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Osa-Andrews B, van Wijk XMR, Herrera Rivera N, Seifert RP, Harris NS, Marin MJ. An Introduction to the Complete Blood Count for Clinical Chemists: White Blood Cells. J Appl Lab Med 2025; 10:459-475. [PMID: 39873240 DOI: 10.1093/jalm/jfaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 12/26/2024] [Indexed: 01/30/2025]
Abstract
BACKGROUND The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort. CONTENT In this primer, the white blood cell (WBC) test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of leukopenia and leukocytosis. SUMMARY The laboratorian's approach to consult cases should be guided by the patient's clinical history and presentation while being able to provide key laboratory-based insights to assist in resolving result discrepancies that may otherwise go unnoticed.
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Affiliation(s)
- Bremansu Osa-Andrews
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Xander M R van Wijk
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States
| | | | - Robert P Seifert
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Neil S Harris
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
| | - Maximo J Marin
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL, United States
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2
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Williams SCP. Profile of Leonard I. Zon. Proc Natl Acad Sci U S A 2023; 120:e2310767120. [PMID: 37467283 PMCID: PMC10400938 DOI: 10.1073/pnas.2310767120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/21/2023] Open
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3
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Gill RC, Levett T, Youssef E. An audit of HIV testing practice in people aged 50 years and over presenting with a known clinical indicator condition in secondary care. HIV Med 2023; 24:231-235. [PMID: 35811462 DOI: 10.1111/hiv.13355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/19/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To evaluate HIV testing of patients aged ≥50 years presenting to secondary care with clinical indicator conditions (CICs) for HIV. METHODS Retrospective audit of electronic records for patients aged ≥50 years discharged from hospital between January 1st and July 31st 2019 who had at least one documented CIC. Patient demographics and HIV testing data were collected from clinical systems (excluding sexual health databases). RESULTS 2478 patients with a CIC were identified. 222 (9.0%) received an HIV test within 31 days of discharge. Patients receiving a test were significantly younger (mean 68.6 versus 75.3 years; P < 0.001) and significantly more men underwent testing than women (60.4% versus 39.6%; P = 0.001). 32 CICs were identified across nine disease systems. By system, those with a haematological CIC were significantly more likely to undergo testing compared with all other CICs combined (P < 0.001). Of individual CICs, patients with Kaposi's sarcoma, hepatitis C, neutropenia, lymphadenopathy, pyrexia of unknown origin and thrombocytopenia (P < 0.001), and seborrhoeic dermatitis, hepatitis B, other unexplained blood dyscrasia, and non-Hodgkin's lymphoma (P < 0.05) were more likely to undergo testing than those presenting with other CICs. Patients with dementia and lung cancer were less likely to undergo testing (P < 0.001). Patients presenting with a greater number of CICs were significantly more likely to undergo testing (P = 0.002). CONCLUSIONS HIV testing among patients aged ≥50 years presenting to secondary care with a CIC is low. Work is needed to improve HIV testing practice in this patient group.
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Affiliation(s)
| | - Tom Levett
- Brighton and Sussex Medical School, Brighton, East Sussex, UK
| | - Elaney Youssef
- Brighton and Sussex Medical School, Brighton, East Sussex, UK
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Comorbid disease in children and adolescents with perinatal HIV infection: A pilot study. ACTA BIOMEDICA SCIENTIFICA 2022. [DOI: 10.29413/abs.2022-7.5-2.8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background. With the increased use of combination antiretroviral therapy, the mortality of people living with HIV has decreased significantly, which has led to an increase of comorbidity and secondary HIV-related pathology in both adults and also in children and adolescents living with HIV infection. The incidence of children and adolescents with HIV infection and those in the general population varies significantly.The aim. To assess the frequency and range of chronic comorbidities in children and adolescents with perinatal HIV infection Methods. We carried out an observational study. Data on the incidence of 161 children with perinatal HIV infection registered in the Irkutsk Regional AIDS Center were copied.Results. Overall incidence of tuberculosis (18633.5 per 100 000 children), diseases of the digestive system (24844.7 per 100 000 children), diseases of the eye and adnexa (28571.4 per 100 000 children), diseases of the nervous system (18012.4 per 100 000 children), mental and behavioral disorders (13,664.6 per 100 000 children) in children with perinatal HIV infection is the higher than in children of comparable age. The overall incidence values of the endocrine system diseases, eating and metabolic disorders, diseases of the ear and mastoid process, diseases of the circulatory system, diseases of the genitourinary system, as well as congenital disorders and chromosomal disorders in children and adolescents with and without perinatal HIV infection are comparable.Conclusion. The prevalence of diseases of the circulatory, respiratory and genitourinary systems in children with perinatal HIV infection is comparable to that in the corresponding population. Prevalence of tuberculosis, anemia, diseases of the gastrointestinal tract, diseases of the eye and adnexa, diseases of the nervous system, mental and behavioral disorders is higher compared to children not exposed to HIV.
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Ayanaw MA, Yabeyu AB, Lenjiso G, Kifle ZD. Prevalence and predictors of thrombocytopenia among HAART naive HIV positive patients at Ambo University Referral Hospital. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2022. [DOI: 10.1016/j.cegh.2022.101049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Kerkar AS, Bhagwat SN, Sharma JH. A Study of Clinical and Serological Correlation of Positive Direct Antiglobulin Test in Blood Bank at a Tertiary Care Center. J Lab Physicians 2022; 14:223-230. [PMID: 36119425 PMCID: PMC9473924 DOI: 10.1055/s-0041-1741442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Objectives
Detection of red cell bound immunoglobulins and/or complement by direct antiglobulin test (DAT) is a crucial serological assay in the diagnosis of autoimmune hemolytic anemia (AIHA). However, DAT may be positive in a variety of clinical conditions with or without hemolysis. We aimed at evaluating the clinical and serological correlation of positive DAT by categorizing the clinical conditions associated with positive DAT, estimating the presence of in vivo hemolysis in case of positive DAT with polyspecific and monospecific antisera and correlating the strength of positive DAT with the presence of hemolysis.
Materials and Methods
The prospective observational study was performed on 200 samples that were positive for DAT with polyspecific antiglobulin reagent as the baseline investigation. These samples were further tested with anti-immunoglobulin G and anti-C3 monospecific DAT reagents to evaluate the type of protein responsible for positive DAT. The antiglobulin tests were performed by tube technique. DAT positivity was graded (1+ to 4 + ) in each patient. Autocontrol test was included. The patients with positive polyspecific DAT were categorized into different clinical conditions. The presence or absence of in vivo hemolysis was evaluated in all clinical categories and also for each grade of positivity with polyspecific and monospecific antiglobulin reagents.
Statistical Analysis
Binomial logistic regression and Mann–Whitney
U
test were applied to between the group analyses. For categorical variables, Fisher's exact test and relative risk were used. The qualitative data were expressed in numbers and percentages.
Results
The highest number of patients (75/200, 37.5%) belonged to the autoimmune diseases group. Tuberculosis and hepatitis C were the main infectious diseases associated with positive DAT. Out of 200 DAT-positive patients, 98 (49%) had in vivo hemolysis and 102 (51%) did not have hemolysis. AIHA (22) and systemic lupus erythematosus (18) were the commonest clinical conditions associated with in vivo hemolysis. All the 11 samples that showed positivity with only anti-C3 reagent did not show any hemolysis. There was statistically significant increase in the incidence of in vivo hemolysis with increasing grades of DAT positivity with all the three antihuman globulin reagents.
Conclusion
There are different disease conditions which show positive DAT with or without hemolysis. So, it is important to clinically and serologically correlate positive DAT results.
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Affiliation(s)
- Alisha Suresh Kerkar
- Department of Transfusion Medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
| | - Swarupa Nikhil Bhagwat
- Department of Transfusion Medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
| | - Jayashree Harihara Sharma
- Department of Transfusion Medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
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Shah B, Karki L, Mandal RK. Anemia among Patients Attending Anti-retroviral Therapy at a Tertiary Care Center: A Descriptive Cross-sectional Study. JNMA J Nepal Med Assoc 2021; 59:1239-1242. [PMID: 35199795 PMCID: PMC9200030 DOI: 10.31729/jnma.6318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 12/04/2021] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Hematologic abnormalities are among the most common complications of infection with Human Immunodeficiency Virus. These abnormalities are due to: impaired hematopoiesis, immune mediated cytopenias and altered coagulation mechanisms. Anemia is the most frequent,however, leukopenia, lymphopenia, and thrombocytopenia have also been observed. The aim of the study was to find the prevalence of anemia in patients attending anti-retroviral therapy at a tertiary care center of Nepal. METHODS The study was a descriptive cross-sectional study conducted from August 2018 to August 2019 in patients attending anti-retroviral therapy at a tertiary care hospital. Ethical approval was obtained from the Institutional Review Board of National Academy of Medical Sciences before starting the study (Reference number 267). Convenient sampling was used for this study. Data were analysed using the Statistical package for Social Sciences version 20. Point estimate at 90% confidence interval was calculated along with frequency and proportion for the binary data. RESULTS The prevalence of anemia among patients attending anti-retroviral therapy centers in our study was found in 29 (58%) (46.55-69.45 at 90% Confidence Interval). Out of those patients, 20 (63%) were male and 9 (50%) were female. The mean hemoglobin value was 11.946±2.51g/dl. CONCLUSIONS The prevalence of anemia among patients attending antiretroviral therapy in our study was found to be high which is consistent with the findings of other similar international studies. These patients should be routinely monitored and treated for the occurrence of hematological abnormalities.
