Jorge Andrade Pinto

Search for poliovirus carriers among people with primary immune deficiency diseases in the United States, Mexico, Brazil, and the United Kingdom.

OBJECTIVE To estimate the rate of long-term poliovirus excretors in people known to have B-cell immune deficiency disorders. METHODS An active search for chronic excretors was conducted among 306 persons known to have immunoglobulin G (IgG) deficiency in the United States, Mexico, Brazil, and the United Kingdom, and 40 people with IgA deficiency in the United States. Written informed consent or assent was obtained from the participants or their legal guardians, and the studies were formally approved. Stool samples were collected from participants and cultured for polioviruses. Calculation of the confidence interval for the proportion of participants with persistent poliovirus excretion was based on the binomial distribution. FINDINGS No individuals with long-term excretion of polioviruses were identified. Most participants had received oral poliovirus vaccine (OPV) and almost all had been exposed to household contacts who had received OPV. Polioviruses of recent vaccine origin were transiently found in four individuals in Mexico and Brazil, where OPV is recommended for all children. CONCLUSION Although chronic poliovirus excretion can occur in immunodeficient persons, it appears to be rare.

Immunochemotherapy for cutaneous leishmaniasis: a controlled trial using killed Leishmania (Leishmania) amazonensis vaccine plus antimonial

Background Leishmaniasis is endemic in 88 countries in the world, and 350 million individuals are at risk of acquiring the disease. Treatment for American cutaneous leishmaniasis (ACL) is long, expensive, and associated with important side‐effects.

Infectious Disease Morbidity Among Young HIV-1–Exposed But Uninfected Infants in Latin American and Caribbean Countries: The National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study

OBJECTIVE. The goal was to describe the frequency, characteristics, and correlates of infectious disease morbidity during the first 6 months of life among HIV-1–exposed but uninfected infants. METHODS. The study population consisted of infants enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study who were HIV-1 uninfected and had follow-up data through the 6-month study visit. Definitive and presumed infections were recorded at study visits (birth, 6–12 weeks, and 6 months). RESULTS. Of 462 HIV-1–uninfected infants with 11644 child-weeks of observation, 283 experienced ≥1 infection. These 283 infants experienced 522 infections (1.8 infections per infant). The overall incidence rate of infections was 4.5 cases per 100 child-weeks of observation. Overall, the most common infections were skin or mucous membrane infections (1.9 cases per 100 child-weeks) and respiratory tract infections (1.7 cases per 100 child-weeks). Thirty-six percent of infants had >1 respiratory tract infection (1.8 cases per 100 child-weeks). Incidence rates of upper and lower respiratory tract infections were similar (0.89 cases per 100 child-weeks and 0.9 cases per 100 child-weeks, respectively). Cutaneous and/or oral candidiasis occurred in 48 neonates (10.3%) and 92 older infants (19.3%). Early neonatal sepsis was diagnosed in 12 infants (26.0 cases per 1000 infants). Overall, 81 of 462 (17.5%) infants were hospitalized with an infection. Infants with lower respiratory tract infections were hospitalized frequently (40.7%). The occurrence of ≥1 neonatal infection was associated with more-advanced maternal HIV-1 disease, tobacco use during pregnancy, infant anemia, and crowding. Lower maternal CD4+ cell counts, receipt of intrapartum antibiotic treatment, and country of residence were associated with postneonatal infections. CONCLUSIONS. Close monitoring of HIV-1–exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.

Pharmacokinetics, safety and efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week results.

Objective:To investigate pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r)-based therapy in HIV-1-infected infants 6 weeks to 6 months of age. Methods:A prospective, multicenter, open-label trial of 21 infants with HIV-1 RNA > 10 000 copies/ml and treated with LPV/r 300/75 mg/m2 twice daily plus two nucleoside reverse transcriptase inhibitors. Intensive pharmacokinetic sampling was performed at 2 weeks and predose concentrations were collected every 8 weeks; safety and plasma HIV-1 RNA were monitored every 4–12 weeks for 24 weeks. Results:Median age at enrollment was 14.7 weeks (range, 6.9–25.7) and 19/21 completed ≥ 24 weeks of study. Although LPV/r apparent clearance was slightly higher than in older children, the median area under the concentration–time curve 0–12 h (67.5 μg.h/ml) was in the range reported from older children taking the recommended dose of 230/57.5 mg/m2. Predose concentrations stabilized at a higher level after the first 2 weeks of study. In as-treated analysis at week 24, 10/19 (53%) had plasma HIV-1 RNA < 400 copies/ml (median change, −3.33 log10 copies/ml); poor adherence contributed to delayed viral suppression, which improved with longer follow-up. Three infants (14%) had transient adverse events of grade 3 or more that were possibly related to study treatment but did not require permanent treatment discontinuation. Conclusion:Despite higher clearance in infants 6 weeks to 6 months of age, a twice daily dose of 300/75 mg/m2 LPV/r provided similar exposure to that in older children, was well tolerated and provided favorable virological and clinical efficacy.

