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1.
Acta Clin Belg ; 79(2): 113-120, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38752847

ABSTRACT

PURPOSE: Heart failure is prevalent among older people and has a poor prognosis. The aim of this study is to identify potential prognostic, geriatric, and cardiac parameters which could help clinicians identify older heart failure patients at high risk for one-year mortality. METHODS: The multicentre, observational cohort study which included 147 heart failure patients aged ≥75 years, hospitalized in the cardiac or geriatric department in two hospitals. One-year survival was the outcome measure. For univariate analysis Chi-square test and independent sample T-test were used; for multivariate analysis Logistic regression and Cox regression for time-dependent analysis. RESULTS: One-year mortality was 28% (41/147). One-year survivors and non-survivors did not differ in the following characteristics: age, gender, sodium level at hospital discharge, ejection fraction, NYHA Class, basic and instrumental activities of daily living, and the presence of a geriatric risk profile. There was a significant lower systolic blood pressure at discharge in non-survivors compared to one-year-survivors (mean 125.26 mmHg vs. 137.59 mmHg). Non-survivors had more severe underlying comorbidities according to the age adjusted Charlson Comorbidity index (CCI) (mean 8.80 vs. 7.40).Both logistic and Cox regression showed a higher risk and rate of mortality with decreasing systolic blood pressure at discharge (OR 0.963, p=0.001 and HR 0.970, p<0.001) and with increasing CCI (OR 1.344, p=0.002 and HR 1.269, p=0.001); the other variables were not significantly related. CONCLUSION: Lower blood pressure and more severe comorbidities, but not functionality nor the presence of a geriatric risk profile, are related to one-year mortality in older, in-hospital heart failure patients.


Subject(s)
Geriatric Assessment , Heart Failure , Humans , Heart Failure/mortality , Heart Failure/physiopathology , Aged , Male , Female , Aged, 80 and over , Prospective Studies , Prognosis , Geriatric Assessment/methods
2.
Int J Infect Dis ; 120: 41-43, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35429644

ABSTRACT

A woman presented with cough, fever, and dyspnea during a twin pregnancy following a 13th in vitro fertilization procedure. Ultimately, she was diagnosed with miliary tuberculosis and tuberculostatic treatment was initiated, complicated by drug-induced hepatotoxicity. In retrospect, previous pelvic tuberculosis had likely been overlooked. This case report highlights the need to recognize tuberculosis as a cause of infertility even in low-incidence countries and emphasizes that the peripartum period is a major risk factor for drug-induced liver injury.


Subject(s)
Pregnancy Complications, Infectious , Tuberculosis, Miliary , Female , Fertilization in Vitro/adverse effects , Fever/complications , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/drug therapy , Pregnancy, Twin , Tuberculosis, Miliary/diagnosis , Tuberculosis, Miliary/drug therapy
3.
BMC Infect Dis ; 20(1): 469, 2020 Jul 02.
Article in English | MEDLINE | ID: mdl-32615981

