Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women

Background

Iron-deficient erythropoiesis results in excess formation of zinc protoporphyrin (ZPP), which can be measured instantly and at low assay cost using portable haematofluorometers. ZPP is used as a screening marker of iron deficiency in individual pregnant women and children, but also to assess population iron status in combination with haemoglobin concentration. We examined associations between ZPP and disorders that are common in Africa. In addition, we assessed the diagnostic utility of ZPP (measured in whole blood and erythrocytes), alone or in combination with haemoglobin concentration, in detecting iron deficiency (plasma ferritin concentration <15 μg/L).

Methods

Single blood samples were collected from a population sample of 470 rural Kenyan women with singleton pregnancies, gestational age 13 to 23 weeks, and haemoglobin concentration ≥90 g/L. We used linear regression analysis to assess associations between ZPP and iron markers (including anaemia), factors known or suspected to be associated with iron status, inflammation markers (plasma concentrations of C-reactive protein and α ₁-acid glycoprotein), infections (Plasmodium infection, HIV infection), and other disorders (α ⁺-thalassaemia, plasma concentrations of total bilirubin, and lactate dehydrogenase). Subsequently, in those without inflammation, Plasmodium infection, or HIV infection, we used logistic discriminant analysis and examined receiver operating characteristics curves with corresponding area-under-the-curve to assess diagnostic performance of ZPP, alone and in combination with haemoglobin concentration.

Results

Individually, whole blood ZPP, erythrocyte ZPP, and erythrocyte protoporphyrin had limited ability to discriminate between women with and without iron deficiency. Combining each of these markers with haemoglobin concentration had no additional diagnostic value. Conventional cut off points for whole blood ZPP (>70 μmol/mol haem) resulted in gross overestimates of the prevalence of iron deficiency.

Conclusions

Erythrocyte ZPP has limited value to rule out iron deficiency when used for screening in conditions with a low prevalence (e.g., 10%). ZPP is of unreliable diagnostic utility when discriminating between pregnant women with and without iron deficiency. Based on these findings, guidelines on the use of ZPP to assess iron status in individuals or populations of pregnant women need review.

Trial registration

NCT01308112 (2 March 2011).

     

The effects of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost.

Worldwide, over 40% of children have iron deficiency anaemia, frequently associated with infections. Certain cytokines are involved in both immune activation/response to infection and iron transport/metabolism. We therefore assessed the relations among iron deficiency, cytokine production and lymphocyte activation markers in 142 hospitalized Malawian children. We examined peripheral blood lymphocyte antigens/cytokine production using four- colour flow cytometry and serum transferrin receptor (TfR) levels, an inverse measure of iron status unaffected by acute illness or infection, with an enzyme-linked immunosorbent assay. Wilcoxon rank sum tests and logistic regression analyses (LRA) were performed. Iron deficiency (TfR > or = 10 microg/ml) versus TfR < 10 microg/ml, was associated with higher percentages of lymphocytes producing: (a) induced or spontaneous IL-6 (medians: induced, 15.9% for iron-deficient children versus 8.8% for iron-replete children, P = 0.002; spontaneous, 24.4% versus 13.0%, P < 0.001) and (b) induced IFN-gamma (medians:18.4% versus 12.4%, P = 0.006). The percentages of CD8(+) T cells spontaneously producing IL-6 and of all lymphocytes producing induced TNF-alpha and IFN-gamma in the same cell had the strongest relationships to iron deficiency (b = + 0.0211, P = 0.005 and b = + 0.1158, P = 0.012, respectively, LRA) and were also positively related to the co-expression of the T cell activation markers HLA DR and CD38. Severe iron deficiency (TfR > or = 30 microg/ml) was associated with the percentage of lymphocytes producing induced IL-4 (medians: 0.5% versus 1.6%, P < 0.010). The cytokine patterns associated with iron deficiency in our study would preserve iron stores but also preferentially retain the activation capabilities of T cells, albeit not necessarily other immune cells, until a critical level of iron depletion is reached.     

