Search

The gut dysbiosis present in chronic kidney disease (CKD) has been associated with anemia. Factors such as the accumulation of gut-derived uremic toxins, increased gut barrier permeability-induced inflammation, and a reduced intestinal production of short-chain fatty acids (SCFAs), all associated with changes in the intestinal microbiota composition in CKD, may lead to the development or worsening of anemia in renal patients. Understanding and addressing these mechanisms related to gut dysbiosis in CKD patients can help to delay the development of anemia and improve its control in this population. One approach is to avoid or reduce the use of drugs linked to gut dysbiosis in CKD, such as phosphate binders, oral iron supplementation, antibiotics, and others, unless they are indispensable. Another approach involves introducing dietary changes that promote a healthier microbiota and/or using prebiotics, probiotics, or symbiotics to improve gut dysbiosis in this setting. These measures can increase the presence of SCFA-producing saccharolytic bacteria and reduce proteolytic bacteria, thereby lowering the production of gut-derived uremic toxins and inflammation. By ameliorating CKD-related gut dysbiosis, these strategies can also improve the control of renal anemia and enhance the response to erythropoiesis-stimulating agents (ESAs) in ESA-resistant patients. In this review, we have explored the relationship between gut dysbiosis in CKD and renal anemia and propose feasible solutions, both those already known and potential future treatments.

Anemia is a common problem in South American camelids (SACs). Infections with Candidatus Mycoplasma haemolamae (CMh), a cell-wall free, hemotropic bacterium, are often suspected to be an important cause of anemia, as the pathogen infects the erythrocytes and is found in the blood of up to 30% of SACs. The information on the clinical signs of animals infected with this pathogen vary widely. Most infections are clinically inapparent. Treatment is usually carried out with oxytetracycline. A detailed overview of the clinical and hematological findings in 13 alpacas infected with Candidatus M. haemolamae (CMh+), based on patients from our university clinic and comparing those findings with the results of 22 negative alpacas (CMh-) is provided. Assignment to both groups was based on the PCR result. No relevant clinical or hematological differences between CMh+ and CMh- were found, the clinical signs in CMh+ were usually due to comorbidities. The examination of a blood smear alone proved to be insufficient; a PCR test should be carried out to confirm or rule out an infection. A critical review of the need for antibiotic treatment on the basis of a positive test result alone is recommended., (© 2024. The Author(s).)

Background: Mycoplasma suis (M. suis) belongs to the group of haemotrophic mycoplasmas and is known as the causative agent of infectious anaemia in pigs. In the last few years valuable insights into the mechanism of adhesion and invasion, shedding patterns and cell tropism of M. suis were gained by the use of new molecular techniques. However, details on M. suis induced lesions as well as the distribution of M. suis in different organs are still lacking. Therefore, seven splenectomised pigs were experimentally infected and clinical and laboratory investigations as well as a detailed histopathological examination were performed. Detection and quantification of M. suis DNA in blood and various tissue samples was done using a quantitative real-time PCR., Results: During the course of experimental infection, periodically occurring signs of infectious anaemia of pigs including severe icteroanaemia, fever, apathy and anorexia were observed. In addition, dermatological manifestations such as haemorrhagic diathesis presenting as petechiae occurred. The most important haematological alterations were normochromic, normocytic anaemia, hypoglycaemia as well as increased bilirubin and urea concentrations. Necropsy revealed predominant evidence of haemolysis with consecutive anaemia, as well as disseminated intravascular coagulation. M. suis was found in all investigated tissues with the highest copy numbers found in the kidneys. In Giemsa stained sections M. suis was only detected red blood cell (RBC)-associated., Conclusion: In the present study, no RBC independent sequestration of M. suis was detected in organs of experimentally infected pigs. Pathological findings are most likely resulting from haemolysis, consecutive anaemia as well as from disseminated intravascular coagulation and subsequent organ impairments.

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-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, 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.

Background: The prevalence of Helicobacter pylori (H. pylori) infection increases with age. However, the relationship between H. pylori infection and anemia in the elderly population remains to be identified. The aim of this study is to explore whether H. pylori infection is associated with anemia in a male elderly cohort., Methods: A cross-sectional study was designed using data collected from asymptomatic male senior citizens (≥ 65 years old) who received an assessment of their health status at the General Hospital of Chinese PLA from January 2015 to December 2015. H. pylori infection was confirmed by the 13 C-urea breath test. Blood samples from the participants were taken to assay for hemoglobin and other erythroid-related indices - serum iron, ferritin, and C-reactive protein (CRP). Anemia was defined as hemoglobin values lower than 120.0 g/L. Charlson Comorbidity Index (CCI) was applied to establish baseline comorbidities., Results: Data from 646 subjects were analyzed. The mean age of the study cohort was 79.4 ± 8.9 years. The overall prevalence of H. pylori infection was 35.3%. The prevalence of anemia in the H. pylori positive group was higher than that in the negative group (5.3% vs. 2.2%, P = .033). Among the patients who had higher CCI scores (> 2), the prevalence of anemia in the H. pylori positive and negative groups were 10.3 and 1.4%, respectively (P = .009). Compared to the H. pylori negative group, the odds ratio for anemia of the H. pylori positive group was 2.53 (P = .033). No correlation between H. pylori infection and serum iron and ferritin levels was found. The mean corpuscular volume of the H. pylori positive and negative group was 91.17 ± 3.94 fl and 91.17 ± 4.09 fl (mean ± SD), respectively (P = .986). The CRP level in the H. pylori positive group was higher than that in the H. pylori negative group (Median: 0.17 mg/dL vs. 0.10 mg/dL, P < .001)., Conclusion: H. pylori infection seems to be associated with normocytic and normochromic anemia in elderly males, especially in those with more comorbidities. Further clinical studies are needed to verify the association.