ABSTRACT

BACKGROUND: Interferon-γ release assays (IGRA) with Resuscitation promoting factor (Rpf) proteins enhanced tuberculosis (TB) screening and diagnosis in adults but have not been evaluated in children. Children often develop paucibacillary TB and their immune response differs from that of adults, which together affect TB disease diagnostics and immunodiagnostics. We assessed the ability of Rpf to identify infection among household TB-exposed children in The Gambia and investigated their ability to discriminate Mycobacterium tuberculosis complex (MTBC) infection from active TB disease in children. METHODS: Detailed clinical investigations were done on 93 household TB-exposed Gambian children and a tuberculin skin test (TST) was administered to asymptomatic children. Venous blood was collected for overnight stimulation with ESAT-6/CFP-10-fusion protein (EC), purified protein derivative and RpfA, B, C, D and E. Interferon gamma (IFN-γ) production was measured by ELISA in supernatants and corrected for the background level. Infection status was defined by IGRA with EC and TB disease by mycobacterial confirmation and/or clinical diagnosis. We compared IFN-γ levels between infected and uninfected children and between infected and TB diseased children using a binomial logistic regression model while correcting for age and sex. A Receiver Operating Characteristics analysis was done to find the best cut-off for IFN-γ level and calculate sensitivity and specificity. RESULTS: Interferon gamma production was significantly higher in infected (IGRA+, n = 45) than in uninfected (IGRA-, n = 20) children after stimulation with RpfA, B, C, and D (P = 0.03; 0.007; 0.03 and 0.003, respectively). Using RpfB and D-specific IFN-γ cut-offs (33.9 pg/mL and 67.0 pg/mL), infection was classified with a sensitivity-specificity combination of 73-92% and 77-72% respectively, which was similar to and better than 65-75% for TST. Moreover, IFN-γ production was higher in infected than in TB diseased children (n = 28, 5 bacteriologically confirmed, 23 clinically diagnosed), following RpfB and D stimulation (P = 0.02 and 0.03, respectively). CONCLUSION: RpfB and RpfD show promising results for childhood MTBC infection screening, and both performed similar to and better than the TST in our study population. Additionally, both antigens appear to discriminate between infection and disease in children and thus warrant further investigation as screening and diagnostic antigens for childhood TB.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Cytokines/immunology , Interferon-gamma Release Tests/methods , Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Mass Screening/methods , Mycobacterium tuberculosis/immunology , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Family Characteristics , Female , Gambia/epidemiology , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Latent Tuberculosis/microbiology , Male , Sensitivity and Specificity , Tuberculin Test
4.
Cytometry B Clin Cytom ; 92(6): 437-444, 2017 11.
Article in English | MEDLINE | ID: mdl-27406947

ABSTRACT

CD4 T-cell counting was introduced in clinical laboratories shortly after the discovery of the human immune deficiency virus (HIV) in the early eighties. In western clinical laboratories, improvements in the CD4 T-cell counting methods were mainly driven by progress in the field of flow cytometry and immunology. In contrast, the development of dedicated CD4 T-cell counting technologies were needs driven. When antiretroviral treatment (ART) was made available on a large scale by international Acquired Immune Deficiency Syndrome (AIDS) relief programs to HIV+ patients living in low income countries in 2003, there was a distinct need for simplified and affordable CD4 T-cell counting technologies. The first decade of 2000, several compact flow cytometers appeared on the market, mainly to the benefit of low income countries with limited resources. More recently, however, portable point-of-care (POC) CD4 T-cell counting devices have been developed especially to improve access to affordable monitoring of HIV+ patients in low income countries. The accuracy of these POC instruments is not yet very well documented as many are still under development and clinical validation but preliminary evidence is encouraging. The new HIV treatment guidelines released by the World Health Organization in 2016 give CD4 T-cell counting a less central role in the management of HIV infection. It is, therefore, to be expected that CD4 T-cell counting will be phased out as a tool to assess eligibility of HIV+ patients for ART in the future. However, CD4 T-cell counting will remain a valuable tool for directing treatment against opportunistic infections. © 2016 International Clinical Cytometry Society.


Subject(s)
CD4 Lymphocyte Count/instrumentation , CD4-Positive T-Lymphocytes/immunology , Flow Cytometry/instrumentation , HIV Infections/diagnosis , Point-of-Care Testing , Anti-HIV Agents/therapeutic use , CD4-Positive T-Lymphocytes/virology , Computers, Handheld/economics , Computers, Handheld/supply & distribution , Developing Countries , Flow Cytometry/economics , HIV/drug effects , HIV/physiology , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/virology , Humans , Immunophenotyping/instrumentation , Immunophenotyping/methods , Mobile Applications/economics , Mobile Applications/supply & distribution , Practice Guidelines as Topic
5.
Int J Tuberc Lung Dis ; 17(3): 336-41, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23407223

