Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice.

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1ß, and TNF-α. Fe lowered lung IL-1α, IL-1ß, plasma IL-1ß, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

Newly recognized Anaplasma sp. in erythrocytes from Gopher Tortoises (Gopherus polyphemus).

BACKGROUND: In 2015, a previously unrecognized intracytoplasmic erythrocytic inclusion was discovered in anemic wild-caught adult gopher tortoises (Gopherus polyphemus). Subsequently, molecular diagnostics revealed this inclusion to be a novel Anaplasma sp. OBJECTIVES: The goal of this study was to morphologically characterize these erythrocytic inclusions by light and transmission electron microscopy (TEM). METHODS: Blood samples were taken from two car-injured wild-caught gopher tortoises for the preparation of Wright-Giemsa stained smears and TEM specimens. CBC data were serially performed and morphologically examined during treatment periods. RESULTS: Studies revealed a moderate to severe anemia with moderate regeneration as indicated by polychromasia and the presence of immature erythroid precursors. In addition, on light microscopy, one to two variably-sized round basophilic stippled paracentral erythrocytic inclusions were present per cell in both animals and involved 10%-25% of erythrocytes. TEM identified the intraerythrocytic inclusions as discrete membrane-bound cytoplasmic vacuoles (morulae) containing membrane-bound bacterial subunits that were of variable size, shape, and electron density. Serial hematologic data indicated complete remission of the infection in response to a single long-term course of doxycycline. CONCLUSIONS: The presence of a regenerative anemia in gopher tortoises from Florida revealed a newly recognized bacterial species that has morphologic characteristics similar to members of the genus Anaplasma.

Molecular detection of vector borne pathogens in anemic and thrombocytopenic dogs in southern Brazil / Detecção molecular de patógenos transmitidos por vetores em cães anemicos e trombocitopenicos no Sul do Brasil

Abstract Arthropod-borne pathogens are medically important because of their ability to cause diseases in their hosts. The purpose of this study was to detect the occurrence of Ehrlichia spp., piroplasmids and Hepatozoon spp. in dogs with anemia and thrombocytopenia in southern Brazil. EDTA-whole blood was collected from 75 domestic dogs presenting anemia or/and thrombocytopenia from Guarapuava, state of Paraná, Brazil. DNA samples were subjected to conventional PCR assays for Ehrlichia spp. (dsb), piroplasmids (18S rRNA) and Hepatozoon spp. (18S rRNA), followed by sequencing and phylogenetic analyses. Among the 75 dogs, one (1.33%) was positive for Hepatozoon sp. and six (8%) were positive for piroplasmids in 18S rRNA cPCR assays. None of the dogs showed positive results in Ehrlichia spp.-cPCR targeting dsb gene. The phylogenetic analyses revealed that three piroplasm sequences were clustered with Rangellia vitalii, while one sequence was grouped with B. vogeli. The only sequence obtained from Hepatozoon spp.-PCR protocol was pooled with H. canis. Therefore, there is urgent need for differential molecular diagnosis of the two piroplasm species cited as etiological agents in clinical cases of canine hemoparasitic diseases, given the higher pathogenic potential of R. vitalii than of B. vogeli.

