Value Of Total Lymphocyte Count Research Articles

Trends of Coagulation Parameters in Human Immunodeficiency Virus Patients.

Background and Objectives: HIV disease is recognized to cause inconsistencies in coagulation via various pathways during infection. Some studies have indicated that HIV-infected patients are prone to developing thrombocytopenia, thrombosis, or autoantibodies that may cause difficulties in diagnosis. This study is intended to measure the trend of coagulation parameters in Sudanese patients with HIV. Materials and Methods: A cross-sectional study was carried out in patients with HIV admitted to the Sudan National AIDS Program (SNAP) from January 2018 to December 2019. Prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), D-dimer (DD), hemoglobin (HB), total lymphocyte count (TLC), platelet count (PLT), and a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13), were evaluated among HIV Sudanese patients. Results: Out of the 44 HIV patients included, 6 (13.6%) were found to have thrombotic thrombocytopenic purpura-like events and 12 (27.2%) had antiphospholipid antibodies, of whom 8 (66.6%) showed anticardiolipin antibody (1gG (75%) and IgM (25%)) and 4 showed lupus anticoagulants. The HB, TLC, and PLT values were found to be significantly lower in HIV patients than in control (p = 0.000, 0.000, and 0.050, respectively). The PT and ADAMTS13 values showed no significant difference between HIV patients and control (p = 0.613 and 0.266, respectively). The PTT, TT, and DD values were found to be augmented in HIV patients versus the control (p = 0.000). Conclusions: Thrombotic thrombocytopenic purpura-like events among HIV Sudanese patients were explored. In addition, antiphospholipid antibodies were strikingly seen in these patients. Additional research is anticipated to confirm these diagnoses.

CORRELATION OF PLATELET TO LYMPHOCYTE RATIO WITH NATIONAL INSTITUTE OF HEALTH STROKE SCALE FOR SEVERITY PREDICTION IN ACUTE ISCHEMIC STROKE

Background: Stroke is the second leading cause of death worldwide and was responsible for an estimated 6.5 million deaths and 113 million DALYs in 2013. In recent years, the platelet to lymphocyte ratio (PLR) has emerged as a well-accepted biomarker for the assessment of overall inammatory status. The aim of the present study was to nd out the role of PLR (Platelet to lymphocyte ratio) in patients of acute ischemic stroke and correlating with NIHSS for predicting the severity. Settings and Design: It is a case control study carried out in 70 cases with acute ischemic stroke and 70 age and gender matched controls. Severity of stroke was determined among cases with the National Institute of Health Stroke Scale (NIHSS) at admission and at discharge. Laboratory investigations were done to calculate Platelet-lymphocyte ration at admission and discharge. Results: 68% of cases were males and 32% were females with a mean age of 59.03± 10.6 years. The platelet count was signicantly higher in cases as compared to controls whereas the value of total lymphocyte count was vice-versa. The majority of cases belonged to NIHSS score 5-15 which is classied as moderate stroke both at the time of admission and at discharge. There was positive correlation between PLR with National Institute of Health Stroke Scale Severity Score (r=0.68, p<0.001). The mean PLR increased with increasing NIHSS score. Conclusions: Platelet to lymphocyte ratio (PLR) is a simple, cost effective and easily obtainable tool in predicting the severity of stroke.

Low Total Lymphocyte Count as the Risk of Hospital Acquired Malnutrition in Children

Background: Hospital Acquired Malnutrition (HAM) is characterized by inadequate nutritional therapy and the risk of developing malnutrition during the hospital stay. In clinical practice, there are many measurements to determine nutritional status. Total lymphocyte count (TLC) is associated with impaired function of immune system in malnutrition. The purpose of this study was to evaluate the prognostic value of TLC to the occurrence of HAM in pediatric patients.Materials and Methods: This an observational study with a prospective cohort design. Subjects were assessed for weight at the first day of hospitalization, then the subjects were followed until they were discharged. Body weight was re-measured on discharge to determine the presence or absence of HAM. This research was conducted at Sanglah Hospital from May-December 2019. Subjects who met the inclusion and exclusion criteria were enrolled in the study.Results: Among 120 subjects, 55 subjects or 45.8% were malnourished on admission. Subjects with a low TLC compared to a normal TLC had a 3.9-fold risk of experiencing hospital acquired malnutrition (95% Confidence Interval: 1.59 to 7.19, p=0.001). Subjects who had a low TLC had HAM of 61.8%, while subjects who had a normal TLC had HAM of 32.3%. In multivariate analysis, low TLC was the only risk factor for HAM in this research.Conclusion: This study proved that low TLC is the risk of HAM. Total lymphocyte count could be used as predictor of the risk of HAM in hospitalization children.Keywords: hospital malnutrition, total lymphocyte, children

Lymphopenia predicts poor prognosis in older gastric cancer patients after curative gastrectomy.