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Affiliation(s)
- Bibhant Shah
- Department of Internal Medicine, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal,Correspondence: Dr. Bibhant Shah, Department of Internal Medicine, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal. , Phone: +977-9845090997
| | - Lochan Karki
- Department of Internal Medicine, National Academy of Medical Sciences, Bir Hospital, Kathmandu, Nepal
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HIV-1 Nef Induces Hck/Lyn-Dependent Expansion of Myeloid-Derived Suppressor Cells Associated with Elevated Interleukin-17/G-CSF Levels. J Virol 2021; 95:e0047121. [PMID: 34106001 PMCID: PMC8354241 DOI: 10.1128/jvi.00471-21] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection causes myelodysplasia, anemia, and accumulation of inflammatory monocytes (CD14+ CD16+) through largely unknown cellular and molecular pathways. The mouse cells thought to be equivalent to human CD14+ CD16+ cells are CD11b+ Gr1+ myeloid-derived suppressor cells (MDSC). We used HIV transgenic (Tg) mouse models to study MDSC, namely, CD4C/Nef Tg mice expressing nef in dendritic cells (DC), pDC, CD4+ T, and other mature and immature myeloid cells and CD11c/Nef Tg mice with a more restricted expression, mainly in DC and pDC. Both Tg strains showed expansion of granulocytic and CD11b+ Gr1low/int cells with MDSC characteristics. Fetal liver cell transplantation revealed that this expansion was stroma-independent and abrogated in mixed Tg/non-Tg 50% chimera. Tg bone marrow (BM) erythroid progenitors were decreased and myeloid precursors increased, suggesting an aberrant differentiation likely driving CD11b+ Gr1+ cell expansion, apparently cell autonomously in CD4C/Nef Tg mice and likely through a bystander effect in CD11c/Nef Tg mice. Hck was activated in Tg spleen, and Nef-mediated CD11b+ Gr1+ cell expansion was abrogated in Hck/Lyn-deficient Nef Tg mice, indicating a requirement of Hck/Lyn for this Nef function. IL-17 and granulocyte colony-stimulating factor (G-CSF) were elevated in Nef Tg mice. Increased G-CSF levels were normalized in Tg mice treated with anti-IL-17 antibodies. Therefore, Nef expression in myeloid precursors causes severe BM failure, apparently cell autonomously. More cell-restricted expression of Nef in DC and pDC appears sufficient to induce BM differentiation impairment, granulopoiesis, and expansion of MDSC at the expense of erythroid maturation, with IL-17→G-CSF as one likely bystander contributor. IMPORTANCE HIV-1 and SIV infection often lead to myelodysplasia, anemia, and accumulation of inflammatory monocytes (CD14+ CD16+), with the latter likely involved in neuroAIDS. We found that some transgenic (Tg) mouse models of AIDS also develop accumulation of mature and immature cells of the granulocytic lineage, decreased erythroid precursors, and expansion of MDSC (equivalent to human CD14+ CD16+ cells). We identified Nef as being responsible for these phenotypes, and its expression in mouse DC appears sufficient for their development through a bystander mechanism. Nef expression in myeloid progenitors may also favor myeloid cell expansion, likely in a cell-autonomous way. Hck/Lyn is required for the Nef-mediated accumulation of myeloid cells. Finally, we identified G-CSF under the control of IL-17 as one bystander mediator of MDSC expansion. Our findings provide a framework to determine whether the Nef>Hck/Lyn>IL-17>G-CSF pathway is involved in human AIDS and whether it represents a valid therapeutic target.
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Duguma N, Tesfaye Kiya G, Adissu Maleko W, Bimerew LG. Hematological parameters abnormalities and associated factors in HIV-positive adults before and after highly active antiretroviral treatment in Goba Referral Hospital, southeast Ethiopia: A cross-sectional study. SAGE Open Med 2021; 9:20503121211020175. [PMID: 34104440 PMCID: PMC8165838 DOI: 10.1177/20503121211020175] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/04/2021] [Indexed: 12/20/2022] Open
Abstract
Objectives Hematological abnormalities of the major blood cell lines are frequently reported in patients with HIV-1 infection, in patients without antiretroviral therapy, and during the advanced stages of the disease. Chronic immune activation and inflammation results in the progressive depletion of CD4+ T-cells play a significant role in the clinical progression and pathogenesis of this infection. This study was aimed at assessing the prevalence of hematological abnormalities and their associated factors before and after the initiation of antiretroviral therapy in adults with HIV-1 infection in a referral hospital. Methods The study was conducted from 1 April to 30 June 2018, at Goba Referral Hospital. A total of 308 HIV-positive adults on treatment were enrolled during the study period. Socio-demographic and clinical data were collected using a structured questionnaire, with pre-highly active antiretroviral therapy data were extracted from medical records while post-treatment immuno-hematological measurements were done on blood samples collected at the time of enrollment. Results The prevalence of anemia, leukopenia, and thrombocytopenia before initiation of antiretroviral treatment was higher, although anemia and thrombocytopenia decreased correspondingly after initiation of treatment leukopenia increased by 4%. Mean values of immuno-hematological parameters before and after treatment initiation were significant (p < 0.05). CD4+ T-cell count <200 cells/µL was the only independent risk factor for anemia and leukopenia before highly active antiretroviral therapy, while stage IV disease, female sex, zidovudine, lamivudine, and nevirapine treatment, and intestinal parasite infection were predictors of anemia after treatment initiation. Conclusion The study revealed that hematological abnormalities are common in HIV infection, while the occurrence of abnormalities after highly active antiretroviral therapy initiation. Different risk factors are associated with hematological abnormalities at pre- and post-highly active antiretroviral therapy with regular monitoring of risk factors, adherence to the early initiation of highly active antiretroviral therapy, and conduct of further longitudinal studies are recommended.
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Affiliation(s)
- Negesso Duguma
- Department of Medical Laboratory Sciences, Madda Walabu University, Goba, Ethiopia
| | - Girum Tesfaye Kiya
- School of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Wondimagegn Adissu Maleko
- School of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia.,Clinical Trial Unit, Jimma University, Jimma, Ethiopia
| | - Lealem Gedefaw Bimerew
- School of Medical Laboratory Sciences, Institute of Health, Jimma University, Jimma, Ethiopia
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Agegnehu CD, Merid MW, Yenit MK. Predictors of Anemia Among Adult HIV Positive Patients on First-Line Antiretroviral Therapy in Northwest Ethiopia: A Retrospective Follow-Up Study. HIV AIDS-RESEARCH AND PALLIATIVE CARE 2021; 13:455-466. [PMID: 33958896 PMCID: PMC8096420 DOI: 10.2147/hiv.s280338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Accepted: 04/13/2021] [Indexed: 11/23/2022]
Abstract
Background Globally, anemia is a common hematological disorder among HIV-infected patients. People with anemia often suffer from impaired physical functioning, psychological distress, and poor quality of life. Therefore, the aim of this study was to determine the incidence of anemia and its determinants among HIV positive individuals in northwest Ethiopia. Methods A total of 486 adult HIV positive patients on the first-line ART with complete information were enrolled in the adult care clinics of northwest Amhara referral hospitals from December 2015 to December 2018. EpiData version 4.2 was used for data entry and Stata version 14 for analysis. Variables having time to event nature were presented with the Kaplan–Meier function. The Cox regression model was used to identify predictors of anemia. Variables with P-values less than 0.2 in the bivariable analysis were considered in the multivariable regression. Adjusted hazard ratio with 95% CI was computed, and variables with less than 0.05 P-values in the multivariable Cox regression were taken as significant predictors of anemia. Results This study noted an overall 26.4 per 100 person-year observations (95% CI: 23.46, 30.74) incidence rate of anemia. According to the multivariable Cox regression, TB co-infection (AHR =1.99, 95% CI: 1.45, 2.74), zidovudine-based regimen (AHR=1.39, 95CI: 1.1, 1.85), CD4 level (AHR= 1.7, 95% CI: 1.23, 2.35), advanced WHO stage (AHR=1.32, 95% CI: 1.01, 1.74), and being underweight (AHR= 1.53, 95% CI: 1.14, 2.07) were predictors of anemia. Conclusion Anemia is a burden among HIV patients in the study setting. Baseline clinical variables, TB co-infection, and zidovudine-based were predictors of anemia. Therefore, early identification of anemia and addressing significant predictors are highly suggested to the study setting.
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Affiliation(s)
- Chilot Desta Agegnehu
- School of Nursing, College of Medicine and Health Sciences and Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia
| | - Mehari Woldemariam Merid
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Melaku Kindie Yenit
- Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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Valiaveettil C, Loutfy M, Kennedy VL, Caddy S, Yudin M, Conway T, Ding E, Sereda P, de Pokomandy A, Kaida A, for the CHIWOS Research Team. High prevalence of abnormal menstruation among women living with HIV in Canada. PLoS One 2019; 14:e0226992. [PMID: 31881068 PMCID: PMC6934328 DOI: 10.1371/journal.pone.0226992] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 12/10/2019] [Indexed: 12/16/2022] Open
Abstract
Objectives To measure the prevalence and correlates of abnormal menstruation among women living with HIV (WLWH) in Canada. Methods We used cross-sectional questionnaire data from the community-based Canadian HIV Women’s Sexual and Reproductive Health Cohort Study (CHIWOS), which enrolled WLWH aged ≥16 from British Columbia (BC), Ontario, and Quebec. For this analysis, we excluded women >45 years, who had primary amenorrhea, were pregnant, on hormonal contraception, or who reported history of endometrial cancer, last menstrual period >12 months ago, or premature ovarian failure. The primary outcome was abnormal menstruation (Yes vs No) based on responses to five questions about menstrual regularity, frequency, volume, duration, and intermenstrual bleeding in the six months prior to interview. An exploratory multivariable logistic regression analysis examined independent correlates of abnormal menstruation. Results Of 1422 women enrolled, 521 (37%) met eligibility criteria. Overall, 55.9% (95% CI:52%-60%) reported abnormal menstruation. In adjusted analyses, abnormal menstruation was associated with having a biologic sister/mother who entered menopause before age 40 (AOR 5.01, 95%CI 1.39–18.03), Hepatitis B co-infection (AOR 6.97, 95%CI 1.52–31.88), current smoking (AOR 1.69, 95%CI 1.55–3.41); and currently taking antiretroviral therapy (ART) (AOR 2.36, 95%CI 1.25–4.45) compared to being ART-naïve. Women in BC had higher adjusted odds of abnormal menstruation (AOR 2.95, 95%CI 1.61–5.39), relative to women in Ontario and Quebec. Conclusions Over half of WLWH in this analysis had abnormal menstruation. Correlates of abnormal menstruation include genetic, socio-behavioural factors (province of residence, smoking), Hepatitis B co-infection, and current ART use.
