title: Characterization of Plasmodium vivax-associated admissions to reference hospitals in Brazil and India.
abstract: BACKGROUND
  The benign character formerly attributed to Plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need for more thorough and comprehensive characterization of the spectrum of resulting clinical complications. Endemic areas exhibit wide variations regarding severe disease frequency. This study, conducted simultaneously in Brazil and India, constitutes, to our knowledge, the first multisite study focused on clinical characterization of P. vivax severe disease.
  
  
  METHODS
  Patients admitted with P. vivax mono-infection at reference centers in Manaus (Amazon - Brazil) and Bikaner (Rajasthan - India), where P. vivax predominates, were submitted to standard thorough clinical and laboratory evaluations in order to characterize clinical manifestations and identify concurrent co-morbidities.
  
  
  RESULTS
  In total, 778 patients (88.0% above 12 years old) were hospitalized at clinical discretion with PCR-confirmed P. vivax mono-infection (316 in Manaus and 462 in Bikaner), of which 197 (25.3%) presented at least one severity criterion as defined by the World Health Organization (2010). Hyperlactatemia, respiratory distress, hypoglycemia, and disseminated intravascular coagulation were more frequent in Manaus. Noteworthy, pregnancy status was associated as a risk factor for severe disease (OR = 2.03; 95% CI = 1.2-3.4; P = 0.007). The overall case fatality rate was 0.3/1,000 cases in Manaus and 6.1/1,000 cases in Bikaner, with all deaths occurring among patients fulfilling at least one severity criterion. Within this subgroup, case fatality rates increased respectively to 7.5% in Manaus and 4.4% in Bikaner.
  
  
  CONCLUSIONS
  P. vivax-associated severity is not negligible, and although lethality observed for complicated cases was similar, the overall fatality rate was about 20-fold higher in India compared to Brazil, highlighting the variability observed in different settings. Our observations highlight that pregnant women and patients with co-morbidities need special attention when infected by this parasite due to higher risk of complications.
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. amsiqueira@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. amsiqueira@gmail.com.|Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Av. Brasil, 4365, Rio de Janeiro, RJ, 21040-360, Brazil. amsiqueira@gmail.com.
authors.forename: André M
authors.initials: AM
authors.lastname: Siqueira
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. marcuslacerda.br@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. marcuslacerda.br@gmail.com.|Centro de Pesquisas Leônidas e Maria Deane, Fundação Oswaldo Cruz, Rua Teresina, 476, Manaus, AM, 69027-070, Brazil. marcuslacerda.br@gmail.com.
authors.forename: Marcus V G
authors.initials: MV
authors.lastname: Lacerda
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. magalhaesbelisa@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. magalhaesbelisa@gmail.com.
authors.forename: Belisa M L
authors.initials: BM
authors.lastname: Magalhães
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. mariapaula.mourao@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. mariapaula.mourao@gmail.com.
authors.forename: Maria P G
authors.initials: MP
authors.lastname: Mourão
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. cardosogisely@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. cardosogisely@gmail.com.
authors.forename: Gisely C
authors.initials: GC
authors.lastname: Melo
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. marcialexandre@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. marcialexandre@gmail.com.
authors.forename: Márcia A A
authors.initials: MA
authors.lastname: Alexandre
authors.affiliation: Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. galecrim@gmail.com.|Gerência de Malaria, Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Av. Pedro Teixeira, 25, Manaus, AM, 69040-000, Brazil. galecrim@gmail.com.
authors.forename: Maria G C
authors.initials: MG
authors.lastname: Alecrim
authors.affiliation: Sardar Patel Medical College, SP Medical College Road, PBM Hospital, Bikaner, Rajasthan, 334001, India. drdkkochar@yahoo.com.
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Kochar
authors.affiliation: Sardar Patel Medical College, SP Medical College Road, PBM Hospital, Bikaner, Rajasthan, 334001, India. drskkochar@rediffmail.com.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kochar
authors.affiliation: Sardar Patel Medical College, SP Medical College Road, PBM Hospital, Bikaner, Rajasthan, 334001, India. drdkkochar@yahoo.com.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Kochar
authors.affiliation: Sardar Patel Medical College, SP Medical College Road, PBM Hospital, Bikaner, Rajasthan, 334001, India. kc_nayak2003@yahoo.com.
authors.forename: Kailash
authors.initials: K
authors.lastname: Nayak
authors.affiliation: ISGlobal, Barcelona Institute for Global Health, Hospital Clínic - Universitat de Barcelona, Carrer Rosselló 132, 5°2ªE, 08036, Barcelona, Spain. hernandoa.delportillo@cresib.cat.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys, 23, 08010, Barcelona, Spain. hernandoa.delportillo@cresib.cat.
authors.forename: Hernando
authors.initials: H
authors.lastname: del Portillo
authors.affiliation: ISGlobal, Barcelona Institute for Global Health, Hospital Clínic - Universitat de Barcelona, Carrer Rosselló 132, 5°2ªE, 08036, Barcelona, Spain. caterina.guinovart@cresib.cat.|Centro de Investigação em Saúde de Manhiça (CISM), Vila da Manhiça, Bairro Cambeve, Rua 12, Distrito da Manhiça, 1929, Maputo, Mozambique. caterina.guinovart@cresib.cat.
authors.forename: Caterina
authors.initials: C
authors.lastname: Guinovart
authors.affiliation: ISGlobal, Barcelona Institute for Global Health, Hospital Clínic - Universitat de Barcelona, Carrer Rosselló 132, 5°2ªE, 08036, Barcelona, Spain. PALONSO@clinic.ub.es.|Centro de Investigação em Saúde de Manhiça (CISM), Vila da Manhiça, Bairro Cambeve, Rua 12, Distrito da Manhiça, 1929, Maputo, Mozambique. PALONSO@clinic.ub.es.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alonso
authors.affiliation: ISGlobal, Barcelona Institute for Global Health, Hospital Clínic - Universitat de Barcelona, Carrer Rosselló 132, 5°2ªE, 08036, Barcelona, Spain. quique.bassat@cresib.cat.|Centro de Investigação em Saúde de Manhiça (CISM), Vila da Manhiça, Bairro Cambeve, Rua 12, Distrito da Manhiça, 1929, Maputo, Mozambique. quique.bassat@cresib.cat.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil / Q000453:epidemiology; D002648:Child; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007194:India / Q000453:epidemiology; D016780:Malaria, Vivax / Q000453:epidemiology*; D008875:Middle Aged; D010966:Plasmodium vivax; D011247:Pregnancy; D012307:Risk Factors; D055815:Young Adult