Background: Pneumonia during pregnancy has been proven to be associated with increased maternal and fetal morbidity and mortality. The management of severe pneumonia in gravid patients is even more challenging. Thus, we summarized the characteristics and pregnancy outcomes of these patients and explored the probable risk factors and predictive factors for pneumonia during pregnancy and the appropriate timing of delivery in severe pneumonia patients., Methods: A retrospective cohort study was conducted with 12 patients who were diagnosed with severe pneumonia complicating pregnancy at Peking Union Medical College Hospital between January 2010 and June 2017. The clinical features, treatment strategies, and pregnancy outcomes were collected from medical records and telephone calls., Results: All 12 patients were in their late second or third trimester. The patients had a higher prevalence of anemia (50%) and preeclampsia (25%) than ordinary pregnant women. Delayed diagnoses were not uncommon. Two mothers died in our series, resulting in a mortality rate of 17%. Two intrauterine deaths were observed. Elective delivery was not performed in any of the four patients in their second trimester. Six of the seven patients who presented after 28 weeks of gestation and had live fetuses underwent emergency deliveries. Preterm births (6/7) and cesarean sections (5/7) were the two leading adverse outcomes in newborns., Conclusions: Anemia, advanced gestational age, and preeclampsia might be associated with the severity of pneumonia. Chest radiographs should be taken as soon as pneumonia is highly suspected to facilitate an early diagnosis. High incidences of adverse fetal outcomes were observed; thus, termination of the pregnancy is recommended for patients in their third trimester when respiratory function deteriorates progressively. However, it might be reasonable to continue pregnancy for those in their first or second trimester.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

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±1.03g/dL] vs. [13.44±1.19g/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., (Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

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.

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.

The role of Helicobacter pylori (H. pylori) infection in haematological system diseases is not well understood. We conducted this retrospective study to explore the association between H. pylori infection and anaemia in the Chinese population. This retrospective study was performed in Aerospace Center Hospital in Beijing. We derived the data from the registration system of the physical population between 2012-2016. Logistic regression models were used to explore the association between H. pylori infection and anaemia. Among 17,791 subjects, there were 7,804 (43.9%) subjects with H. pylori infection and 950 (5.3%) with anaemia. The prevalence of anaemia in the H. pylori (+) group was significantly higher than in the H. pylori (-) group after adjusting for age, sex, marriage, underlying diseases and body mass index. Compared to H. pylori (-), the OR of H. pylori (+) was 1.39 for moderate-to-severe anaemia and 1.05 for mild anaemia. The level of haemoglobin was lower in the H. pylori (+) group than in the H. pylori (-) group. This study indicates that H. pylori infection may be related to anaemia and haemoglobin level in the Chinese population.

Background: Hemotropic mycoplasmas (hemoplasmas), the agents of infectious anemia, have been reported in dogs and cats. Little data are available on hemoplasma infections in Italy. The aim of this study was to evaluate the species of hemoplasmas and their prevalence in dogs and cats of northern Italy., Methods: Blood samples were obtained from 117 candidate blood donor dogs, 278 free-roaming dogs and 227 free-roaming cats in 2014 and 2015. Samples were first screened for hemoplasmas with a SYBR green real time PCR. The positive samples were confirmed by a second SYBR green real time PCR and sequencing. Co-infections were detected using species-specific SYBR green real time PCR., Results: The overall prevalence in dogs was 4.5% (18/395). Among the donors only one dog was positive for Mycoplasma haemocanis (0.8%). The overall prevalence of infection in free-roaming dogs was 6.1% (17/278), which was significantly higher than in candidate donors (P < 0.05). Both M. haemocanis (13/278; 4.7%) and "Candidatus M. haematoparvum" (4/278; 1.4%) were identified. In dogs, no significant association was found between hemoplasma infection and gender, age or origin. The overall prevalence in cats was 13.2% (30/227). All three feline hemoplasma species were detected, i.e. "Candidatus Mycoplasma haemominutum" (28; 12.3%), "Candidatus Mycoplasma turicensis" (11; 4.8%) and Mycoplasma haemofelis (9; 4.0%). Half of the infected cats were co-infected (15; 6.6%) with different species of hemoplasmas. Risk factor analysis confirmed that older age, male gender and FIV positivity are predisposing factors for hemoplasma infection in cats., Conclusion: This study found that candidate blood donor dogs in northern Italy show a negligible risk for hemoplasma infection, confirming the appropriateness of the candidate selection criteria and the low prevalence in the study area. Accordingly, testing for hemoplasma should be considered optional for canine blood donor screening. Hemoplasma infection was instead common in free-roaming cats, and is expected to be non-negligible in owned cats with outdoor access. Feline candidates for blood donation will therefore need to be carefully selected.

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., (© 2017 by The American Society of Hematology.)

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.

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.

