Pre-HAART CD4+ T-Lymphocytes as Biomarkers of Post-HAART Immune Recovery in HIV-Infected Children with or without TB Co-Infection

Abstract Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection.Results We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

Download Full-text

Pre-HAART CD4+ T-Lymphocytes as Biomarkers of Post-HAART Immune Recovery in HIV-TB Co-Infected Children

10.21203/rs.3.rs-47535/v2 ◽

2020 ◽

Author(s):

Vivek Gopalakrishnan ◽

Eliezer Bose ◽

Usha Nair ◽

Yuwei Cheng ◽

Musie Ghebremichael

Keyword(s):

T Lymphocyte ◽

Lymphocyte Count ◽

Diagnostic Performance ◽

Pediatric Patients ◽

Roc Curves ◽

Sub Saharan Africa ◽

Immune Recovery ◽

Infected People ◽

Recovery Times ◽

Sub Saharan

Download Full-text

Pre-HAART CD4+ T-lymphocytes as biomarkers of post-HAART immune recovery in HIV-infected children with or without TB co-infection

BMC Infectious Diseases ◽

10.1186/s12879-020-05458-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Vivek Gopalakrishnan ◽

Eliezer Bose ◽

Usha Nair ◽

Yuwei Cheng ◽

Musie Ghebremichael

Keyword(s):

T Lymphocyte ◽

Lymphocyte Count ◽

Diagnostic Performance ◽

Pediatric Patients ◽

Roc Curves ◽

Sub Saharan Africa ◽

Immune Recovery ◽

Infected People ◽

Recovery Times ◽

Sub Saharan

Abstract Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection. Results We found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions Pre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

Download Full-text

Pre-HAART CD4+ T-Lymphocytes as Biomarkers of Post-HAART Immune Recovery in HIV-Infected Children with or without TB Co-Infection

10.21203/rs.3.rs-47535/v4 ◽

2020 ◽

Author(s):

Vivek Gopalakrishnan ◽

Eliezer Bose ◽

Usha Nair ◽

Yuwei Cheng ◽

Musie Ghebremichael

Keyword(s):

T Lymphocyte ◽

Lymphocyte Count ◽

Diagnostic Performance ◽

Pediatric Patients ◽

Roc Curves ◽

Sub Saharan Africa ◽

Immune Recovery ◽

Infected People ◽

Recovery Times ◽

Sub Saharan

Abstract BackgroundInfection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4+ T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. MethodsThe data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4+ T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection.ResultsWe found that the diagnostic performance of both pre-HARRT treatment CD4+ T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4+ T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. ConclusionsPre-HAART CD4+ T-lymphocyte count and percentage are stronger predictors of immune recovery in TB-negative pediatric patients, suggesting that TB co-infection complicates the treatment of HIV in this cohort. These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

Download Full-text

Pre-HAART CD4+ T-Lymphocytes as Biomarkers of Post-HAART Immune Recovery in HIV-TB Co-Infected Children

10.21203/rs.3.rs-47535/v1 ◽

2020 ◽

Author(s):

Musie Ghebremichael ◽

Vivek Gopalakrishnan ◽

Eliezer Bose ◽

Usha Nair ◽

Yuwei Cheng

Keyword(s):

T Lymphocyte ◽

Lymphocyte Count ◽

Diagnostic Performance ◽

Roc Curves ◽

Sub Saharan Africa ◽

Immune Recovery ◽

Infected People ◽

Kaplan Meier ◽

Recovery Times ◽

Sub Saharan

Abstract Background Infection with the Human Immunodeficiency Virus (HIV) dramatically increases the risk of developing active tuberculosis (TB). Several studies have indicated that co-infection with TB increases the risk of HIV progression and death. Sub-Saharan Africa bears the brunt of these dual epidemics, with about 2.4 million HIV-infected people living with TB. The main objective of our study was to assess whether the pre-HAART CD4 + T-lymphocyte counts and percentages could serve as biomarkers for post-HAART treatment immune-recovery in HIV-positive children with and without TB co-infection. Methods The data analyzed in this retrospective study were collected from a cohort of 305 HIV-infected children being treated with HAART. A Lehmann family of ROC curves were used to assess the diagnostic performance of pre- HAART treatment CD4 + T-lymphocyte count and percentage as biomarkers for post-HAART immune recovery. The Kaplan–Meier estimator was used to compare differences in post-HAART recovery times between patients with and without TB co-infection. Results We found that the diagnostic performance of both pre-HARRT treatment CD4 + T-lymphocyte count and percentage was comparable and achieved accuracies as high as 74%. Furthermore, the predictive capability of pre-HAART CD4 + T-lymphocyte count and percentage were slightly better in TB-negative patients. Our analyses also indicate that TB-negative patients have a shorter recovery time compared to the TB-positive patients. Conclusions These findings suggest that the detection and treatment of TB is essential for the effectiveness of HAART in HIV-infected pediatric patients.