Resumo Agentes transmitidos por artrópodes têm grande importância na medicina veterinária devido à sua capacidade de causar doenças graves em seus hospedeiros. O presente estudo objetivou investigar a ocorrência de três patógenos transmitidos por vetores, Ehrlichia canis, Rangelia vitalii e Hepatozoon canis, em cães na região sul do Brasil. Foram coletadas amostras de sangue total de 75 cães domésticos que apresentavam anemia e/ou trombocitopenia, em Guarapuava, Paraná, Brasil. As amostras de DNA foram submetidas à técnica de PCR convencional para E. canis (dsb), piroplasmídeos (18S rRNA) e Hepatozoon spp. (18S rRNA), seguida de sequenciamento e análises filogenéticas. Das 75 amostras, uma (1,33%) foi positiva para Hepatozoon spp. e seis (8%) foram positivas para Babesia spp. Nenhuma amostra mostrou resultados positivos para Ehrlichia spp. utilizando a detecção pelo gene dsb. As análises filogenéticas revelaram que três sequências obtidas foram agrupadas no mesmo clado que R. vitalii , enquanto uma foi agrupada juntamente com B. vogeli. A única sequência obtida pelo protocolo de PCR para Hepatozoon spp. foi agrupada juntamente com H. canis. Assim, é justificada necessidade de diferenciação das espécies de piroplasmas, através do diagnóstico molecular, como agentes etiológicos nos casos clínicos de hemoparasitose canina, considerando o potencial patogênico de R. vitalii quando comparado à B. vogeli.

Oral iron exacerbates colitis and influences the intestinal microbiome.

Inflammatory bowel disease (IBD) is associated with anaemia and oral iron replacement to correct this can be problematic, intensifying inflammation and tissue damage. The intestinal microbiota also plays a key role in the pathogenesis of IBD, and iron supplementation likely influences gut bacterial diversity in patients with IBD. Here, we assessed the impact of dietary iron, using chow diets containing either 100, 200 or 400 ppm, fed ad libitum to adult female C57BL/6 mice in the presence or absence of colitis induced using dextran sulfate sodium (DSS), on (i) clinical and histological severity of acute DSS-induced colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of 16S rRNA. Increasing or decreasing dietary iron concentration from the standard 200 ppm exacerbated both clinical and histological severity of DSS-induced colitis. DSS-treated mice provided only half the standard levels of iron ad libitum (i.e. chow containing 100 ppm iron) lost more body weight than those receiving double the amount of standard iron (i.e. 400 ppm); p<0.01. Faecal calprotectin levels were significantly increased in the presence of colitis in those consuming 100 ppm iron at day 8 (5.94-fold) versus day-10 group (4.14-fold) (p<0.05), and for the 400 ppm day-8 group (8.17-fold) versus day-10 group (4.44-fold) (p<0.001). In the presence of colitis, dietary iron at 400 ppm resulted in a significant reduction in faecal abundance of Firmicutes and Bacteroidetes, and increase of Proteobacteria, changes which were not observed with lower dietary intake of iron at 100 ppm. Overall, altering dietary iron intake exacerbated DSS-induced colitis; increasing the iron content of the diet also led to changes in intestinal bacteria diversity and composition after colitis was induced with DSS.

Fecal microbiota analysis of children with small intestinal bacterial overgrowth among residents of an urban slum in Brazil / Análise da microbiota fecal de crianças com sobrecrescimento bacteriano no intestino delgado de moradoras de uma favela urbana no Brasil

Abstract Objective: To analyze the fecal microbiota composition of children living in an urban slum in Brazil, with or without small intestinal bacterial overgrowth, and to investigate the occurrence of stunting and anemia. Methods: A total of 100 children were studied, aged 5-11 years, from the municipality of Osasco, São Paulo. Small intestinal bacterial overgrowth was screened through hydrogen and methane breath test with lactulose. Weight and height were measured, and the height-for-age and body mass-for-age anthropometric indexes were calculated. The occurrence of anemia was investigated by capillary hemoglobin. Analysis of bacterial phylum, genus, and species was performed by real-time polymerase chain reaction in fecal samples. Results: Small intestinal bacterial overgrowth was identified in 61.0% of the children. A lower mean of height-for-age Z-score ([−0.48 ± 0.90] vs. [−0.11 ± 0.97]; p = 0.027), as well as capillary hemoglobin ([12.61 ± 1.03 g/dL] vs. [13.44 ± 1.19 g/dL]; p < 0.001) was demonstrated in children with SIBO when compared with children without small intestinal bacterial overgrowth. Children with small intestinal bacterial overgrowth presented a higher frequency of Salmonella spp., when compared to those without small intestinal bacterial overgrowth (37.7% vs. 10.3%; p = 0.002). Higher counts of total Eubacteria (p = 0.014) and Firmicutes (p = 0.038) were observed in children without small intestinal bacterial overgrowth; however, a higher count of Salmonella (p = 0.002) was found in children with small intestinal bacterial overgrowth. Conclusion: Children who lived in a slum and were diagnosed with small intestinal bacterial overgrowth showed lower H/A Z-scores and hemoglobin levels. Furthermore, differences were observed in the fecal microbiota of children with small intestinal bacterial overgrowth, when compared to those without it; specifically, a higher frequency and count of Salmonella, and lower counts of Firmicutes and total Eubacteria.

