Perspective

Recent deaths, microcephaly cases in Brazil linked to Zika virus infection

Brazil’s ministry of health linked two deaths and an unusual increase in the number of cases of microcephaly to Zika virus infection, according to a press release.

If confirmed, the recent deaths would be the first Zika virus-related deaths ever reported, the release said.

Brazil’s Ministry of Health was notified of a man with a history of lupus and chronic use of corticosteroid drugs who was suspected of having dengue fever and died. Instead, reverse transcription PCR identified Zika virus genomes in blood and viscera samples. A 16-year–old patient who died in October also was suspected of having dengue fever; however, a blood analysis performed 1 week after the patient presented with a headache, nausea and rash indicated the presence of Zika virus. Further testing confirmed the results.

Officials from the Brazilian Ministry of Health said that findings are being released as they emerge. They recommend that all patients with Zika virus infection who have worsening conditions be treated with the same protocols used for severe dengue cases.

Zika virus associated with rise in microcephaly cases

The relationship between Zika virus and the increasing occurrence of microcephaly among infants in northeastern Brazil was based on test results that revealed the presence of Zika virus in blood and tissue samples from an infant born with microcephaly who died. An initial analysis suggests the risk of Zika virus infection is associated with the first 3 months of pregnancy, according to Brazil’s Ministry of Health.

Health officials noted the situation is unprecedented in scientific research, and this finding deserves attention.

Considering the increased vulnerability among pregnant women, officials are calling for additional research to investigate the role of Zika virus infection in the human body and how it affects a fetus.

As of Nov. 21, at least 739 cases of microcephaly were reported in nine states in Brazil, mainly in Pernambuco (n = 487), Paraíba (n = 96) and Sergipe (n = 54), according to WHO. However, as of Nov. 27, WHO officials claim they have not yet determined the cause of events.

As previously reported, microcephaly is a condition that affects newborns, in which the occipitofrontal circumference is smaller than average. The condition is diagnosed in children with a head circumference of two standard deviations below the mean compared with similarly aged children. Microcephaly is caused by genetic and environmental factors, leading to developmental problems. The condition is untreatable; however, early detection can boost quality of life.

In response to the recent events, Brazil declared a national public health emergency and the Ministry of Health is conducting clinical, laboratory and ultrasound analyses of infants and mothers. In addition, CDC representatives joined local officials to identify and evaluate additional cases of microcephaly and Zika virus.

A campaign was recently launched to increase cleaning and inspection protocols in mosquito breeding areas, according to the release, and a national plan involving 17 ministries is underway for combating transmission. The country’s ministry of health said plenty of financial resources are available to support their actions, which include extra support for prenatal care, psychosocial care, physical therapy, testing and early stimulation of infants.

Zika virus spreads in the Americas

According to WHO, Zika virus was detected in 14 Brazilian states, including São Paulo, Rio de Janeiro and Rio Grande do Norte, and has since spread to Central America. The first reported case of Zika virus in the Americas occurred in Chile in February 2014, and new infections emerged from the region until June 2014. The Pan American Health Organization (PAHO) and WHO also confirmed that four autochthonous cases of Zika virus infection were reported in Guatemala (n = 1) and El Salvador (n = 3). Recent outbreaks in other countries indicate the virus may spread to regions where the Aedes vector is found.

Due to the increased transmission of Zika virus, officials from the PAHO and WHO recommend that member states in the affected regions monitor cases of Zika virus infection and prepare all levels of health services for potential outbreaks. They also recommend developing a public communications strategy to reduce transmission, particularly in regions where the vector exists.

Brazil’s ministry of health linked two deaths and an unusual increase in the number of cases of microcephaly to Zika virus infection, according to a press release.

If confirmed, the recent deaths would be the first Zika virus-related deaths ever reported, the release said.

Brazil’s Ministry of Health was notified of a man with a history of lupus and chronic use of corticosteroid drugs who was suspected of having dengue fever and died. Instead, reverse transcription PCR identified Zika virus genomes in blood and viscera samples. A 16-year–old patient who died in October also was suspected of having dengue fever; however, a blood analysis performed 1 week after the patient presented with a headache, nausea and rash indicated the presence of Zika virus. Further testing confirmed the results.

Officials from the Brazilian Ministry of Health said that findings are being released as they emerge. They recommend that all patients with Zika virus infection who have worsening conditions be treated with the same protocols used for severe dengue cases.

Zika virus associated with rise in microcephaly cases

The relationship between Zika virus and the increasing occurrence of microcephaly among infants in northeastern Brazil was based on test results that revealed the presence of Zika virus in blood and tissue samples from an infant born with microcephaly who died. An initial analysis suggests the risk of Zika virus infection is associated with the first 3 months of pregnancy, according to Brazil’s Ministry of Health.

Health officials noted the situation is unprecedented in scientific research, and this finding deserves attention.

Considering the increased vulnerability among pregnant women, officials are calling for additional research to investigate the role of Zika virus infection in the human body and how it affects a fetus.