Total lymphocyte count in preoperative peripheral blood is associated with prognosis in various cancers. The predictive value of preoperative total lymphocyte count for survival was assessed in older gastric cancer patients after gastrectomy. A total of 200 gastric cancer patients aged ≥75 years who underwent curative resection from 2000 to 2014 were included in this retrospective study. The cut-off value of total lymphocyte count in preoperative peripheral blood was determined using receiver operating characteristic curve analysis, and the association with prognosis was examined. The cut-off value of total lymphocyte count was 1462/μL, and 94 patients were classified as low total lymphocyte count patients and 106 patients were classified as high total lymphocyte count patients. In univariate analysis, American Society of Anesthesiologists score ≥3, Charlson Comorbidity Index ≥3, total lymphocyte count <1462/μL, stage III, open approach, total gastrectomy, splenectomy and infectious complication were significantly associated with overall survival. In multivariate analysis, total lymphocyte count <1462/μL (P = 0.003), American Society of Anesthesiologists score ≥3 (P = 0.01) and stage III (P = 0.017) were independent prognostic factors. Low total lymphocyte count significantly reduced overall survival in stage I (P = 0.037) and II (P = 0.009) patients, but not stage III patients (P = 0.29). Total lymphocyte count in preoperative peripheral blood can predict postoperative survival of older patients with relatively early-stage gastric cancer. Geriatr Gerontol Int 2019; 19: 1215-1219.

PREDIKSI JUMLAH SEL LIMFOSIT T CD4+ MENGGUNAKAN NILAI TLC (TOTAL LYMPHOCYTE COUNT) PADA PENDERITA HIV/AIDS

AIDS is a severe disease caused by Human Immunodeficiency Virus (HIV) that affects patient's immune system, especially CD4+ Tcells (CD4). Hence, CD4 count is used as parameter to starting ARV treatment or monitoring the progress of the disease. However, themeasurement of CD4 is expensive and available in big hospitals. In small or remote hospitals there are no means to measure the CD4.Some studies suggest that in an area where CD4 count is unavailable, the total lymphocyte count (TLC) of HIV/AIDS patients can roughlybe used to predict CD4 values. This study is aimed to see whether the TLC values can be used to roughly predict the CD4 count of HIV/AIDS patients and to formulate the correlation form between them. A cross sectional study design was applied to 79 blood samples ofHIV/AIDS patients from Clinical Pathology Laboratory of Wahidin Sudirohusodo Hospital from January to September 2007. The bloodsamples were tested for TLC as well as CD4 values. The correlation of TLC and CD4 values was tested with Pearson Correlation Test andthe correlation formula was derived from curve estimation of Regression Analysis. Sensitivity, specificity, PPV and NPV of various cutpoint of TLC (1000, 1200, 1500, 2000) to predict CD4 &lt; 200/ul were determined using cross tabulation Fisher Exact Test. A positivecorrelation was found between TLC and CD4 count (R = 0.528, p &lt; 0.001) with the regression formula is CD4 = 0.09TLC – 1.42.The WHO standard cut point TLC1200/ul give best result for sensitivity, specificity, PPV and NPV: 80.6%, 91.7%, 98.2% and 45.8%,respectively. The cut point of TLC1200 can be used to roughly predict CD4 &lt; 200/ul of HIV/AIDS patients, so, can be use as a mark forstarting ARV therapy in the place were measurement of CD4 is unavailable

Total lymphocyte count in cancer patients with lymphopenia treated with intravenous vitamin C: Results of an observational study

BackgroundLymphopenia commonly occurs in cancer patients and predicts poor prognosis. It is caused by radio- and chemotherapy, with malnutrition and treatment-related oxidative stress playing key roles in its pathogenesis. Tumour-related morbidity is reported to be associated with reduced plasma ascorbate, which is a key physiological antioxidant and essential factor in immune function.MethodA prospective observational study was conducted on 48 cancer patients with lymphopenia (<1500/μL) to investigate the total lymphocyte count (TLC) during four weeks of elective adjuvant treatment with intravenous (iv) vitamin C 7.5 g (Pascorbin®7.5 g) once a week. TLC values at baseline (just prior to start of treatment) and after 4 weeks treatment were compared using descriptive statistics.ResultsAfter 4 weeks iv vitamin C 7.5 g, TLC increased by a mean of 211/μL (p = 0.0018). Subgroup analyses showed that, in patients with severe lymphopenia (n = 25) (TLC <1000/μL), the increase in TLC was greater with a mean rise of 368/μL (p = 0.0004), than in patients (n = 23) with an initial TLC of 1000–1500 (mean rise of 40/μL) (p = 0.6105). TLC increased by at least 240/μL in half of the patients with severe lymphopenia and by more than 610/μL in 25% of patients.ConclusionOur data indicate that iv high-dose vitamin C treatment increases TLC, which strongly implies improvement of immune function, especially in patients with severe lymphopenia. Appropriately-powered, randomized, placebo-controlled trials of iv high-dose vitamin C are now needed to define more precisely its role in the treatment of cancer-related lymphopenia and how this impacts on the patients’ clinical prognosis.

