Active tuberculosis in a patient with Hodgkin's disease. A case report

We report a case of active tuberculosis in a patient with Hodgkin's disease. The two diagnoses were established simultaneously at the Respiratory Disease Unit of the Yalgado National Hospital, Burkina Faso. The clinical presentation was misleading as the signs and symptoms of the two disease are similar. Certain diagnosis was established after isolation of tuberculosis bacilli and histocytology findings for Hodgkin's disease. Both diseases are potentially curable. The clinical course depends on early diagnosis and treatment.     

Caseous pneumonia in a 14-month-old infant

We report a case of caseous pneumonia in a 14-month-old HIV-negative infant. This clinical picture is usually observed in healthy young adults, rarely in infants. The clinical and radiological signs of caseous pneumonia often simulate acute non-tuberculous respiratory disease. Bacteriological confirmation is required, but the diagnosis can be suggested in case of a pulmonary syndrome with no bacterial isolate and unresponsive to well-conducted antibiotic therapy. The clinical course is rapid with caseous involution of the lung. Early diagnosis is required for specific curative treatment and to limit sequelae.     

Clinical trial: interferon alpha-2b continuous long-term therapy vs. repeated 24-week cycles for re-treating chronic hepatitis C

Background  Treatment options are limited for patients with hepatitis C virus who do not experience sustained viral eradication with pegylated interferon and ribavirin therapy.
Aim  To compare, in an open-label, randomized study, long-term continuous interferon alpha-2b treatment with repeated 24-week courses in patients with chronic hepatitis C virus that relapsed after prior interferon monotherapy.
Methods  A total of 499 patients received 24 weeks of interferon alpha-2b, 3 MIU administered 3 TIW. Responders (normal alanine aminotransferase and negative hepatitis C virus -RNA, n  =   244) were then randomized to continuous interferon therapy (1, 2 or 3 MIU TIW depending on response) or cyclical therapy (3 MIU TIW for 24 weeks per relapse). Mean Knodell inflammation (I + II + III) and necrosis (IV) scores at baseline vs. year 2 were compared.
Results  Patients receiving continuous low-dose therapy vs. cycled therapy had larger reductions in inflammation (−3.9 vs. −3.1) and fibrosis (−0.49 vs. −0.24). Among both groups, the mean change was −3.4 for inflammation and −0.36 for fibrosis. Overall, 73% (95% CI: 67–79) of patients experienced reduced inflammation and 28% (95% CI: 22–34) had reduced fibrosis.
Conclusions  Our results suggest hepatitis C virus patients experiencing viral suppression during long-term maintenance therapy with interferon demonstrate histological improvement. Further prospective trials testing this hypothesis are in progress.     

Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa

Metabolism of the antimalarial drug amodiaquine (AQ) into its primary metabolite, N-desethylamodiaquine, is mediated by CYP2C8. We studied the frequency of CYP2C8 variants in 275 malaria-infected patients in Burkina Faso, the metabolism of AQ by CYP2C8 variants, and the impact of other drugs on AQ metabolism. The allele frequencies of CYP2C8*2 and CYP2C8*3 were 0.155 and 0.003, respectively. No evidence was seen for influence of CYP2C8 genotype on AQ efficacy or toxicity, but sample size limited these assessments. The variant most common in Africans, CYP2C8(*)2, showed defective metabolism of AQ (threefold higher K(m) and sixfold lower intrinsic clearance), and CYP2C8(*)3 had markedly decreased activity. Considering drugs likely to be coadministered with AQ, the antiretroviral drugs efavirenz, saquinavir, lopinavir, and tipranavir were potent CYP2C8 inhibitors at clinically relevant concentrations. Variable CYP2C8 activity owing to genetic variation and drug interactions may have important clinical implications for the efficacy and toxicity of AQ.     