Download Full-text

Suboptimal immune recovery during antiretroviral therapy with sustained HIV suppression in sub-Saharan Africa

AIDS ◽

10.1097/qad.0000000000001801 ◽

2018 ◽

Vol 32 (8) ◽

pp. 1043-1051 ◽

Cited By ~ 11

Author(s):

Stefanie Kroeze ◽

Pascale Ondoa ◽

Cissy M. Kityo ◽

Margaret Siwale ◽

Sulaimon Akanmu ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Sub Saharan Africa ◽

Immune Recovery ◽

Sub Saharan ◽

Suboptimal Immune Recovery

Download Full-text

Validity of four clinical prediction scores for pulmonary embolism in a sub-Saharan African setting: a protocol for a Cameroonian multicentre cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2019-031322 ◽

2019 ◽

Vol 9 (10) ◽

pp. e031322

Author(s):

Agnès Esiéné ◽

Paul Owono Etoundi ◽

Joel Noutakdie Tochie ◽

Junette Arlette Mbengono Metogo ◽

Jacqueline Ze Minkande

Keyword(s):

Pulmonary Embolism ◽

Emergency Departments ◽

Diagnostic Performance ◽

Cross Sectional Study ◽

Sub Saharan Africa ◽

Receiver Operating Curve ◽

Clinical Prediction ◽

Sectional Study ◽

Cross Sectional ◽

Sub Saharan

IntroductionPulmonary embolism poses one of the most challenging diagnoses in medicine. Resolving these diagnostic difficulties is more crucial in emergency departments where fast and accurate decisions are needed for a life-saving purpose. Here, clinical pretest evaluation is an important step in the diagnostic algorithm of pulmonary embolism. Although clinical probability scores are widely used in emergency departments of sub-Saharan Africa, no study has cited their diagnostic performance in this resource-constrained environment. This study will seek to assess the performance of four routinely used clinical prediction models in Cameroonians presenting with suspicion of pulmonary embolism at the emergency department.Methods and analysisIt will be a cross-sectional study comparing the sensitivity, specificity, positive and negative predictive values and accuracy of the Wells, Simplified Wells, Revised Geneva and the Simplified Revised Geneva Scores to CT pulmonary angiography as gold standard in all consecutive consenting patients aged above 15 years admitted for clinical suspicion of pulmonary embolism to the emergency departments of seven major referral hospitals of Cameroon between 1 July 2019 and 31 December 2020. The area under the receiver operating curve, calibration plots, Hosmer and Lemeshow statistics, observed/expected event rates, net benefit and decision curve will be measured of each the clinical prediction test to ascertain the clinical score with the best diagnostic performance.Ethics and disseminationClearance has been obtained from the Institutional Review Board of the Faculty of medicine and biomedical sciences of the University of Yaounde I, Cameroon and the directorates of all participating hospitals to conduct this study. Also, informed consent will be sought from each patient or their legal next of kin and parents for minors, before enrolment into this study. The final study will be published in a peer-review journal and the findings presented to health authorities and healthcare providers.

Download Full-text

Diagnostic performance of a novel loop-mediated isothermal amplification (LAMP) assay targeting the apicoplast genome for malaria diagnosis in a field setting in sub-Saharan Africa

Malaria Journal ◽

10.1186/s12936-015-0926-6 ◽

2015 ◽

Vol 14 (1) ◽

Cited By ~ 15

Author(s):

Eniyou C. Oriero ◽

Joseph Okebe ◽

Jan Jacobs ◽

Jean-Pierre Van geertruyden ◽

Davis Nwakanma ◽

...

Keyword(s):

Diagnostic Performance ◽

Lamp Assay ◽

Malaria Diagnosis ◽

Isothermal Amplification ◽

Sub Saharan Africa ◽

Loop Mediated Isothermal Amplification ◽

Sub Saharan ◽

Field Setting ◽

Apicoplast Genome

Download Full-text

Tuberculosis preventive therapy for HIV-infected people in sub-Saharan Africa is cost-effective

AIDS ◽

10.1097/00002030-199908200-00016 ◽

1999 ◽

Vol 13 (12) ◽

pp. 1549-1556 ◽

Cited By ~ 36

Author(s):

Jensa C. Bell ◽

David N. Rose ◽

Henry S. Sacks

Keyword(s):