English

Total Lymphocyte Count (TLC) has been previously evaluated as a surrogate for CD4 counts in the management of HIV especially in resource-limited settings with varying results. This study developed a clinical algorithm of TLC and other significant haematologic parameters to raise the predictive value of TLC in classifying subjects with CD4 count 30 mm/h(sensitivity 57%, specificity 71%, PPV 66%, NPV 68%). A three-step algorithm of TLC 30 mm/h for predicting CD4 count<350 cells/mm3 yielded sensitivity 66%, specificity 82%, PPV 72%, NPV 77% (area under curve AUC 0.79). This algorithm had a higher predictive accuracy making it a better tool than the use of TLC alone in monitoring disease progression in resource-limited settings. Key words: Human Immunodeficiency Virus (HIV), haematologic parameters, surrogate markers.

Prognostic value of total lymphocyte count in cardiac surgery

The aim of this study retrospective cohort was to investigate the prognostic value of preoperative total lymphocyte count in peripheral blood as a predictor of postoperative complications and mortality in cardiac surgery. All adults undergoing cardiopulmonary bypass in 2009. The cohort size was 1 368 patients. Patient characteristics, hospital mortality, postoperative complications, ventilation period, intensive care unit and hospital stay were analysed. Preoperative total lymphocyte count &lt;1 611 cells/L was assotiated with significantly higher mortality by univariate (p&lt;0,0001) and multivariate (p&lt;0,022) analisys. Low preoperative total lymphocyte count was associated with more frequent inotropic support (p&lt;0,001); postoperative heart arrhythmia (p&lt;0,001); hemodialysis-dependent acute renal failure (p&lt;0,001); and a prolonged ventilation period (p=0,001), intensive care unit stay (p&lt;0,001), and hospital stay (p=0,007). Low preoperative total lymphocyte count in peripheral blood is a useful prognostic criterion for evaluation of a complicated postoperative period in cardiosurgical patients.

Efficiency of Hematocrit, Lymphocyte, C-Reactive Protein and Transferrin Levels in Predicting Mortality in Intensive Care Unit Patients

The effectiveness of many physiological parameters and laboratory tests was investigated in predicting mortality. In this study, we investigated hematocrit, C-reactive protein, transferrin and total lymphocyte count along with Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scores of patients who were hospitalized in the intensive care unit. The data were retrospectively analyzed from hospital information management system, doctors' records and nurse observing forms. The mortality rate was 42.6%. The Acute Physiology and Chronic Health Evaluation II scores were significantly higher in cases with mortality compared to those without mortality. The admission and discharge Glasgow Coma Scores were significantly lower in patients who showed mortality compared with patients without mortality. Admission and discharge hematocrit and transferrin values were significantly lower in cases with mortality compared to those without mortality. Discharge C-reactive protein values were significantly higher in cases with mortality compared to those without mortality. Discharge total lymphocyte count values were significantly lower in cases with mortality compared to those without mortality. Consequently, we believe that hematocrit and transferrin values at the time of admission to the intensive care unit and total lymphocyte count and C-reactive protein at the time of discharge from the intensive care unit can be effective in predicting mortality.

Accurate use of neutrophil/lymphocyte ratio from the perspective of laboratory experts