High titre of anti-Ascaris immunoglobulin E associated with bronchial asthma symptoms in 5-year-old rural Bangladeshi children

Background Increasing interest has arisen whether helminthic infections protect against asthma and allergy. The prevalence of wheezing among Bangladeshi children is higher in rural areas where helminthic infectious burden is greater, which is contrary to the general assumption. Objective We therefore examined the association between Ascaris infection, serum level of anti‐Ascaris IgE, which should be investigated differently from the infection, and wheezing in 5‐year‐old children from rural Bangladesh. Methods A total of 219 children who reported wheezing during the previous 12 months and 122 randomly selected age‐matched individuals who had never experienced wheezing were tested for serum levels of total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and cockroach IgEs, and for intestinal helminth infection as well. Results Anti‐Ascaris IgE levels were significantly and independently associated with current wheezing during the previous 12 months [odds ratio (OR) per log_e increment is 1.31 (95% confidence interval (CI) 1.08–1.60), P=0.007], a history of at least four episodes of wheezing [OR per log_e increment is 1.52 (95% CI 1.18–1.96), P=0.001], wheezing with sleep disturbances [OR per log_e increment is 1.35 (95% CI 1.10–1.64), P=0.011] and wheezing with speech disturbances [OR per log_e increment is 1.57 (95% CI 1.19–2.08), P=0.001]. These were adjusted for gender, pneumonia history, parental asthma, Trichuris infection, use of dry leaves as fuel and other specific IgE levels. The prevalence of Ascaris infection by the presence of wheezing was not significantly different (76% vs. 72%, respectively). Conclusion We conclude that a high titre of anti‐Ascaris IgE is associated with an increased risk of asthma symptoms among 5‐year‐old rural Bangladeshi children with a high helminthic infectious load.     

Coxiella burnetii Infection Increases Transferrin Receptors on J774A.1 Cells

Inoculation with viable, but not inactivated, Coxiella burnetii resulted in the increased expression of transferrin receptors (TfR) in the murine macrophage-like cell line J774A.1. This upregulation was evident in immunoblots as early as 6 h postinfection, with TfR levels continuing to increase through the first 24 h of infection. Fluorescent labeling revealed that TfR upregulation occurred throughout infected monolayers, eliminating the possibility that it reflected a response by a minor subset of host cells. In addition, TfR trafficking did not appear to be affected by C. burnetii infection. Consistent with the increase in TfRs, inoculation with viable C. burnetii resulted in a 2.5-fold increase in total cellular iron by 12 h postinoculation. Our further findings that the chelation of intracellular iron arrests C. burnetii replication and that C. burnetii metabolic activities in vitro are affected by iron concentration suggest that TfR upregulation is a salient factor in C. burnetii infection, and we speculate that it may represent a significant virulence mechanism.     

Zinc protoporphyrin assays in patients with alpha and beta thalassaemia trait.

AIMS--To determine the value of the red cell distribution width (RDW) and erythrocyte zinc protoporphyrin (ZPP) concentration in discriminating between iron deficiency, and beta and alpha thalassaemia in a mixed urban Asian population. METHODS--The RDW and ZPP concentrations were measured in 1412 subjects attending for outpatient phlebotomy, with classification into diagnostic groups on the basis of haemoglobin, mean cell haemoglobin, ferritin, HbA2 and haemoglobin electrophoresis. RESULTS--Non-parametric 95% reference ranges for RDW were 11.7-15.7% and for ZPP 38-104 mumol/mol haem. Both RDW and zinc protoporphyrin rose with increasing severity of iron deficiency, but were also raised in significant numbers of subjects with beta and probable alpha thalassaemia. CONCLUSIONS--Measurements of RDW and ZPP do not differentiate between alpha or beta thalassaemia trait and moderate degrees of iron deficiency (hypochromasia without anaemia). ZPP is a more accurate indicator of iron deficiency than RDW and concentrations above 150 mumol/mol haem strongly suggest iron deficiency, usually with anaemia, rather than thalassaemia.     

Mannose-binding lectin and susceptibility to tuberculosis: a meta-analysis

It has been proposed that mannose‐binding lectin (MBL) levels may impact upon host susceptibility to tuberculosis (TB) infection; however, evidence to date has been conflicting. We performed a literature review and meta‐analysis of 17 human trials considering the effect of MBL2 genotype and/or MBL levels and TB infection. No significant association was demonstrated between MBL2 genotype and pulmonary TB infection. However, the majority of studies did not report MBL2 haplotype inclusive of promoter polymorphisms. Serum MBL levels were shown to be consistently elevated in the setting of TB infection. While this may indicate that high MBL levels protect against infection with TB, the increase was also of a degree consistent with the acute‐phase reaction. This analysis suggests that the relatively poorly characterized MBL2 genotypes reported are not associated significantly with susceptibility to pulmonary TB infection, but high MBL serum levels may be.     

Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food‐borne bacterial pathogens

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron‐deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron‐ and infection‐induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin‐2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron‐deficient diet after infection. Next, mice on the iron‐deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host–pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.     

Molecular analysis for patients with IL‐12 receptor β1 deficiency

Autosomal recessive interleukin‐12 receptor β1 (IL‐12Rβ1) deficiency has been described as the most common cause of Mendelian susceptibility to mycobacterial disease (MSMD), characterized by clinical disease due to weakly virulent mycobacteria such as Bacille Calmette–Guérin (BCG) vaccines and environmental mycobacteria (EM) in children who are normally resistant to most infectious agents. Here, we report the cases of five patients with mycobacterial infection, including one with systemic lupus erythematosus (SLE). Blood samples from patients and healthy controls were activated in vitro with BCG, BCG+IL‐12, and BCG+IFN‐γ. The results showed reduced or no production of IFN‐γ after IL‐12 stimulation in all samples. IL‐12Rβ1 expression on the cell surface was negligible or absent. Genetic analysis showed five novel mutations.     

Color atlas of genetics, 2nd edition,by Eberhard Passarge

In 1997, Narchi and Kulaylat, studying the incidence of Down syndrome in infants of gestational diabetic mothers, concluded that maternal diabetes increases the risk for Down syndrome, but failed to control the maternal age in their analysis. Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we analyzed the relationship between Down syndrome and maternal diabetes mellitus, and maternal gestational diabetes, controlling the maternal age through the pair‐matching analysis, stratifying by maternal age and logistic regression analysis. The analyses show that maternal age is related either to Down syndrome as well as to both types of maternal diabetes. Thus, the overall analysis could be confounded by maternal age. Once we controlled the maternal age, the risk of maternal diabetes mellitus for Down syndrome is: odds ratio (OR) = 0.92 (0.41–2.07); P = 0.83. Controlling maternal age in gestational diabetes, the risk is OR = 1.18 (0.61–2.35); P > 0.70. Based on our results, we conclude that Down syndrome is related to maternal age, but does not seem to be related to any type of maternal diabetes. © 2002 Wiley‐Liss, Inc.     

Discriminating between iron deficiency anemia and anemia of chronic disease using traditional indices of iron status vs transferrin receptor concentration

We compared the ability of soluble serum transferrin receptor (TfR) concentration, quantified using the R&D Systems (Minneapolis, MN) enzyme-linked immunosorbent TfR assay, with other, more traditional indicators of iron status (total iron binding capacity [TIBC], mean corpuscular volume [MCV], percent transferrin saturation [%TS], RBC distribution width [RDW], and serum iron concentration [SIC]) for discriminating between patients with iron deficiency anemia (IDA) or anemia of chronic disease (ACD). The TfR concentration was determined in 72 serum samples selected from men and nonpregnant women classified biochemically on the basis of ferritin concentration as having IDA (n = 41) or ACD (n = 31). By using receiver operating characteristic curve analysis, the diagnostic accuracy of the various indicators of iron status that we evaluated for discriminating between IDA and ACD decreased in the following order: TIBC > TfR > MCV > (%TS = RDW) > SIC. There was no significant difference between the diagnostic accuracy of TIBC and TfR. Thus, the routine measurement of TfR offers no advantage over TIBC for discriminating between people with biochemically defined IDA or ACD.     

Frequency of intestinal helminthiasis and its association with iron deficiency and malnutrition in children from western Mexico

OBJECTIVE: To determine intestinal helminthiasis frequency and its association with malnutrition and iron deficiency. Material and METHODS: An analytical cross-over study was carried out on children in the municipality of Comala, Colima, Mexico. Coproparasitoscopic exams in series of three using the Kato-Katz technique were performed in all children. To evaluate the degree ofmalnutrition, the following anthropometric indices were determined: means and z-scores for weight/height, height/age, weight/age. Severe, moderate and minimal iron deficiency was considered when ferritin was: < or = 12 ng/ml, 12 to 18 ng/mL and 19 to 24 ng/mL, respectively. RESULTS: 243 children were studied with an average age of 65.3+/-8.7 months. 60.9% (n = 148) of the children showed a decrease in ferritin levels and 2.5% (n = 6) had anemia. 16% (n = 39) had trichuriasis, 6.9% (n = 17) ascariasis and 5.3% (n = 13) had both parasites. Trichiura infection was associated with declining health (OR 11.0, CI 3.9-30.8; p<0.001) and with iron deficiency, with cut-off points of <24 ng (OR 2.0, CI 1.0-3.9, p = 0.02) and <18 ng/ dL (OR 2.2, CI 1.2-4.2, p= 0.009). Ascaris infection was not associated with malnutrition or iron deficiency. CONCLUSIONS: Trichiura infection was associated with declining health and slight and moderate degrees of iron deficiency.     

