that is, when a woman is killed by an intimate partner, also referred to as intimate femicide) is one possible option of monitoring the impact of policies and programs. So in this study from South Africa, the researchers collected data on and compared the prevalence of intimate femicide at two time points ten years apart (1999 and 2009, between which time points new legislation on gender-based violence was introduced) to examine whether there were any differences.
What Did the Researchers Do and Find?
The researchers analyzed information on female homicide victims, aged 14 years and older, whom they identified from mortuary registers and databases in 2009. The researchers collected cause of death data from the autopsy reports and checked other information via police interview. The researchers then compared these results with a similar study they had conducted for homicides in 1999 but treated each study independently, with a separate statistical analysis, and calculated rates according to the population estimates at each time point.
Using these methods, the researchers found that in 2009, there were 930 female homicides compared to 1,052 in 1999, giving an overall female homicide rate per 100,000 women of 12.9 in 2009 compared to 24.7 in 1999. There was a statistically significant decrease in the rate of non-intimate femicide, with a rate of 8.6 per 100,000 women in 1999 compared to 4.2 in 2009. Although there was some evidence of a decrease in the rate of intimate partner femicide—8.8 per 100,000 women in 1999 compared to 5.6 in 2009—this decrease was not statistically significant. The researchers also found that there was a significant decrease in the rate of fatal shootings (female gun homicides), 7.5 per 100,000 women in 1999 compared to 2.5 in 2009, and that this finding was similar for homicides perpetrated by partners and non-partners (intimate and non-intimate gun homicides). Finally, the researchers found that the overall rate of fatal rapes (female rape homicides) was 3.4 per 100,000 women in 1999 compared to 2.5 in 2009, but again, this difference was not statistically significant. Unfortunately, the researchers found that the odds (chance) of conviction of perpetrators of intimate femicide was unchanged between the two time points (1.11), and the odds of conviction of perpetrators of non-intimate femicides had significantly decreased (0.32).
What Do These Findings Mean?
These findings suggest that, overall, female homicide in South Africa was substantially lower in 2009 than in 1999, but the 2009 figure is still five times the global rate of this crime. The rate of non-intimate femicide declined significantly over the two time points, but there was no statistically significant reduction in intimate femicide. There was a substantial difference in the rate of homicide from gunshot between the two years, most likely explained by gun control legislation. This study has several limitations, including the small number of mortuaries included and the differences in the studies conducted in 1999 and 2009. Nevertheless, this study indicates that a renewed commitment from the South African government is urgently needed to develop policy-driven prevention interventions to reduce female homicide, especially when perpetrated by an intimate partner.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001412.
Violence against Women Online Resources provide lists of sources about violence against women
The World Health Organization website lists some facts about violence against women
The US Centers for Disease Control and Prevention provides more information about intimate partner violence
Sexual Violence Research Initiative provides links to research on sexual violence
doi:10.1371/journal.pmed.1001412
PMCID: PMC3614499  PMID: 23565064
24.  Use of Tandem Mass Spectrometry for Newborn Screening of 6 Lysosomal Storage Disorders in a Korean Population 
Background
We evaluated the performance of multiplex tandem mass spectrometry (MS/MS) in newborn screening for detection of 6 lysosomal storage disorders (LSDs), namely, Niemann-Pick A/B, Krabbe, Gaucher, Fabry, and Pompe diseases and Hurler syndrome.
Methods
We revised the conditions and procedures of multiplex enzyme assay for the MS/MS analysis and determined the precision of our enzyme assay and the effects of sample amounts and incubation time on the results. We also measured the degree of correlation between the enzyme activities in the dried blood spots (DBSs) and those in the leukocytes. DBSs of 211 normal newborns and 13 newborns with various LSDs were analyzed using our revised methods.
Results
The intra- and inter-assay precisions were 2.9-18.7% and 8.1-18.1%, respectively. The amount of product obtained was proportional to the DBS eluate volume, but a slight flattening was observed in the product vs. sample volume curve at higher sample volumes. For each enzyme assay, the amount of product obtained increased linearly with the incubation period (range, 0-24 hr). Passing and Bablok regression analysis revealed that the enzyme activities in the DBSs and those in the leukocytes were favorably correlated. The enzyme activities measured in the DBSs were consistently lower in patients with LSDs than in normal newborns.
Conclusions
The performance of our revised techniques for MS/MS detection and enzyme assays was of the generally acceptable standard. To our knowledge, this is the first report on the use of MS/MS for newborn screening of LSDs in an Asian population.
doi:10.3343/kjlm.2011.31.4.250
PMCID: PMC3190003  PMID: 22016678
Lysosomal storage disorders; Multiplex enzyme assay; Tandem mass spectrometry; Newborn screening
25.  Prioritizing Congenital Syphilis Control in South China: A Decision Analytic Model to Inform Policy Implementation 
PLoS Medicine  2013;10(1):e1001375.
Nicholas Tan and colleagues use a decision analytic model to quantify the impact of the ten-year national syphilis control plan in China and conclude that earlier and more extensive screening are also necessary for reaching policy goals.
Background
Syphilis is a major public health problem in many regions of China, with increases in congenital syphilis (CS) cases causing concern. The Chinese Ministry of Health recently announced a comprehensive 10-y national syphilis control plan focusing on averting CS. The decision analytic model presented here quantifies the impact of the planned strategies to determine whether they are likely to meet the goals laid out in the control plan.