ABSTRACT

SETTING: A human immunodeficiency virus (HIV) clinic in a setting of high tuberculosis (TB) and HIV prevalence. OBJECTIVE: To study the incidence of and factors associated with tuberculin skin test (TST) conversion in HIV patients on antiretroviral therapy (ART). DESIGN: Prospective cohort study of TST-negative, ART-naïve HIV patients (CD4 cell count < 250 cells/l) without active TB. TST was repeated at 2 months and, if negative, at 6 months. TST positivity was defined as an induration of ≥5 mm. Clinical examination, chest X-ray and CD4 cell counts were performed at baseline and follow-up. Proportions and incidence of TST conversion were calculated, and logistic regression analyses were performed. RESULTS: Of the 142 patients, 105 (75.5%) were females. The mean age was 35.9 years (standard deviation 8.1) and the median CD4 cell count was 119 cells/l (interquartile range 42168). The incidence of TST conversion was 30.2/100 person years (95%CI 19.546.8). Conversion was not associated with clinical, CD4 cell count or chest radiography findings. CONCLUSIONS: A high incidence of TST conversion was observed, supporting the World Health Organization recommendation to provide isoniazid preventive therapy (IPT) to all HIV patients in high TB prevalence settings. If case-control programmes choose to provide IPT only to TST-positive patients, repeat TST should be considered following initiation of ART.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Coinfection , HIV Infections/drug therapy , Tuberculin Test , Tuberculosis/diagnosis , Adult , CD4 Lymphocyte Count , Female , HIV Infections/diagnosis , HIV Infections/epidemiology , Humans , Incidence , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prospective Studies , Radiography, Thoracic , Time Factors , Tuberculosis/epidemiology , Uganda/epidemiology
6.
Int J STD AIDS ; 23(11): 810-4, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23155102

ABSTRACT

Numerous studies suggest that herpes simplex virus type 2 (HSV-2) increases the risk of HIV-1 infection but recent clinical trials of HSV-2 suppressive therapy failed to show an effect. We assessed the putative association between HSV-2 and HIV-1 in a population of HIV-concordant-negative, HIV-1-discordant and HIV-1-concordant-positive married couples from Dakar, Senegal. In agreement with previous studies, we observed a strong overall association between HSV-2 and HIV-1 (odds ratio 4.61; P < 0.001). However, this association was mainly determined by a low HSV-2 prevalence in HIV-concordant-negative couples compared with HIV-1-discordant and HIV-1-concordant-positive couples (23% versus 59% and 66%, respectively; P < 0.001). We observed no further differences in HSV-2 prevalence between HIV-1-discordant and HIV-1-concordant-positive couples (59% and 66%, respectively; P = 0.483). Neither the index (59% versus 62%, P = 1.000) nor recipient partners (41% versus 63%, P = 0.131) in HIV-1-discordant and HIV-1-concordant-positive couples showed significant differences in HSV-2 prevalence. HSV-2 does not constitute a clear risk factor for HIV-1 infection in this population.


Subject(s)
Family Characteristics , HIV Infections/epidemiology , HIV-1/isolation & purification , Herpes Genitalis/epidemiology , Herpesvirus 2, Human/isolation & purification , Adult , Coinfection/epidemiology , Coinfection/virology , Comorbidity , Female , HIV Infections/virology , Herpes Genitalis/virology , Humans , Male , Middle Aged , Senegal/epidemiology
7.
Int J Tuberc Lung Dis ; 16(11): 1517-21, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23044447

ABSTRACT

OBJECTIVE: To examine whether hypovitaminosis D is a risk factor for the development of tuberculosis (TB) associated immune reconstitution inflammatory syndrome (IRIS). METHODS: We measured serum 25-hydroxyvitamin D (25D) concentrations in four groups of patients at Mulago Hospital, Kampala, Uganda: 1) patients co-infected with TB and the human immunodeficiency virus (HIV) receiving anti-tuberculosis treatment (HIV+TB+; n = 92) who did and did not develop TB-IRIS after starting antiretroviral treatment (ART), 2) HIV-infected patients without TB (HIV+TB-; n = 20) starting ART, 3) non-HIV-infected individuals with TB (HIV-TB+; n = 27), and 4) those without TB (HIV-TB-; n = 23). RESULTS: The prevalence of optimal 25D levels (>75 nmol/l) was as follows: 59% in HIV+TB+, 65% in HIV+TB-, 63% in HIV-TB+ and 35% in HIV-TB- patients. 25D concentrations decreased during the first 3 months of ART in HIV+TB+ individuals who developed IRIS (P = 0.005) and those who did not (P = 0.002), and in HIV+TB- individuals (P = 0.015); however, 25D concentration in patients who did or did not develop TB-IRIS did not differ. CONCLUSION: The prevalence of optimal vitamin D status was relatively high in HIV-infected patients with and without TB living near the equator. No difference in 25D concentrations was observed between TB-IRIS and non-IRIS. However, 25D concentrations decreased during ART.