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Affiliation(s)
| | - Mona Loutfy
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
| | - V. Logan Kennedy
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
| | - Sheila Caddy
- Department of Obstetrics and Gynecology, University of Alberta, Edmonton, AB, Canada
| | - Mark Yudin
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Department of Obstetrics and Gynecology, St. Michael’s Hospital, Toronto, ON, Canada
| | - Tracey Conway
- Women’s College Research Institute, Women’s College Hospital, Toronto, ON, Canada
| | - Erin Ding
- British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
| | - Paul Sereda
- British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada
| | - Alexandra de Pokomandy
- Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada
- Department of Family Medicine, McGill University, Montreal, QC, Canada
| | - Angela Kaida
- Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
- * E-mail:
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Furler RL, Newcombe KL, Del Rio Estrada PM, Reyes-Terán G, Uittenbogaart CH, Nixon DF. Histoarchitectural Deterioration of Lymphoid Tissues in HIV-1 Infection and in Aging. AIDS Res Hum Retroviruses 2019; 35:1148-1159. [PMID: 31474115 DOI: 10.1089/aid.2019.0156] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Impaired immunity is a common symptom of aging and advanced Human Immunodeficiency Virus type 1 (HIV-1) disease. In both diseases, a decline in lymphocytic function and cellularity leads to ineffective adaptive immune responses to opportunistic infections and vaccinations. Furthermore, despite sustained myeloid cellularity there is a background of chronic immune activation and a decrease in innate immune function in aging. In HIV-1 disease, myeloid cellularity is often more skewed than in normal aging, but similar chronic activation and innate immune dysfunction typically arise. Similarities between aging and HIV-1 infection have led to several investigations into HIV-1-mediated aging of the immune system. In this article, we review various studies that report alterations of leukocyte number and function during aging, and compare those alterations with those observed during progressive HIV-1 disease. We pay particular attention to changes within lymphoid tissue microenvironments and how histoarchitectural changes seen in these two diseases affect immunity. As we review various immune compartments including peripheral blood as well as primary and secondary lymphoid organs, common themes arise that help explain the decline of immunity in the elderly and in HIV-1-infected individuals with advanced disease. In both conditions, lymphoid tissues often show signs of histoarchitectural deterioration through fat accumulation and/or fibrosis. These structural changes can be attributed to a loss of communication between leukocytes and the surrounding stromal cells that produce the extracellular matrix components and growth factors necessary for cell migration, cell proliferation, and lymphoid tissue function. Despite the common general impairment of immunity in aging and HIV-1 progression, deterioration of immunity is caused by distinct mechanisms at the cellular and tissue levels in these two diseases.
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Affiliation(s)
- Robert L. Furler
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Kevin L. Newcombe
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York
| | - Perla M. Del Rio Estrada
- Departmento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas,” CDMX, Mexico DF, Mexico
| | - Gustavo Reyes-Terán
- Departmento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas,” CDMX, Mexico DF, Mexico
| | - Christel H. Uittenbogaart
- Department of Microbiology, Immunology and Molecular Genetics, Medicine-Pediatrics, UCLA AIDS Institute and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California
| | - Douglas F. Nixon
- Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York
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Tamir Z, Seid A, Haileslassie H. Magnitude and associated factors of cytopenias among antiretroviral therapy naïve Human Immunodeficiency Virus infected adults in Dessie, Northeast Ethiopia. PLoS One 2019; 14:e0211708. [PMID: 30759131 PMCID: PMC6373930 DOI: 10.1371/journal.pone.0211708] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 01/18/2019] [Indexed: 12/31/2022] Open
Abstract
Background Hematologic abnormalities involving peripheral blood cell cytopenias are strong predictors of morbidity, mortality and poor antiretroviral therapy (ART) outcomes of HIV infected individuals. However, limited studies are conducted in resource-limited settings of sub-Saharan Africa that have addressed the magnitude and associated factors of cytopenias. This study aimed to investigate the magnitude and associated factors of cytopenias among ART naïve HIV infected adult Ethiopians. Materials and methods A cross-sectional study was conducted among ART naïve HIV infected individuals attending at ART unit of Dessie Referral Hospital between November 01, 2015 and April 30, 2016. A total of 402 adults were included using consecutive sampling. Socio-demographic, clinical and laboratory data of patients were collected. The data were entered to Epi Info version 3.4.3 and analyzed using SPSS version 20 software (SPSS INC, Chicago, IL, USA). Factors associated with cytopenias were analyzed first using bivariate and then multivariate logistic regression models. An odds ratio with 95% confidence interval was used to measure the strength of association. For all statistical significant tests, the cut-off value was set at P<0.05. Results In this study, the overall magnitude of any cytopenia, anemia, leucopenia and thrombocytopenia were 63.4%, 43.5%, 24.4% and 18.7%, respectively. In multivariate logistic regression analysis, severe immunosuppression and WHO clinical stage IV HIV disease were significantly associated with increased prevalence of cytopenias. In addition, older age and younger age showed significant association with increased prevalence of anemia and leucopenia, respectively. Conclusion Frequent occurrence of cytopenias was independently associated with severe immunosuppression and WHO clinical stage IV HIV disease. Further longitudinal multicenter studies are recommended to bolster the findings of this study in order to suggest the need of routine assessment and management of hematological abnormalities for optimal choice of initial antiretroviral agents and prevention of further morbidities.
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Affiliation(s)
- Zemenu Tamir
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
- * E-mail:
| | - Abdurahaman Seid
- Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Wollo University, Dessie, Ethiopia
| | - Haftay Haileslassie
- Department of Medical Laboratory Sciences, College of Health Sciences, Mekelle University, Mekelle, Ethiopia
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14
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Molecular prevalence of parvovirus B19 among HIV1-infected patients in Iran. Med J Islam Repub Iran 2018; 32:113. [PMID: 30815408 PMCID: PMC6387811 DOI: 10.14196/mjiri.32.113] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Indexed: 12/16/2022] Open
Abstract
Background: Different outcomes of parvovirus B19 (B19V) infection in immunocompromised patients, including HIV1-infected persons, may be life-threatening. Considering the hematologic disorders associated with B19V infection, this study aimed to investigate the prevalence of B19V infection among HIV1-infected individuals in Iran.
Methods: Serum samples from 100 HIV1-infected patients were analyzed for B19 viral DNA using real-time PCR assay. COBAS TaqMan HIV-1 test was performed for quantitative measurements of HIV-1 RNA in the patients’ sera.
Results: Real-time PCR analysis revealed that 10 out of 100 cases (10%) were positive for B19V infection. Across various age groups, the B19V infection was more prevalent among patients within the age range of 21-40 years. Higher prevalence of B19V infection was observed among HIV1-infected patients with a viral load of higher than 400 copies/mL.
Conclusion: Despite limitations, this study may set the stage for further evaluations with larger sample sizes to elucidate the potential role of B19V in hematologic disorders, which may result in exacerbation of the disease in HIV1-infected patients. Moreover, as it has been shown that B19V infection can be treated using intravenous immunoglobulin (IVIG) therapy, available treatments may help improve the quality of life in HIV-infected persons.
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15
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Fekene TE, Juhar LH, Mengesha CH, Worku DK. Prevalence of cytopenias in both HAART and HAART naïve HIV infected adult patients in Ethiopia: a cross sectional study. BMC HEMATOLOGY 2018; 18:8. [PMID: 29632668 PMCID: PMC5887186 DOI: 10.1186/s12878-018-0102-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Accepted: 03/23/2018] [Indexed: 11/10/2022]
Abstract
Background In individuals infected with HIV, hematological abnormalities are common and are associated with increased risk of disease progression and death. However, the profile of hematological abnormalities in HIV infected adult patients is not known in Ethiopia. Thus, the aim of this study was to assess the hematological manifestations of HIV infection and to identify the factors associated with cytopenias in both HAART and HAART naïve HIV infected adult patients in Ethiopia. Method We conducted a cross-sectional quantitative study of HIV-infected adult patients attending the ART follow-up clinic of Jimma University Specialized Hospital in Jimma, Ethiopia, from July 2012 to September 2012. We used a structured questionnaire to collect socio-demographic and clinical information. After interviewing, 4 ml of venous blood was drawn from each study subject for hematologic and immunologic parameters. Result The prevalence of anemia, leucopenia, thrombocytopenia and lymphopenia among the study individuals were 51.5%, 13%, 11.1% and 5% respectively. Presence of opportunistic infection (p = 0.001), use of CPT (p = 0.04) and CD4 count < 200 cells/μl (p = 0.002) were associated with an increased risk of anemia. Conclusion Hematologic abnormalities were common in HIV infected adult patients. Of the cytopenias anemia was the most common. Use of CPT was independently associated with increased risk of anemia and leucopenia. Therefore, large scale and longitudinal studies, giving emphasis on the association of CPT and cytopenia, are recommended to strengthen and explore the problem in depth.
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Affiliation(s)
- Tamirat Edie Fekene
- 1Department of internal medicine, College of Public Health and Medical Sciences, Jimma University, P.O. Box376, Jimma, Ethiopia
| | - Leja Hamza Juhar
- 1Department of internal medicine, College of Public Health and Medical Sciences, Jimma University, P.O. Box376, Jimma, Ethiopia
| | | | - Dawit Kibru Worku
- 3Department of Internal Medicine, Bahir Dar University, -79 Bahir Dar, Ethiopia
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Yaseen MM, Abuharfeil NM, Yaseen MM, Shabsoug BM. The role of polymorphonuclear neutrophils during HIV-1 infection. Arch Virol 2017; 163:1-21. [PMID: 28980078 DOI: 10.1007/s00705-017-3569-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 08/14/2017] [Indexed: 12/23/2022]
Abstract
It is well-recognized that human immunodeficiency virus type-1 (HIV-1) mainly targets CD4+ T cells and macrophages. Nonetheless, during the past three decades, a huge number of studies have reported that HIV-1 can directly or indirectly target other cellular components of the immune system including CD8+ T cells, B cells, dendritic cells, natural killer cells, and polymorphonuclear neutrophils (PMNs), among others. PMNs are the most abundant leukocytes in the human circulation, and are known to play principal roles in the elimination of invading pathogens, regulating different immune responses, healing of injured tissues, and maintaining mucosal homeostasis. Until recently, little was known about the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression. This is because early studies focused on neutropenia and recurrent microbial infections, particularly, during advanced disease. However, recent studies have extended the investigation area to cover new aspects of the interactions between HIV-1 and PMNs. This review aims to summarize these advances and address the impact of HIV-1 infection on PMNs as well as the impact of PMNs on HIV-1 disease progression to better understand the pathophysiology of HIV-1 infection.