Background: Global malaria has been on the decline over the past decade due to expansion of interventions. The present study aimed at determining the current status of malaria epidemiology in the context of sustained interventions and seasonal variations in Bolifamba, which represents a typical semi-urban malaria endemic community in the Cameroonian rainforest., Methods: A monthly cross-sectional survey was carried out in Bolifamba, a multi ethnic semi-urban locality on the eastern flanks of Mt Cameroon, for a year during which blood samples were collected from participants and examined for malaria parasites by microscopy. Correlation analysis of seasonal/monthly malaria prevalence was done with weather data from Ekona, a nearby village with a meteorological station. Intervention strategy such as use of Insecticide Treated Bed Net (ITBN) and risk factors such as duration of stay in the locality, age and housing type were also investigated., Results: The results revealed a malaria prevalence of 38.3 % in the rainy season, which was significantly higher than 24.4 % observed in the dry season (P < 0.0001). A high prevalence of asymptomatic malaria which was more than double the prevalence of symptomatic malaria on a monthly basis was observed, 30.7 % vs 17.8 % in the rainy and dry season respectively (p < 0.0001) and asymptomatic malaria was significantly associated with anemia (p < 0.005). April was the peak month of malaria prevalence and coincided with peak periods of both asymptomatic and symptomatic malaria. The Plasmodium falciparum parasite rates in the 2- up to 10-years age group (PfPR(2-10)) was 40.8 %. The regular use of ITBN was significantly associated with low prevalence of 31.7 % as opposed to irregular or non-usage of ITBN 38.2 % (p < 0.05). Log of parasite load was found to initially increase to 2.49 with less than 5 years of stay, and decreased gradually with increasing duration of stay in the locality (p = 0.046). Climatic factors were significantly and positively associated with monthly malaria prevalence and the strongest predictors of malaria prevalence were rainfall and minimum temperature with r values of 0.563 and 0.6 respectively., Conclusions: The study highlights the role of seasonal change in modifying malaria prevalence during the year and the beneficial effect of ITBN. It also underscores a sublime problem of asymptomatic malaria associated with anemia, and indicates that partial immunity is acquired with prolonged stay in Bolifamba. This preliminary result is the basis of ongoing work to identify the antigens involved in acquired immunity.

We report a fatal case of suspected Clostridium (Cl.) perfringens septicemia in a previously healthy woman in her eighties. At first, she presented at the hospital complaining of upper abdominal discomfort and vomiting, and was discharged the next day after ruling out any fatal conditions. However, her condition deteriorated approximately 10h after discharge and she died shortly after. The postmortem computed tomography (PMCT) performed 29h postmortem revealed an excessive systemic gas accumulation compared with the postmortem external appearance and time elapsed since her death, which suggested the presence of a gas-forming infection. Histopathological examination showed diffuse proliferation of Gram-positive bacilli in almost all the organ tissues, especially in blood vessels. Along with these findings, hyperthermia 3h postmortem, and severe anemia and thrombocytopenia without an obvious site of hemorrhage suggested hemolysis due to Cl. perfringens septicemia. These findings suggested the diagnosis before performing the conventional autopsy. To the best of our knowledge, this is the first case report to describe PMCT findings of gas-forming infection and septicemia in contrast with the external appearance and histopathological findings in a medico-legal autopsy setting., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Erythroferrone (ERFE) is an erythropoiesis-driven regulator of iron homeostasis. ERFE mediates the suppression of the iron-regulatory hormone hepcidin to increase iron absorption and mobilization of iron from stores. We examined the role of ERFE in the recovery from anemia of inflammation (AI) induced by injection of heat-killed Brucella abortus. B abortus-treated wild-type mice developed a moderate anemia and reached nadir hemoglobin 14 days after injection and partially recovered by 28 days. We observed that Erfe expression in the bone marrow and the spleen was greatly increased during anemia and peaked at 14 days after injection, a time course similar to serum erythropoietin. To determine whether ERFE facilitates the recovery from anemia, we analyzed Erfe-deficient mice injected with B abortus. Compared with wild-type mice, Erfe-deficient mice exhibited a more severe anemia, had higher hepcidin levels and consequently lower serum iron concentration on days 14 and 21, and manifested impaired mobilization of iron from stores (liver and spleen). Erfe(-/-) mice eventually compensated by further stimulating erythropoiesis and reticulocyte production. Thus, ERFE contributes to the recovery from AI by suppressing hepcidin and increasing iron availability., (© 2014 by The American Society of Hematology.)

Background: Pulmonary tuberculosis and anemia are both prevalent in Tanzania. There is limited and inconsistent literature on the association between anemia and sputum conversion following tuberculosis treatment., Methods: Newly diagnosed sputum smear positive pulmonary tuberculosis patients aged ≥15 years initiating on standard anti tuberculosis therapy were recruited from 14 of 54 tuberculosis clinics in Dar es Salaam. Patients were receiving medication according to the recommended short course Directly Observed Therapy (DOT) strategy and were followed up prospectively until completion of treatment (six months). Patients were evaluated before initiation of TB treatment by performing the following; clinical history, physical examination, complete blood counts, serum biochemistry and sputum microscopy. Sputum smears were re-examined at two months of anti-tuberculosis therapy for presence of acid fast bacilli. Anemia was defined as hemoglobin <13 g/dl (males) or <12 g/dl (females). Log-binomial regression was used to assess the association between anemia and sputum conversion at two months., Results: Of the 1245 patients included in the study, 86% were anemic and 7% were sputum smear positive at two months of anti-tuberculosis therapy. Anemic patients were three times more likely to have sputum positive smear as compared to non-anemic patients at two months (RR = 3.05; 95% CI 1.11-8.40) p = 0.03. The risk for sputum positive smear results increased with severity of anemia (P for trend <0.01)., Conclusion: Baseline anemia is associated with increased risk for persistent positive sputum smears at two months of tuberculosis treatment. Future studies should evaluate the mechanisms for TB-associated anemia as well as the role of intervention for anemia among TB patients.

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.

