The population pharmacokinetics of dapsone were examined in human immunodeficiency virus-infected patients receiving dapsone at a dosage of 100 mg twice weekly for the prevention of Pneumocystis carinii pneumonia. Nonlinear mixed-effect modeling was used to determine the best pharmacostatistical model for the data. A one-compartment open model with first-order absorption and elimination was used as the structural pharmacokinetic model. Several covariates were tested for their influence on pharmacokinetic parameters. Rifampin was found to increase the values of clearance/bioavailability (CL/F) and volume of distribution/ bioavailability (V/F) by approximately 70%. CL/F and V/F were 1.83 liters/h and 69.6 liters, respectively, for patients not taking rifampin. The effect of rifampin on the pharmacokinetic parameters of dapsone was appreciably less than expected on the basis of studies with healthy volunteers. Increased bilirubin levels were associated with a significant decrease in the absorption rate constant (K a ). However, this finding may be considered clinically irrelevant because the post hoc Bayesian estimates of K a for patients with high bilirubin levels (>1.2 mg/dl) were at the lower bound of the values for patients with normal bilirubin levels. The value of K a was 0.957 h ؊1 for a patient with a bilirubin level of 0.7 mg/dl. After inclusion of covariates in the model, the interpatient variability was 35% for CL/F, not significant for V/F, and 85% for K a . Simulation of plasma concentration-versus-time curves indicated that the administration of 100 mg of dapsone biweekly is associated with sustained dapsone levels in the plasma of the majority of the patients. Dosage adjustments for patients concomitantly treated with rifampin may be necessary.
Vaccine-preventable diseases and their related complications are associated with increased morbidity and mortality in patients with altered immunocompetence. Optimised immunisation in this patient population is challenging because of limited data from vaccine trials, suboptimal vaccine efficacy and safety concerns. Reliable efficacy data are lacking among patients with altered immunocompetence, and existing recommendations are mainly based on expert consensus and may vary geographically. Inactivated vaccines can be generally used without risks in this group, but their efficacy may be reduced, and immunisation schedules vary according to local guidelines, age, and type and stage of the underlying disease. Live vaccines, if indicated, should be administered with care because of the risk of vaccine-associated disease. We have reviewed the current evidence on vaccination principles and recommendations in adult patients with secondary immunodeficiencies, including asplenia, HIV infection, stem cell and solid organ transplant, haematological malignancies, inflammatory bowel disease and other chronic disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00404-y.
With the settlement of increasing numbers of immigrants from tropical African countries into Italy over the last decade, the epidemiologic pattern of imported malaria underwent significant change. Italian immigrants originating from endemic areas who revisit their country of origin have exhibited an increasing incidence of malaria: the Italian Ministry of Health recorded an increase of from 14% in 1986 to 40.4% in 1991. This retrospective study reviews the epidemiology of all malaria cases recorded from 1988 to 1991 in a regional reference center in North Eastern Italy. Epidemiologic factors, including the details of their travel experience, were examined for all cases, and the relation of immigrants to Italian-born citizens were compared. Of the 100 cases recorded during this period, 36 were diagnosed in 1988-1989 and 64 in 1990-1991. Immigrants accounted for six times more cases during the latter than during the former time period. Compared to nonimmune short-term travelers, immigrants experienced significantly milder forms of the disease and lower levels of parasitemia (Plasmodium falciparum) on admission. Notably, 10 cases of malaria in immigrants were not recognized at first observation on microbiology. With the advent of this new risk group of immigrants that originate from endemic countries, especially those making occasional short visits to their native countries, this new epidemiologic profile of malaria imported into Italy shows the need for improvement in the areas of prophylaxis, pretravel education, and diagnostic services.
Stereotactic brain biopsy has high diagnostic efficacy and clinical benefit in carefully selected human immunodeficiency virus-infected patients. The procedure should be performed essentially in patients with contrast-enhancing lesions on computed tomography who have a high frequency of treatable cerebral diseases.
Risk of MTCT in Italy is ongoing, even in recent years, underling the need for implementation of the current screening program in pregnancy. Large combination neonatal prophylaxis use in preterm infants was observed, even if data on safety and efficacy in prematures are poor.
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