The main studied aspects were risk factors in order to initial investigate relationship between severe infections and TCD4 cell depletion. Subjects and methods: Cross-sectional studies. 79 patients with severe infection and negative HIV test who were admitted at the Intensive Care Unit and Emergency Department of National Hospital for Tropical Diseases (Vietnam) from April 2017 to March 2018 were evolved in our study. Results: The mean age at diagnosis was 57.4 ± 15.48 years, range: 24 to 90. 60 patients (76%) were males, 19 (24%) were females. This group had many different occupations, including farmer, worker, office staff... Outside the 28 patients with a history of healthy, the risk factors were documented in 15 (18.8%) with habit of smoking and/or drinking, 38 patients (48.1%) had 1 to 3 chronic diseases, including 10 patients with immunodeficiency caused by pathological malignancy (7 patients), autoimmune disease (4 patients) and inborn pituitary failure (1 patient).
Journal of military pharmaco-medicine n02-2019 TCD4 CELL DISORDER IN PATIENTS WITH SEVERE INFECTIONS Bui Vu Huy1; Tran Van Kien1; Ta Thi Dieu Ngan1 SUMMARY Objectives: The main studied aspects were risk factors in order to initial investigate relationship between severe infections and TCD4 cell depletion Subjects and methods: Cross-sectional studies 79 patients with severe infection and negative HIV test who were admitted at the Intensive Care Unit and Emergency Department of National Hospital for Tropical Diseases (Vietnam) from April 2017 to March 2018 were evolved in our study Results: The mean age at diagnosis was 57.4 ± 15.48 years, range: 24 to 90 60 patients (76%) were males, 19 (24%) were females This group had many different occupations, including farmer, worker, office staff Outside the 28 patients with a history of healthy, the risk factors were documented in 15 (18.8%) with habit of smoking and/or drinking, 38 patients (48.1%) had to chronic diseases, including 10 patients with immunodeficiency caused by pathological malignancy (7 patients), autoimmune disease (4 patients) and inborn pituitary failure (1 patient) None of them had a family history of any similar disease All patients had negative HIV test Clinical diagnosis of 79 patients, sepsis disease 43 patients (54.4%), respiratory tract infection 24 patients (30.4%) and central nervous system infection 12 patients (15.2%) The mean value of CD4 cells was 338 ± 254.5 All patients had an infection status with elevated levels of CRP, procalcitonine and white blood cell counts, although only 44.3% of patients were identified pathogens The evidence showed alcoholism condition and smoking were associated with the decline of CD4 cells, but the underlying disease and infectious diseases didn’t related to this situation Conclusion: Severe infections may associate with decrease in CD4 cells on individuals with or without underlying disease It should be interested to diagnosis and treat opportunistic infections as well as preventive treatment after stable disease * Keywords: Autoimmune diseases; Idiopathic CD4 lymphocytopenia; Lymphopenia; Opportunistic infections INTRODUCTION Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers Primary immunodeficiencies are genetically determined and can be hereditary, secondary immunodeficiencies are acquired and much more common [2, 3] In 1986, WHO developed a clinical AIDS case definition The immune status of HIV people can be assessed by measuring the absolute number or percentage of CD4+cells/mm3 Progressive depletion of CD4+ T cells is associated with progression of HIV disease and an increased likelihood of opportunistic infections [4] However, there were a number of reports on the cases of CD4 cell decline in HIV-negative individuals [5, 6] diopathic CD4 lymphocytopenia (ICL) Hanoi Medical University Corresponding author: Bui Vu Huy (drvuhuy@yhaoo.com) Date received: 20/12/2018 Date accepted: 16/01/2019 177 Journal of military pharmaco-medicine n02-2019 was defined in 1992 by the US Centers for Disease Control and Prevention (CDC) as the repeated presence of a CD4+ T-lymphocyte count of fewer than 300 cells per cubic millimeter or of less than 20% of total T cells with no evidence of HIV infection and no condition that might cause depressed CD4 counts [7, 8, 9] An investigation indicated that ICL is a rare entity with no evidence of transmissible agent [7] In addition, CD4 cell