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Affiliation(s)
- Mahmoud Mohammad Yaseen
- Medical Laboratory Sciences, College of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, 22110, Jordan.
| | - Nizar Mohammad Abuharfeil
- Applied Biological Sciences, College of Science and Arts, Jordan University of Science and Technology, Irbid, 22110, Jordan
| | - Mohammad Mahmoud Yaseen
- Public Health, College of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan
| | - Barakat Mohammad Shabsoug
- Chemical Sciences, College of Science and Arts, Jordan University of Science and Technology, Irbid, 22110, Jordan
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17
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Li G, Zhao J, Cheng L, Jiang Q, Kan S, Qin E, Tu B, Zhang X, Zhang L, Su L, Zhang Z. HIV-1 infection depletes human CD34+CD38- hematopoietic progenitor cells via pDC-dependent mechanisms. PLoS Pathog 2017; 13:e1006505. [PMID: 28759657 PMCID: PMC5552321 DOI: 10.1371/journal.ppat.1006505] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Revised: 08/10/2017] [Accepted: 07/02/2017] [Indexed: 01/05/2023] Open
Abstract
Chronic human immunodeficiency virus-1 (HIV-1) infection in patients leads to multi-lineage hematopoietic abnormalities or pancytopenia. The deficiency in hematopoietic progenitor cells (HPCs) induced by HIV-1 infection has been proposed, but the relevant mechanisms are poorly understood. We report here that both human CD34+CD38- early and CD34+CD38+ intermediate HPCs were maintained in the bone marrow (BM) of humanized mice. Chronic HIV-1 infection preferentially depleted CD34+CD38- early HPCs in the BM and reduced their proliferation potential in vivo in both HIV-1-infected patients and humanized mice, while CD34+CD38+ intermediate HSCs were relatively unaffected. Strikingly, depletion of plasmacytoid dendritic cells (pDCs) prevented human CD34+CD38- early HPCs from HIV-1 infection-induced depletion and functional impairment and restored the gene expression profile of purified CD34+ HPCs in humanized mice. These findings suggest that pDCs contribute to the early hematopoietic suppression induced by chronic HIV-1 infection and provide a novel therapeutic target for the hematopoiesis suppression in HIV-1 patients.
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Affiliation(s)
- Guangming Li
- The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America
| | - Juanjuan Zhao
- Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Liang Cheng
- The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America
| | - Qi Jiang
- The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America
| | - Sheng Kan
- Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China
| | - Enqiang Qin
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - Bo Tu
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - Xin Zhang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - Liguo Zhang
- Key laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, China
| | - Lishan Su
- The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America
- Key laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Science, Beijing, China
| | - Zheng Zhang
- The Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States of America
- Research Center for Clinical & Translational Medicine, Beijing 302 Hospital, Beijing, China
- * E-mail:
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18
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Shapiro RM, Zeller MP, Warkentin TE. Sepsis and persisting neutropenia in a drug addict. Am J Hematol 2017; 92:312-316. [PMID: 28052478 DOI: 10.1002/ajh.24639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2016] [Revised: 12/02/2016] [Accepted: 12/31/2016] [Indexed: 12/29/2022]
Affiliation(s)
- Roman M. Shapiro
- Department of MedicineLondon Health Science CentreLondon Ontario Canada
| | - Michelle P. Zeller
- Department of Pathology and Molecular MedicineMichael G. DeGroote School of Medicine, McMaster UniversityHamilton Ontario Canada
- Department of MedicineMichael G. DeGroote School of Medicine, McMaster UniversityHamilton Ontario Canada
| | - Theodore E. Warkentin
- Department of Pathology and Molecular MedicineMichael G. DeGroote School of Medicine, McMaster UniversityHamilton Ontario Canada
- Department of MedicineMichael G. DeGroote School of Medicine, McMaster UniversityHamilton Ontario Canada
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Jin Y, Li Q, Meng X, Xu Q, Yuan J, Li Z, Guo H, Liu Z. Prevalence of anaemia among HIV patients in rural China during the HAART era. Int J STD AIDS 2016; 28:63-68. [PMID: 26672003 DOI: 10.1177/0956462415622866] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The prevalence of anaemia among HIV patients receiving highly active antiretroviral therapy (HAART) in China has not been extensively studied. The purpose of this study was to estimate the prevalence of anaemia among HIV patients receiving HAART in China. This cross-sectional study was conducted based on data in routine record registers. Factors associated with anaemia were evaluated by logistic regression model. Among the 8632 HIV patients in this analysis, the overall prevalence of anaemia was 39.2%, and the prevalence of mild, moderate, and severe anaemia were 27.2%, 10.8%, and 1.2%, respectively. Anaemia was more prevalence among male, older, little time taken HAART and lower CD4 cell count. Patients taken TCM had lower prevalence of anaemia. The prevalence of anaemia among the HIV patients receiving HAART was high in this study. HIV patients with anaemia who are older and have CD4 cells count lower than 200 cells/mL require more attention. Traditional Chinese medicine may be a potential method to lower the frequency of anaemia.
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Affiliation(s)
- Yantao Jin
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Qingya Li
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Xiangle Meng
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Qianlei Xu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Jun Yuan
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Zhengwei Li
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Huijun Guo
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Zhibin Liu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
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20
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Humphrey JM, Walsh TJ, Gulick RM. Invasive Aspergillus Sinusitis in Human Immunodeficiency Virus Infection: Case Report and Review of the Literature. Open Forum Infect Dis 2016; 3:ofw135. [PMID: 27800523 PMCID: PMC5084715 DOI: 10.1093/ofid/ofw135] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Accepted: 06/20/2016] [Indexed: 12/28/2022] Open
Abstract
Invasive Aspergillus (IA) sinusitis is a life-threatening opportunistic infection in immunocompromised individuals, but it is uncommon in human immunodeficiency virus (HIV) infection. To gain a better understanding of the characteristics of IA sinusitis in this population, we present a unique case of chronic IA sinusitis in an HIV-infected patient taking antiretroviral therapy and review the literature summarizing published cases of invasive aspergillosis of the paranasal (n = 41) and mastoid (n = 17) sinuses in HIV-infected individuals. Among these cases, only 4 were reported after 1999, and 98% of patients had acquired immune deficiency syndrome. Orbital invasion occurred in 54% of paranasal sinus cases, whereas intracranial invasion was reported in 53% of mastoid sinus cases. The overall mortality was 79%. We also discuss various clinical and immunologic factors that may play a role in the development of IA and consider the changing epidemiology of aspergillosis in the era of effective antiretroviral therapy.
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Affiliation(s)
- John M Humphrey
- Division of Infectious Diseases , Weill Cornell Medicine , New York, New York
| | - Thomas J Walsh
- Division of Infectious Diseases , Weill Cornell Medicine , New York, New York
| | - Roy M Gulick
- Division of Infectious Diseases , Weill Cornell Medicine , New York, New York
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21
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Nabayigga B, Kellett J, Opio MO. The alertness, gait and mortality of severely ill patients at two months after admission to a resource poor sub-Saharan hospital--Why is post-discharge surveillance not routine everywhere? Eur J Intern Med 2016; 28:25-31. [PMID: 26777607 DOI: 10.1016/j.ejim.2015.12.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Revised: 12/10/2015] [Accepted: 12/15/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND Mortality, the first level of the first tier of the Outcomes Measures Hierarchy used to assess the value of health care, is the only hospital outcome usually measured. Gait and alertness after discharge are important to patients; they capture much of the second level of the first tier of the hierarchy, and are required to more fully assess the benefits, value and quality of care. AIM To assess the alertness, gait and mortality of severely ill patients at two months after admission to a resource poor sub-Saharan hospital. METHODS 193 severely ill patients admitted to a Ugandan hospital were followed up for up to 60 days. RESULTS 34% of patients died, 52% were alert and calm with a stable independent gait, 2% had an unstable gait, 6% were bedridden and 7% were lost to follow-up within 60 days of admission: 7.4% of patients discharged alert with a stable gait died within 30 days and 13.9% within 60 days; 26.9% of patients discharged without a stable gait died within 60 days. Sixty day mortality was 5% if patients had a stable independent gait on admission, 25% if they had an unstable gait or needed help to walk, and 50% if they were bedridden. Simple logistic regression models based on cheap easily available data predicted 30 day mortality, alertness and gait (c statistic of both models 0.89 SE 0.03). CONCLUSION In a resource poor setting gait and alertness assessments are of prognostic value, and practical and informative methods of patient follow-up.
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Affiliation(s)
- Barbara Nabayigga
- Medical Wards, St. Joseph's Kitovu Health Care Complex, Masaka, Uganda
| | - John Kellett
- Thunder Bay Regional Health Sciences Center, Thunder Bay, Ontario, Canada.
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Profile of HIV-Infected Hispanics with Pancytopenia. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2015; 13:ijerph13010038. [PMID: 26703689 PMCID: PMC4730429 DOI: 10.3390/ijerph13010038] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 10/27/2015] [Accepted: 11/05/2015] [Indexed: 12/18/2022]
Abstract
Pancytopenia is seen in late HIV infection; it is associated with medical complications and with decreased survival. We determined the prevalence of pancytopenia at baseline in a cohort of HIV-positive Hispanics living in Puerto Rico, and compared their socio-demographic, immunological and clinical characteristics. A total of 1202 patients enrolled between 2000 and 2010 were included. They were grouped according to pancytopenia status, defined by having: platelets <150,000 μL, white cell count <4000 μL, and hemoglobin <12 g/dL (women) or <13 g/dL (men). Differences were evaluated using Student's t-test, Chi-square test and Kaplan-Meier method. The prevalence of pancytopenia was 8.7%. Patients with pancytopenia had lower BMI and lower CD4 count, as well as higher HIV viral load and higher proportions of unemployment, clinical AIDS and antiretroviral treatment (ART) use (p < 0.05). One-year mortality rate was significantly higher in patients with pancytopenia (18.1% vs. 5.1%, p < 0.001). When stratifying for ART this association persisted for patients who did not receive ART (41.4% vs. 5.2%, p < 0.001), but it was not seen in patients who received treatment (9.2% vs. 5.6%, p = 0.196). Pancytopenia was associated with elements of advanced stages of HIV. ART could reduce the mortality of HIV-patients with pancytopenia to levels comparable to patients without the disorders.
