A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.).

[Apolipoprotein(a) isoforms immunoblotting detection: comparative study of two methods]. / Immunorévélation des isoformes d'apolipoprotéine(a) : étude comparée de deux méthodes.

This study reports the comparison between two methods (chemiluminescence and enzymatic colorimetry) for revelation of apolipoprotein(a) [apo(a)] isoforms by immunoblotting in 102 Ivorian healthy subjects. Apo(a) isoform sizes were determined by sodium dodecyl sulfate-agarose-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting using enzymatic colorimetry or chemiluminescence. Within-run precision was comprised between 4.9% and 9.2% for colorimetry and between 2.9% and 4.6% for chemiluminescence. Both methods have detected apo(a) isoforms in all patients, even when lipoprotein(a) concentrations were under detection limit (0.02 g/L). The two methods were significantly correlated (r = 0.96 to 0.98, p<0.0001). Even though the chemiluminescence method exhibited better performances than the colorimetric method, both techniques could be used indifferently.

Dose-effect relation between regular consumption of 100% cocoa powder and blood pressure in young, healthy black Africans.

BACKGROUND: Some previous works have focused on dose-response relationship between cocoa consumption and blood pressure in Caucasians. As black subjects have lower nitric oxide bioavailability, the aim of this work was to determine the dose-effect relation between cocoa and blood pressure in black Africans. METHOD: One hundred and thirty healthy black African males aged 18-30 were randomly assigned into four groups: three groups consuming 10 g, 5 g, or 2 g of cocoa powder daily for three weeks and one control group that did not consume cocoa. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were measured on day 1 (D1, before any subject consumed cocoa), D8, D15, and D22. Means of the parameters at each of the four visits and changes of the means were compared among the groups. RESULTS: Significant decrease in SBP was noted in consumers of 10 g compared to controls in the 1st week, and compared to consumers of 2 g in the 2nd and 3rd weeks of follow-up. Means and changes of DBP were statistically similar among the four groups. CONCLUSION: Among our cohort, decrease in SBP was significantly greater in the heavy cocoa consumer group (10 g) compared to the low consumer group (2 g), but there was no statistically significant difference when compared with the intermediate consumer group (5 g). The dose-response relationship between cocoa consumption and changes in SBP was not linear. No relationship was found between cocoa consumption and DBP.

Weekly Physiological Changes in Blood Pressure During Three Weeks Daily Consumption of 10 Grams of Cocoa Powder Among Young Black Africans in Côte d'Ivoire.

BACKGROUND: In Caucasians, regular consumption of cocoa induces a drop in arterial blood pressure via an increase in nitric oxide (NO) production. However, black individuals have a different NO biodisponibility compared to Caucasians. The aim of this study was to determine, in black Africans, the physiological variations in arterial blood pressure among cocoa consumers. METHOD: In total, 49 male black African volunteers, aged between 18 and 30 years old, were randomized into two groups; those consuming 10 g of cocoa powder per day (1,680 mg of flavonoids per day) for 3 weeks (consumer group), and those not consuming cocoa (control group). Systolic (SBP) and diastolic blood pressures (DBP), and heart rate (HR) were measured in the morning on an empty stomach (fasting), on day (D) 1 (without cocoa), D8, D15, and D22. Data were collected by groups and by subgroups established according to the level of SBP, DBP, or HR on D1. The means and variations of the means (between D1 and the subsequent days) of the recorded parameters were calculated and compared between groups and between subgroups. RESULTS: On D8, the variations in SBP in the consumer group were significantly different from the control group (-3.72 ± 6.01 versus 0.57 ± 6.66 mmHg; p = 0.02). Between the control and consumer subgroups according to SBP, no statistical difference in the means or variations in SBP was noted. On D8 and D22, the variations in the SBP of consumers with SBP ≥ 110 mmHg on D1 were significantly different from those of other consumers (D8: -6.55 ± 5.96 versus -1.1 ± 4.93 mmHg; p = 0.01; D22: -6.63 ± 7.77 versus 0.35 ± 5.58 mmHg; p = 0.01). In the subgroups with a DBP < 75 mmHg on D1, the mean DBP of the consumers was significantly lower than that of the controls on D8 (65 ± 5 versus 69 ± 6 mmHg; p = 0.03). CONCLUSION: In young black African men living in Côte d'Ivoire, regular consumption of cocoa resulted in a decrease in SBP and DBP. The decrease in SBP appeared to be greater the higher the baseline SBP was.

