Publications by authors named "Kleber Luz"

26 Publications

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A prospective, multicentre, cohort study to assess the incidence of dengue illness in households from selected communities in Brazil (2014-2018).

Int J Infect Dis 2021 Apr 21;108:443-453. Epub 2021 Apr 21.

Instituto de Tecnologia em Imunobiológicos Bio-Manguinhos/Fiocruz, Avenida Brasil 4.365, Manguinhos, Rio de Janeiro - RJ, 21.040-900, Brazil.

Objectives: To estimate the incidence of dengue infection across geographically distinct areas of Brazil.

Methods: This prospective, household-based, cohort study enrolled participants in five areas and followed them up for up to 4 years (2014-2018). Dengue seroprevalence was assessed at each scheduled visit. Suspected dengue cases were identified through enhanced passive and active surveillance. Acute symptomatic dengue infection was confirmed through reverse-transcriptase quantitative polymerase chain reaction in combination with an antigenic assay (non-structural protein 1) and serology.

Results: Among 3300 participants enrolled, baseline seroprevalence was 76.2%, although only 23.3% of participants reported a history of dengue. Of 1284 suspected symptomatic dengue cases detected, 50 (3.9%) were laboratory-confirmed. Based on 8166.5 person-years (PY) of follow-up, the incidence of laboratory-confirmed symptomatic infection (primary endpoint) was 6.1 per 1000 PY (95% confidence interval [CI]: 4.5, 8.1). Incidence varied substantially in different years (1.8-7.4 per 1000 PY). The incidence of inapparent primary dengue infection was substantially higher: 41.7 per 1000 PY (95% CI: 31.1, 54.6).

Conclusions: Our findings, highlighting that the incidence of dengue infection is underestimated in Brazil, will inform the design and implementation of future dengue vaccine trials.

Clinical Trial Registration: NCT01751139.
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http://dx.doi.org/10.1016/j.ijid.2021.04.062DOI Listing
April 2021

Barriers and facilitators to populational adherence to prevention and control measures of COVID-19 and other respiratory infectious diseases: a rapid qualitative evidence synthesis protocol.

BMJ Open 2021 01 29;11(1):e045529. Epub 2021 Jan 29.

Department of Physical Therapy, Graduate Program in Physical Therapy, Federal University of Rio Grande do Norte, Natal, RN, Brazil

Introduction: The current COVID-19 pandemic has increased the need for populational adherence to measures for the prevention and control of respiratory infectious diseases. However, their effectiveness depends on the population's preventive behaviour, which may be divergent from public policies. Therefore, this study aims to summarise and evaluate the evidence on barriers and facilitators to populational adherence to prevention and control measures in COVID-19 and other respiratory infectious diseases.

Methods And Analysis: We will search on MEDLINE, Embase and PsycINFO for studies focusing on adults receiving protective behaviour recommendations to combat COVID-19 and other respiratory infectious diseases. The searches will be carried out from database's inception to the present. We will include studies that use qualitative methods in their data collection and analysis and studies that use mixed methods if they include any qualitative methods of analysis. Studies published in English, Portuguese and Spanish will be included. Two review authors will independently screen the studies for inclusion and extract data. We will assess the quality of the included studies using the Critical Skills Appraisal Programme tool. For the assessment of the confidence in the synthesised findings, we will use the GRADE-Confidence in the Evidence from Reviews of Qualitative research. Data analysis will be conducted using the best-fit framework approach based on adapted dimensions from the Health Belief Model and the Behaviour Change Wheel.

Ethics And Dissemination: This study will be conducted on published evidence, and thus, no ethical approval is required. The findings of this rapid qualitative evidence synthesis will be disseminated to academic audiences, health policy-makers and the general population. We will publish the results in peer-reviewed journals, present our findings in conferences, and disseminate results via social media. We also aim to present the research findings in plain language and disseminate the knowledge to the general population to increase public interest.

Prospero Registration Number: CRD42020205750.
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http://dx.doi.org/10.1136/bmjopen-2020-045529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849319PMC
January 2021

Chikungunya virus ECSA lineage reintroduction in the northeasternmost region of Brazil.

Int J Infect Dis 2021 Apr 18;105:120-123. Epub 2021 Jan 18.