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23
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Fan HW, Guo FP, Li YJ, Li N, Li TS. Prevalence of thrombocytopenia among Chinese adult antiretroviral-naïve HIV-positive patients. Chin Med J (Engl) 2015; 128:459-64. [PMID: 25673446 PMCID: PMC4836247 DOI: 10.4103/0366-6999.151078] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART)-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. METHODS We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. RESULTS A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P = 0.006 and P = 0.044, respectively). The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm 3 (3.3%) and >350 cells/mm 3 (2.8%) compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1%) (P = 0.002 and P = 0.005, respectively). The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001). We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7%) versus men who have sex with men (3.9%) (P = 0.002) and versus heterosexual transmission (3.9%) (P = 0.001). In binary logistic regression analyses, age ≥ 50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018), 2.091 (95% CI: 1.078, 4.055, P = 0.029) and 2.259 (95% CI: 1.028, 4.962, P = 0.042), respectively. CONCLUSIONS Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years), HCV-Ab positivity and lower CD4+ cell count are associated with an increased risk of thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.
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Affiliation(s)
| | | | | | | | - Tai-Sheng Li
- Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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Martin C, Poudel-Tandukar K, Poudel KC. HIV symptom burden and anemia among HIV-positive individuals: cross-sectional results of a community-based positive living with HIV (POLH) study in Nepal. PLoS One 2014; 9:e116263. [PMID: 25551656 PMCID: PMC4281119 DOI: 10.1371/journal.pone.0116263] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 12/03/2014] [Indexed: 11/19/2022] Open
Abstract
Background Previous research has reported high rates of anemia in people living with HIV/AIDS (PLWHA) in hospital or tertiary care settings. The objective of this community-based study was to measure the prevalence of anemia and describe the risk factors, with a specific emphasis on HIV symptom burden, in PLWHA in the Kathmandu Valley, Nepal. Methods We conducted a cross-sectional survey of 319 PLWHA residing in the Kathmandu Valley, Nepal. We recruited participants from five non-governmental organizations in the Kathmandu Valley. Descriptive statistics and multivariable logistic regression analyses were used. Results Our study found a 55.8% prevalence of anemia in PLWHA in the Kathmandu Valley. The prevalence of anemia among the participants with first, second, third, and fourth quartiles of HIV symptom burden was 44.8%, 49.3%, 60.3%, and 69.6%, respectively. Compared to the participants with lowest level of HIV symptom burden, the participants with highest level of HIV symptom burden were more likely to have anemia (adjusted odds ratio = 2.14; 95% confidence interval = 1.07 to 4.30). Conclusion Due to a high prevalence of anemia in a community-based sample of PLWHA, HIV patients should be counseled on their risk of developing anemia and encouraged to seek timely care for HIV symptoms.
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Affiliation(s)
- Catherine Martin
- Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States of America
| | - Kalpana Poudel-Tandukar
- Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States of America
| | - Krishna C. Poudel
- Department of Public Health, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, United States of America
- * E-mail:
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Moniuszko M, Moniuszko A, Puciłowska J, Kisluk K, Jeznach M, Grzeszczuk A, Flisiak R, Bodzenta-Lukaszyk A. Delayed diagnosis of human immunodeficiency virus infection in a patient with non-specific neurological symptoms and pancytopenia: a case report. J Med Case Rep 2014; 8:104. [PMID: 24666756 PMCID: PMC3978083 DOI: 10.1186/1752-1947-8-104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 01/23/2014] [Indexed: 11/10/2022] Open
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Shi X, Sims MD, Hanna MM, Xie M, Gulick PG, Zheng YH, Basson MD, Zhang P. Neutropenia during HIV infection: adverse consequences and remedies. Int Rev Immunol 2014; 33:511-536. [PMID: 24654626 PMCID: PMC4873957 DOI: 10.3109/08830185.2014.893301] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2014] [Indexed: 12/19/2022]
Abstract
Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient's association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients.
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Affiliation(s)
- Xin Shi
- Department of Surgery, Beaumont Health System-Royal Oak, Royal Oak, MI, USA
| | - Matthew D Sims
- Department of Infectious Disease, Beaumont Health System-Royal Oak, Royal Oak, MI, USA
| | - Michel M Hanna
- Department of Infectious Disease, Beaumont Health System - Troy, Troy, MI, USA
| | - Ming Xie
- Department of Pathology, Beaumont Health System - Troy, Troy, MI, USA
| | - Peter G Gulick
- Department of Internal Medicine, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA
| | - Yong-Hui Zheng
- Department of Microbiology and Molecular Genetics, College of Human Medicine
| | - Marc D Basson
- Department of Surgery, Beaumont Health System-Royal Oak, Royal Oak, MI, USA
| | - Ping Zhang
- Department of Surgery, Beaumont Health System-Royal Oak, Royal Oak, MI, USA
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Kyeyune R, Saathoff E, Ezeamama AE, Löscher T, Fawzi W, Guwatudde D. Prevalence and correlates of cytopenias in HIV-infected adults initiating highly active antiretroviral therapy in Uganda. BMC Infect Dis 2014; 14:496. [PMID: 25209550 PMCID: PMC4165997 DOI: 10.1186/1471-2334-14-496] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2014] [Accepted: 09/03/2014] [Indexed: 11/12/2022] Open
Abstract
Background Cytopenias are the most common HIV-associated hematological abnormality. Cytopenias have been associated with several factors including sex, race/ethnicity, geographical location and comorbidities such as tuberculosis, hepatitis B infection, fever and oral candidiasis. Cytopenias become more prevalent as HIV progresses and are often fatal. Data from resource-limited settings about the prevalence and correlates of cytopenia are limited. Therefore we conducted this cross-sectional study to assess the prevalence and correlates of cytopenia among adult AIDS patients at initiation of HAART in Uganda. Methods 400 HIV-infected subjects who were HAART-naïve or on HAART for ≤ 6 months were enrolled into the Multivitamins, HAART and HIV/AIDS Trial. Anemia was defined according to WHO guidelines as any hemoglobin concentration < 12 g/dl for non-pregnant females and < 13 g/dl for males. Leucopenia and thrombocytopenia were defined using study site laboratory reference ranges for lack of generally accepted definitions for these 2 cell lines as leucopenia if white blood cell count < 2.75 × 109 cells/litre and thrombocytopenia if platelets < 125 × 109 cells/litre for females and < 156 × 109 cells/litre for males. Univariate and bivariate analyses were done to describe the patient population and log-binomial regression was used to quantify the correlates of cytopenia. Results Sixty five percent of the 400 subjects had at least one form of cytopenia. Anemia occurred in 47.8%, leucopenia in 24.3%, thrombocytopenia in 8.3%, bicytopenia in 21.9% and only 2 had a pancytopenia. Cytopenia was more prevalent in females (prevalence ratio [PR]:1.33, 95% confidence interval [CI]:1.12-1.59); CD4 count category 50 to <200 (PR: 0.75, 95% CI: 0.64 -0.88) and CD4 count category 200 to <350 (PR: 0.74, 95% CI: 0.59 - 0.92) compared to CD4 count category <50; normal BMI (PR: 0.82, 95% CI:0.68-1.00) and overweight BMI (PR: 0.64, 95% CI:0.50- 0.82) compared to underweight BMI and those with a history or presence of oral candidiasis. Conclusions Cytopenias are a frequent complication in HIV-infected adults at initiation of HAART in Uganda. The presence of any cytopenia was associated with female sex, decreasing CD4 count and decreasing body mass index. Prospective studies in resource-limited settings on the trend in HIV-related cytopenias are needed.
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Affiliation(s)
- Rachel Kyeyune
- Infectious Diseases Institute, Makerere College of Health Sciences, P,O Box 22418, Kampala, Uganda.
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Santiago-Rodríguez EJ, Mayor AM, Fernández-Santos DM, Ruiz-Candelaria Y, Hunter-Mellado RF. Anemia in a cohort of HIV-infected Hispanics: prevalence, associated factors and impact on one-year mortality. BMC Res Notes 2014; 7:439. [PMID: 25005803 PMCID: PMC4099091 DOI: 10.1186/1756-0500-7-439] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 06/20/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Anemia occurs frequently in HIV-infected patients and has been associated with an increased risk of death in this population. For Hispanic subjects, information describing this blood disorder during HIV is scarce. Therefore, the present study examined data from a cohort of HIV-positive Hispanics to determine the prevalence of anemia, identify its associated factors, and evaluate its relationship with one-year mortality. METHODS This study included 1,486 patients who enrolled between January, 2000 and December, 2010 in an HIV-cohort in Bayamón, Puerto Rico. Data were collected through personal interviews and medical record abstractions. To determine the factors independently associated with anemia, a multivariable logistic regression model was used. Kaplan-Meier and Cox proportional hazards models were also performed to estimate survival time and to predict death risk. RESULTS The prevalence of anemia at enrollment was 41.5%. Factors independently associated with increased odds of anemia were: unemployment (OR = 2.02; 95% CI 1.45-2.79), CD4 count <200 cells/μL (OR = 2.66; 95% CI 1.94-3.66), HIV viral load ≥100,000 copies/mL (OR = 1.94; 95% CI 1.36-2.78), white blood cell count <4,000 cells/μL (OR = 2.42; 95% CI 1.78-3.28) and having clinical AIDS (OR = 2.39; 95% CI 1.39-4.09). Overweight (OR = 0.43; 95% CI 0.32-0.59) and obese (OR = 0.44; 95% CI 0.29-0.67) BMI's were independently associated with reduced odds of anemia. Survival differed significantly by anemia status (log-rank test: p < 0.001). One-year mortality estimates were: 30.8%, 23.3%, 8.4% and 2.5%, for patients with severe, moderate, mild and no anemia, respectively. Having anemia at baseline was independently associated with an increased one-year mortality risk (severe anemia: HR = 9.06; 95% CI: 4.16-19.72; moderate anemia: HR = 6.51; 95% CI: 3.25-13.06; mild anemia: HR = 2.53; 95% CI: 1.35-4.74). CONCLUSIONS A high prevalence of anemia at enrollment was observed in this cohort of HIV-infected Hispanics. Unemployment and several adverse prognostic features of HIV infection were independently associated with this blood disorder. Anemia resulted to be the strongest predictor of one-year mortality, evidencing a dose-response effect. Further investigations are needed to evaluate whether recovering from anemia is associated with longer survival, and to identify the types of anemia affecting this particular group of HIV patients.