Subject(s)
HIV Infections/complications , Immune Reconstitution Inflammatory Syndrome/etiology , Tuberculosis/complications , Vitamin D Deficiency/complications , Adult , Anti-HIV Agents/therapeutic use , Antitubercular Agents/therapeutic use , Female , Follow-Up Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Immune Reconstitution Inflammatory Syndrome/epidemiology , Male , Prevalence , Prospective Studies , Risk Factors , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Uganda/epidemiology , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/epidemiology , Young Adult
8.
Parasitology ; 138(11): 1392-9, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21819638

ABSTRACT

Mathematical models predict that the future of epidemics of drug-resistant pathogens depends in part on the competitive fitness of drug-resistant strains. Considering metacyclogenesis (differentiation process essential for infectivity) as a major contributor to the fitness of Leishmania donovani, we tested its relationship with pentavalent antimony (SbV) resistance in clinical lines. Different methods for the assessment of metacyclogenesis were cross-validated: gene expression profiling (META1 and SHERP), morphometry (microscopy and FACS), in vitro infectivity to macrophages and resistance to complement lysis. This was done on a model constituted by 2 pairs of reference strains cloned from a SbV-resistant and -sensitive isolate. We selected the most adequate parameter and extended the analysis of metacyclogenesis diversity to a sample of 20 clinical lines with different in vitro susceptibility to the drug. The capacity of metacyclogenesis, as measured by the complement lysis test, was shown to be significantly higher in SbV-resistant clinical lines of L. donovani than in SbV-sensitive lines. Together with other lines of evidence, it is concluded that L. donovani constitutes a unique example and model of drug-resistant pathogens with traits of increased fitness. These findings raise a fundamental question about the potential risks of selecting more virulent pathogens through massive chemotherapeutic interventions.


Subject(s)
Antimony Sodium Gluconate/pharmacology , Leishmania donovani/drug effects , Leishmaniasis, Visceral/drug therapy , Life Cycle Stages/drug effects , Macrophages/drug effects , Animals , Antiprotozoal Agents/pharmacology , Drug Resistance/drug effects , Drug Resistance/genetics , Flow Cytometry , Gene Expression Profiling , Humans , Leishmania donovani/classification , Leishmania donovani/genetics , Leishmania donovani/growth & development , Leishmania donovani/isolation & purification , Leishmania donovani/pathogenicity , Leishmaniasis, Visceral/parasitology , Life Cycle Stages/genetics , Macrophages/parasitology , Molecular Typing , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Real-Time Polymerase Chain Reaction
9.
Int J Tuberc Lung Dis ; 13(3): 317-22, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19275790

ABSTRACT

OBJECTIVES: To assess the diversity of Mycobacterium tuberculosis strains in Cotonou, Benin, and the risk factors associated with clustering. METHODS: We analysed one sputum sample from 194 consecutive new pulmonary tuberculosis (TB) cases using two genotyping methods: spoligotyping and the 12 loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR). The data obtained were compared to the SpolDB4.0 database. RESULTS: We have found that spoligotype 61, highly predominant in West Africa, was also the most prevalent strain in Cotonou. We observed that the Beijing family represented 10.3% of strains and was associated with resistance to streptomycin. We also confirmed that combining spoligotyping and MIRU-VNTR provided a higher discriminatory power than the two techniques used individually. CONCLUSION: Spoligotype 61 and Beijing genotype are the most prevalent genotypes of M. tuberculosis in Cotonou.


Subject(s)
Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Pulmonary/epidemiology , Tuberculosis/epidemiology , Bacterial Typing Techniques , Benin/epidemiology , DNA Fingerprinting , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Female , Genetic Variation , Humans , Interspersed Repetitive Sequences , Male , Minisatellite Repeats , Species Specificity , Sputum/microbiology
10.
Int J Tuberc Lung Dis ; 12(6): 683-5, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18492337

ABSTRACT

Despite a theoretical risk of transfer of bacilli from a positive to a negative smear, bulk staining is routinely performed in many laboratories. To assess this risk in our laboratory, two smears were made from each sputum specimen and stained with auramine: one smear was stained on a rack and the second using the bulk method. Smears were read blind using a fluorescence microscope. A total of 811 sputum specimens were analysed. No acid-fast bacilli transfer was observed even when staining solution jars had not been renewed for 3 days. Bulk staining is rapid and cheap, and could be used in laboratories with a high workload in low-resource settings.


