Experience of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017: advances and challenges

Luciano Pamplona de Góes Cavalcanti Kiliana Nogueira Farias da Escóssia Adriana Rocha Simião Pâmela Maria Costa Linhares Antônio Afonso Bezerra Lima Kilma Wanderley Lopes Deborah Nunes de Melo Braga Izabel Leticia Cavalcante Ramalho Leda Maria Simões Mello Regina Lúcia Sousa do Vale Francisca Kalline de Almeida Barreto Rhaquel de Morais Alves Barbosa Oliveira Antônio Silva Lima Neto Fernanda Montenegro de Carvalho Araújo About the authors

Abstract

Objective:

to describe the experience and preliminary results of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017.

Methods:

the Committee investigates and discusses all suspected cases of arbovirus deaths reported by the epidemiological surveillance service.

Results:

a total of 443 suspected arbovirus deaths were reported, 220 (49.7%) of which were confirmed; of these, 88.2% were from chikungunya and 11.8% from dengue; the median age of chikungunya deaths was higher when compared to dengue (77 versus 56 years) and the time until death was also longer when compared to dengue (38 versus 12 days); median time for case closure was 54.5 days; in 2017, Ceará confirmed 80.4% of Brazilian chikungunya deaths.

Conclusion:

the investigation of deaths showed that CHIK viruses were responsible for the majority of arboviral deaths in the state of Ceará, in 2017.

Keywords:
Arboviruses; Dengue; Chikungunya Virus; Surveillance; Mortality

Introduction

The triple arbovirus epidemic scenario in the Northeast Brazilian region poses many challenges for health services.11. Perdigão ACB, Ramalho ILC, Guedes MIF, Braga DNM, Cavalcanti LPGC, Melo MEL, et al. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases. Mem Inst Oswaldo Cruz [Internet]. 2016 Sep [cited 2019 Jul 11];111(9):588-91. Available from: Available from: http://www.scielo.br/pdf/mioc/v111n9/0074-0276-mioc-0074-02760160140.pdf . doi: 10.1590/0074-02760160140
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This scenario emerged following isolation of the dengue virus (DENV) as long ago as the 1980s, and more recently, with the detection of the chikungunya fever virus (CHKV) in 2014 and the Zika fever virus (ZIKV) in 2015.