Laboratório de Genética Celular e Molecular, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. Electronic address:

The Northeast region of Brazil registered the second-highest incidence proportion of Chikungunya fever in 2019. In that year, an outbreak consisting of patients presenting with febrile disease associated with joint pain was reported by the public primary health care service in the city of Natal, in the state of Rio Grande do Norte, in March 2019. At first, the aetiological agent of the disease was undetermined. Since much is still unknown about chikungunya virus' (CHIKV) genomic diversity and evolutionary history in this northeasternmost state, we used a combination of portable whole-genome sequencing, molecular clock, and epidemiological analyses that revealed the reintroduction of the CHIKV East-Central-South-African (ECSA) lineage into Rio Grande do Norte. We estimated that the CHIKV ECSA lineage was first introduced into Rio Grande do Norte in early June 2014, while the 2019 outbreak clade diverged around April 2018, during a period of increased Chikungunya incidence in the Southeast region, which might have acted as a source of virus dispersion towards the Northeast region. Together, these results confirm that the ECSA lineage continues to spread across the country through interregional importation events, likely mediated by human mobility.
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http://dx.doi.org/10.1016/j.ijid.2021.01.026DOI Listing
April 2021

Efficacy of a dengue vaccine candidate (TAK-003) in healthy children and adolescents two years after vaccination.

J Infect Dis 2020 Dec 15. Epub 2020 Dec 15.

Takeda Pharmaceuticals International AG., Zurich, Switzerland.

Background: Takeda's dengue vaccine is under evaluation in an ongoing Phase 3 efficacy study; we present an update after 2 years.

Methods: 20,099 children (4-16 years old) were randomized to receive two doses of TAK-003 or placebo three months apart and are under long-term febrile surveillance to detect dengue by serotype-specific RT-PCR. (NCT02747927).

Results: Cumulative efficacy against dengue over ~27 months since first dose was 72.7% (95% CI: 67.1 - 77.3), which included efficacy of 67.0% (95% CI: 53.6 - 76.5) in dengue-naïve and 89.2% (82.4 - 93.3) against hospitalized dengue. In the second year after vaccination, a decline in efficacy was observed [56.2% (42.3 - 66.8)] with the largest decline in 4 - 5 year-old children [24.5% (-34.2 - 57.5)]; efficacy was 60.6% (43.8 - 72.4) in 6 - 11 year and 71.2% (41.0 - 85.9) in 12 - 16 year age groups. As TAK-003 efficacy varies by serotype, changes in serotype dominance partially contributed to the efficacy differences in year by year analysis. No related serious adverse events occurred during the second year.

Conclusion: TAK-003 demonstrated continued benefit independent of baseline serostatus in reducing dengue with some decline in efficacy during the second year. Three-year data will be important to see if efficacy stabilizes or declines further.
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http://dx.doi.org/10.1093/infdis/jiaa761DOI Listing
December 2020

Zika and Dengue Interactions in the Context of a Large Dengue Vaccine Clinical Trial in Latin America.

Am J Trop Med Hyg 2021 01;104(1):136-144

2Clinical Sciences Department, Sanofi Pasteur, Swiftwater, Pennsylvania.

A phase III dengue vaccine trial including 9- to 16-year-olds in Latin America (NCT01374516) was ongoing at the time of a Zika outbreak. We explored interactions between dengue and Zika, in the context of dengue vaccination. Symptomatic virologically confirmed Zika (VCZ) was evaluated using acute-phase sera from febrile participants (January 2013-March 2018). Neutralizing antibody geometric mean titers (GMTs) were evaluated pre- and post-Zika outbreak (months 25 and 72) in 2,000 randomly selected participants. Baseline dengue serostatus was determined using the plaque reduction neutralization test or inferred post hoc using nonstructural protein 1 IgG ELISA at M13 (case-cohort analysis). Vaccine efficacy against VCZ and serologically suspected Zika (SSZ) was estimated. Overall, 239/10,157 (2.4%) acute-phase samples were VCZ positive during the study. Dengue vaccine efficacy against VCZ was 27.8% (95% CI: 0.3; 47.7) among baseline dengue-seropositive participants. No vaccine effect was evident against SSZ. Zika antibody GMTs increased from pre- to post-Zika epidemic, with smaller increases observed for participants who were dengue seropositive at baseline than for those who were dengue seronegative: post-/pre-Zika GMT ratios for baseline dengue-seropositive participants were 21.5 (vaccine group) and 30.8 (placebo); and for dengue seronegatives, 88.1 and 89.5, respectively. Dengue antibody GMTs post-Zika were higher in dengue vaccine and placebo recipients with SSZ than those without SSZ in both dengue seropositives and seronegatives. Dengue vaccine did not enhance symptomatic Zika illness in dengue-seropositive individuals, rather it reduced the risk of VCZ. Zika infection boosted preexisting vaccine-induced or naturally occurring dengue-neutralizing antibodies.
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http://dx.doi.org/10.4269/ajtmh.20-0635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790115PMC
January 2021