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Affiliation(s)
| | | | | | | | - Robert F Hunter-Mellado
- Retrovirus Research Center, Universidad Central del Caribe School of Medicine, 00960-6032 Bayamón, Puerto Rico.
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Serum microRNAs in HIV-infected individuals as pre-diagnosis biomarkers for AIDS-NHL. J Acquir Immune Defic Syndr 2014; 66:229-37. [PMID: 24675587 DOI: 10.1097/qai.0000000000000146] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). DESIGN Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months). METHODS A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility. RESULTS Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively. CONCLUSIONS Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.
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Cytomegalovirus Appendicitis in Human Immunodeficiency Virus Infection. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2014. [DOI: 10.1097/ipc.0000000000000112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Wondimeneh Y, Muluye D, Ferede G. Prevalence and associated factors of thrombocytopenia among HAART-naive HIV-positive patients at Gondar University Hospital, northwest Ethiopia. BMC Res Notes 2014; 7:5. [PMID: 24387326 PMCID: PMC3916076 DOI: 10.1186/1756-0500-7-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Accepted: 01/02/2014] [Indexed: 12/17/2022] Open
Abstract
Background Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with progression of disease. However, its magnitude and associated factors in HAART naive HIV positive patients is not known in Ethiopia. Therefore, the aim of this study was to determine the prevalence and associated factors of thrombocytopenia in HAART naïve HIV positive patients. Methods A retrospective study was carried out among HAART naive HIV positive patients at Gondar University Hospital, Northwest Ethiopia, from September 2011 through August 2012. Socio-demographic variables and immunohematological (platelets and CD4+ T cells) values were carefully reviewed from medical records. Associated factors and outcomes were assessed using logistic regression. Results A total of 390 HAART naive HIV positive patients with a mean age of 33.65 years and a range of 18–70 years were reviewed. The overall prevalence of thrombocytopenia was 23(5.9%). The mean CD4 count was 288 ± 188.2 cells/μL. HIV patients whose age ≥ 50 years old were 2.5 times more likely to have thrombocytopenia and those patients whose CD4 count < 350 were 2.6 times more likely to have thrombocytopenia than HIV patients whose CD4 count ≥500. However, CD4 count was not statistically associated with prevalence of thrombocytopenia (P > 0.05). Conclusion As CD4 counts of HIV patients decreasing, they have more likely to have thrombocytopenia. Therefore, early diagnosis and treatment of thrombocytopenia in these patients are necessary.
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Affiliation(s)
| | | | - Getachew Ferede
- School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, P,O, Box 196, Gondar, Ethiopia.
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Shen Y, Wang Z, Lu H, Wang J, Chen J, Liu L, Zhang R, Zheng Y. Prevalence of anemia among adults with newly diagnosed HIV/AIDS in China. PLoS One 2013; 8:e73807. [PMID: 24058490 PMCID: PMC3776781 DOI: 10.1371/journal.pone.0073807] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2013] [Accepted: 07/29/2013] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND The prevalence of anemia among antiretroviral-naïve HIV-infected patients in China has not been well characterized. We conducted a cross-sectional study to estimate the prevalence of anemia among Chinese adults with newly diagnosed HIV/AIDS. METHODS One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients in China were selected during 2009 and 2010. Serum samples obtained from each individual were collected to measure hemoglobin levels. Demographics and medical histories were recorded. Factors associated with the presence of anemia were analysed by logistic regression. RESULTS Among the 1948 patients, 75.8% were male. Median age was 40 years (range: 18-80 years). The overall prevalence of anemia among HIV-infected patients was 51.9% (51.5% among men, 53.2% among women). The prevalences of mild anemia, of moderate anemia, of severe anemia were 32.4%, 17.0%, and 2.5%, respectively. The prevalence of anemia was higher among ethnic minority patients than among the Han patients (70.9% versus 45.9%). The prevalence of anemia increased with increasing age (49.6%, 53.5% and 60.1% among patients who were 18-39, 40-59, and ≥ 60 years of age respectively) and with decreasing CD4 count (14.0%, 22.4%, 50.7%, and 74.6% among patients with CD4 count of ≥ 350, 200-349, 50-199, and <50 cells/mm(3) respectively). The logistic regression analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of anemia. CONCLUSIONS Anemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS, but severe anemia is less prevalent in this population. Older age, lower CD4 count and minority ethnicity are associated with an increased risk of anemia.
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Affiliation(s)
- Yinzhong Shen
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Zhenyan Wang
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Hongzhou Lu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jiangrong Wang
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jun Chen
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Li Liu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Renfang Zhang
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yufang Zheng
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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Mathews SE, Srivastava D, Balayadav R, Sharma A. Association of hematological profile of human immunodeficiency virus-positive patients with clinicoimmunologic stages of the disease. J Lab Physicians 2013; 5:34-7. [PMID: 24014966 PMCID: PMC3758702 DOI: 10.4103/0974-2727.115929] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
AIM This work was carried out to study the hematologic profile of human immunodeficiency virus (HIV)-positive patients and its association with the clinicoimmunologic stage of the disease. MATERIALS AND METHODS A total of 187 patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines were included in this study. Patients in the study population were divided into two groups: (1) Group A (antiretroviral therapy (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment naïve patients (ART-N). The patients were tested for hemoglobin (Hb), total red blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC), platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm. The group or categorical data were tested for statistical significance using Chi-square test and Z-test. The difference was reported as significant if P < 0.05. RESULTS (1) Anemia (predominantly normocytic normochromic) was prevalent in 40.1%, with slightly higher prevalence in those not receiving ART. It occurred with high frequency in patients with immunological (42.05%) and clinical acquired immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an asymptomatic HIV infection with CD4 > 200/μl (28.57%). Patients on zidovudine (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2) Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.
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Affiliation(s)
- Sujata E Mathews
- Department of Medicine, Dr. Ram Manohar, Lohia Hospital and Post Graduate Institute of Medical Research, New Delhi, India
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Bone Marrow Abnormalities in HIV Disease. Mediterr J Hematol Infect Dis 2013; 5:e2013033. [PMID: 23795271 PMCID: PMC3684351 DOI: 10.4084/mjhid.2013.033] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 05/16/2013] [Indexed: 11/08/2022] Open
Abstract
INTRODUCTION Hematological abnormalities are a common complication of HIV infection. Bone marrow abnormalities occur in all stages of HIV infection. Present work was carried out to study the bone marrow abnormalities in patients with HIV/AIDS. METHODS 160 patients of HIV +ve were included in the study. A complete blood count, relevant biochemical investigations, CD4 counts were done, besides a thorough history and clinical examination. HIV positive patients were classified as those having AIDS and those without AIDS according to NACO criteria. Bone marrow examination was performed for indication of anemia, leucopenia, pancytopenia and thrombocytopenia. RESULTS As per CDC criteria 59.81% patients had AIDS in 107 patients. The most common hematological abnormality was anemia, seen in 93.12% patients. Bone marrow was normocellular in 79.06% of non-AIDS and 79.68% of AIDS, hypocellular in 13.95% of non-AIDS and 12.5% of AIDS, hypercellular in 06.97% of non-AIDS and 07.81 % of AIDS patients. Dysplasia was statistically and significantly associated with anemia. For myelodysplasia in bone marrow in HIV patients we noted granulocytic dysplasia in 4.65% in Non - AIDS and 14.06% AIDS patients. Erythroid dysplasia was found in 9.30% in Non - AIDS, 12.5% in AIDS group. Thrombocytopenia was seen in 4 cases of ART (4.93%) and 3 cases (4.68%) of AIDS group. Abnormal cells like plasma cell, histiocyte and toxic granule were found in bone marrow. CONCLUSIONS Myelodysplasia was more common in AIDS than in non AIDS patients. Granulocytic series is most commonly associated with evidence of dysplasia. Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Thus bone marrow study is imperative to methodically observe and follow clinical and laboratory aberration in such patients in order to improve our diagnostic and therapeutic skills pertinent to HIV/AIDS.
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Gibellini D, Clò A, Morini S, Miserocchi A, Ponti C, Re MC. Effects of human immunodeficiency virus on the erythrocyte and megakaryocyte lineages. World J Virol 2013; 2:91-101. [PMID: 24175233 PMCID: PMC3785048 DOI: 10.5501/wjv.v2.i2.91] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Revised: 01/07/2013] [Accepted: 01/13/2013] [Indexed: 02/05/2023] Open
Abstract
Anaemia and thrombocytopenia are haematological disorders that can be detected in many human immunodeficiency virus (HIV)-positive patients during the development of HIV infection. The progressive decline of erythrocytes and platelets plays an important role both in HIV disease progression and in the clinical and therapeutic management of HIV-positive patients. HIV-dependent impairment of the megakaryocyte and erythrocyte lineages is multifactorial and particularly affects survival, proliferation and differentiation of bone marrow (BM) CD34+ haematopoietic progenitor cells, the activity of BM stromal cells and the regulation of cytokine networks. In this review, we analyse the major HIV-related mechanisms that are involved in the genesis and development of the anaemia and thrombocytopenia observed in HIV positive patients.