Subject(s)
Bacteriological Techniques , Microscopy, Fluorescence , Sputum/microbiology , Humans , Staining and Labeling , Tuberculosis, Pulmonary/diagnosis
11.
Acta Clin Belg ; 62(2): 126-9, 2007.
Article in English | MEDLINE | ID: mdl-17547295

ABSTRACT

The Immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy for HIV is well known. We describe an HIV seropositive woman, presenting 2 IRIS episodes associated with Mycobacterium tuberculosis. Exceptional was that the last episode occurred 4 years after initiating antiretroviral treatment, when her CD4+ lymphocyte count had been around 300 cells/mm3 for one year.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Anti-Retroviral Agents/immunology , Inflammation/etiology , Tuberculosis/drug therapy , AIDS-Related Opportunistic Infections/immunology , Adult , Anti-Retroviral Agents/adverse effects , Female , Humans , Syndrome , Time Factors , Tuberculosis/complications , Tuberculosis/immunology
12.
Clin Exp Immunol ; 143(3): 435-44, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16487242

ABSTRACT

Particular human leucocyte antigen (HLA) polymorphisms have been associated with a reduced risk of HIV transmission. However, protective alloimmune responses expected to result from such a genetic predisposition have not been demonstrated. To this end, we analysed and compared cellular and humoral alloimmune responses in a cohort of female sex workers who remained human immunodeficiency virus (HIV)-seronegative despite more than 3 years of high-risk sexual activity (ESN FSWs) with those of low-risk HIV-seronegative female blood donors in Abidjan, Côte d'Ivoire. ESN FSWs showed significantly lower allostimulated CD69 expression and secretion of interferon-gamma, macrophage inflammatory protein (MIP)-1beta and RANTES (regulated upon activation, normal T-cell expressed and secreted) by lymphocytes than controls. In contrast, ESN FSWs showed significantly higher mitogen-stimulated CD69 expression and secretion of tumour necrosis factor-alpha and MIP-1beta than controls. Suppression of cellular alloimmune responses among ESN FSWs was associated with a higher self-reported frequency of unprotected sex. Levels of anti-HLA class I alloantibodies in plasma were not significantly different between ESN FSWs and controls. These findings indicate that frequent sexual exposure to multiple partners results in suppression rather than activation of cellular alloimmune responses. Our data support the hypothesis that suppressed cellular alloimmune responses may play a role in protection against HIV infection.


Subject(s)
HIV Infections/immunology , HIV Seronegativity/immunology , HIV-1/pathogenicity , Sex Work , Adult , Autoantibodies/biosynthesis , Cytokines/biosynthesis , Female , Genetic Predisposition to Disease , Histocompatibility Antigens Class I/immunology , Humans , Immune Tolerance , Immunity, Cellular , Isoantigens/immunology , Lymphocyte Culture Test, Mixed , Middle Aged , T-Lymphocyte Subsets/immunology , Unsafe Sex
13.
Clin Exp Immunol ; 140(1): 138-48, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15762885

ABSTRACT

Because of the paucity of plasma HIV RNA viral load (VL) tests in resource-poor settings, the CD4(+) T cell count is often used as the sole laboratory marker to evaluate the effectiveness of antiretroviral therapy (ART) in HIV-infected patients. In untreated patients, the level of activated T cells is positively correlated with VL and represents a prognostic marker of HIV infection. However, little is known about its value to predict early drug failure, taking into account the relatively high non-specific immune activation background observed in many resource-limited tropical countries. We assessed the use of immune activation markers (expression of CD38 and/or human leucocyte antigen-DR on CD8(+) lymphocytes) to predict virological response to ART in a cohort of HIV-1 infected patients in Abidjan, Côte d'Ivoire. Correlations between VL, absolute CD4(+) T cell counts and immune activation levels were examined in 111 HIV patient samples at baseline and after 6 and 12 months of therapy. The percentage of CD38(+) CD8(+) T cells appeared to be the best correlate of VL. In contrast, changes in CD4(+) T cell counts provided a poor correlate of virological response to ART. Unfortunately, CD38(+) CD8(+) percentages lacked specificity for the determination of early virological drug failure and did not appear to be reliable surrogates of RNA viral load. CD38(+) CD8(+) T cell percentages may, rather, provide a sensitive estimate of the overall immune recovery, and be a useful extra laboratory parameter to CD4 counts that would contribute to improve the clinical management of HIV-infected people when VL testing facilities are lacking.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , CD8-Positive T-Lymphocytes/immunology , HIV Infections/drug therapy , HIV-1/immunology , ADP-ribosyl Cyclase/immunology , ADP-ribosyl Cyclase 1 , Adult , Antigens, CD/immunology , Area Under Curve , Biomarkers/analysis , Cohort Studies , Female , HIV Infections/immunology , HLA-DR Antigens/immunology , Humans , Male , Membrane Glycoproteins , ROC Curve , Treatment Outcome , Viral Load/methods
14.
Int J STD AIDS ; 15(8): 523-8, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15307962