Update on the treatment of musculoskeletal manifestations in chikungunya fever: a guideline.

Rev Soc Bras Med Trop 2020 31;53:e20190517. Epub 2020 Jul 31.

Departamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, PE, Brasil.

Since the emergence of the chikungunya virus in Brazil in 2014, more than 700,000 cases have been reported throughout the country, corresponding to one-third of all cases reported in the Americas. In addition to its high attack rates, resulting in hundreds of thousands of cases, the disease has high chronicity rates with persistent joint manifestations for more than 3 months, which can spread to more than half of the patients affected in the acute phase. Pain associated with musculoskeletal manifestations, often disabling, has an effect on patients' quality of life at different stages of the disease. Currently, the challenge faced by specialists is identifying the best therapy to be instituted for symptom relief despite the limited number of published intervention studies. In 2016, a multidisciplinary group published pharmacological treatment protocols for pain in patients with chikungunya, which was incorporated into the guidelines for clinical management of the Brazilian Ministry of Health in 2017; in that same year, a consensus was published by the Brazilian Society of Rheumatology about diagnosis and treatment. After 5 years of experience with chikungunya epidemics, in 2019, specialists involved in the protocols of the Brazilian Society of Rheumatology and Brazilian Ministry of Health prepared an update with the main objective of developing flowcharts for the therapeutic approach of musculoskeletal manifestations in adult patients to enable specialists at different levels of healthcare to spread and apply this guideline in a systematic and simplified manner.
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http://dx.doi.org/10.1590/0037-8682-0517-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405653PMC
August 2020

Case Report: Combination Therapy with Liposomal Amphotericin B, N-Methyl Meglumine Antimoniate, and Pentamidine Isethionate for Disseminated Visceral Leishmaniasis in a Splenectomized Adult Patient.

Am J Trop Med Hyg 2020 02;102(2):268-273

Department of Infectious Diseases, Hospital Giselda Trigueiro, Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.

In immunocompromised patients, visceral leishmaniasis (VL) can present with atypical clinical symptoms that include poor response to treatment. No optimal therapeutic regimen is available for such cases. In a splenectomized male patient, we observed a disseminated form of the disease in the liver, bone marrow, lymph nodes, and gastrointestinal tract. There was an apparent clinical improvement when he was initially treated with liposomal amphotericin B (L-AmB), but this was followed by a relapse involving severe clinical symptoms. He was finally treated successfully with a combination of L-AmB, meglumine antimoniate, and pentamidine isethionate. It is important to include asplenia as an immunosuppressive condition that induces exotic VL pathologies. In such cases, combination anti- drug therapy should be considered.
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http://dx.doi.org/10.4269/ajtmh.18-0999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008324PMC
February 2020

Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents.

N Engl J Med 2019 11 6;381(21):2009-2019. Epub 2019 Nov 6.