Impact of highly active antiretroviral therapy (HAART) on the incidence of opportunistic infections, hospitalizations and mortality among children and adolescents living with HIV/AIDS in Belo Horizonte, Minas Gerais State, Brazil

The impact of highly active antiretroviral therapy (HAART) can be evaluated using indicators, such as rates of opportunistic infections, hospitalizations by cause of infection, and associated death. This study aimed to estimate the impact of HAART on the incidence of these indicators, in children and adolescents with HIV/AIDS. It was a hybrid cohort study; 371 patients were followed from 1989 to 2003. In December 2003, 76% of the patients were still being followed, while 12.1% had died, 9.5% had dropped out, and 2.4% had been transferred. The overall rate of opportunistic infections was 18.32 infections/100 persons-year and 2.63 in the pre- and post-HAART periods, respectively. In the multivariate analysis, the risk of developing an opportunistic infection was 5.4 times greater and 3.3 times greater for hospitalization risk before HAART. Respiratory causes represented 65% of the hospitalizations and they were reduced by 44.6% with therapeutic intervention. The average hospital stay of 15 days was reduced to 9. There was a post-HAART decline in deaths of 38%. This study demonstrates the effectiveness of HAART in significantly reducing opportunistic infections, hospitalizations, and deaths in this Brazilian cohort.

Immunochemotherapy in American Cutaneous Leishmaniasis: Immunological Aspects before and after Treatment

In this study, we evaluated the immune response of patients suffering from cutaneous leishmaniasis treated with two distinct protocols. One group was treated with conventional chemotherapy using pentavalent antimonium salts and the other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was combined with the antimonium salt. Our results show that, although no differences were observed in the necessary time for complete healing of the lesions between the two treatments, peripheral blood mononuclear cells from patients treated by chemotherapy showed smaller lymphoproliferative responses at the end of the treatment than those from patients in the immunochemotherapy group. Furthermore, IFN-gamma production was also different between the two groups. While cells from patients in the chemotherapy group produced more IFN-gamma at the end of treatment, a significant decrease in this cytokine production was associated with healing in the immunochemotherapy group. In addition, IL-10 production was also less intense in this latter group. Finally, an increase in CD8+ -IFN-gamma producing cells was detected in the chemotherapy group. Together these results point to an alternative treatment protocol where healing can be induced with a decreased production of a potentially toxic cytokine.

Avaliação de atopia em crianças respiradoras bucais atendidas em centro de referência

OBJECTIVE: A mouth breather is someone who uses his/her oral cavity as main airway during breathing. This is a syndrome with several etiologies, but allergic rhinitis plays a key role due to its high prevalence. The aim of this study was to assess the presence of atopy among mouth-breathing patients referred to a tertiary care center in the metropolitan region of Belo Horizonte, Brazil. METHODS: Cross-sectional, descriptive study carried out at Hospital das Clinicas of Universidade Federal de Minas Gerais. Patients aged 2 to 12 years, admitted between November 2002 and April 2004, were included. Parents or surrogates completed a comprehensive questionnaire, and patients were submitted to a skin test for inhalant allergens. A total of 140 patients participated in the study. Those with a positive result for at least one allergen were regarded as atopic. The statistical analyses were made using SPSS, with univariate analyses followed by logistic regression. RESULTS: Of 140 patients, 44.3% (62/140) obtained positive results on the allergic test. Mites were the most predominant allergens, with a positive rate of 100% among atopic patients. In the multivariate analysis, atopy was significantly associated with the male sex (p = 0.05), presence of asthma (p = 0.014), lower number of people sleeping in the same room with the patient (p = 0.005), absence of passive smoking (p = 0.005) and absence of sleep apnea (p = 0.003). CONCLUSION:The high prevalence of positive results on the allergic test highlights the importance of allergologic investigation in mouth-breathers, since allergy has specific treatments that may reduce morbidity in these patients when properly used.