DENV circulation was confirmed in Brazil in 1982 and the first epidemic occurred in 1986-1987,33. Teixeira MG, Barreto ML, Guerra Z. Epidemiologia e medidas de prevenção do dengue. Inf Epidemiol SUS [Internet].1999 dez [citado 2019 jul 11];8(4):5-33. Disponível em: Disponível em: http://scielo.iec.gov.br/pdf/iesus/v8n4/v8n4a02.pdf . doi: 10.5123/S0104-16731999000400002
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while the first severe cases began with effect from 199044. Schatzmayr HG. Dengue situation by year 2000. Mem Inst Oswaldo Cruz [Internet]. 2000 [cited 2019 Jul 11];95(Suppl 1):179-81. Available from: Available from: http://www.scielo.br/pdf/mioc/v95s1/v95s1a30.pdf . doi: 10.1590/S0074-02762000000700030
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In Northeast Brazil, the state of Ceará stands out owing to the number of cases since 1986, as well as the number of severe cases and high lethality.77. Oliveira RMAB, Araújo FMC, Cavalcanti LPGC. Entomological and epidemiological aspects of dengue epidemics in Fortaleza, Ceará, Brazil, 2001-2012. Epidemiol Serv Saúde [Internet]. 2018 Feb [cited 2019 Jul 11];27(1):e201704414. Available from: Available from: http://www.scielo.br/pdf/ress/v27n1/en_2237-9622-ress-27-01-e201704414.pdf . doi: 10.5123/S1679-49742018000100014
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The first autochthonous chikungunya cases were confirmed in Brazil, in Oiapoque, in the state of Amapá, during the second half of 2014,99. Honório NA, Camara DCP, Calvet GA, Brasil P. Chikungunya: uma arbovirose em estabelecimento e expansão no Brasil. Cad Saúde Pública [Internet]. 2015 May [cited 2019 Jul 11];31(5):906-8. Available from: Available from: http://www.scielo.br/pdf/csp/v31n5/en_0102-311X-csp-31-5-0906.pdf . doi: 10.1590/0102-311XPE020515
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following confirmation of the introduction of CHKV in Central America the year before.1010. Yakob L, Clements ACA. A mathematical model of chikungunya dynamics and control: the major epidemic on Réunion Island. PLoS One [Internet]. 2013 Mar [cited 2019 Jul 11];8(3):e-57448. Available from: Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057448 . doi: 10.1371/journal.pone.0057448
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CHKV was also detected in a further six Brazilian states in 2014 and in 2015 it spread to more than 690 municipalities.1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância das Doenças Transmissíveis. Preparação e resposta à introdução do vírus Chikungunya no Brasil [Internet]. Brasília: Ministério da Saúde; 2014 [citado 2019 jul 11]. 100 p. Disponível em: Disponível em: http://bvsms.saude.gov.br/bvs/publicacoes/preparacao_resposta_virus_chikungunya_brasil.pdf
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The first autochthonous cases in the state of Ceará were confirmed in 2015. Two large epidemics were confirmed in 2016 and 2017, with incidence rates of 320.2/100,000 inhabitants and 1,149.2/100,000 inhabitants, respectively.1414. Secretaria de Saúde do Estado do Ceará. Boletim Epidemiológico Arboviroses: monitoramento dos casos de dengue, chikungunya e zika [Internet]. Fortaleza: Secretaria de Saúde do Estado do Ceará; 2019 [citado 2018 jul 10]. Disponível em: Disponível em: https://www.saude.ce.gov.br/wp-content/uploads/sites/9/2018/06/Boletim-Arboviroses-SE-45_2018.pdf
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Autochthonous ZIKV transmission was confirmed in Brazil in May 2015,1313. Ministério da Saúde (BR). Monitoramento dos casos de dengue, febre de chikungunya e febre pelo vírus Zika até a Semana Epidemiológica 32, 2016. Bol Epidemiol [Internet]. 2016 [citado 2019 jul 11];47(33):1-10. Disponível em: Disponível em: http://portalsaude.saude.gov.br/images/pdf/2016/setembro/16/2016-028---Dengue-SE32.pdf
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following isolation of the virus in suspected dengue cases.1515. Zanluca C, Melo VC, Mosimann AL, Santos GIV, Santos CN, Luz K. First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz [Internet]. 2010 Jun [cited 2019 Jul 11];110(4):569-72. Available from: Available from: http://www.scielo.br/pdf/mioc/v110n4/0074-0276-mioc-0074-02760150192.pdf . doi: 10.1590/0074-02760150192
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Its association with microcephaly cases was subsequently confirmed,1717. Cauchemes S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet [Internet]. 2016 May [cited 2019 Jul 11];387(10033):2125-32. Available from: Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00651-6/fulltext . doi: 10.1016/S0140-6736(16)00651-6
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and shortly afterwards classified as congenital Zika virus syndrome (CZS),1818. Pan American Health Organization. World Health Organization. Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas − epidemiological alert [Internet]. Washington, DC: Pan American Health Organization; 2015 [cited 2019 Jul 10]. Available from: Available from: https://www.paho.org/hq/dmdocuments/2015/2015-dec-1-cha-epi-alert-zika-neuro-syndrome.pdf