decline have also been reported in patients with severe viral infections [10], severe septic shock [11], and even in relation to nutritional status [12] In recent year, National Hospital for Tropical Diseases in Vietnam has been receiving a number of the cases of CD4 cell decline in HIV-negative [1] This led to the interest of clinicians to launch a survey in an attempt which characterizes this newly evolving entity Most of knowledge about the associated conditions with ICL comes from case reports due to lack of information of this condition The aim of our study was: To collect severe infection cases with their CD4 to study its different important aspects The main studied aspects were risk factors in order to initial investigate relationship between severe infections and TCD4 cell depletion SUBJECTS AND METHODS Subjects 79 patients with severe infection who were admitted at the Intensive Care Unit (ICU) and Emergency Department of National Hospital for Tropical Disease (Vietnam) from April 2017 to March 2018 178 Methods * Design: Cross-sectional study On admission, patients were examined according to Surviving Sepsis Campaign Guideline 2016 [13] We systematically searched for a known primary or secondary immunodeficiency, including viral infection (for example HIV, HTLV, transient viral infection) [10], tuberculosis [11], malignancy (lymphoma or solid tumor), autoimmune and/or inflammatory disorders (for example, Sjögren syndrome, sarcoidosis, systemic lupus erythematous, granulomatosis) and nutritional status [2] History of risk factors, such as: chronic diseases, habit, and occupation were also compiled from medical records [7, 9] Searches for a known immunodeficiency were performed according to knowledge at the time of diagnosis and during follow-up During follow-up, unusual infections, neoplasms, and related symptoms were recorded Only the patients who were suspected TCD4 cell disorder by clinicians were done CD4 test [2,10] Acute treatment of infections was given in standard guideline Data were analyzed based on symptoms of any infection known to be associated with lymphocytopenia In this study, we classified TCD4 according to the HIV/AIDS type [3] Patients were classified into disease groups based on clinical and/or laboratory manifestations at diagnosis or during follow-up: sepsis disease (SD), respiratory tract infections (RTI) and central nervous system infections (CNSI) Patients could be classified in more than group Patients with HIV positive were excluded Journal of military pharmaco-medicine n02-2019 The data were analyzed by using SPSS software version 23.0 The results were shown in 95%CI, mean and standard deviation The mean values were compared, using t-test, the X2 or Fisher exact test Table 2: Frequencies of different variables in study patients Variables Sex RESULTS Table 1: Clinical diagnosis and classification of CD4 cell counts of 79 patients n Age % Clinical diagnosis n % Male 60 76.0 Female 19 24.0 20 - 29 3.8 30 - 39 10.1 40 - 49 11 13.9 50 - 59 17 21.5 60 - 69 21 26.6 70 - 79 14 17.7 Sepsis 43 54.4 80 - 89 5.1 Respiratory tract infections 24 30.4 ≥ 90 1.3 Central nervous system infections 12 15.2 Farmer 7.6 Worker 2.5 Office staff 11.4 Retiree 25 31.7 Other 37 46.8 Drinking and smoking 10.1 Drinking 6.3 Smoking 2.5 Cardiology 21 26.6 Diabetes 13 16.5 Chronic lung disease 8.9 Pathological malignancy 8.9 Former tuberculosis 8.9 Chronic liver disease 7.6 Gout 7.6 Autoimmune disease 5.1 Chronic kidney disease 3.8 Inborn pituitary failure 1.3 Occupation Classified TCD4 None or not significant (≥ 500) 15 19.0 Mild (350 - 499) 15 19.0 Advanced (201 - 349) 20 25.3 Severe (≤ 200) 29 36.7 29 36.7 Death During the study period from April 2017 to March 2018, 79 patients were enrolled, accounting for 3.4% of the total patients in both ICU and Emergency Department Clinical diagnosis of 79 patients with severe infection were studied, including: SD 43 patients (54.4%), RTI 24 patients (30.4%) and CNSI 12 patients (15.2%) Of the 79 patients assessed for CD4+T-cell counts, the percentage of patients with severe CD4 counts was 36.7%, an average decrease of 25.3%, a mild decrease and a normal range of 19.0% 29 patients (36.7%) died due to their opportunistic infections Habit History disease 179 Journal of military pharmaco-medicine n02-2019 60 patients (76%) were males, 19 patients (24%) were females The mean age at the time of diagnosis (of