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Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol 2013; 139:9-29. [PMID: 23270895 DOI: 10.1309/ajcp50aeeygrewuz] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
New-onset pancytopenia can be caused by a wide variety of etiologies, leading to a diagnostic dilemma. These etiologies range from congenital bone marrow failure to marrow space-occupying lesions, infection, and peripheral destruction, to name a few. Bone marrow examination, in addition to a detailed clinical history, is often required for an accurate diagnosis. The purpose of this review is to provide a brief overview of many of the causes of new-onset pancytopenia in adults and children, with emphasis on bone marrow findings and recommendations of additional testing and clinical evaluation when needed, with the overall aim of aiding the pathologist's role as a consultant to the patient's treating physician.
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Gill AF, Ahsan MH, Lackner AA, Veazey RS. Hematologic abnormalities associated with simian immunodeficieny virus (SIV) infection mimic those in HIV infection. J Med Primatol 2012; 41:214-24. [PMID: 22620272 DOI: 10.1111/j.1600-0684.2012.00543.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds. METHODS Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS. RESULTS Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared with non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection. CONCLUSIONS Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggests that, like in HIV infection, hematologic abnormalities are major complications of SIV infection.
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Affiliation(s)
- Amy F Gill
- Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USA
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Karpelowsky J, Millar AJW. Surgical implications of human immunodeficiency virus infections. Semin Pediatr Surg 2012; 21:125-35. [PMID: 22475118 DOI: 10.1053/j.sempedsurg.2012.01.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Pediatric HIV (human immunodeficiency virus) is a pandemic predominantly in sub-Saharan Africa. Approximately 2.2 million children aged less than 15 years are infected with HIV, representing almost 95% of the total number of children globally infected with HIV. Therefore, increasing numbers of HIVi or -exposed but uninfected children can be expected to require a surgical procedure to assist in the diagnosis of an HIV/acquired immune deficiency syndrome-related complication, to address a life-threatening complication of the disease, or for routine surgery encountered in HIV-unexposed children. HIVi children may present with both conditions unique to HIV infection and surgical conditions routine in pediatric surgical practice. HIV exposure confers an increased risk of complications and mortality for all children after surgery, whether they are HIV infected or not. This risk of complications is higher in the HIVi group of patients. These findings seem to be independent of whether patients undergo an elective or emergency procedure, but the risk of an adverse outcome is higher for a major procedure. Surgical implications of HIV infection are comprehensively reviewed in this article.
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Parinitha S, Kulkarni M. Haematological changes in HIV infection with correlation to CD4 cell count. Australas Med J 2012; 5:157-62. [PMID: 22952560 DOI: 10.4066/amj.20121008] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND HIV infection is associated with a wide range of haematological abnormalities. METHODS AND OBJECTIVES The objectives in this study were to study haematological changes in HIV patients and to correlate them with CD4 cell counts. Two hundred and fifty HIV positive patients referred to the haematology laboratory section for complete haemogram in whom CD4 count was done were included in the study. Haematologic parameters and CD4 counts were studied in each of these patients. Descriptive statistics were applied. Association between two attributes was calculated by chi-square test and p value less than 0.05 was considered statistically significant. RESULTS Among 250 patients, anaemia was seen in 210 (84%) cases. The most common type was normocytic normochromic (40.4%). Lymphopenia was seen in 163 (65.2%) cases and thrombocytopenia in 45 (18%) cases. The majority of cases (70%) had CD4 cell counts below 200 cells/mm(3). Fifty-four cases (21.6%) had CD4 counts between 200 to 499 cells/mm(3) and 21 (8.4%) cases had CD4 counts more than 500 cells/ mm(3.) In patients with CD4 counts less than 200 cells/mm(3), anaemia was seen in 91.4% cases, leucopenia in 26.8% cases, lymphopenia in 80% cases and thrombocytopenia in 21.7% cases. CONCLUSION Haematologic manifestations of HIV infection are common and more frequent with progression of disease. The present study revealed a significant increase in the number of cases of anaemia, and lymphopenia, with decreasing CD4 cell counts. Thrombocytopenia is also seen but does not show significant increase with disease progression. The study also highlights the importance of simultaneously treating HIV patients for haematologic manifestations to reduce morbidity.
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Affiliation(s)
- Ss Parinitha
- SDM College of Medical Sciences and Hospital, Dharwad
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Pan R, Wang J, Nardi MA, Li Z. The inhibition effect of anti-GPIIIa49-66 antibody on megakaryocyte differentiation. Thromb Haemost 2011; 106:484-90. [PMID: 21713325 DOI: 10.1160/th11-03-0153] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Accepted: 05/23/2011] [Indexed: 01/10/2023]
Abstract
We previously reported that patients with early-onset HIV-1 ITP developed a unique anti-platelet integrin GPIIIa antibody against the GPIIIa49-66 epitope. Anti-GPIIIa49-66 antibody-induced platelet fragmentation requires sequential activation of the platelet 12-lipoxygenase (12-LO) and NADPH oxidase to release reactive oxygen species (ROS). 12-LO is upstream of the NADPH oxidase pathway and 12(S)-HETE, the product of 12-LO, induces the same oxidative platelet fragmentation as anti-GPIIIa49-66. Since the megakaryocyte (MK) is the progenitor cell for platelets, we have investigated the effect of anti-GPIIIa49-66 on MK differentiation and, in particular, the potential role of anti-GPIIIa49-66 induced ROS in this process. We first show that polyclonal anti-GPIIIa49-66 antibody isolated from HIV-1 ITP patients inhibits MK proliferation 2.5-fold in in vitro culture of human cord blood CD34+ cells driven by thrombopoietin (TPO). We also observe a three-fold decrease in the number of MK colony-forming units in the presence of a human monoclonal anti-GPIIIa49-66 antibody. However, we could not detect ROS release in DCFH-loaded mouse megakaryoblastic cells L8057 treated with anti-GPIIIa49-66 antibody. In addition, 12(S)-HETE does not inhibit the in vitro differentiation of L8057 cells induced by TPO. In fact, we found a dose dependent increase in the percentage of CD41 positive cells (from 17.1% to 48.7%) in in vitro culture of L8057 cells treated with various concentrations of H2O2 (from 5 to 20 μM). We therefore conclude that the anti-GPIIIa49-66 antibody inhibits MK differentiation through β3 integrin signalling independent of ROS release.
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Affiliation(s)
- Ruimin Pan
- Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
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Mouhari-Toure A, Patassi A, Nabroulaba K, Djadou K, Edou K, Nyametso D, Aho K, Saïbou A, Kombaté M, Kpanla K, Niman K, Togbossi A, Agodomou E, Wotogbe A, Tadona M, Singo A, Déku K, Pitche P. Profil biologique des patients adultes infectés par le VIH à l’initiation du traitement antirétroviral au Togo. Med Mal Infect 2011; 41:229-34. [DOI: 10.1016/j.medmal.2010.11.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2010] [Revised: 09/14/2010] [Accepted: 11/19/2010] [Indexed: 10/18/2022]
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Kim B, Kim J, Hwang S, Lee Y, Park J, Moon S, Choi J, Song J, Jeong J, Pai H. Vitamin B12 Deficiency Megaloblastic Anemia in a Patient with Acquired Immunodeficiency Syndrome. Infect Chemother 2011. [DOI: 10.3947/ic.2011.43.3.266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Affiliation(s)
- Bongyoung Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jieun Kim
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Soonwoo Hwang
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Yuhwa Lee
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Junghwan Park
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Shinje Moon
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jiyoung Choi
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Juneseok Song
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jongheon Jeong
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Hyunjoo Pai
- Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
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Pastori D, Esposito A, Mezzaroma I. Immunomodulatory Effects of Intravenous Immunoglobulins (IVIGs) in HIV-1 Disease: A Systematic Review. Int Rev Immunol 2010; 30:44-66. [DOI: 10.3109/08830185.2010.529975] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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44
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Calis JCJ, Phiri KS, Vet RJWM, de Haan RJ, Munthali F, Kraaijenhagen RJ, Hulshof PJM, Molyneux ME, Brabin BJ, Boele van Hensbroek M, Bates I. Erythropoiesis in HIV-infected and uninfected Malawian children with severe anemia. AIDS 2010; 24:2883-7. [PMID: 20871386 PMCID: PMC2998037 DOI: 10.1097/qad.0b013e32833fed27] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Anemia is common in HIV infection, but the pathophysiology is poorly understood. Bone marrow analysis in 329 severely anemic (hemoglobin <5 g/dl) Malawian children with (n = 40) and without (n = 289) HIV infection showed that HIV-infected children had fewer CD34(+) hematopoietic progenitors (median 10 vs. 15‰, P = 0.04) and erythroid progenitors (2.2 vs. 3.4‰, P = 0.05), but there were no differences in erythrocyte viability and maturation in later stages of erythropoiesis. Despite an HIV-associated reduction in early red cell precursors, subsequent erythropoiesis appears to proceed similarly in HIV-infected and HIV-uninfected children with severe anemia.
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Affiliation(s)
- Job C J Calis
- Global Child Health Group, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
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45
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Midzi N, Mtapuri-Zinyowera S, Mapingure M, Sangweme D, Chirehwa M, Brouwer K, Mudzori J, Hlerema G, Mutapi F, Kumar N, Mduluza T. Consequences of polyparasitism on anaemia among primary school children in Zimbabwe. Acta Trop 2010; 115:103-11. [PMID: 20175980 DOI: 10.1016/j.actatropica.2010.02.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2009] [Revised: 02/05/2010] [Accepted: 02/13/2010] [Indexed: 10/19/2022]
Abstract
The effect of concomitant infection with schistosomes, Plasmodium falciparum and soil transmitted helminths (STHs) on anaemia was determined in 609 Zimbabwean primary school children. P. falciparum, haemoglobin levels and serum ferritin were determined from venous blood. Kato Katz, formal ether concentration and urine filtration techniques were used to assess prevalence of Schistosoma mansoni, STHs and Schistosoma haematobium infections. The prevalence of S. haematobium, S. mansoni, P. falciparum, hookworm, Trichuris trichiura and Ascaris lumbricoides were 52.3%, 22.7%, 27.9%, 23.7%, 2.3% and 2.1%, respectively. The overall prevalence of anaemia and iron deficiency anaemia (IDA) were 48.4% (277/572) and 38.1% (181/475). Haemoglobin levels among children who had P. falciparum, S. haematobium and hookworm were lower than negative individuals, p<0.001, p<0.001 and p=0.030, respectively. The prevalence of anaemia and IDA in co-infections was almost double that in single infection. Children with P. falciparum/STHs/schistosome and schistosomes/P. falciparum co-infections recorded higher prevalence of anaemia and IDA (80.8% and 57.4%, respectively) than other combinations, p<0.001. Logistic regression revealed that, age group > or = 14 years, P. falciparum, S. haematobium light and heavy infections, and S. mansoni moderate and heavy infection, hookworm light infection were predictors of anaemia. This study suggests that integrated school based de-worming and malaria control have the potential to reduce the burden of anaemia.