Resumo Objetivo: Analisar a composição da microbiota fecal de crianças moradoras de uma favela urbana no Brasil, com e sem sobrecrescimento bacteriano no intestino delgado, e investigar a ocorrência de déficit de crescimento e anemia. Métodos: Foram estudadas 100 crianças, com idade entre 5 e 11 anos, na cidade de Osasco, São Paulo. Sobrecrescimento bacteriano no intestino delgado foi pesquisado por teste respiratório do hidrogênio e metano no ar expirado com lactulose. Foram mensurados peso, estatura e calculados os índices antropométricos estatura para idade e índice de massa corporal para idade. Foi investigada a ocorrência de anemia, pela avaliação da hemoglobina capilar. A análise dos filos, gêneros e espécies bacterianas em amostras de fezes foi realizada por polymerase chain reaction em tempo real. Resultados: Sobrecrescimento bacteriano no intestino delgado foi diagnosticado em 61,0% das crianças avaliadas. Foi verificada menor média do escore Z do índice estatura para idade (-0,48±0,90 vs.-0,11±0,97 DP) e de hemoglobina capilar (12,61±1,03 vs. 13,44±1,19 g/dL) no grupo de crianças com sobrecrescimento bacteriano no intestino delgado, quando comparadas àquelas sem sobrecrescimento bacteriano no intestino delgado (p < 0,05). Nas crianças com sobrecrescimento bacteriano no intestino delgado foi observada maior frequência de Salmonella spp., quando comparadas àquelas sem sobrecrescimento bacteriano no intestino delgado (37,7% vs. 10,3%; p = 0,002). Maior contagem de Eubactérias totais (p = 0,014) e Firmicutes (p = 0,038) foi observada nas crianças sem sobrecrescimento bacteriano no intestino delgado, enquanto que as crianças com sobrecrescimento bacteriano no intestino delgado apresentaram maior contagem de Salmonella (p = 0,002). Conclusão: Nas crianças com diagnóstico de sobrecrescimento bacteriano no intestino delgado verificaram-se menores valores de estatura para idade e de hemoglobina. Foram constatadas diferenças na microbiota fecal das crianças com sobrecrescimento bacteriano no intestino delgado, especificamente, maior frequência e contagem de Salmonella spp. e menores contagens de Firmicutes e Eubactérias totais.

Delivery strategies for malaria chemoprevention with monthly dihydroartemisinin-piperaquine for the post-discharge management of severe anaemia in children aged less than 5 years old in Malawi: a protocol for a cluster randomized trial.