Cost Effective ◽

Preventive Therapy ◽

Sub Saharan Africa ◽

Infected People ◽

Sub Saharan

Download Full-text

Towards malaria microscopy at the point-of-contact: an assessment of the diagnostic performance of the Newton Nm1 microscope in Uganda

Parasitology ◽

10.1017/s0031182014000833 ◽

2014 ◽

Vol 141 (14) ◽

pp. 1819-1825 ◽

Cited By ~ 10

Author(s):

J. RUSSELL STOTHARD ◽

BETTY NABATTE ◽

JOSE C. SOUSA-FIGUEIREDO ◽

NARCIS B. KABATEREINE

Keyword(s):

Confidence Interval ◽

Positive Predictive Value ◽

Predictive Value ◽

Blood Cells ◽

Diagnostic Performance ◽

White Blood Cells ◽

Sub Saharan Africa ◽

Resource Poor ◽

Sub Saharan ◽

Malaria Microscopy

SUMMARYMalaria microscopy in sub-Saharan Africa is often restricted by access to light microscopes. To address this gap, a novel portable inverted monocular microscope, the Newton Nm1, was designed and is now commercially available. Its diagnostic performance was assessed in a blinded-slide trial at ×1000 (oil) of Giemsa-stained thick blood films against a conventional microscope as undertaken by four Ugandan Ministry of Health technicians. With the Newton Nm1, diagnostic performance was: sensitivity 93·5% (95% confidence interval (CI) 78·6–99·2%), specificity 100·0% (95% CI 82·4–100·0%), positive predictive value 100·0% (95% CI 88·1–100·0%) and negative predictive value 90·5% (95% CI 69·6–98·8%). Discordance was due to a systematic error underestimating parasitaemia by ~45%; when counting Plasmodium parasites against 200 white blood cells, blood films with low parasitaemia (i.e. <100 μL−1 of blood) could be overlooked and misclassified. By contrast, specificity was excellent with no false positives encountered. Whilst proven useful, especially in resource-poor environments, it is still unclear how we can ensure the uptake of the Newton Nm1 within sub-Saharan Africa.

Download Full-text

Validation of Microcapillary Flow Cytometry for Community-Based CD4+ T Lymphocyte Enumeration in Remote Burkina Faso

The Open AIDS Journal ◽

10.2174/1874613601004010171 ◽

2010 ◽

Vol 4 (1) ◽

pp. 171-175 ◽

Cited By ~ 4

Author(s):

Cybèle A Renault ◽

Arouna Traore ◽

Rhoderick N Machekano ◽

Dennis M Israelski

Keyword(s):

Flow Cytometry ◽

T Lymphocyte ◽

Rank Correlation ◽

Sub Saharan Africa ◽

Spearman Rank Correlation ◽

Community Based ◽

Blood Samples ◽

Spearman Rank ◽

Sub Saharan ◽

Spearman Rank Correlation Coefficient

BackgroundCD4+ T lymphocyte enumeration plays a critical role in the initiation and monitoring of HIV-infected patients on antiretroviral therapy. There is an urgent need for low-cost CD4+ enumeration technologies, particularly for use in dry, dusty climates characteristic of many small cities in Sub-Saharan AfricaDesignCross-sectional studyMethodsBlood samples from 98 HIV-infected patients followed in a community HIV clinic in Ouahigouya, Burkina Faso were obtained for routine CD4+ T lymphocyte count monitoring. The blood samples were divided into two aliquots, on which parallel CD4+ measurements were performed using microcapillary (Guava EasyCD4) and dedicated (Becton Dickinson FACSCount) CD4+ enumeration systems. Spearman rank correlation coefficient was calculated, and the sensitivity, specificity and positive predictive value (PPV) for EasyCD4 <200 cells/µL were determined compared to the reference standard FACSCount CD4 <200 cells/µLResultsMean CD4 counts for the EasyCD4 and FACSCount were 313.75 cells/µL and 303.47 cells/µL, respectively. The Spearman rank correlation coefficient was 0.92 (p<0.001). Median values using EasyCD4 were higher than those with the FACSCount (p=0.004). For a CD4<350 cells/uL, sensitivity of the EasyCD4 was 93.9% (95%CI 85.2-98.3%), specificity was 90.6% (95% CI 75.0-98.0%), and PPV was 95.4% (95%CI 87.1-99.0%)ConclusionUse of the EasyCD4 system was feasible and highly accurate in the harsh conditions of this remote city in Sub-Saharan Africa, demonstrating acceptable sensitivity and specificity compared to a standard operating system. Microcapillary flow cytometry offers a cost-effective alternative for community-based, point-of-care CD4+ testing and could play a substantial role in scaling up HIV care in remote, resource-limited settings

Download Full-text