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with great impact on Public Health, especially in the Northeast, where 83.6% of all Brazilian cases were reported in 2015 and 2016.1919. França GVA, Pedi VD, Garcia MHO, Carmo GMI, Leal MB, Garcia LP. Síndrome congênita associada à infecção pelo vírus Zika em nascidos vivos no Brasil: descrição da distribuição dos casos notificados e confirmados em 2015-2016. Epidemiol Serv Saúde [Internet]. 2018 Jul [cited 2019 Jul 11];27(2):e2017473. Available from: Available from: http://www.scielo.br/pdf/ress/v27n2/2237-9622-ress-27-02-e2017473.pdf . doi: 10.5123/s1679-49742018000200014
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Even 30 years after detection of dengue in Brazil, despite all government efforts since then, dengue lethality has remained above the suggested maximum level of 1%.2020. Teixeira MG, Siqueira Jr JB, Ferreira GLC, Bricks L, Joint G. Epidemiological trends of dengue disease in Brazil (2000-2010): a systematic literature search and analysis. PLoS Negl Trop Dis [Internet]. 2013 Dec [cited 2019 Jul 11];7(12):e2520. Available from: Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002520 . doi: 10.1371/journal.pntd.0002520
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In turn, prior to the epidemic on Reunion Island, chikungunya fever had not been associated with high mortality rates;2121. Economopoulou A, Domínguez M, Helynck B, Sissoko D, Wichimann O, Quenel P, et al. Atypical chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion. Epidemiol Infect [Internet]. 2009 Apr [cited 2019 Jul 11];137(4):534-41. Available from: Available from: https://www.ncbi.nlm.nih.gov/pubmed/18694529 . doi: 10.1017/S0950268808001167
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however, recent publications have challenged the conventional view of CHIKV infection not being deadly.2121. Economopoulou A, Domínguez M, Helynck B, Sissoko D, Wichimann O, Quenel P, et al. Atypical chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion. Epidemiol Infect [Internet]. 2009 Apr [cited 2019 Jul 11];137(4):534-41. Available from: Available from: https://www.ncbi.nlm.nih.gov/pubmed/18694529 . doi: 10.1017/S0950268808001167
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22. Hoz JM, Bayona B, Viloria S, Accini JL, Juan-Vergara HS, Viasus D. Fatal cases of chikungunya virus infection in Colombia: diagnostic and treatment challenges. J Clin Virol [Internet]. 2015 Aug [cited 2019 jul 11];69:27-9. Available from: Available from: https://www.sciencedirect.com/science/article/abs/pii/S1386653215001663?via%3Dihub . doi: 10.1016/j.jcv.2015.05.021
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-2323. Freitas ARR, Cavalcanti L, Von Zuben AP, Donalisio MR. Excess mortality related to Chikungunya epidemics in the context of co-circulation of other arboviruses in Brazil. PLoS Currents [Internet]. 2017 Nov [cited 2019 Jul 11];9. Available from: Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731794/ . doi: 10.1371/currents.outbreaks.14608e586cd321d8d5088652d7a0d884
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While severe or atypical manifestations of CHIKV infection reach 1%, the overall lethality rate of these complications can reach 30%.2424. Couderc T, Lecuit M. Chikungunya virus pathogenesis: from bedside to bench. Antivir Res [Internet]. 2015 Sep [cited 2019 Jul 11];121:120-31. Available from: Available from: https://www.sciencedirect.com/science/article/pii/S0166354215001655?via%3Dihub . doi: 10.1016/j.antiviral.2015.07.002
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After more than 30 years of DENV surveillance in Brazil, notwithstanding the progress made, it was only with effect from 2016 that more robust evidence was found of dengue-associated deaths which had not been detected by passive surveillance services. In cities where death investigation services are sensitive and articulated with surveillance teams and laboratories, lethality can increase threefold, suggesting that dengue deaths may be underestimated in many places.2525. Braga DNM. Aspectos laboratoriais e anatomopatológicos no diagnóstico da dengue no Ceará em 2011 e 2012: papel do serviço de verificação de óbitos de Fortaleza. [dissertação]. Fortaleza (CE): Universidade Federal do Ceará; 2014. Disponível em: http://www.repositorio.ufc.br/handle/riufc/9544
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,2626. Cavalcanti LP, Braga DN, Silva LM, Aguiar MG, Castiglioni M, Silva Júnior JU, et al. Postmortem diagnosis of Dengue as an epidemiological surveillance tool. Am J Trop Med Hyg [Internet]. 2016 Jan [cited 2019 Jul 11];94(1):187-92. Available from: Available from: http://www.ajtmh.org/docserver/fulltext/14761645/94/1/187.pdf?expires=1563120508&id=id&accname=guest&checksum=F6690A5195803FF3D4B71F7322B55A5D . doi: 10.4269/ajtmh.15-0392
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The Brazilian Ministry of Health, in face of the first chikungunya and Zika deaths in 2015, adapted its dengue death investigation protocols for arbovirus death investigation.1313. Ministério da Saúde (BR). Monitoramento dos casos de dengue, febre de chikungunya e febre pelo vírus Zika até a Semana Epidemiológica 32, 2016. Bol Epidemiol [Internet]. 2016 [citado 2019 jul 11];47(33):1-10. Disponível em: Disponível em: http://portalsaude.saude.gov.br/images/pdf/2016/setembro/16/2016-028---Dengue-SE32.pdf
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In 2017, the state of Ceará reported Brazil’s largest chikungunya epidemic, with 137,424 (73.9%) cases. In addition, Ceará notified 80.1% of Brazil’s chikungunya deaths in 2017. Dengue and Zika also circulated in Ceará, with 24,879 and 2,343 confirmed cases, respectively.