Early Initiation of Lopinavir/Ritonavir in Infants Less Than 6 Weeks of Age: Pharmacokinetics and 24 Week Safety and Efficacy

Background: With increasing recognition of the benefits of early antiretroviral therapy initiation in perinatally HIV-infected infants, data are needed regarding the pharmacokinetics (PK), safety, and efficacy of recommended first-line protease inhibitors such as lopinavir/ritonavir (LPV/r). Methods: A prospective, phase I/II, open-label, dose-finding trial evaluated LPV/r at a dose of 300/75 mg/m2 twice daily plus 2 nucleoside analogs in HIV-1-infected infants ≥14 days to <6 weeks of age. Intensive 12-hour PK evaluations were performed after 2 weeks of LPV/r therapy, and doses were modified to maintain LPV predose concentrations >1 μg/mL and area under the curve (AUC) <170 μg hr/mL. Results: Ten infants enrolled [median age 5.7 (range, 3.6–5.9) weeks] with median HIV-1 RNA of 6.0 (range, 4.7–7.2) log10 copies/mL; all completed 24 weeks of follow-up. Nine completed the intensive PK evaluation at a median LPV dose of 267 (range, 246–305) mg/m2 q12 hours; median measures were AUC = 36.6 (range, 27.9–62.6) μg hr/mL; predose concentration = 2.2 (range, 0.99–4.9) μg/mL; maximum concentration = 4.76 (range, 2.84–7.28) μg/mL and apparent clearance (L/h/m2) = 6.75 (range, 2.79–12.83). Adverse events were limited to transient grade 3 neutropenia in 3 subjects. By week 24, 2 of 10 subjects had experienced a protocol-defined virologic failure. Conclusions: Although the LPV AUC in this population was significantly lower than that observed in infants ages 6 weeks to 6 months, LPV/r-based antiretroviral therapy in doses of 300/75 mg/m2 BID was well tolerated and resulted in virologic control in 8 of 10 infants by 24 weeks. Additional investigation is needed to understand the long-term implications of the lower LPV exposure in this age group.

Evaluation of atopy among mouth-breathing pediatric patients referred for treatment to a tertiary care center

OBJECTIVE A mouth breather is someone who uses his/her oral cavity as the main airway during breathing. This is a syndrome with several etiologies, but allergic rhinitis plays a key role due to its high prevalence. The aim of this study was to assess the presence of atopy among mouth-breathing patients referred to a tertiary care center in the metropolitan region of Belo Horizonte, Brazil. METHODS Cross-sectional, descriptive study carried out at Hospital das Clínicas of Universidade Federal de Minas Gerais. Patients aged 2 to 12 years, admitted between November 2002 and April 2004, were included. Parents or surrogates completed a comprehensive questionnaire, and patients were submitted to a skin test for inhalant allergens. A total of 140 patients participated in the study. Those with a positive result for at least one allergen were regarded as atopic. The statistical analyses were made using SPSS, with univariate analyses followed by logistic regression. RESULTS Of 140 patients, 44.3% (62/140) obtained positive results on the allergic test. Mites were the most predominant allergens, with a positive rate of 100% among atopic patients. In the multivariate analysis, atopy was significantly associated with the male sex (p = 0.05), presence of asthma (p = 0.014), lower number of people sleeping in the same room with the patient (p = 0.005), absence of passive smoking (p = 0.005) and absence of sleep apnea (p = 0.003). CONCLUSION The high prevalence of positive results on the allergic test highlights the importance of allergologic investigation in mouth-breathers, since allergy has specific treatments that may reduce morbidity in these patients when properly used.

Management of human immunodeficiency virus-infected pregnant women at Latin American and Caribbean sites.

OBJECTIVE: To describe the management of a population of human immunodeficiency virus (HIV)–infected pregnant women in Latin America and the Caribbean, and to assess factors associated with maternal viral load of 1,000 copies/mL or more and with infant HIV-1 infection. METHODS: Eligibility criteria were enrollment in the prospective cohort study as of March 2006; delivery of a liveborn, singleton infant; and completion of the 6-month postpartum or postnatal visit. RESULTS: Of 955 women enrolled in Argentina, the Bahamas, Brazil, and Mexico, 770 mother-infant pairs were eligible. At enrollment, most women were relatively healthy (87% asymptomatic, 59% with viral load less than 1,000 copies/mL, 62% with CD4+% of 25% or more). Most (99%) received antiretrovirals during pregnancy (56% prophylaxis, 44% treatment), and 38% delivered by cesarean before labor and before ruptured membranes. Only 18% of women had a viral load of 1,000 copies/mL or more after delivery (associated in adjusted analyses with receipt of antiretrovirals at conception, CD4+% [lower], viral load [higher], and country at enrollment, enrollment late in pregnancy, and inversely related to antiretroviral regimen [two nucleoside or nucleotide analogue reverse transcriptase inhibitors plus one nonnucleoside reverse transcriptase inhibitor] during pregnancy). None of the infants breastfed, and all received antiretroviral prophylaxis. Seven infants became infected (0.91%; 95% confidence interval 0.37–1.86). Low birth weight infants and those whose mothers had a low CD4+% at hospital discharge after delivery and were not receiving antiretrovirals at enrollment were at higher risk of HIV infection. CONCLUSION: Only a minority of women had a viral load of 1,000 copies/mL or more around delivery, and mother-to-child transmission of HIV occurred rarely (1%). LEVEL OF EVIDENCE: II