From Takeda Vaccines, Singapore (S. Biswal); Centro de Atención e Investigación Médica, Bogota (H.R.), and Centro de Estudios en Infectología Pediatrica, Centro Médico Imbanaco and Department of Pediatrics, Universidad del Valle, Cali (P.L., E.L.-M.) - both in Colombia; the Department of Infectious Diseases at Hospital del Niño Dr. José Renán Esquivel, Sistema Nacional de Investigación at Secretaria Nacional de Ciencia y Tecnologia (SENACYT), Centro de Vacunación Internacional (Cevaxin), Panama City, Panama (X.S.-L., J.J.); the Research Institute for Tropical Medicine, Muntinlupa (C.B.-T.), and the University of the Philippines Manila, Ermita (L.B.) - both in the Philippines; Srinagarind Hospital, Khon Kaen University, Khon Kaen (P.K.), and the Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University (C.S.), and Phramongkutklao Hospital (V.W.), Bangkok - all in Thailand; Hospital Maternidad Nuestra Senora de Altagracia, Santo Domingo, Dominican Republic (L.R.); National Autonomous University of Nicaragua, Leon (F.E.); Center for Clinical Management of Dengue and Dengue Haemorrhagic Fever, Negombo General Hospital, Negombo, Sri Lanka (L.K.F.); Universidade Federal Do Espirito Santo, Hospital Universitário Cassiano Antônio de Moraes, Vitória (R.D.), Instituto de Medicina Tropical da Universidade Federal do Rio Grande do Norte, Natal (K.L.), and Universidade Federal de Mato Grosso do Sul, Campo Grande (R.V.C.) - all in Brazil; Takeda Pharmaceuticals International, Zurich, Switzerland (A.B., M.B., M.R., I.L., S. Bizjajeva); and Takeda Vaccines, Boston (D.W.).

Background: Dengue, a mosquito-borne viral disease, was designated a World Health Organization top 10 threat to global health in 2019.

Methods: We present primary efficacy data from part 1 of an ongoing phase 3 randomized trial of a tetravalent dengue vaccine candidate (TAK-003) in regions of Asia and Latin America in which the disease is endemic. Healthy children and adolescents 4 to 16 years of age were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. Participants presenting with febrile illness were tested for virologically confirmed dengue by serotype-specific reverse-transcriptase polymerase chain reaction. The primary end point was overall vaccine efficacy in preventing virologically confirmed dengue caused by any dengue virus serotype.

Results: Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). Efficacy trends varied according to serotype. The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively).

Conclusions: TAK-003 was efficacious against symptomatic dengue in countries in which the disease is endemic. (Funded by Takeda Vaccines; TIDES ClinicalTrials.gov number, NCT02747927.).
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http://dx.doi.org/10.1056/NEJMoa1903869DOI Listing
November 2019

Childhood Sarcoidosis mimicking Tuberculosis:A case report.

Rev Soc Bras Med Trop 2019 Jul 18;52:e20180229. Epub 2019 Jul 18.

Departamento de Doenças Infecciosas, Instituto de Medicina Tropical do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.

Sarcoidosis is a rare multisystem chronic inflammatory disease in children. We present a case of a five-year-old child with clinical features mimicking several diseases, including tuberculosis. After failure of treatment based on the suspected diagnosis, an axillary lymph node biopsy showed noncaseating granulomas compatible with sarcoidosis and appropriate treatment was then started.
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http://dx.doi.org/10.1590/0037-8682-0229-2018DOI Listing
July 2019

Combination therapy with liposomal amphotericin b (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate in a refractory visceral leishmaniasis case.

Rev Soc Bras Med Trop 2018 May-Jun;51(3):393-396

Departamento de Doenças Infecciosas, Instituto de Medicina Tropical do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.

Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.
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http://dx.doi.org/10.1590/0037-8682-0398-2017DOI Listing
July 2018

Pharmacologic management of pain in patients with Chikungunya: a guideline.

Rev Soc Bras Med Trop 2016 Nov-Dec;49(6):668-679

Programa Nacional de Controle da Dengue, Ministério da Saúde, Brasília, Brazil.

From the arrival of Chikungunya virus in the Americas in 2013 until March 2016, approximately two million cases of the disease have been reported. In Brazil, the virus was identified in 2014 and thousands of people have been affected. The disease has high attack rates, infecting 50% of a population within a few months. Approximately 50% of infected people develop chronic symptoms lasting for months or years. Joint involvement is the main clinical manifestation of Chikungunya. It is characterized by swelling and intense pain that is poorly responsive to analgesics, both in the acute and chronic phase of the disease. This significantly compromises quality of life and may have immeasurable psychosocial and economic repercussions, constituting therefore, a serious public health problem requiring a targeted approach. Physicians are often not familiar with how to approach the management of pain, frequently prescribing limited analgesics, such as dipyrone, in sub-therapeutic doses. In addition, there are few published studies or guidelines on the approach to the treatment of pain in patients with Chikungunya. Some groups of specialists from different fields have thus developed a protocol for the pharmacologic treatment of Chikungunya-associated acute and chronic joint pain; this will be presented in this review.
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http://dx.doi.org/10.1590/0037-8682-0279-2016DOI Listing
April 2017

Management of infection by the Zika virus.