opportunistic infection) was 57.4 ± 15.48 years The youngest patient was 24 years old and the oldest patient was 90 years old This group had many different occupations, including farmer, worker, office staff Beside the 28 patients with a history of healthy, the risk factor investigate were documented in 15 patients (18.8%) with habits smoking and/or drinking, while 38 patients (48.1%) had to chronic diseases, including 10 patients with immunodeficiency caused by pathological malignancy (7 patients), autoimmune disease (4 patients) and inborn pituitary failure (1 patient) None had a family history of any similar disease [2] All patients had of negative HIV test Chart 1: Comparison of severe infected groups with levels of TCD4 cell depletion All diseases groups of SD, RTI and CNSI were detected at different levels of decline of CD4 cells Table 3: Clinical, CD4 count and organ function in 79 study patients Severe infected patient Sepsis ( ± SD) Respiratory infections Central nervous system infections ( ± SD) ( ± SD) Total ( ± SD) Day of illness 14.3 ± 18.23 8.0 ± 5.77 18.1 ± 24.51 13.0 ± 16.92 Mean age (year) 58.0 ± 14.34 58.3 ± 17.86 53.4 ± 15.10 57.4 ± 15.48 Day of treatment 18.8 ± 15.46 16.9 ± 14.75 22.7 ± 18.66 18.8 ± 15.67 TCD4 (cell/mm ) 333 ± 214.4 411 ± 338.4 207 ± 118.0 338 ± 254.5 CRP (mg/L) 174 ± 101.8 147 ± 105.4 88 ± 87.6 152 ± 104.1 Procalcitonine (nag/mL) 23.9 ± 5.35 4.6 ± 1.92 11.7 ± 8.27 15.3 ± 3.17 White blood cell (G/L) 12.5 ± 8.17 12.8 ± 6.29 13.9 ± 5.38 12.8 ± 7.21 180 Journal of military pharmaco-medicine n02-2019 Platelet (G/L) 159 ± 146.5 230 ± 165.8 232 ± 191.2 191 ± 161.6 Red blood cell (T/L) 3.6 ± 0.86 3.9 ± 0.74 4.0 ± 0.86 3.8 ± 0.83 Urea (mmol/L) 11.4 ± 6.75 7.8 ± 5.02 8.6 ± 6.59 9.9 ± 6.39 Creatinine (µmol/L) 143 ± 80.4 103 ± 45.3 90 ± 49.2 123 ± 70.1 AST (U/L) 202 ± 46.5 132 ± 48.1 127 ± 89.7 169 ± 32.1 ALT (U/L) 109 ± 22.6 122 ± 47.6 90 ± 59.8 110 ± 20.8 Mean values of TCD4 differed between diseases groups, mean CD4 cell counts in CNSI group was 207 ± 118.0, in SD group was 333 ± 214.4 and RTI group was 411 ± 338.4, respectively Patients in all three disease groups had an infection status with elevated levels of CRP, procalcitonine and white blood cell counts Similarly, renal function (urea and creatinine) and liver enzyme (ALT, AST) were also affected Table 4: The relationship between pathogen infection and level of CD4 cell decline Level of CD4 cell Pathogen Severe n (%) Advanced n (%) Mild n (%) (1.3) (2.5) (2.5) (1.3) (2.5) a (2.5) b (1.3) (1.3) a (0) (1.3) Total n (%) p (1.3) (7.6) 0.660 d (6.3) 0.374 (1.3) (6.3) 0.834 d (3.8) 0.797 Not significant n (%) Bacteria A baumannii K pneumoniae S ureus P aeruginosa E coli S pneumoniae S maltophilia Salmonella Aeromonas veronii M tuberculosis (1.3) b c (0) (2.5) (1.3) c (0) (1.3) (1.3) (0) (2.5) 0.444 (0) (0) (2.5) 0.712 (1.3) (1.3) (0) (0) (1.3) (0) (1.3) 0.229 (1.3) (0) (0) (0) (1.3) 0.627 (0) (0) (0) (1.3) (1.3) 0.229 (1.3) (0) (0) (0) (1.3) 0.627 e (0) (3.8) f,g (2.5) (10.1) 0.258 f (0) (3.8) 0.479 g (0) (2.5) 0.688 Fungi C albicans C tropicalis (3.8) (2.5) Aspergilus fumigatus (1.3) e B heamulonii (1.3) e (0) (1.3) (0) (1.3) (0) (0) (0) (1.3) 0.627 Trichosporon asahii (0) (0) (1.3) (0) (1.3) 0.229 Penicillium marneffei (0) (0) (0) (1.3) (1.3) 0.229 17 (21.5) 13 (16.5) (8.7) (8.7) 44 (55.7) 0.616 Unidentifiable pathogen (a, b, c, d, e, f, g: Pathogens were isolated on the same patient) 181 Journal of military pharmaco-medicine n02-2019 Table 5: Comparison of related risk factors in severe infected conditions with levels of TCD4 cell depletion Level of CD4 cell Risk fators p Severe Advanced Mild Not significant n (%) n (%) n (%) n (%) 15 (51.7) 14 (70.0) 10 (66.7) 11 (73.3) 0.426 (0) (1.3) (5.1) (3.8) 0.019 Drinking (1.3) (1.3) (1.3) (2.5) 0.316 Smoking (2.5) (0) (0) (0) 0.149 01 underlying disease (11.4) (11.4) (7.6) (7.6) 0.786 02 underlying diseases (6.3) (5.1) (5.1) (3.8) 0.909 ≥ 03 underlying diseases (0) (1.3) (1.3) (1.3) 0.593 01 pathogen 11 (13.9) (6.3) (6.3) (8.9) 0.596 02 pathogens (0) (2.5) (3.8) (1.3) 0.119 (1.3) (0) (0) (0) 0.627 Age ≥ 55 years old Habit Drinking and smoking History Pathogens ≥ 03 pathogens Bacterial pathogens were found in all three groups (CNS, SD and RTI), but M tuberculosis was only found in the CNS Fungal infections were mainly detected in SD group, although only 44.3% of patients in all three groups were identified pathogens The results of