Dear editor I read with great interest the recent published article “Neutrophil/lymphocyte ratio in patients with atrial septal aneurysm” by Demir and Demir.1 In this study, researchers compared the neutrophil/lymphocyte ratio (NLR) between patients with atrial septal aneurysm (ASA) and controls. It was reported that patients with ASA have higher NLR compared with controls.1 There are some points that we would like to address from this study. Firstly, a white blood cell (WBC) count of more than 12,000 cells per μL, or less than 4,000 cells per μL, was mentioned as one of the exclusion criteria.1 However, the authors did not state why these values were used as the limits for inclusion. Whether a WBC count of more than 12,000 cells per μL is accepted as an indicator of inflammation or infection is unclear, and there is no mention of the literature that this value is based on, or which device (brand/model) was used for the WBC count. The WBC reference ranges may vary depending on many factors such as the population studied, the individual laboratory, and the instruments (eg, types of collection tubes) or measurement methods used (eg, waiting period prior to analysis).2,3 Secondly, despite comparing groups based on neutrophil and lymphocyte counts, there was no exclusion criteria specified for these parameters. According to Horne et al,4 and as stated in the study,1 high neutrophil, monocyte, and NLR counts, as well as low lymphocyte counts, are independently related to increased cardiovascular events. However, in this study, Table 2 shows an increased total lymphocyte count (TLC) in controls (2,911±837 cells per mm3) draws attention rather than the low TLC of patients (1,862±625 cells per mm3).1 A TLC significantly higher than 2,900 lymphocytes in a μL of blood is generally considered to be an indicator of lymphocytosis in adults.3 If you accept 2,900 cells per mm3 as the upper limit of the TLC, the differential diagnosis of lymphocytosis should be given to the controls included in the study. However, in several other sources 4,000 cells per mm3 is regarded as the upper limit of the TLC.5,6 Additionally, although the TLC obtained from the patient group was relatively lower than in the control group, all results were within the reference values.3 Therefore, it would not be correct to declare that the patient group had a low TLC. On the basis of this information, evaluation of the percentage of lymphocytes and neutrophils may also be important in patient groups with borderline TLC values. Automated blood counting instruments should provide percentage values for each type of WBC count. Thirdly, the measurement of NLR was suggested as an indicator of increased risk of arrhythmia, based on the association found between ASA and NLR in the study, however the physiopathological causes supporting this conclusion were not thoroughly discussed.1 NLR has been used frequently to predict outcomes in patients with cancer and coronary artery disease.7,8 Systemic inflammation is thought to be a risk factor for cardiovascular disease, and NLR, which integrates the detrimental effects of neutrophilia (an indicator of inflammation) and lymphopenia (an indicator of physiological stress), has emerged as a useful prognostic marker.8 Possible causes affecting neutrophil/lymphocyte counts and the confounding factors which have a considerable effect on the clinical availability of NLR should be discussed in more detail in this study population. Finally, NLR itself alone without other inflammatory markers may not accurately provide information about the prognosis of the patients. There are studies evaluating soluble P- and E-selectin, interleukin-6, and high-sensitivity C-reactive protein (hs-CRP) as indices of prothrombogenic and proinflammatory activity in a similar group of patients.9,10 While assessing the predictive values of parameters like NLR (derived from the ratios), and comparing them for validity and accuracy, proven markers will provide more reliable results every time. In conclusion, the types of collection tubes, waiting period prior to analysis, instrumental parameters and reference ranges for each parameter must be specified as they are easily affected by analytical and preanalytical variables in studies based on laboratory results.11

Absolute lymphocyte count as a surrogate marker for CD4+ cell count in monitoring of antiretroviral therapy, Northwest Ethiopia: retrospective evaluation

ObjectiveTo determine the use of total lymphocyte count as a surrogate marker for CD4+ cell count among HIV infected patients at the University of Gondar Hospital. MethodsA retrospective cross sectional study was conducted at the University of Gondar Hospital antiretroviral therapy laboratory from December 2011 to May 2012. Data on CD4+ cell count, total lymphocyte count, sex, and age were collected from 2964 HIV infected patients and analyzed using SPSS version 16 computer software. ResultsTotal lymphocyte count was significantly correlated with CD4+ cell count (P<0.001; r2=0.434). The sensitivity, specificity, positive predictive value, negative predictive value of total lymphocyte count<1 200 cells/mm3 to predict CD4+ cell count <200 cells/mm3 was 57.8%, 86.4%%, 34.1%, 86.39%, respectively. A total lymphocyte count<1 000cells/mm3 was found to have suboptimal sensitivity (69.0%), and specificity (85.0%) for predicting a CD4+ cell count <200 cells/mm3. ConclusionsTotal lymphocyte count and CD4+ cell count was positively correlated. Hence, lymphocyte count less than or equal to 1 000/mm3 can be used as a cutoff value in place where there is no CD4+ cell counting machine.