Ann Clin Microbiol Antimicrob 2016 Sep 29;15(1):57. Epub 2016 Sep 29.

Hospital Aliança, R. Juracy Magalhães Júnior, 2096, Salvador, BA, CEP 41920-000, Brazil.

A panel of national experts was convened by the Brazilian Infectious Diseases Society in order to organize the national recommendations for the management of zika virus infection. The focus of this document is the diagnosis, both clinical and laboratorial, and appropriate treatment of the diverse manifestations of this infection, ranging from acute mild disease to Guillain-Barré syndrome and also microcephaly and congenital malformations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043598PMC
http://dx.doi.org/10.1186/s12941-016-0172-yDOI Listing
September 2016

Pathology of congenital Zika syndrome in Brazil: a case series.

Lancet 2016 Aug 29;388(10047):898-904. Epub 2016 Jun 29.

Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Atlanta, GA, USA. Electronic address:

Background: Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection.

Methods: In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains.

Findings: Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015.

Interpretation: These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(16)30883-2DOI Listing
August 2016

Secondary transmission of cryptosporidiosis associated with well water consumption: two case studies.

Rev Soc Bras Med Trop 2016 Apr;49(2):260-2

Instituto de Medicina Tropical do Rio Grande do Norte, Natal, Rio Grande do Norte, Brasil.

Cryptosporidiosis is a very prominent disease in the field of public health, and usually causes diarrhea. We describe two immunocompetent patients who presented with chronic diarrhea that was ultimately found to be caused by continuous exposure to well water contaminated with the microbial cysts (oocysts) of the Cryptosporidium spp parasite. We describe the patients' histories and possible explanations for their prolonged symptoms.
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http://dx.doi.org/10.1590/0037-8682-0232-2015DOI Listing
April 2016

Zika virus damages the human placental barrier and presents marked fetal neurotropism.

Mem Inst Oswaldo Cruz 2016 May 29;111(5):287-93. Epub 2016 Apr 29.

Laboratório de Virologia Molecular, Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba, PR, Brasil.

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.
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http://dx.doi.org/10.1590/0074-02760160085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878297PMC
May 2016

Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015.

MMWR Morb Mortal Wkly Rep 2016 Feb 19;65(6):159-60. Epub 2016 Feb 19.

Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).
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http://dx.doi.org/10.15585/mmwr.mm6506e1DOI Listing
February 2016

[Zika Virus: A Review to Clinicians].

Acta Med Port 2015 Nov-Dec;28(6):760-5. Epub 2015 Dec 31.

Global Health and Tropical Medicine. Instituto de Higiene e Medicina Tropical. Universidade NOVA de Lisboa. Lisboa. Portugal.

Zika virus is a flavivirus related to Dengue virus, yellow fever virus and West Nile virus. It is considered an emerging arbovirus transmitted by mosquitos of the genus Aedes. Its first description took place in 1947 in the Zika Forest in Uganda, isolated on Rhesus monkey used as bait to study the yellow fever virus. Sporadic cases have been detected in African countries and at the end of the 70's in Indonesia. In 2007, epidemics were described in Micronesia and other islands in the Pacific Ocean and more recently in Brazil. Clinical picture is characterized as a 'dengue-like' syndrome, with abrupt onset of fever and an early onset evanescent rash, often pruritic. Occasionally the disease has been associated with Guillain-Barré syndrome. Nevertheless, until now deaths and complications caused by the disease were not reported. The diagnosis can be performed by PCR or by IgG and IgM antibodies detection. The rapid spread of the virus and its epidemic potential are especially problematic in countries where there are the circulation of other arboviruses which imposes difficulties in the differential diagnosis and healthcare burden. Control measures are the same recommended for dengue and chikungunya which are based in health education and vector control.
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March 2018

First report of autochthonous transmission of Zika virus in Brazil.

Mem Inst Oswaldo Cruz 2015 Jun 9;110(4):569-72. Epub 2015 Jun 9.

