Celina Maria Turchi Martelli

Potential plasma markers of type 1 and type 2 leprosy reactions: a preliminary report

BackgroundThe clinical management of leprosy Type 1 (T1R) and Type 2 (T2R) reactions pose challenges mainly because they can cause severe nerve injury and disability. No laboratory test or marker is available for the diagnosis or prognosis of leprosy reactions. This study simultaneously screened plasma factors to identify circulating biomarkers associated with leprosy T1R and T2R among patients recruited in Goiania, Central Brazil.MethodsA nested case-control study evaluated T1R (n = 10) and TR2 (n = 10) compared to leprosy patients without reactions (n = 29), matched by sex and age-group (+/- 5 years) and histopathological classification. Multiplex bead based technique provided profiles of 27 plasma factors including 16 pro inflammatory cytokines: tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), interleukin (IL)- IL12p70, IL2, IL17, IL1 β, IL6, IL15, IL5, IL8, macrophage inflammatory protein (MIP)-1 alpha (MIP1α), 1 beta (MIP1β), regulated upon activation normal T-cell expressed and secreted (RANTES), monocyte chemoattractrant protein 1 (MCP1), CC-chemokine 11 (CCL11/Eotaxin), CXC-chemokine 10 (CXCL10/IP10); 4 anti inflammatory interleukins: IL4, IL10, IL13, IL1Rα and 7 growth factors: IL7, IL9, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF).ResultsElevations of plasma CXCL10 (P = 0.004) and IL6 (p = 0.013) were observed in T1R patients compared to controls without reaction. IL6 (p = 0.05), IL7 (p = 0.039), and PDGF-BB (p = 0.041) were elevated in T2R. RANTES and GMCSF were excluded due to values above and below detection limit respectively in all samples.ConclusionPotential biomarkers of T1R identified were CXCL10 and IL6 whereas IL7, PDGF-BB and IL6, may be laboratory markers of TR2. Additional studies on these biomarkers may help understand the immunopathologic mechanisms of leprosy reactions and indicate their usefulness for the diagnosis and for the clinical management of these events.

Genetic and immunological evidence implicates interleukin 6 as a susceptibility gene for leprosy type 2 reaction.

In leprosy, type 1 reaction (T1R) and type 2 reaction (T2R) are major causes of nerve injury and permanent disabilities. A previous study on plasma levels of 27 cytokines in patients with T1R or T2R and controls with nonreactional leprosy identified the gene for interleukin 6 (IL-6) as a candidate for genetic analysis. Two nested case-control studies were built from a cohort of 409 patients with leprosy from central Brazil, monitored for T1R and T2R. There was evidence for association between T2R and IL-6 tag single-nucleotide polymorphisms rs2069832 (P = .002), rs2069840 (P = .03), and rs2069845 (P = .04), with information on the entire IL-6 locus, as well as functional IL-6 variant rs1800795 (P = .005). Moreover, IL-6 plasma levels in patients with T2R correlated with IL-6 genotypes (P = .04). No association was found between IL-6 variants and T1R. Identifying genetic predictive factors for leprosy reactions may have a major impact on preventive strategies.

Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: Regional analyses according to the endemic context

OBJECTIVEnTo conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil.nnnMETHODSnAn age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South+Southeast (low endemicity) and one for the North+Northeast+Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real).nnnRESULTSnA universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R

Prevalence and incidence of dengue virus and antibody placental transfer during late pregnancy in central Brazil

16.89 (US

Modelling the Force of Infection for Hepatitis A in an Urban Population-Based Survey: A Comparison of Transmission Patterns in Brazilian Macro-Regions

7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs.nnnCONCLUSIONSnUniversal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program.