Background: High seroprevalence of parvovirus B19 (B19V) coinfection with Plasmodium falciparum has been previously reported. However, the impact of B19V-infection on the clinical course of malaria is still elusive. In this study, we investigated the prevalence and clinical significance of B19V co-infection in Gabonese children with malaria., Methods: B19V prevalence was analyzed in serum samples of 197 Gabonese children with P. falciparum malaria and 85 healthy controls using polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct DNA-sequencing., Results: B19V was detected in 29/282 (10.28%) of Gabonese children. B19V was observed more frequently in P. falciparum malaria patients (14.21%) in comparison to healthy individuals (1.17%) (P<0.001). Notably, the mild-malaria group revealed significantly lower hematocrit levels in B19V/P. falciparum co-infection than in P. falciparum mono-infection (P<0.05). Genetic analysis revealed a predominance of B19V genotype-1 (71.43%) in the studied population. However, B19V-genotype 2 was observed significantly more often in children with severe-malaria than in mild-malaria (P=0.04)., Conclusion: Our findings reveal that B19V-infection is frequent in Gabonese children with P. falciparum malaria and signifies a possible contribution of B19V on the clinical course of malaria in a genotype-dependent manner. B19V co-infection should be considered as a additional diagnostic measure in malaria patients with life threatening anemia.

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., (Copyright 2013, NMJI.)

Case Description: A 7-year-old Quarter Horse gelding used for unsanctioned racing was examined because of fever and anorexia., Clinical Findings: Physical examination revealed fever, tachycardia, and tachypnea. Results of a CBC indicated anemia and mild thrombocytopenia. Results of microscopic examination of a blood smear indicated piroplasms in erythrocytes, consistent with Babesia spp. Regulatory authorities were contacted, and results of serologic testing at the National Veterinary Services Laboratories confirmed acute Babesia equi infection., Treatment and Outcome: Equids on the home premises of the index horse were placed under quarantine. Those equids were tested for piroplasmosis, and 6 of 63 horses had positive results for B equi. Another horse that had previously been housed on the index premises also had positive results for B equi. Competent tick vectors for piroplasmosis organisms were not identified. All 8 horses with piroplasmosis were Quarter Horses that participated in unsanctioned racing and were trained by the same person. Two of the horses were illegally removed from the index premises; these 2 horses and the other horse with piroplasmosis that was previously housed on the index premises could not be found. The other 5 horses with piroplasmosis were euthanized. Investigators concluded that transmission of B equi among horses was most likely iatrogenic., Clinical Relevance: The United States has been considered piroplasmosis free. However, veterinarians should consider piroplasmosis in horses with signalments and clinical signs similar to those of the index horse of this report. Regulatory authorities should be contacted regarding horses in which piroplasmosis is suspected.

Background: In heavily endemic malaria areas, it is almost inevitable that malarial infection will be associated with anaemia, although malaria may not be the prime cause of it. Anaemia is a major public health problem in Cameroon. We hypothesized that, factors other than falciparum malaria account for anaemia in the study area., Methods: A longitudinal study was conducted among 351 Plasmodium falciparum positive children to determine the prevalence, risk factors and the perception of anaemia by the caregivers in a semi-rural community. The investigative methods included the use of a structured questionnaire, clinical evaluation and laboratory investigations., Results: At enrolment the overall prevalence of anaemia as assessed by Hb concentration (Hb < 11 g/dl) was 80.3% (282). Following treatment the prevalence of persistent anaemia was 6% and 46.2% of the children achieved haematological recovery by day 42. Exploratory multiple linear regression analysis showed the following; parasitaemia density (P < 0.01), enlarged spleen (P < 0.05), duration of fever > 2 days (P < 0.01), high white blood cell count (P < 0.001), sex (P < 0.05), iron status indicators (ferritin and transferrin) (P < 0.001), level of education of the caregiver (P < 0.05), management of onset of malaria by caregiver (P < 0.005) and wasting (P < 0.05) to be risk factors for anaemia in children with falciparum infection. Approximately 75.5% (265) of the caregivers had some knowledge about anaemia., Conclusion: The identified risk factors revealed the important contributors to the pathogenesis of anaemia in the Mount Cameroon region. Control efforts should therefore be directed towards proper health education emphasizing on proper health seeking behaviour and attitudes of the population.

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.

Hemotrophic mycoplasmas, bacteria without cell walls whose niche is the erythrocytes of their hosts, have never been cultivated in vitro. Therefore, knowledge of their pathogenesis is fundamental. Mycoplasma suis infects pigs, causing either acute fatal hemolytic anemia or chronic low-grade anemia, growth retardation, and immune suppression. Recently, the complete genomes of two hemotrophic mycoplasma species, M. suis and M. haemofelis, were sequenced, offering new strategies for the analysis of their pathogenesis. In this study we implemented a proteomic approach to identify M. suis proteins during acute infection by using tandem mass spectrometry. Twenty-two percent of the predicted proteins encoded in M. suis strain KI&#95;3806 were identified. These included nearly all encoded proteins of glycolysis and nucleotide metabolism. The proteins for lipid metabolism, however, were underrepresented. A high proportion of the detected proteins are involved in information storage and processing (72.6%). In addition, several proteins of different functionalities, i.e., posttranslational modification, membrane genesis, signal transduction, intracellular trafficking, inorganic ion transport, and defense mechanisms, were identified. In its reduced genome, M. suis harbors 65.3% (strain Illinois) and 65.9% (strain KI&#95;3806) of the genes encode hypothetical proteins. Of these, only 6.3% were identified at the proteome level. All proteins identified in this study are present in both M. suis strains and are encoded in more highly conserved regions of the genome sequence. In conclusion, our proteome approach is a further step toward the elucidation of the pathogenesis and life cycle of M. suis as well as the establishment of an in vitro cultivation system.