The purpose of this article was to describe the experience and the preliminary results of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017.

Methods

This is an experience report on the creation of a death investigation committee, the objective of which was to investigate all suspected arbovirus deaths reported to the health services in Ceará. In face of the increasing number of suspected arbovirus deaths, Ceará State Health Department convened a group of professionals and created a multidisciplinary and interinstitutional arbovirus death investigation committee through Ordinance No. 2,099, dated November 29, 2016. The group is comprised of specialists in infectious diseases, epidemiology, pathology, general practice, pharmacy, nursing, physiotherapy and biology, working in sectors such as epidemiological surveillance, health care, infectious diseases reference hospitals, Public Health laboratories, universities and death investigation services.

This committee has weekly meetings, on Tuesdays, to present and discuss all suspected cases of arbovirus deaths notified by the epidemiological surveillance system in Ceará. Notification may be done via the Notifiable Diseases Information System (SINAN), the Death Investigation Service (SVO) or even by health centers. A Committee secretary convenes the weekly meeting by e-mail sent to all members and informing of cases to be discussed.

The Committee members present available information on each case, based on investigations carried out in households, outpatient services, hospitals and laboratories, as well as by the SVO when autopsies are performed. Each case is presented by the practitioner who conducted the investigation and is then discussed based on the available information. After this presentation and discussion between Committee members, the case may be closed for not being an arbovirus case, confirmed for chikungunya, dengue or Zika, or confirmed for another arbovirus; or may even remain under investigation, according to the Ministry of Health case definition. In cases that remain under investigation, searching for complementary information is recommended as this is needed to conclude the investigation and to close the case.

Ministry of Health recommendations for laboratory diagnosis of arboviruses comprise serology tests (rapid test and/or Elisa), NS1, RT-qPCR, virus isolation or post mortem examinations such as immunohistochemistry. In these cases, serum, blood or viscera are used.

Results

In 2017, 443 suspected cases of arbovirus deaths were reported. Among these notified deaths, 312 (70.4%) were suspected cases of chikungunya and the remaining (131; 29.6%) were suspected dengue cases. No suspected cases of Zika deaths were notified that year. Of the notified deaths, 220 (49.7%) were confirmed, 222 (50.1%) were ruled out and one (0.3%) remains under investigation.

Among the confirmed cases, 179 (81.4%) were laboratory-confirmed with a positive result for at least one among the available techniques, while the other 31 (18.6%) cases were confirmed by clinical-epidemiological criteria. The main causes of the non-arbovirus deaths were leptospirosis, influenza and bacterial meningitis, among others.

Of the notified chikungunya deaths, 194 (62.2%) were confirmed in 29 (15.8%) different municipalities. The municipality of Fortaleza stands out, with 144 (74.2%) of the state’s confirmed deaths. Taking confirmed chikungunya deaths, 103 (53.1%) were male, with median age of 77 years (<1 to 105). The median time between the first symptoms and date of death was 14 days, with 75.0% of deaths occurring within up to 38 days (post-acute phase of the disease). The average time for chikungunya death investigation closure by the Committee was 81 days, with median time of 55 days (Table 1).