Association of Linear Growth Impairment in Pediatric Crohn's Disease and a Known Height Locus: A Pilot Study

The etiology of growth impairment in Crohn's disease (CD) has been inadequately explained by nutritional, hormonal, and/or disease‐related factors, suggesting that genetics may be an additional contributor. The aim of this cross‐sectional study was to investigate genetic variants associated with linear growth in pediatric‐onset CD. We genotyped 951 subjects (317 CD patient–parent trios) for 64 polymorphisms within 14 CD‐susceptibility and 23 stature‐associated loci. Patient height‐for‐age Z‐score < ?1.64 was used to dichotomize probands into growth‐impaired and nongrowth‐impaired groups. The transmission disequilibrium test (TDT) was used to study association to growth impairment. There was a significant association between growth impairment in CD (height‐for‐age Z‐score < ?1.64) and a stature‐related polymorphism in the dymeclin gene DYM (rs8099594) (OR = 3.2, CI [1.57–6.51], p = 0.0007). In addition, there was nominal over‐transmission of two CD‐susceptibility alleles, 10q21.1 intergenic region (rs10761659) and ATG16L1 (rs10210302), in growth‐impaired CD children (OR = 2.36, CI [1.26–4.41] p = 0.0056 and OR = 2.45, CI [1.22–4.95] p = 0.0094, respectively). Our data indicate that genetic influences due to stature‐associated and possibly CD risk alleles may predispose CD patients to alterations in linear growth. This is the first report of a link between a stature‐associated locus and growth impairment in CD.     

Iron‐overload and genotypic expression of HFE mutations H63D/C282Y and transferrin receptor Hin6I and BanI polymorphism in German patients with hereditary haemochromatosis

Gene variations of HFE, a HLA‐class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR‐Hin6I and TfR‐BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy‐eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 ± 3174 vs. 463 ± 224 µg L^?1, P < 0.0001) and transferrin saturation (86 ± 18% vs. 62 ± 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 ± 165 vs. 138 ± 95 µmol g^?1, P = 0.028) and liver iron index (6.4 ± 2.8 vs. 3.2 ± 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR‐Hin6I and TfR‐BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake.     

Association of the IL‐10 receptor A536G (S138G) loss‐of‐function variant with multiple sclerosis in Tunisian patients

Interleukin‐10 (IL‐10), a potent anti‐inflammatory T‐cell cytokine, has been shown to be a regulatory cytokine that is associated with disease remission in multiple sclerosis (MS) and exerts its activity through its cognate cell surface receptor complex, IL‐10 receptor 1 (IL‐10R1) and IL‐10R2. The purpose of this study was to investigate the IL‐10R1 S138G loss‐of‐function polymorphism (A536G: rs3135932) for possible influence on susceptibility and outcome of MS in Tunisian patients. A total of 103 Tunisian MS patients and 160 control subjects were studied. Genomic DNA samples were extracted from leukocytes and used to investigate S138G polymorphism in IL‐10R1 gene by multiplex allele‐specific polymerase chain reaction. Associations between G allele [odds ratio (OR) = 5.57; 95% confidence intervals (CI) = 3.26–9.54; p = 10^?7], GG genotypes [OR = 10.41; 95% CI = 2.28–47.58; p = 0.0007] and AG genotype [OR = 4.14; 95% CI = 2.16–7.93; p = 0.000016] with the risk development of MS were found. In contrast, the AA genotype seemed to be associated with protection against MS [OR = 0.17; 95% CI = 0.09–0.30; p = 10^?7]. No association was found between S138G SNP and clinical features or disease activity of MS patients. In conclusion, our results suggest that S138G loss‐of‐function polymorphism of the IL‐10R1 may be important risk factor in increasing susceptibility to MS.     