Instituto de Medicina Tropical, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.
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http://dx.doi.org/10.1590/0074-02760150192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501423PMC
June 2015

Prospective cohort study with active surveillance for fever in four dengue endemic countries in Latin America.

Am J Trop Med Hyg 2015 Jul 26;93(1):18-23. Epub 2015 May 26.

To prepare for a Phase III dengue vaccine efficacy trial, 20 investigational sites were selected for this observational study to identify dengue infections in a closed cohort (N = 3,000 children 9-16 years of age). Of 255 acute febrile episodes experienced by 235 children, 50 (21.3%) were considered serologically probable dengue, and 18 (7.7%) were considered virologically confirmed (i.e., dengue NS1 antigen positive) dengue cases. Considering the disease-free and at-risk period from study start to onset of symptoms, the overall incidence density of acute febrile episodes was 17.7 per 100 person-years of follow-up, ranging from 15.3 in Colombia to 22.0 in Puerto Rico. This study showed that all sites were capable of capturing and following up acute febrile episodes within a specific timeframe among the established cohort and to detect dengue cases.
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http://dx.doi.org/10.4269/ajtmh.13-0663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497892PMC
July 2015

Efficacy of a tetravalent dengue vaccine in children in Latin America.

N Engl J Med 2015 Jan 3;372(2):113-23. Epub 2014 Nov 3.

The authors' affiliations are listed in the Appendix.

Background: In light of the increasing rate of dengue infections throughout the world despite vector-control measures, several dengue vaccine candidates are in development.

Methods: In a phase 3 efficacy trial of a tetravalent dengue vaccine in five Latin American countries where dengue is endemic, we randomly assigned healthy children between the ages of 9 and 16 years in a 2:1 ratio to receive three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. The children were then followed for 25 months. The primary outcome was vaccine efficacy against symptomatic, virologically confirmed dengue (VCD), regardless of disease severity or serotype, occurring more than 28 days after the third injection.

Results: A total of 20,869 healthy children received either vaccine or placebo. At baseline, 79.4% of an immunogenicity subgroup of 1944 children had seropositive status for one or more dengue serotypes. In the per-protocol population, there were 176 VCD cases (with 11,793 person-years at risk) in the vaccine group and 221 VCD cases (with 5809 person-years at risk) in the control group, for a vaccine efficacy of 60.8% (95% confidence interval [CI], 52.0 to 68.0). In the intention-to-treat population (those who received at least one injection), vaccine efficacy was 64.7% (95% CI, 58.7 to 69.8). Serotype-specific vaccine efficacy was 50.3% for serotype 1, 42.3% for serotype 2, 74.0% for serotype 3, and 77.7% for serotype 4. Among the severe VCD cases, 1 of 12 was in the vaccine group, for an intention-to-treat vaccine efficacy of 95.5%. Vaccine efficacy against hospitalization for dengue was 80.3%. The safety profile for the CYD-TDV vaccine was similar to that for placebo, with no marked difference in rates of adverse events.

Conclusions: The CYD-TDV dengue vaccine was efficacious against VCD and severe VCD and led to fewer hospitalizations for VCD in five Latin American countries where dengue is endemic. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01374516.).
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http://dx.doi.org/10.1056/NEJMoa1411037DOI Listing
January 2015

Mycobacterium fortuitum-related lymphadenitis associated with the varicella-zoster virus.

Rev Soc Bras Med Trop 2014 Jan-Feb;47(1):119-21

Universidade Federal do Rio Grande do Norte, NatalRN, Curso de Medicina, Universidade Federal do Rio Grande do Norte, Natal, RN.

Lymphadenitis caused by non-tuberculous mycobacteria is an uncommon manifestation in immunocompetent individuals. Here, we report a case of Mycobacterium fortuitum infection in a previously healthy 9-year-old patient who developed cervical lymphadenitis evolving to a suppurative ulcer associated with a varicella-zoster virus infection. We discuss the relationship between the varicella-zoster virus and the immune response of the host as an explanation for the unusual progression of the case.
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http://dx.doi.org/10.1590/0037-8682-0166-2013DOI Listing
May 2014

Acute primary actinomycosis involving the hard palate of a diabetic patient.

