Cohorte de nacimientos en un área hiperendémica en dengue en el nordeste de Brasil: métodos y resultados preliminares

Braga, Cynthia; Albuquerque, Maria de Fátima Pessoa Militão de; Cordeiro, Marli Tenório; Castanha, Priscila M. S.; Ramesh, Anita; Alexander, Neal; Mello, Maria Júlia G. de; Marques Jr, Ernesto T. A.; Martelli, Celina M. Turchi

doi:10.1590/0102-311X00095815

Cynthia Braga

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brasil.

Maria de Fátima Pessoa Militão de Albuquerque

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Marli Tenório Cordeiro

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Priscila M. S. Castanha

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Anita Ramesh

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, U.K.

Neal Alexander

Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, U.K.

Maria Júlia G. de Mello

Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brasil.

Ernesto T. A. Marques Jr

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Center for Vaccine Research, University of Pittsburgh, Pittsburgh, U.S.A.

Celina M. Turchi Martelli

Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Brasil.

Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brasil.

Correspondence C. Braga. Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz. Av. Moraes Rego s/n, Recife, PE 50670-420, Brasil.braga@cpqam.fiocruz.br

Contributors

C. Braga participated in the design, planning and coordination of data collection, data analysis plan and writing of the paper. M. F. P. M. Albuquerque participated in the study design, plan of analysis and drafting the article. M. T. Cordeiro participated in the planning, coordination of the activities of processing and analysis of laboratory tests and writing the article. P. M. S. Castanha participated in the planning, coordination of the activities of processing and analysis of laboratory tests and writing the article. A. Ramesh, N. Alexander, M. J. G. Mello, E. T. A. Marques Jr. and C. M. T. Martelli participated in the study design, plan of analysis and drafting the article.

Phase	Measurements
Baseline (2011-2012)
Maternal data (at delivery)	Sociodemographic: age, skin color (white, black, mixed race or indigenous), level of schooling (in years), family income (in multiples of the minimum wage)
	Clinical: smoking status, self-report of fever or dengue fever during current pregnancy, episodes of sexual transmitted diseases, urinary tract infections, yellow fever vaccination status, type of delivery, placenta abnormalities
	Laboratory: serologic tests (DENV-specific IgM and IgG, DENV specific IgG-subclass, PRNT); reverse transcriptase – polymerase chain (RT-PCR)
Newborn data	Clinical: gestational age, Apgar score (1st and 5th min), sex, birth weight
	Laboratory (umbilical cord): serologic tests (DENV-specific IgM and IgG, DENV specific IgG-subclass, PRNT); RT-PCR (carried out when the parturient reported fever in the seven days preceding the childbirth)
	Maternal and cord blood samples taken, serum aliquots stored at -80ºC
Scheduled follow-up and evaluation of acute febrile event (2011-2014)
Child data	Clinical data: vaccination status, breastfeeding (exclusive, mixed, not breastfed), signs and symptoms during the consultation (fever, diarrhea, rash, cough, dyspnea, runny nose and swelling), febrile illness since the last consultation
	Anthropometric measures: weight, length
	Vital signs: temperature, heart and respiratory rate
	Blood sample taken, serum aliquots stored at -80ºC
	Laboratory tests: serologic tests (DENV-specific IgM and IgG, DENV specific IgG-subclass, PRNT); RT-PCR , blood cell count , hematocrit *
	Laboratory assays: enhancing activity of maternal transferred antibodies will be tested in a random subset of the cohort

Characteristics	Followed (n = 354)	Not followed (n = 60)	Difference (95%CI)	p-value
Maternal
Age in years [Mean (SD)]	23.5 (6.2)	24.5 (6.3)	-0.9 (-2.7; 0.7)	0.866 *
Self-identified race
Mixed	238 (67.2)	40 (66.7)	0.3 (-6.9; 7.6)	0.931 **
Others	116 (32.8)	20 (33.3)
Individual income (multiples of minimum wage) [n (%)]
No paid work	209 (62.2)	31 (56.4)	2.9 (-4.2; 10.2)	0.409 **
≥ 1	127 (37.8)	24 (43.6)
Years of schooling [n (%)]
> 8	202 (57.1)	35 (58.3)	-0.6 (-7.7; 6.2)	0.854 **
≤ 8	152 (42.9)	25 (41.7)
Maternal anti-dengue IgG *** [n (%)]
Positive	328 (95.9)	56 (93.3)
Negative	14 (4.1)	4 (6.7)	7.6 (-11.9; 27.2)	0.374 **
Maternal anti-dengue IgM ^# [n (%)]
Positive	57 (16.6)	9 (15.0)
Negative	287 (83.4)	51 (85.0)	1.4 (-7.7; 10.6)	0.761 **
Children
Gestational age (weeks) [mean (SD)]	39.3 (1,1)	39.4 (1.2)	-0.093 (-0.4; 0.2)	0.721 **
Birth weight (g) [mean (SD)]	3,293 (365,8)	3,324 (469,5)	-30.6 (-135.6; 74.3)	0.716 **
Sex [n (%)]
Female	180 (50.9)	30 (50.0)
Male	174 (49.2)	30 (50.0)	0.4 (-6.4; 7.2)	0.903 **
Anti-dengue IgG umbilical cord * [n (%)]
Positive	309 (96.3)	54 (96.4)
Negative	12 (3.7)	2 (3.6)	-0.6 (-9.3; 18.1)	0.951 **

Characteristics
Baseline
Maternal
Dengue serotype specific antibodies (IgG) * [n (%)]
None	37 (10.8)
DENV-3	179 (52.3)
DENV-4	1 (0.29)
DENV-1/DENV-2	2 (0.6)
DENV-1/DENV-3	5 (1.5)
DENV-2/DENV-3	2 (0.6)
DENV-2/DENV-4	1 (0.3)
DENV-3/DENV-4	100 (29.3)
DENV-1/DENV-2/DENV-3	4 (1.2)
DENV-1/DENV-3/DENV-4	4 (1.2)
DENV-2/DENV-3/DENV-4	3 (0.9)
DENV-1/DENV-2/DENV-3/DENV-4	4 (1.2)
Frequency of serotype-specific dengue infection * [n (%)]
DENV-1	19 (5.5)
DENV-2	18 (4.7)
DENV-3	302 (87.8)
DENV-4	113 (32.9)
Number of previous dengue infection * [n (%)]
None	37 (10.8)
1	180 (52.6)
2	110 (32.2)
3-4	15 (4.4)
Children
Anti-dengue IgG antibodies (umbilical cord) ** [n (%)]
Positive	309 (96.3)
Negative	12 (3.7)
Anti-dengue IgM *** and/or RT-PCR ^#[positive/examined (%)]
1^st follow-up	29/299 (9.7)
2^nd follow-up	21/287 (7.3)
3^rd follow-up	34/294 (11.5)
Acute febrile syndrome [events/total (%)]
Children with febrile event	138/354 (38.9)
Suspected dengue cases among febrile events	56/138 (40.5)
Virologically-confirmed dengue cases among suspected	15/56 (26.7)
DENV serotypes ^#
DENV-1	5
DENV-2	2
DENV-3	2
DENV-4	6

[TFN1] * Suspected dengue case or fever of unknown origin.

Cohorte de nacimientos en un área hiperendémica en dengue en el nordeste de Brasil: métodos y resultados preliminares

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