A 2-year-old East Friesian sheep imported from Australia exhibited severe anemia after contagious pustular dermatitis in Hokkaido, Japan. Hemoplasma infection was confirmed in blood smears. Both Mycoplasma ovis and 'Candidatus Mycoplasma haemovis' were detected by PCR and sequence analyses. In the epidemiological analysis, dual pathogens were detected in 6 of 12 (50.0%) sheep imported from Australia with the infected ewe at the same time, 1 of 5 (20.0%) sheep introduced from a domestic farm in Hokkaido, and in 1 of 16 (6.3%) sheep from an epidemiologically unrelated ranch. It is the first clinical case of sheep to confirm coinfection of these pathogens in Japan.

Background & Objectives: Severe anaemia in Plasmodium falciparum (Pf) associated malaria is a leading cause of death despite low levels of parasitaemia. In an effort to understand the pathogenesis of anaemia we studied expression level of RBC complement regulatory proteins, CR1 (CD35), CD55 and CD59 with haemoglobin status in a group of malaria cases from Assam, Goa and Chennai, and in healthy controls., Methods: Flowcytometry was used to study expression of CR1, CD55 and CD59 in 50 Pf cases and 30 normal healthy volunteers. Giemsa stained thick and thin blood films were used for microscopic detection and identification of malarial parasites and parasite count., Results: No correlation was found between degree of expression of RBC surface receptors CR1, CD55 and CD59 with haemoglobin level. However, expression of CD55 was less in malaria cases than in healthy controls., Interpretation & Conclusions: The present findings indicate that malaria infection changes the expression profile of complement regulatory protein CD55 irrespective of severity status of anaemia. Further studies are needed to explore the pathophysiology of anaemia in malaria cases in Assam where expression of RBC complement receptors appears to be low even in normal healthy population.

Among 62 children with mild malaria, cerebral malaria, or severe malarial anemia, we analyzed the transcription of different var gene types. There was no difference in parasitemia level or body temperature between groups. However, a significantly different expression pattern was observed in children with cerebral malaria, compared with that in patients in the other 2 groups: children with cerebral malaria had lower expression of the upsA subtype but higher expression of the upsB and upsC subtypes. Furthermore, expression of human genes responsive to tumor necrosis factor and hypoxia correlated with distinct ups types.

Host susceptibility to infection is controlled in large measure by the genetic makeup of the host. Spirochetes of the genus Borrelia include nearly 40 species of vector-borne spirochetes that are capable of infecting a wide range of mammalian hosts, causing Lyme disease and relapsing fever. Relapsing fever is associated with high-level bacteremia, as well as hematologic manifestations, such as thrombocytopenia (i.e., low platelet numbers) and anemia. To facilitate studies of genetic control of susceptibility to Borrelia hermsii infection, we performed a systematic analysis of the course of infection using immunocompetent and immunocompromised inbred strains of mice. Our analysis revealed that sensitivity to B. hermsii infections is genetically controlled. In addition, whereas the role of adaptive immunity to relapsing fever-causing spirochetes is well documented, we found that innate immunity contributes significantly to the reduction of bacterial burden. Similar to human infection, the progression of the disease in mice was associated with thrombocytopenia and anemia. Histological and fluorescence in situ hybridization (FISH) analysis of infected tissues indicated that red blood cells (RBCs) were removed by tissue-resident macrophages, a process that could lead to anemia. Spirochetes in the spleen and liver were often visualized associated with RBCs, lending support to the hypothesis that direct interaction of B. hermsii spirochetes with RBCs leads to clearance of bacteria from the bloodstream by tissue phagocytes.

Although anemia frequently occurs in poststreptococcal acute glomerulonephritis (PSAGN), severe anemia is rare. We report severe normocytic, normochromic anemia (hematocrit, 19.8%) in PSAGN in a 6-year-old girl with edema, macrohematuria, and proteinuria for 1 month. The potential causes of severe anemia found in this case were: 1) longer duration of massive hematuria from onset of macrohemauria to treatment, 2) a level of erythropoietin much lower than that in cases of iron deficiency anemia, and 3) hemodilution. We speculate that these factors combined to cause an unusual case of severe anemia in PSAGN.

Four pasture-fed Japanese Black cows showed the main clinical symptoms of severe hemoglobinuria at different periods between 2003 and 2007. Hematological analyses at the first consultation revealed severe anemia, and biochemical analyses indicated both severe hemolysis and disruption of hepatic function. Although the first 2 patients died, the hemoglobinuria and general condition of the remaining 2 cows, who were immediately initiated on large doses of antibiotics, improved within 3 days. Clostridium haemolyticum was detected by polymerase chain reaction (PCR) analysis of the blood sample of 1 of the infected cows. Anti-fascioliasis medicine is administered, and since then, no case of hemoglobinuria has been observed. The cows were diagnosed with bacillary hemoglobinuria, and they represent the first few cases in Japan.