Effect of a bis-thiazolium compound on the biosynthesis of Plasmodium falciparum phospholipids.

In the eukaryotic cell, phospholipids can be biosynthesized by two pathways, one from choline and the other one from ethanolamine. The functional effectiveness of each pathway depends on the type of the cell. Thiazolium designed-drugs have shown, under in vivo conditions, antiplasmodial and antimalarial activities with inhibition of the phospholipids biosynthesis. This study aimed to discover the pathways involved in the biosynthesis of phospholipids in Plasmodium and deduce the biochemical steps inhibited by T4, a bis-thiazolium bromide drug. We compared the uptake of radiolabeled precursors and their selective incorporation in the phospholipids of cultured Plasmodium-infected and -uninfected erythrocytes which revealed that phosphatidylcholine of Plasmodium is synthesized both from choline and ethanolamine (4.7 vs 1.9 nmol/10(10) cells x h(-1)). T4 has no effect on the biosynthesis of phosphatidylethanolamine but T4 inhibited, in a selective way, the in vitro uptake of choline. However no enzymes in the biosynthesis of phospholipids seem to be inhibited by T4 but rather an inhibition of choline entry into the parasite.

[Immune, inflammatory, and nutritional protein profile in children with iron deficiency in Côte d'Ivoire]. / Déficit en fer, profil protéique immunitaire, inflammatoire et nutritionnel chez l'enfant de Côte-d'Ivoire.

Throughout the world and particularly in sub-Saharan Africa, deficiencies in trace elements constitute a real public health problem because of the insufficient nutritional quality of food. These trace elements are necessary for many of the body's biochemical reactions. The role of microelements such as vitamin A and zinc has been established in the functioning of the immune system and secretion of inflammatory reaction proteins, but the role of iron in these functions remains to be elucidated. The sample consists of 186 children (3/4) 80 with an iron deficiency and 106 with normal iron status. They range in age from 5 to 15 years and all attend school in the department of Adzope. The study excluded all children with parasites that might affect blood iron, protein and other hematological indicators, in particular, Plasmodium falciparum, Giardia intestinalis, Trichomonas intestinalis, Ascaris lumbricoides, and Ancylostoma. Inflammatory, immune and nutritional proteins were measured by radial immunodiffusion (Mancini's method). Ferritin was measured by a specific immunoenzymatic assay. Hematological indicators were tested by an automatic blood cell counter. Nutritional status was estimated by the weight/height ratio (W/H). This analysis showed that iron deficiency was associated with reduced IgG levels (p < 0.05), although immunoglobulins A and M remained stable (p > 0.05. Iron deficiency was also associated with reduced levels of thyroxine-binding prealbumin (TBPA) and albumin (p < 0.05). Inflammatory proteins did not differ significantly between the two groups (p > 0.05). Furthermore, the prognostic inflammatory and nutritional index (PINI) did not show any inflammatory, vital or nutritional risk, because it was lower than or equal to 2. Finally, malnutrition was not observed in the iron-deficient children: the difference in the weight/height ratio (W/H = 96.58 +/- 2.4%) between the children with iron deficiency and those with normal iron status (98.7 +/- 4.3%) did not differ significantly. The reduced IgG associated with iron deficiency may be attributed to the role that iron plays in the proliferation and maturation of lymphocytes. Reduced iron levels would thus lead to slowing down the hematopoietic mechanism, resulting in a decrease in B lymphocyte production and thus inevitably a reduction in IgG synthesis. The reduction in albumin and TBPA associated with the iron deficiency but in the absence of any sign of malnutrition (W/H > 96%) or inflammatory risk (PINI < 2) in either study group shows that iron may play a dominant role during protein synthesis. Iron deficiency might limit the energy of cellular tissues, leading to a reduction in RNA activity (transcription and translation), which would in turn decrease ribosome activity in tissues and thus reduce amino acid synthesis in cells, resulting in the reduction observed in protein synthesis. The lack of difference between the study groups in inflammatory proteins, notably CRP and alpha1-GPA, indicates that iron deficiency does not appear to be related to an inflammatory process. This study of children without any apparent clinical signs of iron deficiency shows that such a deficiency may be associated with a disruption in protein production. The proteins concerned include IgG, TBPA and albumin. The public authorities should pay particular attention to improving children's diets, especially their micronutrient levels, including for iron, vitamin A and zinc.