ABSTRACT

Our objective was to study the evolution of CD4 cell count five years after starting highly active antiretroviral treatment (HAART) in a clinical setting. The study was performed at the HIV outpatient clinic, Institute of Tropical Medicine, Antwerp. All patients (n = 225) who started HAART in 1997, who had a CD4 cell count within six months prior to starting HAART and who were subsequently followed for at least two years were included. Change in CD4 cell count after start of HAART and the influence of patient and clinical factors were investigated using graphical exploration, endpoint analysis and mixed-effects linear regression. The mean CD4 cell count at start of HAART was 280 cells/mm(3). At the five-year endpoint of the study the mean increase in CD4 cell count was 333 cells/mm(3), while 79% of the patients had a viral load less than 400 copies/mL. There was a significant negative correlation between increase in CD4 cell count at five years and time since first positive HIV test at start of HAART (P = 0.021). Patients who ever had a HAART interruption of more than seven days had a significantly lower increase in CD4 cell count than those who did not (225 cells/mm(3) compared with 438 cells/mm(3); P < 0.001). A mixed-effects linear regression model additionally suggested a significant impact of exposure to antiretrovirals prior to HAART (P = 0.03). Overall, the recovery of CD4 cell count after five years of HAART is good, although therapy interruptions have an important negative impact.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Outcome Assessment, Health Care , Adult , Ambulatory Care Facilities , Belgium , CD4 Lymphocyte Count , Female , HIV Infections/blood , HIV Infections/immunology , Humans , Male , Viral Load
15.
Int J STD AIDS ; 15(8): 538-42, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15307965

ABSTRACT

Monitoring the efficacy of highly active antiretroviral treatment (HAART) is crucial if disease progression and the emergence of viral mutants are to be avoided. Classical viral load monitoring is too expensive for large-scale use in resource-limited settings. Three alternative measures, CD4 count, total lymphocyte count (TLC) and haemoglobin, were evaluated as surrogate markers of treatment success (viral load below detection level) among 710 HIV-positive patients who started HAART in an HIV treatment centre in Belgium. TLC correlated well with changes in CD4 counts during HAART, but an increase in TLC alone was a poor predictor of treatment success. A combination of increases in both haemoglobin levels and TLC proved a reliable predictor of successful treatment outcome comparable to the increase in CD4 count, but its specificity and sensitivity were low.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/virology , Adult , Biomarkers , CD4 Lymphocyte Count , Female , Humans , Male , Patient Compliance , Predictive Value of Tests , Sensitivity and Specificity , Viral Load
16.
Parasite Immunol ; 26(1): 29-36, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15198643

ABSTRACT

In recently exposed communities, intensity of schistosomiasis infection increases as children age and then drops again in adulthood, indicating that host maturity is an important aspect of resistance to schistosomiasis. We investigated whether the cellular immune response to the parasite was correlated with age in subjects with similar daily patterns of exposure, current intensities of infection and number of years of exposure. The cellular immune response of subjects with either 'low' (under 200 eggs per gram (EPG)) or 'high' (over 400 EPG) intensities of infection was investigated, in a recently established focus where subjects had similar histories of exposure and number of years of experience with Schistosoma mansoni. Subject's whole blood was cultured with adult worm antigen (AWA), a mixture of phytohaemagglutinin (PHA) and lipopolysaccharide (LPS), or left unstimulated, and culture supernatants were tested for IL-4, IL-5, IL-10 and IFN-gamma. Children and adults tended to respond differently to schistosome antigen. The most statistically significant illustration of this was the negative correlation between age and IL-5 produced by samples from people with low intensities of infection cultured with AWA (P < 0.003, P < 0.05 after Bonferroni correction). IL-10 produced by samples cultured with PHA and LPS was also notably lower in children than in adults, although not formally significant after Bonferroni correction. This indicates that it is possible for age, independently of intensity of infection or experience with the parasite, to influence the immune response to schistosomiasis.