Nutritional Status and Short-Term Outcome of Hip Arthroplasty

To review nutritional status and outcome of 90 patients who underwent total hip arthroplasty (THA) or hemiarthroplasty. Records of 51 women and 39 men aged 26 to 96 (median, 71) years who underwent elective THA (n=48) for osteoarthritis, or trauma-related THA (n=10) or hemiarthroplasty (n=32) for subcapital femoral neck fractures using an uncemented femoral stem were retrospectively reviewed. Patient demographics and intra- and post-operative complications were recorded. Patient co-morbidities were assessed according to the Charlson grading system. Nutritional status was assessed using haematological markers of serum albumin (ALB) level and total lymphocyte count (TLC). Samples were taken on the day of the operation and within 24 hours of operation. Suboptimal nutrition was defined as a serum ALB level of <3.5 g/dl and a TLC of <1.50 cells/mm. 86% of trauma patients and 30% of elective patients were malnourished preoperatively (p<0.001). Preoperatively, more males than females had suboptimal ALB levels (28% vs. 8%, p=0.033) and TLC (82% vs. 31%, p<0.001). Age was inversely proportional to preoperative ALB and TLC values; patients older than 75 years had significantly lower values. Of those staying >7 days in hospital, 67% were aged >75 years as opposed to 31% were aged ≤ 75 years (p=0.001). Male gender, old age, and presentation with trauma were risk factors for suboptimal nutritional parameters (p<0.001 for all). Patients with suboptimal ALB and TLC values had a significantly longer stay in hospital (p=0.032 and p=0.021, respectively). The rate of malnourishment was significantly higher in patients having trauma-related surgery than in those having elective surgery. Malnourished patients are at greater risk of prolonged hospital stay. Preoperative nutritional assessment may be useful in predicting patients at high surgical risk.

Predictors of clinical failure in HIV/AIDS patients on antiretroviral therapy in a resource limited setting, Nigeria: A comparative study

BackgroundThe monitoring of HIV-infected individuals on ARV may be clinical or laboratory. Viral load testing is the backbone of accessing treatment failure but Nigeria is faced with the challenge of the high cost of viral load testing hence its less usage in most centres. The prospective study evaluated possible markers that could distinguish clinically failing and stable HIV/AIDS patients on ARV in resource-limited countries like Nigeria. Material and methodsThe 72 HIV-1 infected patients on ARV that consecutively attended ART clinic in December, 2010 at General Hospital, Ugep, Cross River State were reviewed for CD4 values, white blood cell count (WBC), total lymphocyte count (TLC), platelet count, haematocrit, mean corpuscular haemoglobin concentration (MCHC), potassium, creatinine, glucose, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The results were compared with standard references, between clinically failing and stable patients, and between clinically failing patients that switched drugs and those that maintained their drugs. ResultsOf the 72 patients, 19.4% had clinical failing conditions and there were more female than male patients. Of the clinically failing patients, 42.9% switched drugs in the course of treatment. TLC and CD4 values were significantly lower (p<0.05 and p<0.02 respectively) in clinically failing patients than clinically stable patients. Only ALT levels in clinically failing patients that maintained their drugs were significantly lower (p<0.01) than in those clinically failing patients that switched drugs. ConclusionsApart from CD4 count, TLC is a reliable prognostic marker for disease progression in HIV/AIDS patients on ARV in our centres where viral load is not readily available. ALT levels may be used to determine HIV/AIDS failing patients that switched drugs.

Correlation of CD4+ T cell count with total lymphocyte count, haemoglobin and erythrocyte sedimentation rate levels in human immunodeficiency virus type-1 disease

Background: Studies in human immunodeficiency virus (HIV) infected adults have demonstrated association of total lymphocyte count (TLC) <1200/mm 3 and subseqnent disease progression or mortality. The association of other surrogate makers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression has also been suggested. This study was carried out to determine the relationship of CD4-positive T lymphocyte counts with TLC, Hb and ESR in HIV-infected individuals. Methods: The study population comprised of 215 antiretroviral treatment naive HIV-1 infected adults. The CD4 positive T cell counts, TLC, Hb and ESR of study participants were measured. Spearman's rank order correlation and Receiver Operating Characteristic were used for statistical analyses. Result: The sensitivity, specificity, positive and negative likelihood ratios for cut-off value of TLC <1200/mm 3 for predicting CD4 counts <200 cells/mm 3 and <350 cells/mm 3 were 9.4%, 100%, not measurable and 1.1, and 6.1 %, 98.8 %, 5.13 and 0.95, respectively. The association of Hb (<10, 11, 12 g/dl and <10, 12, 14 g/dl for CD4 counts <200 cells/mm 3 and <350 cells/mm 3, respectively), and ESR (<10, 20 and 30 mm fall after 1 hour) with these two CD4 counts cut-off values were suboptimal. Conclusion: This study reveals the poor association of TLC, Hb, and ESR with CD4 counts in HIV infected adults, thus highlighting the need to review the utility of these surrogate markers, for predicting CD4 counts in people living with HIV/AIDS.