Dengue infection in pregnancy and transplacental transfer of anti-dengue antibodies in Northeast, Brazil

BackgroundMaternal dengue antibodies are considered to play a significant role in dengue pathogenesis among infants. Determining the transplacental specific antibody transfer is invaluable for establishing the optimal vaccination age among infants in endemic regions.MethodsWe conducted a cross-sectional study among pairs of maternal and corresponding umbilical cord blood samples in public hospitals. The prevalence and incidence of dengue infection were determined in 505 pairs of pregnant women and neonates during a large outbreak (2009–2010) in central Brazil. The women were interviewed at late pregnancy to assess current or past symptoms of dengue. All parturients and their neonates were screened using Dengue IgG Indirect ELISA (Panbio) to assess previous dengue exposure. A semi-quantitative measurement of the IgG antibody expressed by the index ratio was calculated using optical density (OD) values according to the manufacturer’s instructions. The studied population of parturients and their offspring was also screened for recent dengue infection by the Dengue IgM-capture ELISA (Panbio). Those participants with history of fever and two or more symptoms of dengue at least 10 days before the delivery were also tested for the dengue NS1 antigen using the Dengue Early ELISA (Panbio) and RT-PCR.ResultsThe mean maternal age was 25.8 (SDu2009=u20096.4), and 83.6% of deliveries were between 37 and 41 weeks. Approximately half of the 505 women and neonates were IgG-seropositive, yielding 99.3% co-positive mother-child frequency of antibody transfer (Kappau2009=u20090.96). The incidence of dengue infection was 2.8% (95% CI 1.4–4.4%) among the women considering 14 IgM-positive results and one DENV2 detected by RT-PCR. The dengue NS1 antigen was undetectable in the matched pairs.ConclusionThis study provides critical data on the prevalence of transplacental transferred maternal-infant anti-dengue antibodies and incidence of infection. The design of future vaccine trials should consider diverse regional epidemiological scenarios.

Costing Dengue Fever Cases and Outbreaks: Recommendations from a Costing Dengue Working Group in the Americas

Background This study aimed to identify the transmission pattern of hepatitis A (HA) infection based on a primary dataset from the Brazilian National Hepatitis Survey in a pre-vaccination context. The national survey conducted in urban areas disclosed two epidemiological scenarios with low and intermediate HA endemicity. Methods A catalytic model of HA transmission was built based on a national seroprevalence survey (2005 to 2009). The seroprevalence data from 7,062 individuals aged 5–69 years from all the Brazilian macro-regions were included. We built up three models: fully homogeneous mixing model, with constant contact pattern; the highly assortative model and the highly assortative model with the additional component accounting for contacts with infected food/water. Curves of prevalence, force of infection (FOI) and the number of new infections with 99% confidence intervals (CIs) were compared between the intermediate (North, Northeast, Midwest and Federal District) and low (South and Southeast) endemicity areas. A contour plot was also constructed. Results The anti- HAV IgG seroprevalence was 68.8% (95% CI, 64.8%–72.5%) and 33.7% (95% CI, 32.4%–35.1%) for the intermediate and low endemicity areas, respectively, according to the field data analysis. The models showed that a higher force of infection was identified in the 10- to 19-year-old age cohort (∼9,000 infected individuals per year per 100,000 susceptible persons) in the intermediate endemicity area, whereas a higher force of infection occurred in the 15- to 29-year-old age cohort (∼6,000 infected individuals per year per 100,000 susceptible persons) for the other macro-regions. Conclusion Our findings support the shift of Brazil toward intermediate and low endemicity levels with the shift of the risk of infection to older age groups. These estimates of HA force of infection stratified by age and endemicity levels are useful information to characterize the pre-vaccination scenario in Brazil.

Estimated Incidence and Genotypes of HIV-1 among Pregnant Women in Central Brazil