this study suggested that there was only a correlation between CD4 cell levels of depletion and habit of drinking and smoking DISCUSSION Our article described the clinical and immunologic characteristics of 79 patients with severe infections who were also suspected of having immunodeficiency by clinicians [1, 2] To assess the immune status of patients, we used the CD4 count test in this study Results of CD4 cell count in 79 patients showed CD4 cell 182 count below 500 cells/mm was 64 (81%) in patients with severe infections and at different levels: severe CD4 36.7%, average decrease of 25.3%, slight decrease and normal range of 19.0% (table 1) The mean value of CD4 cells was 338 ± 254.5 with a range of 14 to 1,123 cells/mm3 (table 3) All 79 patients were excluded from HIV following WHO Guidelines [4] Journal of military pharmaco-medicine n02-2019 In this study population, the demographic indicators showed that patients belong to many different professions such as workers, farmers, office workers, retirees and were no apparent predilection to one geographical area They were only diagnosed upon development of opportunistic infections Some factors suggested unusual condition in these patients such as the ratio of male and female was 3.2/1 and a mean age was 57.4 ± 15.48 However the youngest patient was 24 years old and the oldest patient was 90 years old These situations were often reported in patients with ICL [6, 8, 9] While primary immunodeficiency was common at school age [2] Of the 79 patients studied, excluding 12 patients (15.19%) with diseases associated with impaired immunity was mentioned by previous reports, as pathological malignancy patients (8.9%), autoimmune disease patients (5.4%) and inborn pituitary failure patients (1.3%) [2, 3] or a number of patients suffered from chronic diseases, or some other had a habit of smoking and drinking, but 28 patients (35.44%) still had completely healthy medical history without any habits or abnormalities [2] However, all 79 patients were assessed in this study had the manifestations of infection as increased in indicators CRP, procalcitonine, leukocyte 35 patients (43.3%) had been identified with at least one infection caused by bacteria or fungi and 28 patients (35.5%) infected with pathogen, patients (7.6%) co-infected with pathogens and patients (1.3%) co-infected with pathogens Immunosuppression was reported in patients who died of sepsis and multiple organ failure [11] In addition, we did not find the virus etiology in these patients [2, 10] A long-term illness is also considered to be the cause of CD4 cell decline, but in this study the average duration of illness before the patient's admission was 13 days The evidence showed an alcoholism condition and smoking was associated with the decline of CD4 cells, but the underlying disease and infectious diseases not related to this situation (table 5) However, patients with counted CD4 cells after 14 days of treatment showed that the number of cells increased significantly from 304 ± 226.6 cells on admission to 482 ± 327.6 cells Thus, the recovery of CD4 cells is associated with treatment of severe infections CONCLUSION In people with severe infections may associate a decrease in CD4 cells on individuals with or without underlying disease It should be interested to diagnosis and treat opportunistic infections as well as preventive treatment after stable disease REFERENCES Bui Vu Huy, Vu Minh Dien, Nguyen Van Kinh Report on three patients with decline of CD4 T cells unknown 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Kevin P High Nutrition, immunity, and infection, chapter 11 Mandell, Douglas, and Bennett‟s principles and practice of infectious diseases, edited by John E Bennett, Raphael Dolin, Martin J Blaser Eighth edition Elsevier Inc 2015, pp.125-133e2 ... agent [7] In addition, CD4 cell decline have also been reported in patients with severe viral infections [10], severe septic shock [11], and even in relation to nutritional status [12] In recent... patients were enrolled, accounting for 3.4% of the total patients in both ICU and Emergency Department Clinical diagnosis of 79 patients with severe infection were studied, including: SD 43 patients. .. people with severe infections may associate a decrease in CD4 cells on individuals with or without underlying disease It should be interested to diagnosis and treat opportunistic infections as