Simultaneous Chlamydia trachomatis and HPV infection in pregnant women

Pregnancy is associated with HPV infection and with Chlamydia trachomatis (CT) infection mostly due to the natural immunosuppression. In addition, pregnancy associated to CT infection can lead to adverse conditions to the woman and fetus, and CT is also believed to be a co‐factor in human immunodeficiency virus infection and HPV‐induced cervical cancer. The aim of this study was to establish the odds ratios (OR) of CT infection in to HPV‐infected pregnant women and vice versa of women stratified by age (<25 years) and marital status. This work is part of a national multicentric transversal study carried out in six Brazilian cities supported by the Ministry of Health of Federal Government of Brazil in 2003. Cervical scrapes of 371 pregnant women were sampled. We performed a hybrid capture‐2 technique to diagnose these samples on HPV and CT infection, and the women responded a questionnaire. Significant association was observed between nonstable marital status and hr‐HPV infection [OR = 2.61 (1.38–4.97) P = 0.003)], and age <25 years old [OR = 2.26 (1.09–4.71) P = 0.029]. Nonstable marital status was also associated with lr‐HPV infection [OR = 2.67 (1.59–4.50) P < 0.001), and age <25 years old [OR = 2.55 (1.51–4.32) P < 0.001). Fifty of the 371 pregnant women were infected with hr‐HPV (13.5%) and 111 (30.0%) were infected with lr‐HPV. The coinfections of HPV and CT were found in 31 women, that is, 8.36% of the pregnant women (P < 0.001). The high rate of simultaneous CT and HPV infection in pregnant women favors the recommendation to screen pregnant women for both CT and HPV. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Evaluation of iron status: zinc protoporphyrin vis-a-vis bone marrow iron stores

Zinc protoporphyrin (ZPP) in the red cells is an indicator of iron status in the bone marrow (BM) and can be easily measured by Protofluor-Z Hematofluorometer from Helena Laboratories. It is well known that bone marrow iron is a gold standard for the diagnosis of iron deficiency anemia (IDA) even in the pre-latent phase. Hence, it was considered pertinent to evaluate the diagnostic utility of ZPP in comparison with bone marrow iron stores. 107 random BM were selected over a period of 2(1/2) years; in each case, RBC indices where recorded along with ZPP and Perls' Prussian blue reaction for BM iron stores. The specificity and sensitivity were found to be 77.8% and sensitivity 69.8%, respectively. However, the sensitivity increased up to 96.2% when Hb, RBC indices and ZPP were considered for the diagnosis of IDA.     

Clinical implications of interferon‐γ genetic and epigenetic variants

Interferon‐γ (IFN‐γ) is an integral and critical molecule of the immune system, with multiple functions, mostly related to the T helper type 1 (Th1) response to infection. It is critical for defence against mycobacterial infection and is of increasing interest in defence against fungi. In this article, we review the genetic and epigenetic variants affecting IFN‐γ expression and investigate its role in disease, with an emphasis on fungal diseases such as invasive and chronic pulmonary aspergillosis. Over 347 IFN‐γ gene variants have been described, in multiple ethnic populations. Many appear to confer a susceptibility to disease, especially tuberculosis (TB) and hepatitis, but also some non‐infectious conditions such as aplastic anaemia, cervical cancer and psoriasis. Several epigenetic modifications are also described, increasing IFN‐γ expression in Th1 lymphocytes and reducing IFN‐γ expression in Th2 lymphocytes. Recombinant IFN‐γ administration is licensed for the prophylaxis of infection (bacterial and fungal) in patients with the phagocyte functional deficiency syndrome chronic granulomatous disease, although the benefits appear limited. Interferon‐γ therapy is given to patients with profound defects in IFN‐γ and interleukin‐12 production and appears to be beneficial for patients with invasive aspergillosis and cryptococcal meningitis, but the studies are not definitive. A high proportion of patients with chronic pulmonary aspergillosis are poor producers of IFN‐γ in response to multiple stimuli and could also benefit from IFN‐γ administration. The investigation and management of patients with possible or demonstrated IFN‐γ deficiency in adulthood is poorly studied and could be greatly enhanced with the integration of genetic data.     