Pneumocystis jirovecii prophylaxis discontinuation based upon total lymphocyte count in HIV-infected adults treated with antiretroviral therapy

Pneumocystis jirovecii pneumonia (PCP) prophylaxis may be discontinued when CD4 is > or =200 cells/mm(3) for three months in response to highly active antiretroviral therapy (HAART). Unlike CD4, the total lymphocyte count (TLC) is inexpensive and widely available in resource-constrained countries. Paired TLC and CD4 values of HIV-infected patients attending an HIV clinic from 1998 to 2005 were analysed by Spearman's correlation. The sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristics (ROC) using TLC cut-off points between > or =1400 and > or =2000 cells/mm(3) to predict CD4 > or =200 cells/mm(3) were calculated. Next, a cohort of patients who had a TLC < or = 1200 cells/mm(3) and subsequently achieved various TLC cut-off points sustained over three months while receiving HAART was identified. Subjects with subsequent CD4 > or =200 cells/mm(3) in response to HAART were considered to have negligible risk for PCP. There was significant correlation between TLC and CD4 in 46,250 observations from 4307 individuals (r = 0.695, P < or = 0.001). The area under the ROC curve was 0.85 (95% CI = 0.85-0.86). In the historical cohort analysis, 85% and 70% of subjects who achieved TLC > or = 2000 cells/mm(3) and > or =1400, respectively, had a corresponding CD4 > or = 200 cells/mm(3). A sustained rise in TLC in response to HAART may potentially serve as a criterion for discontinuing PCP prophylaxis in resource-constrained countries.

Low Sensitivity of Total Lymphocyte Count as a Surrogate Marker to Identify Antepartum and Postpartum Indian Women Who Require Antiretroviral Therapy

Some studies support the use of total lymphocyte count (TLC) as a surrogate marker for CD4 cell count to guide antiretroviral therapy (ART) initiation. However, most of these studies have focused on nonpregnant adults. In light of expanding ART access through prevention of mother-to-child transmission (PMTCT)-plus programs in resource-limited settings, we assessed the sensitivity, specificity, and positive predictive value (PPV) of TLC for predicting low CD4 counts in antepartum and postpartum women in Pune, India. CD4, TLC, and hemoglobin were measured at third trimester, delivery, and 6, 9, and 12 months postpartum (PP) in a cohort of 779 HIV-infected women. Optimal TLC cutoff for predicting CD4 <200 cells/mm3 was determined via logistic regression where sensitivity, specificity, PPV, and an area under the receiver operating characteristic (ROC) curve were calculated. Among the 779 women enrolled, 16% had WHO clinical stage 2 or higher and 7.9% had CD4 <200 cells/mm3. Using 2689 TLC-CD4 pairs, the sensitivity, specificity, and PPV of TLC <1200 cells/mm3 for predicting CD4 <200 cells/mm3 was 59%, 94%, and 47%, respectively. The sensitivity of TLC <1200 cells/mm3 cutoff ranged between 57% and 62% for time points evaluated. Addition of hemoglobin <12 g/dL or <11 g/dL increased the sensitivity of TLC to 74% to 92% for predicting CD4 <200 cells/mm3 but decreased the specificity to 33% to 69% compared to TLC alone. A combination of TLC, hemoglobin, and WHO clinical staging had the highest sensitivity but lowest specificity compared to other possible combinations or use of TLC alone. The sensitivity and specificity of TLC <1200 cells/mm3 to predict a CD4 <350 cells/mm3 was 31% and 99%, respectively. Our data suggest that antepartum and PP women with TLC <1200 cells/mm3 are likely to have CD4 <200 cells/mm3. However, the sensitivity of this TLC cutoff was low. Between 45% and 64% of antepartum and PP women requiring initiation of ART may not be identified by using TLC alone as a surrogate marker for CD4 <200 cells/mm3. The WHO-recommended TLC cutoff of <1200 cells/mm3 is not optimal for identifying antepartum and PP Indian women who require ART.

Is total lymphocyte count a reliable predictor of the CD4 lymphocyte cell count in resource-limited settings?