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46
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Sloand EM, Klein HG, Banks SM, Vareldzis B, Merritt S, Pierce P. Epidemiology of thrombocytopenia in HIV inlection. Eur J Haematol 2009; 48:168-72. [PMID: 1348479 DOI: 10.1111/j.1600-0609.1992.tb00591.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Thrombocytopenia is a known complication of human immunodeficiency virus Type-1 (HIV-1) infection, and more data need to be collected on its frequency, severity, and clinical sequelae. We determined the frequency of thrombocytopenia and its relationship to other HIV infection characteristics from a review of records of 1004 HIV-infected patients attending two outpatient clinics in Washington, D.C. The self-reported sources of HIV-1 exposure were male homosexual activity (68%), bisexual activity (10%), heterosexual activity (6%), and intravenous drug use (15%). Fifty-nine percent of the individuals were white, 37% were black and 94% were male. Fifteen percent had AIDS. Thrombocytopenia occurred more frequently in subjects with AIDS (21.2%) than in HIV-infected individuals who did not fit clinical criteria for AIDS (9.2%) (p less than 0.001). Patients with few CD4-positive cells and an advanced stage of disease were more likely to have low platelet counts: 30% with an absolute CD4 cell count lower than 200/mm3 vs 8% with CD4 counts between 200 and 500 (p less than 0.00001), and 18.5% with Stage IV disease compared to 7.6% in Stage II (p less than 0.001) had platelet counts less than 150,000/mm3. Thrombocytopenia was more frequent in white males and older subjects. Although subjects infected by heterosexual exposure had a lower frequency of thrombocytopenia, intravenous drug users and homosexual men exhibited similar frequencies of thrombocytopenia. Of all subjects with platelet counts less than 50,000/mm3, 40% reported bleeding and 1 died of an intracranial hemorrhage. Thrombocytopenia occurs frequently in HIV-infected people, primarily in those with AIDS, low CD4 cell numbers, and advanced stages of diseases.
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Affiliation(s)
- E M Sloand
- National Heart, Lung, and Blood Institute, Bethesda, MD 20892
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Abstract
Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcgamma receptors (HCV), and platelet production may be impaired by infection of megakaryocyte (MK) bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management.
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MESH Headings
- Humans
- Purpura, Thrombocytopenic, Idiopathic/diagnosis
- Purpura, Thrombocytopenic, Idiopathic/etiology
- Purpura, Thrombocytopenic, Idiopathic/metabolism
- Purpura, Thrombocytopenic, Idiopathic/physiopathology
- Purpura, Thrombocytopenic, Idiopathic/therapy
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Affiliation(s)
- Douglas B Cines
- University of Pennsylvania School of Medicine, Department of Pathology and Laboratory Medicine, Philadelphia, PA 19104, USA.
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48
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Ono E, Dos Santos AMN, Machado DM, Succi RCDM, Amed AM, Salomão R, Kallás EG, de Moraes-Pinto MI. Immunologic features of HIV-1-infected women on HAART at delivery. CYTOMETRY PART B-CLINICAL CYTOMETRY 2008; 74:236-43. [PMID: 18393385 DOI: 10.1002/cyto.b.20418] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The conjoint effect of HIV infection and pregnancy on the immune system of women submitted to the prophylactic antiretroviral therapy presently recommended is still poorly understood. METHODS We evaluated 44 HIV-infected women (HIV) and 45 HIV-negative women (CT) at parturition and we compared them to 20 healthy nonpregnant women (NP). Immunophenotyping of lymphocytes was done by four-color flow cytometry. RESULTS All HIV-infected women received HAART during pregnancy and 56.8% had viral load <50 copies/mL at delivery. CD4+T cells/mm(3) were lower in HIV (447) than CT (593) and NP (738) (P < 0.05). CD8+T cells/mm(3) were higher in HIV (799) than CT (384) and NP (395) (P < 0.05). NK cells/mm(3) were lower in HIV (146) than in CT (253) and NP (198) (P < 0.05). CD38 expression on CD4+T and on CD8+T cells was higher in HIV (CD4:12.1; CD8:14.9) than in CT(CD4:9.2; CD8:10.2) and NP(CD4:8.6; CD8:6.0) (P < 0.05). However, CD56 expression on CD8+T cells (a marker of cytolytic effector function) was lower in HIV(7%) than in CT(12%) and NP(9%) (P < 0.05). CONCLUSIONS Even with low levels of viremia, HIV-infected women at delivery showed a different immunologic profile from both healthy non-HIV-infected women in the puerperium and nonpregnant women, with lower CD4+T and higher CD8+T cells, high levels of CD38 expression, but low CD56 expression on CD8+T cells and low NK cell numbers.
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Affiliation(s)
- Erika Ono
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil
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Prost S, Le Dantec M, Augé S, Le Grand R, Derdouch S, Auregan G, Déglon N, Relouzat F, Aubertin AM, Maillere B, Dusanter-Fourt I, Kirszenbaum M. Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPARgamma/STAT5 signaling pathway in macaques. J Clin Invest 2008; 118:1765-75. [PMID: 18431514 DOI: 10.1172/jci33037] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2007] [Accepted: 02/06/2008] [Indexed: 02/05/2023] Open
Abstract
Infection of primates by HIV-1 and SIV induces multiple hematological abnormalities of central hematopoietic origin. Although these defects greatly contribute to the pathophysiology of HIV-1 infection, the molecular basis for altered BM function remains unknown. Here we show that when cynomolgus macaques were infected with SIV, the multipotent potential of their hematopoietic progenitor cells was lost, and this correlated with downregulation of STAT5A and STAT5B expression. However, forced expression of STAT5B entirely rescued the multipotent potential of the hematopoietic progenitor cells. In addition, an accessory viral protein required for efficient SIV and HIV replication and pathogenicity, "Negative factor" (Nef), was essential for SIV-mediated impairment of the multipotent potential of hematopoietic progenitors ex vivo and in vivo. This newly uncovered property of Nef was both conserved between HIV-1 and SIV strains and entirely dependent upon the presence of PPARgamma in targeted cells. Further, PPARgamma agonists mimicked Nef activity by inhibiting STAT5A and STAT5B expression and hampering the functionality of hematopoietic progenitors both ex vivo and in vivo. These findings have extended the role of Nef in the pathogenicity of HIV-1 and SIV and reveal a pivotal role for the PPARgamma/STAT5 pathway in the regulation of early hematopoiesis. This study may provide a basis for investigating the potential therapeutic benefits of PPARgamma antagonists in both patients with AIDS and individuals with hematopoietic disorders.
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Affiliation(s)
- Stéphane Prost
- Immunovirology Division and Innovative Therapy Division, Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France.
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Wickramasinghe SN, Beatty C, Shiels S, Tomlinson DR, Harris JR. Ultrastructure of the bone marrow in HIV infection: evidence of dyshaemopoiesis and stromal cell damage. CLINICAL AND LABORATORY HAEMATOLOGY 2008; 14:213-29. [PMID: 1451401 DOI: 10.1111/j.1365-2257.1992.tb00368.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The ultrastructure of bone marrow cells was studied in nine patients infected with the human immunodeficiency virus (HIV). Two of these (cases 1 and 3) were thrombocytopenic, had never suffered from opportunistic infections and had not received any drugs prior to the time of study. A number of ultrastructural abnormalities were found in a variable proportion of the affected cell types in all nine patients. These were: (a) an increased prevalence of multivesicular bodies within several cell types and of abnormalities of the nuclear membrane in neutrophil granulocytes, (b) an increase in the size of the Golgi apparatus and in the quantity of endoplasmic reticulum in neutrophil granulocytes, (c) dysplastic features, including multiple long intranuclear clefts and large cytoplasmic vacuoles in some erythroblasts and (d) vacuolation of the plasma cells. Other abnormalities seen in a proportion of the patients were: (a) cylindrical confronting cisternae (CCC) in some of the lymphocytes, macrophages (phagocytic reticular cells), non-phagocytic reticular cells (including adventitial cells) and endothelial cells of marrow sinusoids, (b) tubuloreticular structures (TRS) in some lymphocytes, plasma cells, monocytes and endothelial cells and (c) precipitates of protein within occasional erythroblasts and marrow reticulocytes. There was also a striking and hitherto undescribed abnormality of the structure of the nucleus in intersinusoidal and perisinusoidal non-phagocytic reticular cells. This was seen in six patients, including case 3, and was characterized by the extensive detachment of masses of abnormally electron-dense heterochromatin from the nuclear membrane, the presence of a uniformly thin layer of electron-dense material at the inner surface of the areas of nuclear membrane denuded of heterochromatin masses and an abnormal electron lucency of areas containing euchromatin. The CCC and TRS were found in the six patients with the lowest number of circulating CD4-positive T cells. The precipitation of protein within erythroid cells may have been caused by the oxidant effect of dapsone or high doses of co-trimoxazole. The abnormalities in the stromal cells and in particular the nuclear changes seen in the non-phagocytic reticular cells support the possibility that one of the mechanisms underlying the cytopenia in patients infected with HIV may be a disturbance of the microenvironmental regulation of haemopoiesis.
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Affiliation(s)
- S N Wickramasinghe
- Department of Haematology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK
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