Although knowledge of feline haemotropic mycoplasmas (haemoplasmas) has dramatically improved in recent years, some issues still remain to be elucidated. The aim of the current study was to evaluate the prevalence of feline haemoplasma infections in blood samples collected from cats in northern Italy. A convenience-sample of 307 cats (40 anaemic; 258 non-anaemic; nine with unknown haematocrit [HCT]) was investigated using polymerase chain reaction assays. Furthermore, the date of blood collection, signalment and clinicopathological data were retrospectively evaluated to assess predictors and risk factors for infection. Haemoplasma infections were highly prevalent in the sample investigated with an overall prevalence of 18.9% (95% confidence interval: 14.5-23.3%). The prevalence for the three feline haemoplasmas was 17.3% for 'Candidatus Mycoplasma haemominutum' (CMhm), 5.9% for Mycoplasma haemofelis (Mhf) and 1.3% for 'Candidatus Mycoplasma turicensis' (CMt). Feline immunodeficiency virus-positive status represented a risk factor for infection with an odds ratio of 4.19 (P=0.02). Moreover, a higher prevalence was observed in summer (odds ratio 1.78; P=0.04) which may be consistent with arthropod-borne disease transmission. Cats infected with Mhf showed significantly lower HCT (P=0.03), haemoglobin values (P=0.02) and red blood cell counts (P=0.04), lower mean corpuscular haemoglobin concentration (P<0.01) and higher white blood cell counts (P<0.01) when compared with non-infected cats.

Objective: To evaluate the efficacy of the fluoroquinolone pradofloxacin in the treatment of cats experimentally infected with Mycoplasma hemofelis., Animals: 23 young adult specific-pathogen-free cats., Procedures: Cats were inoculated with M hemofelis from a chronically infected donor and assigned to 1 of 4 treatment groups: a doxycycline group, a low-dose-pradofloxacin group, a high-dose-pradofloxacin group, and an untreated control group. Treatment was initiated for 14 days when M hemofelis infection was detected via PCR assay and clinical signs of hemoplasmosis were present. Cats that had negative PCR assay results after treatment were administered a glucocorticoid and monitored via PCR assay for an additional 4 weeks., Results: All cats yielded positive results for M hemofelis via conventional PCR and quantitative PCR assays and developed anemia. The low-dose-pradofloxacin group had significantly lower M hemofelis copy numbers than the doxycycline group. Six cats treated with pradofloxacin yielded negative results during treatment. Of those cats, 4 yielded negative conventional PCR assay results and all yielded negative quantitative PCR assay results for M hemofelis 1 month after administration of high-dose glucocorticoids., Conclusions and Clinical Relevance: Pradofloxacin had anti-M hemofelis effects similar to those of doxycycline. In addition, pradofloxacin may be more effective at long-term M hemofelis organism clearance than doxycycline.

Toll-like receptors (TLRs) are key factors of innate immunity that detect pathogen invasion and trigger a host response. TLR4 can mediate a response through adaptor molecules, MyD88 or TRIF. In the present study, streptomycin-treated MyD88(-/-), Tlr4(-/-), Trif (Lps2/Lps2), and C57BL/6 wild-type (WT) mice were infected with either Shiga toxin (Stx)-producing or non-producing Escherichia coli O157:H7. Moderate to severe clinical signs of disease developed in MyD88(-/-) (n = 21/21), Tlr4(-/-) (n = 12/16), Trif (Lps2/Lps2) (n = 7/15) and WT mice (n = 6/20) infected with Stx-producing E. coli O157:H7 but not in mice inoculated with the Stx non-producing strain (n = 0/54, P < 0.001). MyD88(-/-) mice infected with Stx-producing E. coli O157:H7 developed the most severe disease and had the highest bacterial burden. Hematological analysis of sick MyD88(-/-) mice showed reduced red blood cell counts and reticulocytosis, suggesting hemolysis. Thrombocytopenia developed in MyD88(-/-), Trif (Lps2/Lps2), and WT mice, and creatinine levels were elevated in both MyD88(-/-) and WT mice infected with the Stx-producing strain. Renal histopathology showed evidence of glomerular capillary congestion, tubular desquamation, and fibrinogen deposition, and intestinal histopathology showed mucosal injury, edema, and inflammation in sick mice. Administration of purified Stx2 to MyD88(-/-) and WT mice led to severe disease in both groups, suggesting that MyD88(-/-) mice are not more sensitive to Stx than WT mice. As MyD88(-/-) mice developed the most severe disease hematological and pathological changes, the results suggest that dysfunctional innate immune responses via MyD88 enhanced Stx-induced disease.

Detection of hemotropic Mycoplasma spp. infection was attempted in cats by PCR using whole blood without DNA extraction. A total 46 of 54 (85%) cats with suspected Mycoplasma spp. infection showed a positive reaction, corresponding completely with the results of standard PCR testing. The direct PCR assay was sensitive enough to detect more than 0.0061% parasitemia for ;C. M. haemominutum' and 0.0075% parasitemia for M. haemofelis. These data indicate that the direct PCR assay might be sufficient for use as a tool in clinical examinations.

Objective: To determine prevalences of various hemoplasma species among cats in the United States with possible hemoplasmosis and identify risk factors for and clinicopathologic abnormalities associated with infection with each species., Design: Cross-sectional study. Animals-310 cats with cytologic evidence of hemoplasmosis (n = 9) or acute or regenerative anemia (309)., Procedures: Blood samples were tested by means of a broad-spectrum conventional PCR assay for hemoplasma DNA and by means of 3 separate species-specific real-time PCR assays for DNA from "Candidatus Mycoplasma haemominutum" (Mhm), Mycoplasma haemofelis (Mhf), and "Candidatus Mycoplasma turicensis" (Mtc)., Results: Overall prevalences of Mhm, Mhf, and Mtc infection were 23.2% (72/310), 4.8% (15/310), and 6.5% (20/310), respectively. Mixed infections were detected in 20 (6.5%) cats. Cats infected with hemoplasmas were more likely to be male than were uninfected cats. Infection with FeLV or FIV was significantly associated with infection with Mhf. Compared with uninfected cats, cats infected with Mhf had higher reticulocyte counts, nucleated RBC counts, and mean corpuscular volume; cats infected with Mhm had higher mean corpuscular volume; and cats infected with Mtc had higher monocyte counts., Conclusions and Clinical Relevance: Results supported the suggestion that these 3 hemoplasma species commonly occur among cats in the United States and that pathogenicity of the 3 species varies.