Methods and Findings
Our model incorporated data on age-stratified fertility, female adult syphilis cases, and empirical syphilis transmission rates to estimate the number of CS cases associated with prenatal syphilis infection on a yearly basis. Guangdong Province was the focus of this analysis because of the availability of high-quality demographic and public health data. Each model outcome was simulated 1,000 times to incorporate uncertainty in model inputs. The model was validated using data from a CS intervention program among 477,656 women in China. Sensitivity analyses were performed to identify which variables are likely to be most influential in achieving Chinese and international policy goals. Increasing prenatal screening coverage was the single most effective strategy for reducing CS cases. An incremental increase in prenatal screening from the base case of 57% coverage to 95% coverage was associated with 106 (95% CI: 101, 111) CS cases averted per 100,000 live births (58% decrease). The policy strategies laid out in the national plan led to an outcome that fell short of the target, while a four-pronged comprehensive syphilis control strategy consisting of increased prenatal screening coverage, increased treatment completion, earlier prenatal screening, and improved syphilis test characteristics was associated with 157 (95% CI: 154, 160) CS cases averted per 100,000 live births (85% decrease).
Conclusions
The Chinese national plan provides a strong foundation for syphilis control, but more comprehensive measures that include earlier and more extensive screening are necessary for reaching policy goals.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, 1.5 million pregnant women are infected with syphilis, a bacterial infection that is usually transmitted during sexual contact but that can also pass from a mother to her unborn child. In many of these women, the disease is detected through routine antenatal testing and is successfully treated with penicillin. But among those women who are not treated, about half experience adverse outcomes—the death of their baby during early or late pregnancy (fetal death and stillbirth, respectively) or soon after birth (neonatal death), or the birth of an infected baby. Babies born with syphilis (congenital syphilis) often fail to thrive and can develop problems such as blindness, deafness, and seizures if not treated. In 2008, syphilis in pregnancy contributed to 305,000 fetal deaths, stillbirths, and neonatal deaths, and 215,000 babies were affected by other adverse consequences of congenital syphilis. Yet congenital syphilis is simple and cheap to eliminate—a few injections of penicillin can clear the infection in a pregnant woman, and screening all pregnant women for syphilis is feasible even in low-resource settings.
Why Was This Study Done?
Congenital syphilis has recently reemerged in China. In the 1990s, there were very few cases of congenital syphilis in China, but by 2009, the reported incidence of congenital syphilis had risen to 139 cases per 100,000 live births. In 2010 the Chinese Ministry of Health announced a ten-year National Syphilis Prevention and Control Plan (NSCP) that, in line with World Health Organization (WHO) recommendations, aims to reduce the incidence of congenital syphilis to fewer than 30 cases per 100,000 live births by 2015 and to fewer than 15 cases per 100,000 live births by 2020. China's strategy for achieving these targets includes increasing prenatal syphilis screening coverage to 80% in urban areas and 60% in rural areas, increasing treatment rates among infected women to 90% in urban areas and 70% in rural areas, and increasing syphilis awareness among adults. But will this strategy be sufficient? Here, the researchers develop a mathematical model to quantify the likely impact of the NSCP's strategy on the incidence of congenital syphilis in southern China.
What Did the Researchers Do and Find?
The researchers developed a decision analytic model in which women move through a sequence of health states from uninfected, through infection and pregnancy, and to the development of congenital syphilis, and fed data collected in Guangdong Province between 2005 and 2008 on women's fertility, female syphilis cases, and syphilis transmission rates into the model. The researchers checked that their model provided estimates of the incidence of congenital syphilis that matched the reported incidence for Guangdong Province (internal validation) and the reported incidence in a congenital syphilis intervention program in Shenzhen, Guangdong (external validation). They then used their model to identify which parts of the NSCP strategy are likely to have the greatest effect on the incidence of congenital syphilis. Increasing prenatal screening coverage was the single most effective strategy for the reduction of congenital syphilis, but neither this strategy alone nor implementation of the whole NPSC strategy achieved the plan's target outcomes. By contrast, a four-pronged approach (95% coverage of prenatal screening, 75% of screening during the first two-thirds of pregnancy, 95% treatment completion, and having an accurate screening test) reduced the estimated incidence of congenital syphilis cases to 27 per 100,000 live births.
What Do These Findings Mean?
These findings suggest that although the NSCP is a strong foundation for control of congenital syphilis in China, more comprehensive measures will be needed to reach the plan's policy goals. In particular, the findings suggest that earlier and more extensive screening will be needed to reduce the incidence of congenital syphilis to below 30 cases per 100,000 live births, WHO's benchmark for congenital syphilis control. The accuracy of these findings is limited by the assumptions included in the model and by the data fed into it. Moreover, because the data included in the model came from Guangdong Province, these findings may not apply elsewhere in China or in other countries. Nevertheless, this study illustrates the importance of using multi-pronged approaches to address the complex problem of congenital syphilis control and identifies some strategies that are likely to improve the control of this important public health problem.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001375.
The World Health Organization provides information on sexually transmitted infections, including details of its strategy for the global elimination of congenital syphilis, the investment case for the elimination of mother-to-child transmission of syphilis, and regional updates on progress towards elimination (some information is available in several languages)
The US Centers for Disease Control and Prevention has a fact sheet on syphilis
The UK National Health Service Choices website also has a page on syphilis
MedlinePlus provides information on congenital syphilis and links to additional syphilis resources (in English and Spanish)
Haiti: Congenital Syphilis on the Way Out is a YouTube video describing the introduction of rapid diagnostic tests for syphilis in remote parts of Haiti
doi:10.1371/journal.pmed.1001375
PMCID: PMC3551934  PMID: 23349624

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