Study published in Nature investigates resurgence of dengue after Zika epidemic

Study points out that a large part of the population when infected by the Zika virus may have produced cross-immunity against dengue, which decreased the number of cases between 2017 and 2018

A study published in May in the scientific journal Nature Communications entitled Lying in wait: the resurgence of dengue virus after the Zika epidemic in Brazil attempted to understand what factors determined the decline in the number of dengue cases in Brazil in 2017 and 2018, years after the triple epidemic of the Zika, dengue and Chikungunya viruses, which occurred in 2016. The research also analyzed the origins of the viruses that caused the 2019 epidemic in Brazil, when 2.1 million cases were registered. According to the Ministry of Health, 273,193 probable dengue cases were recorded in Brazil in the same year. The dengue virus is one of the greatest threats to public health in tropical regions, especially in Brazil, where annual epidemics lead to the illness of thousands of people. The results of this study reveal that the virus can withstand periods of low susceptibility in the population and reappear when conditions are right. An important finding was that environmental conditions were probably not the main cause of fluctuations in the incidence of dengue in Brazil. In addition, public health interventions after the Zika epidemic may have impacted transmission.

According to the researcher from the Department of Epidemiology of Microbial Diseases, at Yale University, in the United States, Anderson Brito, one of the authors of the study, the drastic drop in the number of dengue cases was due in part to the low rate of transmission of the disease virus, due to the reduction in the number of people susceptible to the main serotypes in circulation at the time: dengue 1 and dengue 2. Another probable explanation is the vector control campaigns that took place in 2016, in response to Zika, not only in Brazil, but also in several Latin American countries, which were supported by the Pan American Health Organization (PAHO), and substantial efforts by local governments to eliminate mosquitoes, he highlights. For Dr. Brito, this may explain why, in addition to Brazil, all the regions most affected by dengue also saw a sharp drop in the number of cases of the disease. In order to accurately understand how dengue virus strains can remain undetected for long periods of low transmission, further research is needed.

The study focused mainly on two states: Paraíba, in northeastern Brazil, and São Paulo, in southeastern Brazil. Located in different regions of the country, different municipalities in these states have had recent large outbreaks of dengue, after years of low incidence. In 2014, the number of reported cases was low in both states, but in 2015 and 2016, they increased in many municipalities. In 2017, the incidence dropped to historical lows in Paraíba and São Paulo, reaching levels that resemble those of 2014. In 2018, some municipalities in these states suffered major outbreaks, however it was in 2019 that dengue fever resurfaced with full force, returning with record peaks in São Paulo, while in Paraíba it resurfaced in specific municipalities, mainly around the metropolitan region of the capital João Pessoa.

“The dengue outbreaks in 2018 and 2019, in Paraíba and São Paulo, were caused, respectively, by strains of dengue virus serotype 1 and 2 that have been circulating in Brazil for about 10 years. These strains persisted in the country even in the period of low transmission (2017 and 2018), and then reemerged in large local outbreaks, when all conditions were favorable to the emergence of cases”, details Dr. Brito. The results of the study suggest that, compared to other studies already published, a large part of the population was infected by the Zika virus, which may have produced cross-immunity against the dengue virus resulting in a large decrease in the number of cases in 2017 to 2018. . This effect may also have been caused by the increase in population immunity, due to the high rates of infection by the dengue virus itself in the years prior to 2016 or a combination of these factors.

The study combined genomic, ecological and epidemiological data to investigate the dynamics of the viruss reappearance. Genomic sequencing of the dengue virus from samples collected in the Northeast and Southeast of Brazil was used to investigate the reason why few cases of the disease were reported in 2017 and 2018 and the origins of the viruses that caused the 2019 epidemic. The research was developed in partnership by researchers from Fiocruz Pernambuco; North American universities of Yale, Florida and Notre Dame; from the University of São Paulo (USP/Ribeirão Preto) and from the Rega Institute for Medical Research (Belgium).

Impact of COVID-19 on notifications

Every year, Brazil faces a constant threat caused by dengue. In 2020, almost a million probable cases were recorded according to the Ministry of Health. In 2021, until mid-April, there are 228.485 probable cases of the disease. The number shows a drop of 65.7% in comparison to the same period last year, according to the Epidemiological Bulletin. The most likely hypotheses are reduced human mobility and underreporting due to the pandemic. Although, so far, the country still does not face an epidemic, the disease turns on an alert. There are currently more than 205 thousand probable cases. “Fearing COVID-19, many people, especially in 2020, avoided being exposed to hospital environments, a factor that may have favored underreporting of symptomatic cases. In addition, as viruses (dengue and Zika) depend on mosquitoes to be transmitted from one person to another, the restriction of circulation of people in Brazilian cities certainly also made it difficult to transmit these arboviruses over long distances, since mosquito flights cover small areas (a few hundred square meters)”, he says. Professor Brito also notes that mosquito-borne viruses remain in circulation, even if in low transmission, and all they need is favorable conditions to resurface in major outbreaks of the diseases they cause.

The pandemic also impacted the epidemiological survey and many Brazilian municipalities failed to carry out the Rapid Survey of Infestation Index by Aedes Aegypti (LIRAa). “Environmental management to prevent mosquitoes from proliferating is essential. In other words, the lack of a survey on Aedes aegypti infestation may favor dengue outbreaks, especially when conditions are favorable for viral transmission, such as temperature, humidity, mosquitoes and susceptible people. When these factors are present, arboviruses such as the dengue virus, Zika, and Chikungunya circulate more easily”, points out Dr. Brito. The researcher emphasizes that as the symptoms of these diseases are similar, the genetic sequencing of samples from symptomatic individuals is ideal for the identification of the infectious agent.

In a comparison between COVID-19 and arboviral diseases caused by flaviviruses, they have more characteristic symptoms, which serve to differentiate the diagnosis. However, some symptoms such as fever and myalgia are shared among these diseases, which can raise doubts. “This pandemic showed the importance of molecular diagnosis of viruses. Dengue is often diagnosed based on symptoms, and the lack of more precise molecular tests, such as RT-PCR or sequencing, has allowed the Zika virus to circulate in Brazil for more than a year without being detected, probably with cases being reported with dengue, based only on the symptoms. I hope that this pandemic will leave a legacy of greater availability and use of molecular tests, for the early detection of viral outbreaks”, emphasizes the researcher.

Finally, Dr. Brito recognizes that the rapid transmission of COVID-19 and the high load it imposes on health systems suddenly are the main reasons of concern for health managers. “The pandemic has pushed hospitals and health professionals to the limit, and knowing that other health issues continue to exist, treatable diseases are not being diagnosed or monitored in a timely manner. And even with the vaccination in progress, protection measures are essential to preserve lives and the capacity of health systems to provide adequate care”, he concludes.