Background: The goals of this study were to develop and apply conventional (c) and real-time TaqMan polymerase chain reaction (PCR) assays for Mycoplasma haemofelis (Mhf), 'Candidatus Mycoplasma haematoparvum' (Mhp), and 'Candidatus Mycoplasma haemominutum' (Mhm) to blood samples of cats to determine the epidemiology of these infections in cats., Hypothesis: Cats are infected with >2 hemoplasma species, and organism load correlates with disease induced by these organisms., Animals: Blood samples from 263 anemic and nonanemic cats were used., Methods: A retrospective study was conducted., Results: Forty-seven (18%) samples were positive. Three samples (1%) yielded 170 base pair cPCR products, 1 of which was positive for Mhf using real-time PCR. Forty-four samples (17%) yielded 193 base pair cPCR products, 40 of which were positive for Mhm using real-time PCR. Organism loads ranged from 375 X 10(6)/mL to 6.9 x 10(6)/mL of blood. Sequencing of cPCR products from samples testing negative using real-time PCR identified 2 Mhp-like sequences, 1 Mhm-like sequence, and 1 sequence resembling 'Candidatus Mycoplasma turicensis'. Cats infected with Mhm were less likely to be anemic than uninfected cats. Older age, outdoor exposure, feline immunodeficiency virus (FIV) seropositivity, cutaneous squamous cell carcinoma (SCC), and stomatitis were associated with Mhm infection. Cats from the Sacramento Valley were more often infected with Mhm than cats from the San Francisco bay area., Conclusions and Clinical Importance: Cats may be infected with 4 hemoplasma species. The association between Mhm infection, FIV, and SCC may reflect outdoor roaming status of infected cats. The clustered distribution of infection suggests an arthropod vector in transmission.

Aim: To unravel the possible association of malondialdehyde (MDA) and fructosamine in anemic H pylori infected patients and to observe the alteration in MDA and fructosamine levels in these patients after treatment for one month., Methods: Fructosamine, MDA and glucose were estimated in 22 anemic H pylori infected patients and 16 healthy controls. Hematological parameters were also evaluated in both the groups using Sysmex-K-100 automated cell counter. The H pylori infected patients were randomly divided into two groups. H pylori infected patients in Group I received both iron supplementation and anti-H pylori therapy, while patients in Group II received only iron supplementation. All the biochemical and hematological parameters were estimated after one month of treatment., Results: In anemic H pylori infected patients, while MDA (5.41 +/- 2.16 vs 2.26 +/- 0.50; P < 0.05) and fructosamine (2.64 +/- 0.93 vs 1.60 +/- 0.35; P < 0.05) were significantly increased, iron (32.72 +/- 14.93 vs 110.25 +/- 26.58; P < 0.05), hemoglobin (6.9 +/- 2.6 vs 12.66 +/- 0.74; P < 0.05) and ferritin (28.82 +/- 16.27 vs 140.43 +/- 30.72; P < 0.05) levels were significantly decreased compared with the controls. With partial correlation analysis, fructosamine was found to have a significant positive correlation with MDA. In Group I, while MDA level decreased significantly (3.11 +/- 1.73 vs 5.50 +/- 2.46; P < 0.05), there was a significant increase in iron (84.09 +/- 29.51 vs 36.09 +/- 17.81; P < 0.05), hemoglobin (10.40 +/- 1.11 vs 7.42 +/- 1.90; P < 0.05) and ferritin (116.91 +/- 63.34 vs 30.46 +/- 17.81; P < 0.05) levels after one month. There was no significant change in the levels of fructosamine in group I after treatment. Similarly, no significant alterations were noted in the levels of MDA, fructosamine, hemoglobin or ferritin in Group II patients after one month of treatment., Conclusion: An increased level of fructosamine and MDA was found in anemic H pylori infected patients. Present data supports the premise that lipid peroxides per se do play a role in the glycation of plasma proteins. Furthermore, the findings from this study indicate that treatment for both anemia and H pylori infections is required for lowering the levels of lipid peroxides in these patients.

Hemoplasmas are known causes of anemia in some cats and some Bartonella species have been associated with anemia in people and in dogs. In this retrospective study, we used polymerase chain reaction (PCR) assays to determine the prevalence rates of Mycoplasma haemofelis, 'Candidatus M haemominutum', A phagocytophilum, Ehrlichia species, and Bartonella species DNA in the blood of cats with anemia and a control group of healthy cats. DNA of the organisms was amplified from 22 of 89 cats with anemia (24.7%) and 20 of 87 healthy cats (23.0%). DNA of a hemoplasma was amplified from 18 of 89 cats with anemia (20.2%) and 13 of 87 healthy cats (14.9%); DNA of a Bartonella species was amplified from five of 89 cats with anemia (5.6%) and seven of 87 healthy cats (8.0%). There were no statistically significant differences detected between groups.