Subject(s)
Cytokines/biosynthesis , Leukocytes, Mononuclear/immunology , Schistosoma mansoni/immunology , Schistosomiasis mansoni/immunology , Adolescent , Adult , Aged , Aging , Animals , Antigens, Helminth/immunology , Cell Culture Techniques , Child , Humans , Interferon-gamma/biosynthesis , Interleukin-10/biosynthesis , Interleukin-4/biosynthesis , Interleukin-5/biosynthesis , Leukocytes, Mononuclear/metabolism , Middle Aged
17.
Trop Med Int Health ; 8(2): 100-8, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12581433

ABSTRACT

In an epidemic focus in northern Senegal, adults had lower intensities of infection than adolescents, a phenomenon that could not be attributed to immunity acquired over the previous 10-15 years of exposure to the parasite because all age groups had had the same number of years' experience of the worm. This article considers whether this pattern could have been because of higher levels of exposure to the parasite in younger age groups. Personal contact with infected water was recorded using a questionnaire in Schistosoma mansoni foci not more than 3 years old and in another, 10-year-old focus. Many aspects of contact (e.g. frequency, duration or time of day of contact) may contribute to the number of encounters with infective cercariae (true exposure), so various assumptions regarding the relationship between water contact and true exposure were tested resulting in a range of exposure indices. People reported a mean of 4.4 separate contacts, and spent a median of 57 min per day in water. Patterns of water contact differed depending on the exposure index used, e.g. considering duration, males spent a longer time in water than females (P < 0.001). But using frequency, females had more contacts with water than males in most villages (P < 0.001). Generally, exposure levels dropped as people become aged (P < 0.001) and residents of the older focus were more exposed than residents of other foci (P < 0.002). Intensity of (re)infection was not related to exposure either alone or in models incorporating age, sex and/or village irrespective of the index used. There is therefore evidence that age, sex and place of residence determine exposure but none to suggest that exposure had an influence on the relationship between these factors and intensity of infection. We propose therefore that in this population other factors have principal importance in determining intensity of infection.


Subject(s)
Disease Outbreaks , Environmental Exposure/adverse effects , Schistosomiasis mansoni/epidemiology , Water Supply , Adolescent , Adult , Age Factors , Aged , Animals , Anthelmintics/therapeutic use , Child , Female , Humans , Male , Middle Aged , Parasite Egg Count , Praziquantel/therapeutic use , Prevalence , Recurrence , Rural Health , Schistosoma mansoni/isolation & purification , Schistosomiasis mansoni/drug therapy , Seasons , Senegal/epidemiology
18.
J Med Virol ; 65(4): 765-76, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11745943

ABSTRACT

Specific neutralizing epitope changes have been observed in a chimpanzee infected naturally with SIVcpz, which differ from HIV-1 infecting humans. To characterize further these changes, a longitudinal study of env genomic sequence variation of SIVcpz-ant isolates was undertaken in this animal. The V1 and V2 regions of the env were determined to arise from specific recombination events. To determine whether recombination of the V1 and V2 domains was possibly associated with the emergence of neutralization escape viruses, envelope sequences and gene length polymorphisms from PBMC and plasma viral variants were studied over a 7-year period. PBMCs and plasma-associated infectious virus titers as well as plasma RNA viral loads were monitored longitudinally. The first 5 viruses isolated from the plasma were found to be neutralization escape variants. Sequence analysis of their V1 and the V2 regions indicated that a 20 amino acid stretch of the V1 region had undergone recombination and was also associated with the emergence of isolates eliciting strong neutralization responses. These findings support the hypothesis that recombination of the V1 and V2 regions of the envelope play a role in neutralization escape of SIVcpz in chimpanzees infected naturally. Furthermore, the data confirm that the neutralizing antibody response plays an important role in the decline of plasma infectious virus titers in HIV-1 related SIVcpz nonpathogenic infection.