A systematic approach to understand the mechanism of action of the bisthiazolium compound T4 on the human malaria parasite, Plasmodium falciparum.

BACKGROUND: In recent years, a major increase in the occurrence of drug resistant falciparum malaria has been reported. Choline analogs, such as the bisthiazolium T4, represent a novel class of compounds with strong potency against drug sensitive and resistant P. falciparum clones. Although T4 and its analogs are presumed to target the parasite's lipid metabolism, their exact mechanism of action remains unknown. Here we have employed transcriptome and proteome profiling analyses to characterize the global response of P. falciparum to T4 during the intraerythrocytic cycle of this parasite. RESULTS: No significant transcriptional changes were detected immediately after addition of T4 despite the drug's effect on the parasite metabolism. Using the Ontology-based Pattern Identification (OPI) algorithm with an increased T4 incubation time, we demonstrated cell cycle arrest and a general induction of genes involved in gametocytogenesis. Proteomic analysis revealed a significant decrease in the level of the choline/ethanolamine-phosphotransferase (PfCEPT), a key enzyme involved in the final step of synthesis of phosphatidylcholine (PC). This effect was further supported by metabolic studies, which showed a major alteration in the synthesis of PC from choline and ethanolamine by the compound. CONCLUSION: Our studies demonstrate that the bisthiazolium compound T4 inhibits the pathways of synthesis of phosphatidylcholine from choline and ethanolamine in P. falciparum, and provide evidence for post-transcriptional regulations of parasite metabolism in response to external stimuli.

[Reversible immunosuppression, liver and kidney markers, calcium and phosphorus in the healthy rabbit]. / Immunosuppression reversible, marqueurs du foie, des reins et metabolisme phosphocalcique chez le lapin sain.

AIM: The aim of this study was to determine one or several doses of Methylprednisolone ( MP) who leads a long time of immunosuppression without disrupting phosphor and calcium, liver and kidney markers at the healthy rabbit. MATERIAL AND METHODS: This study was made to fifteen rabbit. Five (5) batches were constituted according to Nacl and Methylpredmisolone administered dose by body weight. Control batch ( Nacl 0,9%); batch I (2,5mg / kg MP); batch II ( 5mg / kg MP); batch III ( 10mg / kg MP) and batch IV ( 15 mg / kg MP). Biochemical parameters were measured by chemical and enzymatic methods. RESULTS: The results of this study showed an immunosuppression during seven days with 10 and 15 mg / kg of MP doses (P < 0.05). The biochemical disturbances were only observed with 15 mg / kg dose where calcium was lowered to day 15 and TGO increased to day 3 according to day 0 (P < 0.05). CONCLUSION: This study showed that the doses which lead a long time of immunosuppression ( 7 days) are 10 and 15 mg / kg of MP, then the dose which does not disrupt the biochemical parameters is 10 mg / kg of MP.

[Effect of the minor and moderate malnutrition on immunity, inflammatory and nutritional proteins at Côte d'Ivoire child]. / Effet des Malnutritions Mineure et Moderee sur les Proteines Immunitaires, Inflammatoires et Nutritionnelles Chez L'Enfant en Cote D'Ivoire.

This study was realiszed in Côte d'Ivoire at the children from 5 to 15 years old. The purpose of this study was to determine the alteration of immunity, inflammatory and nutritional proteins at 142 children (30 minor and 12 moderated malnutrition). The nutritional state or the state of malnutrition was to appreciate by Weight/height ratio which is the most usued by far. Immunity, inflammatory and nutritional proteins were measured by radical immunodiffusion according to Mancini. The results of this study showed that the Albumin was lowered (p<0.01) during the moderate and minor malnutrition in comparison to the children.On the other hand, it was observed an increased of CRP in both forms of malnutrition (p<0.05).Also, the index prognostic nutritional and inflammatory who, allows to appreciate simultaneously the inflammatory and nutritional state (PINI) was increased in the malnutrition moderated with regard to the minor malnutrition and to the children (p<0.05).Besides, immunity proteins remain unchanged in both forms of malnutrition in comparison to the healthy children (p<0.05). Finally, this study shows that the moderate and malnutrition are associated with an inflammatory process and of protein consumption notably the Albumin .These observations suggest that determination of the nutritional status requires the use of the clinical method coupled with the biological examinations.