During an 18-mo period (May 2002-November 2003), 10 animals in a herd of 19 reindeer (Rangifer tarandus) at the National Animal Disease Center (NADC) experienced episodes of anemia. Affected animals had histories of weight loss, unthriftiness, occasionally edema of dependent parts and moderate anemia characterized by microcytosis or macrocytosis, hypochromasia, schistocytosis, keratocytosis, acanthocytosis, and dacryocytosis. Numerous basophilic punctate to ring-shaped bodies, measuring less than 1.0 microm, were found on the surface of red blood cells and were often observed encircling the outer margins of the cells. Based on cytologic findings, DNA preparations from selected affected animals in the NADC herd and one animal from a private herd experiencing similar episodes of anemia were assayed by polymerase chain reaction (PCR) for the presence of hemotropic bacteria using primers targeting the 16S rRNA genes of Mycoplasma (Eperythrozoon) suis, Mycoplasma (Haemobartonella) haemofelis, Anaplasma marginale, Anaplasma spp., and Ehrlichia spp. Amplification products were detected from four of the affected animals using primers specific for the 16S rRNA gene of M. haemofelis and Mycoplasma haemocanis. Product from one of the animals was sequenced and internal primers were designed from the resulting sequence to perform a nested PCR assay. Samples from 10 reindeer were positive using the nested PCR reaction and products from seven animals were sequenced; BLAST searches and phylogenetic analysis were performed on the resulting sequences. Sequence data from six animals revealed homology to an organism most closely related to Mycoplasma ovis, Mycoplasma wenyonii, and Mycoplasma haemolamae; sequence from a single animal was most closely related to M. haemofelis and M. haemocanis. This represents the first identification of a haemomycoplasma species in reindeer. Although several animals were also infected with abomasal nematodes, the presence of this newly described haemomycoplasma may have contributed to the anemic syndrome.

This study was undertaken to determine whether Haemobartonella felis (Mycoplasma haemofelis), the causative bacterial agent of feline infectious anemia, infects nondomestic cats. Routine complete blood count and polymerase chain reaction (PCR) were performed to detect the gene for 16S ribosomal RNA for the organism. Sixty-four blood samples were collected from 54 nondomestic cats, including tigers (Panthera tigris), cheetahs (Acinonyx jubatus), lions (P. leo), mountain lions (Felis concolor), snow leopards (P. unica), and a jaguar (P. onca). Some cats were sampled on two or three different dates. Two tigers were positive for H. felis by PCR analysis. As previously described in domestic cats, the parasitemia appears to be intermittent in nondomestic cats.

Objective: To investigate the effects of preexisting FeLV infection or FeLV and feline immunodeficiency (FIV) coinfection on the pathogenicity of the small variant of Haemobartonella felis (Hfsm, California variant) in cats., Animals: 20 FeLV infected, 5 FeLV-FIV coinfected, and 19 retrovirus-free cats., Procedures: A client-owned cat, coinfected with FeLV and Hfsm, was the source for Hfsm. Inoculum 1 (FeLV free) was obtained by passage of source Hfsm through 4 FeLV-resistant cats. Inoculum 2 was obtained by further passage of Hfsm (inoculum 1) through 2 specific pathogen-free cats., Results: A mild-to-moderate anemia started 21 days after inoculation, with its nadir occurring at 35 to 42 days after inoculation. Infection with Hfsm induced greater decrease in hemoglobin concentration in FeLV infected cats, compared with retrovirus free cats. Reticulocytosis, macrocytosis, and polychromasia of erythrocytes developed in anemic cats regardless of retrovirus infection status. Mean neutrophil counts decreased during the hemolytic episode. For most cats, the anemia was transient. Four FeLV infected cats, 1 of which was also FIV infected, developed fatal FeLV-associated myeloproliferative diseases. Of the surviving cats, 8 died over the next 24 months from other FeLV-related diseases. Hemolysis did not recur after the initial episode. Inoculum 1 induced more severe anemia than inoculum 2., Conclusions and Clinical Relevance: Our results support the clinical observation that cats coinfected with FeLV and H felis develop more severe anemia than cats infected with H felis alone. Infection with Hfsm may induce myeloproliferative disease in FeLV infected cats. The small variant of H felis may lose pathogenicity by passage through FeLV-free cats.

Objectives: To describe clinical and laboratory findings associated with cats experimentally infected by inoculation with the 2 recognized genotypes of Hemobartonella felis (small variant, Hfsm; large variant, Hflg) and to determine the response of cats to treatment with azithromycin., Animals: 18 young adult domestic shorthair cats of both sexes., Procedures: Cats were inoculated with H felis and monitored weekly, using CBC counts and a polymerase chain reaction (PCR) designed to detect both genetic variants of H felis. Beginning 26 days after inoculation, 11 cats were administered azithromycin (15 mg/kg of body weight, PO, q 12 h, for 7 days)., Results: Inoculation resulted in coinfection with Hflg and Hfsm, and both variants were detected by PCR. Clinical abnormalities and anemia were most severe in Hflg- and dual-infected cats. Results of PCR and CBC were positive for H felis in 112/112 (100%) and 42/112 (37.5%), respectively, samples collected after inoculation. Administration of azithromycin had little effect on clinical variables, including anemia. All cats, regardless of treatment with azithromycin, had positive results for the PCR at the end of the study period., Conclusions and Clinical Relevance: In these cats, Hflg was more pathogenic than Hfsm, and coinfection with both variants was detected. Results of the PCR were superior to results of CBC for detecting infection with H felis. Azithromycin administered at the dose and duration reported here was not efficacious for the treatment of cats with hemobartonellosis.