Table 1
- Main characteristics associated with deaths analyzed by the Arbovirus Death Investigation Committee in Ceará, 2017

Regarding dengue, 26 deaths (19.8%) were confirmed in seven municipalities. Fortaleza stands out with 19 (73.1%) of these deaths. Thirteen women died (50.0%), with median age of 56 years (<1 to 93). Among the confirmed dengue deaths, median time with the disease was 6 days, with up to 12 days for 75.0% of confirmed cases. However, considering investigation difficulties, average time for dengue death investigation closure was 96 days, with a median time of 53 days (Table 1).

Deaths in which clinical suspicion of arbovirus occurred during autopsy, notified by the Ceará State Death Investigation Service (SVO/CE) as suspected dengue or chikungunya cases, had positive cerebrospinal fluid sample laboratory results. 27.0% of confirmed cases had positive IgM and/or AgNS1 cerebrospinal fluid results for dengue. 35.0% of confirmed chikungunya deaths had positive Ac IgM and/or RT-qPCR cerebrospinal fluid results.

Discussion

The characteristics of chikungunya deaths were very distinct from those of dengue deaths in terms of time with the disease until death and the median age of the cases. Whereas dengue deaths frequently occurred during the first week of the disease, this pattern was not repeated in chikungunya cases. Most chikungunya deaths seem to occur during the post-acute or even chronic phase of the disease. This poses yet another challenge for investigation of these deaths since infection generally decompensates underlying diseases, hindering investigation of the real cause of death and case closure.2727. Cavalcanti LPG, Freitas ARR, Brasil P, Cunha RV. Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya. Mem Inst Oswaldo Cruz [Internet]. 2017 Aug [cited 2019 Jul 11];112(8):583-5. Available from: Available from: http://www.scielo.br/pdf/mioc/v112n8/0074-0276-mioc-112-8-0583.pdf . doi: 10.1590/0074-02760160537
http://www.scielo.br/pdf/mioc/v112n8/007...
Age at which death occurs also stands out: in Ceará, with regard to dengue, in recent years the age at which death occurs has tended to decrease,66. Cavalcanti LP, Coelho IC, Vilar DC, Holanda SG, Escóssia KN, Souza-Santos R. Clinical and epidemiological characterization of dengue hemorrhagic fever cases in northeastern Brazil. Rev Soc Bras Med Trop [Internet]. 2010 Jul-Aug [cited 2019 Jul 11];(43):355-8. Available from: Available from: http://www.scielo.br/pdf/rsbmt/v43n4/a03v43n4.pdf . doi: 10.1590/S0037-86822010000400003
http://www.scielo.br/pdf/rsbmt/v43n4/a03...
,2020. Teixeira MG, Siqueira Jr JB, Ferreira GLC, Bricks L, Joint G. Epidemiological trends of dengue disease in Brazil (2000-2010): a systematic literature search and analysis. PLoS Negl Trop Dis [Internet]. 2013 Dec [cited 2019 Jul 11];7(12):e2520. Available from: Available from: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0002520 . doi: 10.1371/journal.pntd.0002520
https://journals.plos.org/plosntds/artic...
while most chikungunya deaths occurred in the elderly or older adults.

Moreover, the tendency of the cause of these deaths among the elderly to be more overlooked draws attention, considering the fact that their families rarely allow autopsies to be performed to confirm the cause. Another interesting finding was proof of central nervous system infection, given the positivity of Ac IgM, Ag and viral genome in the cerebrospinal fluid of many of these patients who died. An earlier study, carried out with patients referred by the Ceará Death Investigation Service, showed that dengue positivity in cerebrospinal fluid reached 48.8% for the DENV-2 and DENV-3 serotypes circulating at the time of the study.2828. Araújo FM, Araújo MS, Nogueira RM, Brilhante RS, Oliveira DN, Rocha MF, et al. Central nervous system involvement in dengue: a study in fatal cases from a dengue endemic area. Neurology [Internet]. 2012 Mar [cited 2019 Jul 11];78(10):736-42. Available from: Available from: https://n.neurology.org/content/78/10/736.long . doi: 10.1212/WNL.0b013e31824b94e9
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In 2017 DENV-1 was in circulation, suggesting the possibility of this serotype having infected the central nervous system less than the serotypes studied earlier. With regard to the chikungunya virus, past studies showed neurological manifestations in India and on Reunion Island.2929. Lewthwaite P, Vasanthapuram R, Osborne JC, Begum A, Plank JLM, Shankar MV, et al. Chikungunya virus and central nervous system infections in children, India. Emerg Infect Dis [Internet]. 2009 Feb [cited 2019 Jul 11];15(2):329-31. Available from: Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662654/ . doi: 10.3201/eid1502.080902
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,3030. Lemant J, Boisson V, Winer A, Thibault L, Andre H, Tixier F, et al. Serious acute chikungunya virus infection requiring intensive care during the Reunion Island outbreak in 2005-2006. Crit Care Med [Internet]. 2008 Sep [cited 2019 Jul 11];36(9):2536-41. Available from: Available from: https://insights.ovid.com/pubmed?pmid=18679124 . doi: 10.1097/CCM.0b013e318183f2d2
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The results of the death analysis strongly suggest that these arboviruses play an important role in deaths of patients with central nervous system infection.