BACKGROUND: Children initially hospitalized with severe anaemia in Africa are at high risk of readmission or death within 6 months after discharge. No intervention strategy specifically protects children during the post-discharge period. Recent evidence from Malawi shows that 3 months of post-discharge malaria chemoprevention (PMC) with monthly treatment with artemether-lumefantrine in children with severe malarial anaemia prevented 31% of deaths and readmissions. While a confirmatory multi-centre trial for PMC with dihydroartemisinin-piperaquine is on going in Kenya and Uganda, there is a need to design and evaluate an effective delivery strategy for this promising intervention. METHODS: This is a cluster-randomized trial with 5 arms, each representing a unique PMC delivery strategy. Convalescent children aged less than 5 years and weighing more than 5 kg admitted with severe anaemia and clinically stable are included. All eligible children will receive dihydroartemisinin-piperaquine at 2, 6 and 10 weeks after discharge either: 1) in the community without an SMS reminder; 2) in the community with an SMS reminder; 3) in the community with a community health worker reminder; 4) at the hospital with an SMS reminder; or 5) at the hospital without an SMS reminder. For community-based strategies (1, 2 and 3), mothers will be given all the PMC doses at the time of discharge while for hospital-based strategies (4 and 5) mothers will be required to visit the hospital each month. Each arm will consist of 25 clusters with an average of 3 children per cluster giving approximately 75 children and will be followed up for 15 weeks. The primary outcome measure is uptake of complete courses of PMC drugs. DISCUSSION: The proposed study will help to identify the most effective, cost-effective, acceptable and feasible strategy for delivering malaria chemoprevention for post-discharge management of severe anaemia in under-five children in the Malawian context. This information is important for policy decision in the quest for new strategies for malaria control in children in similar contexts. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02721420 . Protocol registered on 29 March 2016.The study was not retrospectively registered but there was a delay between date of submission and the date it first became available on the registry.

Infant anemia is associated with reduced TLR-stimulated cytokine responses and increased nasopharyngeal colonization with Moxarella catarrhalis.

Anemia is a major public health problem in young children. Reports on the role of anemia on infectious diseases remained controversial. We aim to investigate the effect of anemia on innate immunity, nasopharyngeal bacterial colonization, and subsequent infectious outcome. Blood tests were examined at the age of 12 months. TLR-induced cytokine production was assessed by ELISA. Bacteria from nasopharyngeal specimens were identified with traditional culture. Clinical infectious diseases were followed yearly until 3 years of age. Result showed that of the 423 infants, 72 had hemoglobin level ≤ 11 g/dL, among which 55% had normal iron level. There was significant association between hemoglobin level and TLR1-2, and 4 induced IL-6 (p = 0.04, 0.02) and that of TLR4 stimulated TNF-α response (p = 0.04). Children with anemia had higher nasopharyngeal colonization with Moxarella catarrhalis. Clinical analysis did not show anemia to be associated with infectious morbidity. However, children who developed LRTIs had mean lower ferritin levels. We speculated that iron might be the key factor related to infectious morbidity. Thus, to investigate the role of anemia in infectious diseases, it is important to first consider the prevalence of iron deficit, since the incidence of iron deficiency-induced anemia may vary among different regions.

Bartonella henselae infection in a dog with recalcitrant ineffective erythropoiesis.

Ineffective erythropoiesis was diagnosed in an 8-year-old male castrated Labrador Retriever. Despite treatment with immunosuppressive therapy for suspected immune-mediated erythrocyte maturation arrest, resolution of the nonregenerative anemia was not achieved. Following documentation of Bartonella henselae bacteremia by Bartonella alpha proteobacteria growth medium (BAPGM) enrichment blood culture, immunosuppressive therapy was discontinued, and the anemia resolved following prolonged antibiotic therapy. Bartonella immunofluorescent antibody testing was negative, whereas B henselae western blot was consistently positive. The contribution of B henselae bacteremia to ineffective erythropoiesis remains unknown; however, the potential role of B henselae in the pathophysiology of bone marrow dyscrasias warrants additional investigation.

A Severe Case of Murine Typhus Presenting With Anemia and Severe Thrombocytopenia.

We discuss a child with severe thrombocytopenia and mild anemia admitted to the Hematology service who quickly deteriorated to a life-threatening state. However, once rickettsial disease was considered in the differential diagnosis and empiric doxycycline begun, she quickly and fully recovered. A diagnostic panel, including Rickettsia typhi serology, confirmed the diagnosis of murine typhus but this occurred weeks after she had recovered. Given the potential severity of rickettsial diseases and the ease of modern travel across geographic borders, hematology-oncology providers everywhere must consider rickettsial diseases in their differential diagnosis of critically ill children and begin empiric therapy with doxycycline promptly.