J Oral Maxillofac Surg 2014 Mar;72(3):537-41

Professor, Oral Pathology Postgraduate Program, Department of Dentistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Actinomycosis is a relatively rare infection caused by saprophytic bacteria of the oral cavity and gastrointestinal tract that can become pathogenic. The chronic hyperglycemia of diabetes mellitus induces events that promote structural changes in various tissues and are associated with problems in wound healing. This infection remains largely unknown to most clinicians because of its different presentations, and palatal involvement is extremely rare. This report describes the case of a 46-year-old woman who was diagnosed with actinomycosis involving the hard palate. The main clinical, histopathologic, and therapeutic characteristics and differential diagnosis of actinomycosis are reviewed. To date, 3 cases of actinomycosis involving the hard palate have been reported.
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http://dx.doi.org/10.1016/j.joms.2013.08.006DOI Listing
March 2014

Rhinocerebral zygomycosis in a diabetic patient.

Rev Soc Bras Med Trop 2011 Mar-Apr;44(2):257-9

Hospital Giselda Trigueiro, Departamento de Infectologia, Universidade Federal do Rio Grande do Norte, Natal, RN, Brasil.

Rhinocerebral zygomycosis is the most frequent form of fungal infection caused by members of the Zygomycetes class. A fatal case of rhinocerebral zygomycosis caused by Rhizopus (oryzae) arrhizus with histopathological and mycological diagnosis is reported in a diabetic patient.
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http://dx.doi.org/10.1590/s0037-86822011000200027DOI Listing
October 2011

Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis.

Rev Soc Bras Med Trop 2010 Jul-Aug;43(4):393-5

Department of Infectious Diseases, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Introduction: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL.

Methods: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-gamma, TNF-alpha and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed.

Results: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-alpha, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-gamma was lower in the VL patients (p < 0.05).

Conclusions: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.
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http://dx.doi.org/10.1590/s0037-86822010000400011DOI Listing
April 2011

Presence of antibodies against Leishmania chagasi in haemodialysed patients.

Trans R Soc Trop Med Hyg 2009 Jul 23;103(7):749-51. Epub 2009 Feb 23.

Department of Infectious Diseases, UFRN, Natal, Rio Grande do Norte, RN, Brazil.

In the last decades there has been an increase in cases of visceral leishmaniasis complicating the post-transplant phase, mainly following kidney transplantation. The aim of this study was to evaluate the reactivity of haemodialysed patients using IFAT. Blood samples of 310 individuals from Natal, RN, Brazil, were collected and analysed. Data regarding blood transfusion, cause of end-stage renal disease and duration of haemodialysis were also analysed. In total, 69 patients (22.3%) were positive by IFAT. This study suggests that antibody detection should be performed in this group of patients since they are possible candidates for kidney transplantation.
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http://dx.doi.org/10.1016/j.trstmh.2009.01.003DOI Listing
July 2009

Reversible vanishing bile duct syndrome induced by carbamazepine.

Eur J Gastroenterol Hepatol 2002 Sep;14(9):1019-22

Laboratório Médico de Patologia Getulio de Oliveira Sales, Natal, Rio Grande do Norte, Brazil.

Carbamazepine, a widely used anticonvulsant, can induce hepatotoxicity, usually evolving with an acute hepatitis that ceases after drug withdrawal. Carbamazepine-induced vanishing bile duct syndrome (VBDS) is a rare complication and has seldom been reported in the medical literature. This report presents a case of a 26-year-old male who had onset of epilepsy at 12 months of age and was initially treated with phenobarbital. Carbamazepine (1200 mg/day) was added in June 1996 when he was 22 years old to control the frequency of seizures. Two years later, during a routine investigation, elevation of serum gamma-glutamyltransferase (GGT) levels was detected. For this reason, the patient was weaned off carbamazepine, followed 6 months later by complete withdrawal of the drug. The first liver biopsy disclosed total absence of interlobular bile ducts (IBD) in 30 portal tracts. Fourteen months later, a control biopsy showed the presence of IBD in eight of 14 portal tracts. There was also a decrease of GGT levels detected 27 months after withdrawal of carbamazepine. This case illustrates the ductopenic effect of carbamazepine when used for a prolonged time, as reported in three previous publications. However, this is the first case in which there was a remission of the VBDS and bile duct regeneration after withdrawal of the drug.
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http://dx.doi.org/10.1097/00042737-200209000-00014DOI Listing
September 2002