Subject(s)
Antibodies, Viral/immunology , Pan troglodytes/virology , Simian Immunodeficiency Virus/genetics , Viral Envelope Proteins/genetics , Amino Acid Sequence , Animals , Gene Products, env/chemistry , Gene Products, env/genetics , Leukocytes, Mononuclear/virology , Molecular Sequence Data , Neutralization Tests , Pan troglodytes/blood , Polymorphism, Genetic , Recombination, Genetic , Sequence Alignment , Sequence Analysis, Protein , Simian Immunodeficiency Virus/immunology , Simian Immunodeficiency Virus/isolation & purification , Time Factors , Viral Load
19.
J Med Virol ; 64(4): 398-401, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11468722

ABSTRACT

The prevalence of the CCR2b-V64I mutation among human immunodeficiency virus (HIV)-seropositive and -seronegative female workers and the potential effect of heterozygosity of this mutation on HIV-1 plasma RNA viral load and markers of immune activation were assessed. CCR2b-V64I was detected by polymerase chain reaction, followed by restriction enzymes analysis; plasma viral load was measured by the Amplicor HIV-1 monitor assay and CD4(+) T-cell counts and markers of immune activation by standard three-color FACscan flow cytometry. Of the 260 female workers, 56 (21.5%) were heterozygous for CCR2b-V64I, and 8 (3%) were homozygous. Of the 99 HIV-seronegative female workers, 19 (19.2%) were heterozygous for the CCR2b-V64I mutation compared with 37 (23%) of the 161 HIV-seropositive FSW (P = 0.47). In a univariate analysis of viral load among HIV-seropositive FSW, no difference was noted between those heterozygous for or without the mutation; both groups had plasma viral loads of 5.0 log(10) copies/ml. After controlling for the effects of CD4(+) T-cell counts in a multivariate analysis, no significant difference was observed between the groups in viral load or in markers of immune activation. The data suggest that the presence of the CCR2b mutation has no effect on HIV-1 plasma viral load and markers of immune activation in our study population. The finding that the frequency of this mutation is similar in HIV-seropositive and -seronegative female workers suggests that its presence is not associated with increased risk of HIV infection.


Subject(s)
Chemokine CCL2/genetics , HIV Infections/genetics , HIV Seropositivity/genetics , HIV-1 , Receptors, Chemokine/genetics , Receptors, HIV/genetics , Adult , Cohort Studies , Cote d'Ivoire , Female , HIV Infections/immunology , HIV Infections/virology , HIV Seronegativity/genetics , HIV Seronegativity/immunology , HIV Seropositivity/immunology , HIV Seropositivity/virology , Heterozygote , Homozygote , Humans , Polymorphism, Genetic , Receptors, CCR2 , Viral Load
20.
J Infect Dis ; 183(9): 1405-8, 2001 May 01.
Article in English | MEDLINE | ID: mdl-11294674

ABSTRACT

Plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and markers of immune activation were compared among HIV-1-infected female sex workers (FSWs) with (n=112) and without (n=88) sexually transmitted diseases (STDs) in Abidjan, Côte d'Ivoire. After adjustment for CD4+ T cells, the median virus load was 2.5-fold higher among HIV-seropositive FSWs with STDs than among those without an STD (P=.053). Median virus load was higher for FSWs with a genital ulcer (P=.052) or gonorrhoea (P=.058) than for FSWs without any STD. Median levels of markers of immune activation (CD38 and HLA-DR on CD8+ T cells, soluble tumor necrosis factor-alpha receptor II, and beta(2)-microglobulin) tended to be elevated, albeit nonsignificantly, among FSWs in the STD group. These findings have important public health implications in elaborating strategies for decreasing disease progression and transmission of HIV among FSWs.


Subject(s)
HIV Infections/immunology , HIV-1/immunology , Sex Work , Sexually Transmitted Diseases/epidemiology , Viral Load , Adult , Biomarkers/blood , CD4 Lymphocyte Count , Cote d'Ivoire/epidemiology , Cross-Sectional Studies , Cytokines/analysis , Cytokines/immunology , Disease Progression , Female , Gonorrhea/epidemiology , Gonorrhea/virology , HIV Infections/epidemiology , HIV Infections/transmission , HIV Seropositivity , HIV-1/genetics , Humans , RNA, Viral/blood , Sexually Transmitted Diseases/immunology , Sexually Transmitted Diseases/virology
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