BACKGROUNDnDengue affects nearly 400 million people annually worldwide and considered one of the most serious health threats in tropical and subtropical countries.nnnOBJECTIVEnTo analyze the occurrence of dengue infection among the parturient who have formed the baseline of an ongoing birth cohort study in the city of Recife, Northeast of Brazil.nnnSTUDY DESIGNnFrom March 2011 to May 2012, we recruited 417 parturients with low-risk pregnancies at maternity ward who agreed to a follow-up of their babies. Dengue infection was accessed through DENV RT-PCR and anti-dengue antibodies (IgM and IgG). The prevalence of IgG antibodies in the parturients and their concepts were determined. The concordance among the pairs was tested using Kappa. The association of recent infection (IgM and/or DENV RT-PCR positive) with the maternal characteristics and clinical features of the neonates was analyzed through logistic regression.nnnRESULTSnThe prevalence of IgG antibodies in the maternal and cord blood samples was 95.1% (95% CI: 92.6-96.9%) and 95.8% (95% CI: 93.4-97.5%), respectively, with high agreement between maternal-cord pairs (Kappa=0.93). The prevalence of recent infection was 10.6% (95% CI: 7.9-14.2%) in the parturients. Reported fever during pregnancy was associated to recent infection (p=0.023).nnnCONCLUSIONnThe data draw attention for the high frequency of anti-dengue antibodies in the women studied and for the high occurrence of infection during pregnancy in this region of Brazil. There is a need for further studies to better characterize dengue infection in pregnant women.

Contributions from the systematic review of economic evaluations: the case of childhood hepatitis A vaccination in Brazil

OBJECTIVESnThe overall aim of this article was to present a step-by-step guideline for determining the costs associated with dengue in dengue-endemic countries of the Latin American and the Caribbean region and to illustrate how each of these steps can be applied in dengue costing studies.nnnMETHODSnAn expert panel was convened to develop standards for costing dengue so that over the next decade, decision makers will have access to improved information on the true cost of dengue in endemic countries of the Latin American and the Caribbean region. We described the outcome of the expert panel meeting, which resulted in the provision of a step-by-step dengue costing guideline that aims to provide direction to planners and program managers on how to estimate dengue economic burden studies, and provide a discussion forum of the methods used to cost dengue fever cases and outbreaks in a manner that should be accessible to persons with some familiarity with a cost study.nnnRESULTSnThe guideline includes nine sequential steps: 1) definition of the scope of the study; 2) identification of the target population; 3) description of the study perspective; 4) definition of the time horizon; 5) calculation of the sample size; 6) definition of the unit of analysis; 7) identification of the cost items; 8) measurement and valuation of the cost items; and 9) handling of uncertainty. The trade-off between accurate, patient-level cost estimates and data availability constraints is discussed.nnnCONCLUSIONSnThe current guideline is the result of constructive collaboration among a multidisciplinary research team to better ascertain the true economic burden of dengue across countries of the region.

Zika virus and microcephaly – Authors' reply

Objective To estimate the incidence of HIV-1 infection among pregnant women from central-western Brazil. Design Observational cross-sectional study. Methods A total of 54,139 pregnant women received antenatal HIV screening from a network of public healthcare centers in 2011. The incidence of confirmed HIV-1 infection was estimated using the Serological Testing Algorithms for Recent HIV Seroconversion (STARHS) methodology and BED-capture enzyme immunoassay (BED-CEIA). The yearly incidence was calculated, and adjusted incidence rates were estimated. For a subgroup of patients, protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and sequenced after performing a nested polymerase chain reaction. Results Of the participants, 20% had a pregnancy before the age of 18 and approximately 40% were experiencing their first pregnancy. Of the 54,139 pregnant women screened, 86 had a confirmed HIV-1 diagnosis, yielding an overall prevalence of 1.59 cases per 1000 women (95% CI 1.27–1.96). A higher prevalence was detected in the older age groups, reflecting cumulative exposure to the virus over time. Among the infected pregnant women, 20% were considered recently infected according to the BED-CEIA. The estimated incidence of HIV infection was 0.61 per 1000 person-years (95% CI 0.33-0.89); the corrected incidence was 0.47 per 1000 person-years (95% CI 0.26-0.68). In a subgroup of patients, HIV-1 subtype C (16.7%) was the second most prevalent form after subtype B (66.7%); BF1 recombinants (11.1%) and one case of subtype F1 (5.5%) were also detected. Conclusion This study highlights the potential for deriving incidence estimates from a large antenatal screening program for HIV. The rate of recent HIV-1 infection among women in their early reproductive years is a public health warning to implement preventive measures.