Maternal obesity, obstetric interventions and post-partum anaemia increase the risk of post-partum sepsis: a population-based cohort study based on Swedish medical health registers.

BACKGROUND: The objective was to estimate whether maternal obesity and/or obstetric interventions are associated with diagnosed maternal post-partum sepsis. METHODS: A retrospective observational cohort study including all deliveries in Sweden between 1997 and 2012 (N = 1,558,752). Cases of sepsis (n = 376) were identified by International Classification of Diseases, (ICD-10) codes A40, A41 and O 85 in the Medical Birth Register and the National Patient Register. The reference population was non-infected, and therefore, women with any other infection diagnosis and/or with dispensed antibiotics within eight weeks post-partum were excluded. Information on dispensed drugs was available in the prescribed drug Register. Women with sepsis were compared with non-infected women concerning maternal characteristics and obstetric interventions. Adjusted odds ratios (aOR) were determined using the Mantel-Haenszel technique. Adjustments were made for maternal age, parity and smoking. RESULTS: Obese women (body mass index ≥30) had a doubled risk of sepsis (3.6/10,000) compared with normal weight women (2.0/10,000) (aOR 1.85 (95%CI: 1.37-2.48)). Induction of labour (aOR 1.44 (95%CI: 1.09-1.91)), caesarean section overall (aOR 3.06 (95%CI: 2.49-3.77)) and elective caesarean section (aOR 2.41 (95%CI: 1.68-3.45)) increased the risk of sepsis compared with normal vaginal delivery. Post-partum anaemia due to acute blood loss was associated with maternal sepsis (aOR 3.40 (95%CI: 2.59-4.47)). CONCLUSIONS: Maternal obesity, obstetric interventions and post-partum anaemia due to acute blood loss increased the risk of diagnosed post-partum sepsis indicating that interventions in obstetric care should be considered carefully and anaemia should be treated if resources are available.

Effects of Dietary Iron Modulation on Gut Microbial Composition and Function in Monogastrics: A Review.

Dietary iron is a crucial nutrient element for biological processes of both hosts and gut microbiota. Deficiency in dietary iron is a highly common disorder in the developing locations of the world and can be healed by oral iron administration or complementary iron diet. While the redundant iron that enters the gut lumen leads to negative effects, and modulates the gut microbial composition and function. Such modulation led to a significant effect on vital biological pathways of the host, including metabolic disease (obesity and type 2 diabetes), metabolites (SCFA, blood glucose and cholesterol), bile acid metabolism, endocrine, neural, and other well-being patterns. This review covers the multifaceted aspects of different nutritional iron stress on the composition and function of microbial gut in monogastrics and consequential health conditions as well as it reveals unclear points that need further studies.

Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota.

Bone marrow suppression is an adverse effect associated with many antibiotics, especially when administered for prolonged treatment courses. Recent advances in our understanding of steady-state hematopoiesis have allowed us to explore the effects of antibiotics on hematopoietic progenitors in detail using a murine model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia, with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of peripheral blood. Bone marrow progenitor analysis revealed depletion of hematopoietic stem cells and multipotent progenitors across all subtypes. Granulocytes and B cells were also diminished in the bone marrow, whereas the number of CD8+ T cells increased. Reductions in progenitor activity were not observed when cells were directly incubated with antibiotics, suggesting that these effects are indirect. Hematopoietic changes were associated with a significant contraction of the fecal microbiome and were partially rescued by fecal microbiota transfer. Further, mice raised in germ-free conditions had hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and antibiotic therapy of germ-free mice caused no additional abnormalities. The effects of antibiotics were phenocopied in Stat1-deficient mice, with no additional suppression by antibiotics in these mice. We conclude that microbiome depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1 signaling and alters T-cell homeostasis, leading to impaired progenitor maintenance and granulocyte maturation. Methods to preserve the microbiome may reduce the incidence of antibiotic-associated bone marrow suppression.

Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA), but controversial in anemia of inflammation (AI). Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA) model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet) prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

Helicobacter pylori Infection Induces Anemia, Depletes Serum Iron Storage, and Alters Local Iron-Related and Adult Brain Gene Expression in Male INS-GAS Mice.

Iron deficiency anemia (IDA) affects > 500 million people worldwide, and is linked to impaired cognitive development and function in children. Helicobacter pylori, a class 1 carcinogen, infects about half of the world's population, thus creating a high likelihood of overlapping risk. This study determined the effect of H. pylori infection on iron homeostasis in INS-GAS mice. Two replicates of INS-GAS/FVB male mice (n = 9-12/group) were dosed with H. pylori (Hp) strain SS1 or sham dosed at 6-9 weeks of age, and were necropsied at 27-29 weeks of age. Hematologic and serum iron parameters were evaluated, as was gene expression in gastric and brain tissues. Serum ferritin was lower in Hp SS1-infected mice than uninfected mice (p < 0.0001). Infected mice had a lower red blood cell count (p<0.0001), hematocrit (p < 0.001), and hemoglobin concentration (p <0.0001) than uninfected mice. Relative expression of gastric hepcidin antimicrobial peptide (Hamp) was downregulated in mice infected with Hp SS1 compared to sham-dosed controls (p<0.001). Expression of bone morphogenic protein 4 (Bmp4), a growth factor upstream of hepcidin, was downregulated in gastric tissue of Hp SS1-infected mice (p<0.001). Hp SS1-infected mice had downregulated brain expression of tyrosine hydroxylase (Th) (p = 0.02). Expression of iron-responsive genes involved in myelination (myelin basic protein (Mbp) and proteolipid protein 2 (Plp2)) was downregulated in infected mice (p = 0.001 and p = 0.02). Expression of synaptic plasticity markers (brain derived neurotrophic factor 3 (Bdnf3), Psd95 (a membrane associated guanylate kinase), and insulin-like growth factor 1 (Igf1)) was also downregulated in Hp SS1-infected mice (p = 0.09, p = 0.04, p = 0.02 respectively). Infection of male INS-GAS mice with Hp SS1, without concurrent dietary iron deficiency, depleted serum ferritin, deregulated gastric and hepatic expression of iron regulatory genes, and altered iron-dependent neural processes. The use of Hp SS1-infected INS-GAS mice will be an appropriate animal model for further study of the effects of concurrent H. pylori infection and anemia on iron homeostasis and adult iron-dependent brain gene expression.

Helicobacter pylori and extragastric diseases.

While Helicobacter pylori infection was initially revealed to be associated only with some gastroduodenal diseases, further studies have shown its possible role in several extragastric diseases. For idiopathic thrombocytopenic purpura, sideropenic anemia, and vitamin B12 deficiency, the diagnosis of H. pylori infection is recommended, and there are many other conditions such as cardiovascular, neurological, dermatological, and respiratory diseases in which H. pylori may possibly play a role. Interestingly, a potential role has also been described for GI neoplastic diseases, including colorectal and pancreatic cancer. Different mechanisms of action have been proposed, ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This review summarizes the results of the most relevant studies published on this topic over the last year.

Distinct roles for hepcidin and interleukin-6 in the recovery from anemia in mice injected with heat-killed Brucella abortus.