Although the depletion of CD4 T cells remains the most reliable marker for estimating the degree of immunosuppression in HIV-1-infected individuals, several authors have investigated the possible prognostic and predictive role offered by total lymphocyte count (TLC) as a surrogate of the CD4 cell count in resource-limited settings (RLS). TLC offers the advantages of being less expensive and less complicated than the CD4 cell count. In addition, the equipment needed is already available in most RLS. Despite these potential advantages, papers recently published on this issue do not demonstrate that TLC fulfils the rigorous requirements as to sensitivity and specificity, particularly needed when methods already proved to be accurate detectors of immunosuppression (such as CD4 cell count) are available [1–6]. The rapid tests for diagnosing HIV infection in adolescents and adults are an example of this, having replaced enzyme-linked immunosorbent assay and Western blot in RLS, not only because of their lower cost, but also because of their good mean sensitivity and specificity (98.5 and 93.4%, respectively). The aim of this study was to assess the impact of considering TLC alone on the introduction of antiretroviral therapy in an asymptomatic HIV-infected African population undergoing regular CD4 lymphocyte controls in the framework of a highly active antiretroviral therapy protocol. Moreover, the effectiveness of TLC as a marker of immunosuppression was compared with that of another marker, the body mass index (BMI), requiring the simple measurement of the anthropometrical parameters of weight and height. The study was carried out from March 2002 to May 2003 by analysing 651 paired TLC and CD4 lymphocyte counts collected from asymptomatic patients (1–2 World Health Organization clinical staging) followed in a day hospital for individuals with HIV infection managed by the Community of Sant'Egidio in cooperation with the Ministry of Health of Mozambique. The day hospital, located in Matola-Maputo, Mozambique, is part of the DREAM programme (Drug Resource Enhancement against AIDS and Malnutrition) [7]. TLC was measured by an Act-5 Diff Beckman automated blood-analyser; lymphocyte-phenotyping was performed by ‘lyse-non-wash’ flow-cytometry (EPICS-MCL XL, Beckman Coulter, Johannesburg, South Africa). In 468 cases, BMI was also available, calculated on the same day the patients’ blood was collected. The mean value of TLC was 1935 cells/mm3 (range 200–13 800; SD ± 1035); average BMI was 22.04 (range 11.02–40.06; SD ± 4.17). CD4 lymphocytes were less than 200 cells/mm3 in 277 cases (42.4%). The two-tail Pearson correlation between the CD4 cell count and the other two variables gave a value of r = 0.341 and r = 0.314 for BMI and TLC, respectively (P < 0.001 in both cases) (Table 1).Table 1: CD4 cell count, total lymphocyte count and body mass index: values and statistical correlations.A further analysis was performed by binary logistic regression, to resolve the heterogeneity between dependent and independent variables (although dichotomization of the variables is always required). CD4 cell counts (dependent variable) were divided into two groups, above or below 200 cells/mm3 (the threshold under which patients should receive antiretroviral treatment). The threshold value for the dichotomization of TLC was 1200 cells/mm3, considered a marker of serious immunosuppression according to World Health Organization guidelines for RLS. For BMI, 18 was chosen as the threshold value that indicates malnutrition. The two independent variables were separately compared with dependent variables in order to evaluate their predictive effectiveness. The classification capability of the two models was 65.2% for BMI and 67.6% for TLC; sensitivity was 47 and 48.9%, respectively, whereas specificity was 78.5% for BMI and 81.3% for TLC (Table 1). Consequently, using TLC as a marker for introducing therapy would have resulted in initiating antiretroviral treatment for approximately 20% of patients who could wait according to international guidelines. At the same time, TLC would have excluded from treatment approximately 50% of those having an indication for starting therapy. Interestingly, using BMI instead of TLC would have led to similar results. In confirmation of the results of binary logistic regression, the use of receiving operating characteristics curves for the two variables considered demonstrated that neither TLC nor BMI had the ability to provide accurate discrimination (29% for TLC and 32% for BMI). In conclusion, the use of TLC as a surrogate for the CD4 cell count appears to be unjustified, as it does not fulfil the minimal requirements of validity, whereas it appears to provide a level of information comparable with a simple evaluation of the anthropometric status (such as BMI), which is also indicative of the patients’ clinical condition. The low sensitivity of TLC delays therapeutic decisions, and may lead to disease progression and death in some immunosuppressed patients who could have taken advantage of therapy. Moreover, starting treatment in a significant percentage of patients, in the absence of serious immunosuppression, would overcome the economic advantage obtained by substituting TLC for CD4 cell count.

Alternatives to HIV-1 RNA concentration and CD4 count to predict mortality in HIV-1-infected children in resource-poor settings.

Cheaper, simpler alternatives to CD4 lymphocyte count and HIV-1 RNA detection for assessing the prognosis of HIV-1 infection are needed for resource-poor settings. However, little is known about the predictive value of alternative assays, in particular in children. We assessed the prognostic value of total lymphocyte count, immune complex-dissociated p24 antigen, white blood cell count, packed-cell volume (haematocrit), and serum albumin for mortality in 376 HIV-1-infected, mainly African-American or Hispanic children enrolled during March, 1988 to January, 1991. In a Cox proportional hazards model, including all assay-alternatives to CD4 and RNA, total lymphocyte count (p<0.0001) and serum albumin (p=0.0107) independently predicted mortality. Further assessment of these markers is warranted in resource-poor settings.