Glutathione S-transferase M1 (GSTM1) polymorphism is associated with atopic dermatitis susceptibility in a Korean population

Atopic dermatitis (AD) is a chronic pruritic skin condition affecting as much as 15% of children in industrialized countries. While the underlying pathophysiology of AD is not entirely understood, several studies have suggested that AD may mediated by oxidative stress. Glutathione S‐transferases (GSTs) are a class of polymorphic enzymes that function to protect against oxidative stress. To identify any possible associations between GSTs polymorphisms and AD susceptibility, the prevalence of two specific polymorphisms –GSTM1 and GSTT1 (homozygous deletion vs. undeleted) – were quantified by multiplex PCR in 145 patients with AD and 267 healthy controls. In individuals with AD, GSTM1/GSTT1 polymorphisms were compared with family history of AD, age of disease onset, disease severity [per SCORing Atopic Dermatitis (SCORAD)], serum IgE level and presence of other allergic diseases. While the GSTM1‐null genotype was found to be significantly associated with AD (P = 0.033, OR = 1.579, 95% CI = 1.037–2.403), the correlation between the GSTT1‐null genotype and AD did not reach statistical significance (P = 0.577, OR = 1.125, 95% CI = 0.744–1.702). The GSTM1‐null genotype was also found to be significantly associated with a childhood onset of AD, the absence of other allergic diseases, and a family history of AD. In combination, these results suggest that GSTM1 is associated with AD susceptibility in Korean subjects.     

Injection drug use is an independent risk factor for iron deficiency and iron deficiency anemia among HIV-seropositive and HIV-seronegative women

The risk factors for iron deficiency and iron deficiency anemia among female injection drug users are not well characterized. We measured hemoglobin and plasma ferritin and obtained demographic information and injection drug use history in the last 6 months in a cross-sectional study of 200 female injection drug users (134 HIV-positive and 66 HIV-negative). The women were participants in a natural history study, the AIDS Linked to Intravenous Experiences study in Baltimore, Maryland. In multivariate analyses adjusting for age, hepatitis C virus status, and HIV status, injection drug use within the last 6 months was associated with iron deficiency (odds ratio [OR] = 2.61, 95% confidence interval [CI]: 1.33 to 5.09) and iron deficiency anemia (OR = 6.65, 95% CI: 2.33 to 18.9). Among 134 HIV-positive women, injection drug use in the last 6 months was associated with iron deficiency (OR = 2.43, 95% CI: 1.08 to 5.48) and iron deficiency anemia (OR = 6.05, 95% CI: 1.82 to 20.1) in multivariate analyses adjusting for hepatitis C virus status and CD4 lymphocyte count. Injection drug use seems to be associated with iron deficiency and iron deficiency anemia. Further longitudinal studies are needed to gain insight into the nature of this association.     

Demographics,socio‐behavioral factors,and drug use patterns: What matters in spontaneous HCV clearance?

Hepatitis C virus (HCV), an emerging bloodborne pathogen, causes chronic liver disease frequently except in about 10–20% of infections which undergo spontaneous resolution. Investigating factors that influence viral clearance is essential to understand the natural history of this infection and establishing novel strategies for prevention and treatment. HCV clearance was estimated in a unique cohort of 1,260 HIV and HBV negative current drug users enrolled for a hepatitis B vaccination study. It was defined as the inability to detect viral RNA using a PCR method in presence of serum anti‐HCV antibody EIA. Associated demographic and socio‐behavioral factors including drug use patterns were identified from the enrolled subjects using multivariate regression analysis. 33.3% (420/1260) of drug users were found positive for anti‐HCV antibodies and 14.8% (62/420) of these individuals achieved viral clearance (negative PCR test). Race or ethnicity of the participants was the only significant factor associated with HCV clearance. Hispanics (OR = 3.4, 95% CI: 1.3–8.5, P = 0.01) and Caucasians (OR = 3.1, 95% CI: 1.5–6.6, P = 0.003) had significantly higher odds of clearing the virus compared to African Americans when adjusted for age and gender. None of the socio‐behavioral factors including alcohol intake and drug use patterns were significant determinants of HCV clearance. Racial or ethnic differences in HCV clearance were observed in this study suggesting an important role of host genetic susceptibility factors in determining the clinical course of this disease. Further research is needed to examine these genetic associations of host–virus relationships. J. Med. Virol. 84:235–241, 2012. © 2011 Wiley Periodicals, Inc.