Anti-Pfs25 Human Plasma Reduces Transmission of Plasmodium falciparum Isolates That Have Diverse Genetic Backgrounds

Pfs25 is a leading candidate for a malaria transmission-blocking vaccine whose potential has been demonstrated in a phase 1 trial with recombinant Pfs25 formulated with Montanide ISA51. Because of limited sequence polymorphism, the anti-Pfs25 antibodies induced by this vaccine are likely to have transmission-blocking or -reducing activity against most, if not all, field isolates. To test this hypothesis, we evaluated transmission-blocking activities by membrane feeding assay of anti-Pfs25 plasma from the Pfs25/ISA51 phase 1 trial against Plasmodium falciparum parasites from patients in two different geographical regions of the world, Thailand and Burkina Faso. In parallel, parasite isolates from these patients were sequenced for the Pfs25 gene and genotyped for seven microsatellites. The results indicate that despite different genetic backgrounds among parasite isolates, the Pfs25 sequences are highly conserved, with a single nonsynonymous nucleotide polymorphism detected in 1 of 41 patients in Thailand and Burkina Faso. The anti-Pfs25 immune plasma had significantly higher transmission-reducing activity against parasite isolates from the two geographical regions than the nonimmune controls (P < 0.0001).     

Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation

Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis.     

Novel controlled attenuation parameter for noninvasive assessment of steatosis using Fibroscan(®): validation in chronic hepatitis C

Summary. A novel controlled attenuation parameter (CAP) has been developed for Fibroscan^® to assess liver steatosis, simultaneously with liver stiffness measurement (LSM). We assessed CAP diagnostic accuracy in a large cohort of patients with chronic hepatitis C (CHC) virus. A total of 615 patients with CHC, who underwent both Fibroscan^® and liver biopsy, were analysed. Fibrosis was graded using METAVIR score. Steatosis was categorized by visual assessment as S₀: steatosis in <10% of hepatocytes, S₁: 11–33%, S₂: 34–66% and S₃: 67–100%. Performances of CAP and liver stiffness were determined using receiver operating characteristic (ROC) curve analysis and cross‐validated using the bootstrap method. The Obuchowski measure was used to assess overall accuracy of CAP and to differentiate between steatosis grades. In multivariate analysis, CAP was related to steatosis (P < 10^?15) independently of fibrosis stage (which was related to LSM). The areas under ROC curves using CAP to detect steatosis were 0.80 (95% CI, 0.75–0.84) for S ≥ S₁, 0.86 (0.81–0.92) for S ≥ S₂ and 0.88 (0.73–1) S = S₃. CAP exhibited a good ability to differentiate steatosis grades (Obuchowski measure = 0.92). Performance of LSM for fibrosis assessment confirmed results from previous studies. CAP is a novel tool to assess the degree of steatosis and both fibrosis and steatosis can be evaluated noninvasively during the same procedure using Fibroscan^®, in patients with CHC.     

Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow

Chronic hepatitis C is one of the leading causes of chronic liver disease with approximately 170 million people infected worldwide. Sustained virological response (SVR) is equivalent to viral eradication and associated with a reduction in the risk of cirrhosis. Nowadays the treatment for hepatitis C virus (HCV) genotype 1 chronic infection is the addition of direct acting antivirals (DAA) with a protease inhibitor (telaprevir or boceprevir) to the pegylated interferon (PEG-IFN) plus ribavirin (RBV) regimen. The future management of patients with these new molecules will require good clinical practice, knowledge of indications, management of side effects and monitoring for antiviral resistance. Certain major medical needs are still unmet and require studies in special populations (HIV-HCV coinfected patients, transplanted patients, etc.…) and also in HCV non-1 genotype patients and in non-responders. Second generation DAA are in development. Combinations of antivirals with additive potency that lack cross resistance and with a good safety profile may provide new regimens in the future to make HCV the first chronic viral infection eradicated worldwide with a finite duration of combination DAA therapy without IFN. The aim of this review is to summarize mechanisms of action and results obtained with DAAs.