The relatively excessive time taken to close some cases involving death is due to the poor structure of some services and the lack of immunohistochemical tests in Ceará, showing an important limitation of death surveillance.

Given this new scenario, surveillance services struggle to close chikungunya death cases, because of doubts especially in cases with underlying disease decompensation, such as diabetes.2727. Cavalcanti LPG, Freitas ARR, Brasil P, Cunha RV. Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya. Mem Inst Oswaldo Cruz [Internet]. 2017 Aug [cited 2019 Jul 11];112(8):583-5. Available from: Available from: http://www.scielo.br/pdf/mioc/v112n8/0074-0276-mioc-112-8-0583.pdf . doi: 10.1590/0074-02760160537
http://www.scielo.br/pdf/mioc/v112n8/007...
Frequently, issues such as whether chikungunya decompensated underlying diseases that led to death, or whether chikungunya evolved in an unsatisfactory way owing to the presence of some underlying disease, are part of Committee’s routine when discussing cases. Another aspect to be considered is excessive medication absorbed by patients with chikungunya, mostly with no medical guidance, and whether there was any type of iatrogenic procedure during care for these patients.

The work of the Ceará Arbovirus Death Investigation Committee has shown that deaths associated with CHIKV infection are not brought to light by health authorities for many reasons, including : (i) shortcomings in the service offered to patients; (ii) association of chikungunya with the exacerbation of other existing diseases, resulting in deaths attributed exclusively to previous existing diseases, because of the lack of a thorough investigation that could classify CHIKV infection as the primary or secondary cause of death; (iii) the fact that severe chikungunya cases affect elderly patients, requiring a long stay in hospital, facilitating lethal hospital infections rarely associated with the initial infection condition; and (iv) the clinical expression of the disease with nonspecific symptoms and the occurrence of cases with atypical manifestations, especially neurological ones (encephalitis, meningitis), may confuse diagnosis.2323. Freitas ARR, Cavalcanti L, Von Zuben AP, Donalisio MR. Excess mortality related to Chikungunya epidemics in the context of co-circulation of other arboviruses in Brazil. PLoS Currents [Internet]. 2017 Nov [cited 2019 Jul 11];9. Available from: Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731794/ . doi: 10.1371/currents.outbreaks.14608e586cd321d8d5088652d7a0d884
https://www.ncbi.nlm.nih.gov/pmc/article...
,2727. Cavalcanti LPG, Freitas ARR, Brasil P, Cunha RV. Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya. Mem Inst Oswaldo Cruz [Internet]. 2017 Aug [cited 2019 Jul 11];112(8):583-5. Available from: Available from: http://www.scielo.br/pdf/mioc/v112n8/0074-0276-mioc-112-8-0583.pdf . doi: 10.1590/0074-02760160537
http://www.scielo.br/pdf/mioc/v112n8/007...

References

Publication Dates

  • Publication in this collection
    02 Dec 2019
  • Date of issue
    2019

History

  • Received
    17 Nov 2018
  • Accepted
    28 June 2019
Secretaria de Vigilância em Saúde - Ministério da Saúde do Brasil Brasília - Distrito Federal - Brazil
E-mail: leilapgarcia@gmail.com