Authors' Reply: Total Lymphocyte Count as a Surrogate for CD4+ Lymphocyte Count in African Patients Coinfected With HIV and Tuberculosis

To the Editor: We thank Drs. Wood and Post for their response to our article. Further data in this area can only help establish the value of total lymphocyte count (TLC) as a useful clinical tool in developing countries. The data presented by Wood and Post-show that, in patients with tuberculosis (TB) and HIV infection, a TLC of <1,250 cells/mm3 is predictive of a CD4+ lymphocyte count of <200/mm3. This finding is not at variance with our own results, which predict that a TLC of 1,300-1,500 cells/mm3 is a surrogate for a CD4 count of <200 cells/mm3. It is difficult to comment on Wood and Post's findings regarding the predictive value of a TLC of 1,250-1,500 cells/mm3 for a CD4+ count of <200 cells/mm3, as their sample size (n = 15) was small (see their Table 2). Wood and Post also presented data on 831 HIV-positive patients, 128 of whom had pulmonary TB (see their Fig. 1). These data showed that, in the absence of TB, positive predictive values decline rapidly at TLCs >1,000 cells/mm3. It should be stressed that the data we presented were derived from patients coninfected with HIV and TB, as was clearly stated. However, we also demonstrated a fall-off in the positive predictive values at the higher TLC range. The aim of our study was to define a surrogate cutoff for a CD4+ count in the lower range of 200-500 cells/mm3—a range we consider to be of greater clinical significance in patient management. We thoroughly endorse the sentiments of Wood and Post that the TLC as a surrogate for the CD4+ lymphocyte count is particularly relevant in developing countries where access to flow cytometry is limited and TB is the most common opportunistic infection in HIV disease. D. J. Martin; J. G. M. Sim MRC AIDS Virus Research Unit; National Institute for Virology; University of the Witwatersrand; Sandringham, South Africa

Total Lymphocyte Count as a Surrogate for CD4+ Lymphocyte Count in African Patients Coinfected With HIV and Tuberculosis

To the Editor: Martin et al. (1) recently reported significant increases in CD4+ T cells following standard tuberculosis (TB) therapy in HIV-infected individuals. This observation is of practical importance since patients assessed at the beginning of TB therapy may have their level of immunosuppression overestimated. We also welcomed their look at the usefulness of the total lymphocyte count (TLC) as a marker of severe immunosuppression in patients with HIV and TB. We have analyzed the concurrent TLCs and CD4+ T cell counts of 831 HIV-positive patients (128 with pulmonary TB) attending an HIV clinic in Cape Town (South Africa). This analysis demonstrated a significantly (p < 0.001) increased predictive value of a low TLC for <200 CD4+ T cells/mm3 in the presence of TB (Table 1). This increased predictive value in patients with TB may be the result of the predominant decline of CD4+ T cells caused by TB infection relative to CD8+ T cells (2,3). Martin et al. appear to have calculated positive predictive values (PPVs) for <200 CD4+ T cells by including all lymphocyte counts lower than a given value; this approach results in a marked overestimation of the true predictive value, especially in the higher ranges of lymphocyte counts. The PPV so calculated is also overestimated if a large proportion of a study population has advanced HIV disease. A more useful PPV can be calculated by only analyzing observations limited to given ranges of lymphocyte counts. PPVs calculated for increments of 250 lymphocytes for our 831 patients are shown in Fig. 1. In the absence of TB, positive predictive values decline rapidly at TLCs >1,000 cells/mm3. These PPVs are similar to those calculated from tabulated data presented by Blatt et al. (4). In the presence of tuberculosis, a rapid decline in PPV occurs at a TLC >1,250 cells/mm3(Table 2). Our data indicate that, in patients with tuberculosis and HIV infection, a TLC of <1,250 cells/mm3 rather than <1,500 cells/mm3 is a more appropriate surrogate marker for CD4+ T lymphopenia. Different methodology may have resulted in the choice of a higher TLC cutoff by Martin et al. The increased power of TLC as a surrogate for CD4+ T cell count in patients infected with HIV and tuberculosis is particularly relevant in developing countries where access to flow cytometry is limited and tuberculosis is the most common opportunistic infection in HIV disease. Robin Wood; Frank Post Department of Medicine; University of Cape Town; Cape Town, South AfricaFIG. 1: . The positive predictive value of incremental ranges of total lymphocyte counts for identifying CD4+ T cell lymphopenia is shown (2,044 paired observations in 831 HIV-positive patients).