Anemia of inflammation (AI) is commonly observed in chronic inflammatory states and may hinder patient recovery and survival. Induction of hepcidin, mediated by interleukin 6, leads to iron-restricted erythropoiesis and anemia. Several translational studies have been directed at neutralizing hepcidin overexpression as a therapeutic strategy against AI. However, additional hepcidin-independent mechanisms contribute to AI, which are likely mediated by a direct effect of inflammatory cytokines on erythropoiesis. In this study, we used wild-type, hepcidin knockout (Hamp-KO) and interleukin 6 knockout (IL-6-KO) mice as models of AI. AI was induced with heat-killed Brucella abortus (BA). The distinct roles of iron metabolism and inflammation triggered by interleukin 6 and hepcidin were investigated. BA-treated wild-type mice showed increased expression of hepcidin and inflammatory cytokines, as well as transitory suppression of erythropoiesis and shortened red blood cell lifespan, all of which contributed to the severe anemia of these mice. In contrast, BA-treated Hamp-KO or IL-6-KO mice showed milder anemia and faster recovery compared with normal mice. Moreover, they exhibited different patterns in the development and resolution of anemia, supporting the notion that interleukin 6 and hepcidin play distinct roles in modulating erythropoiesis in AI.

Disseminated histoplasmosis: a comparative study of the clinical features and outcome among immunocompromised and immunocompetent patients.

BACKGROUND: Disseminated histoplasmosis is a chronic granulomatous disease caused by the dimorphic fungus, Histoplasma capsulatum. Clinical presentation can vary from the acute pulmonary to the chronic disseminated form. In India, disseminated histoplasmosis often presents with pyrexia of unknown origin with a presentation similar to 'disseminated tuberculosis' involving the adrenal glands and bone marrow. Due to rarity of the disease, data are lacking regarding its clinical presentation and outcome among immunocompromised and immunocompetent patients. METHODS: During January 2000 to December 2010, we identified 37 patients of disseminated histoplasmosis and attempted to characterize the differences between immuno- compromised and immunocompetent patients. Demographic characteristics, clinical presentation, risk factors, laboratory findings, diagnostic yield, treatment received and prognosis were noted and compared between the two groups. RESULTS: Eleven of 37 patients with disseminated histo- plasmosis were immunocompromised and 26 were immuno- competent. Comparison of their clinical features showed a higher frequency of skin lesions in the immunocompromised compared to the immunocompetent group (54.5% v. 11.5%). Pancytopenia and anaemia were more common among the immunocompromised (81.8%) compared to the immunocompetent (46.2%) group. In the immuno- compromised patients, the diagnosis was made most often by bone marrow aspirate and culture (72.7%) compared to the immunocompromised group where the diagnosis was most often obtained by adrenal gland biopsy and fungal cultures (57.7%). The cure rate was significantly higher in the immunocompetent group (73% v. 45%). CONCLUSION: The clinical presentation and outcome of patients with disseminated histoplasmosis differs among immunocompromised and immunocompetent patients.

Increased hepcidin expression in multibacillary leprosy

Iron is essential for all organisms and its availability can control the growth of microorganisms; therefore, we examined the role of iron metabolism in multibacillary (MB) leprosy, focusing on the involvement of hepcidin. Erythrograms, iron metabolism parameters, pro-inflammatory cytokines and urinary hepcidin levels were evaluated in patients with MB and matched control subjects. Hepcidin expression in MB lesions was evaluated by quantitative polymerase chain reaction. The expression of ferroportin and hepcidin was evaluated by immunofluorescence in paucibacillary and MB lesions. Analysis of hepcidin protein levels in urine and of hepcidin mRNA and protein levels in leprosy lesions and skin biopsies from healthy control subjects showed elevated hepcidin levels in MB patients. Decreases in haematologic parameters and total iron binding capacity were observed in patients with MB leprosy. Moreover, interleukin-1 beta, ferritin, soluble transferrin receptor and soluble transferrin receptor/log ferritin index values were increased in leprosy patients. Hepcidin was elevated in lepromatous lesions, whereas ferroportin was more abundant in tuberculoid lesions. In addition, hepcidin and ferroportin were not colocalised in the biopsies from leprosy lesions. Anaemia was not commonly observed in patients with MB; however, the observed changes in haematologic parameters indicating altered iron metabolism appeared to result from a mixture of anaemia of inflammation and iron deficiency. Thus, iron sequestration inside host cells might play a role in leprosy by providing an optimal environment for the bacillus.