As of Nov. 21, at least 739 cases of microcephaly were reported in nine states in Brazil, mainly in Pernambuco (n = 487), Paraíba (n = 96) and Sergipe (n = 54), according to WHO. However, as of Nov. 27, WHO officials claim they have not yet determined the cause of events.

As previously reported, microcephaly is a condition that affects newborns, in which the occipitofrontal circumference is smaller than average. The condition is diagnosed in children with a head circumference of two standard deviations below the mean compared with similarly aged children. Microcephaly is caused by genetic and environmental factors, leading to developmental problems. The condition is untreatable; however, early detection can boost quality of life.

In response to the recent events, Brazil declared a national public health emergency and the Ministry of Health is conducting clinical, laboratory and ultrasound analyses of infants and mothers. In addition, CDC representatives joined local officials to identify and evaluate additional cases of microcephaly and Zika virus.

A campaign was recently launched to increase cleaning and inspection protocols in mosquito breeding areas, according to the release, and a national plan involving 17 ministries is underway for combating transmission. The country’s ministry of health said plenty of financial resources are available to support their actions, which include extra support for prenatal care, psychosocial care, physical therapy, testing and early stimulation of infants.

Zika virus spreads in the Americas

According to WHO, Zika virus was detected in 14 Brazilian states, including São Paulo, Rio de Janeiro and Rio Grande do Norte, and has since spread to Central America. The first reported case of Zika virus in the Americas occurred in Chile in February 2014, and new infections emerged from the region until June 2014. The Pan American Health Organization (PAHO) and WHO also confirmed that four autochthonous cases of Zika virus infection were reported in Guatemala (n = 1) and El Salvador (n = 3). Recent outbreaks in other countries indicate the virus may spread to regions where the Aedes vector is found.

Due to the increased transmission of Zika virus, officials from the PAHO and WHO recommend that member states in the affected regions monitor cases of Zika virus infection and prepare all levels of health services for potential outbreaks. They also recommend developing a public communications strategy to reduce transmission, particularly in regions where the vector exists.

    Perspective
    Andi L. Shane

    Andi L. Shane

    The significance of transmission of Zika virus from pregnant women to fetus likely depends on a number of host factors, including acuity of infection, levels of viremia, timing in gestation when infection occurs and the health of pregnant woman. It is important to ensure that pregnant women receive prenatal and postnatal care and are informed about avoiding contact with mosquitoes and using bed nets and other personal protective measures.

    Zika virus infection may be less severe than dengue virus infections. The onset of fever with Zika virus may be faster and the duration may be shorter than that with dengue. While dengue infections are more likely to be severe, fatalities associated with Zika virus infections have been noted.

    For United States-based clinicians, awareness of Zika virus is important. The emergence of this virus in Brazil emphasizes the importance of obtaining a thorough travel history and considering a Zika virus infection in a person who has been in an endemic area. Most importantly, resources should be devoted to the understanding of the epidemiology, transmissibility, and short- and long-term clinical outcomes associated with Zika virus infection. We are only beginning to understand the clinical manifestations of infection with this virus.

    Due to concern that Zika virus outbreaks could occur, health care systems should prepare protocols for screening and treatment (supportive care).

    • Andi L. Shane, MD, MPH, MSc
    • Associate Professor of Pediatric Infectious Disease and Global Health Marcus Professor of Hospital Epidemiology and Infection Control Emory University School of Medicine and Children’s Healthcare of Atlanta

    Disclosures: Shane reports no relevant financial disclosures.

    Perspective

    Jonathan Davis

    Peter D. Murray, MD, MSM

    Peter D. Murray

    Measuring the head circumference of an infant is an important part of the ongoing evaluation of both growth and development throughout childhood. An infant born with microcephaly or an infant born with a normal head circumference that subsequently does not grow at a normal rate (consistent with established norms) may be an early indicator of an underlying neurologic injury that may be acquired (eg, infection), congenital, or genetic in nature.

    While it is well-recognized that head circumference is an important anthropomorphic measurement, there is inconsistency in the definition of microcephaly as well as standardized diagnostic evaluations. Microcephaly is usually defined as a head circumference of at least two standard deviations (SD) below the mean with some authors advocating for further distinguishing among mild, moderate and severe microcephaly. It is important to note that all anthropomorphic measurements may vary depending on ethnic, racial and cultural differences, so international standard curves for head circumference may not be well-justified.

    The pathogenesis of microencephaly can involve two major mechanisms: 1) abnormal brain development related to an in utero insult occurring during cellular migration; or 2) an insult to a previously normal brain resulting in a reduction of synapses. Congenital infections, such as cytomegalovirus (CMV) or even Zika virus, are associated with microcephaly through disruption of cell proliferation and neuronal migration leading to polymicrogyria and white matter injury that can be seen on MRI.

    In addition to a thorough examination to look for associated syndromic features, imaging (eg, head ultrasound or MRI) may be warranted. Of concern in cases of microcephaly is the potential for delayed development. The prognosis varies depending on the underlying cause, but microcephaly related to a congenital infection carries a worse prognosis than isolated microcephaly. Head circumference also correlates with intellectual outcome with worse IQ scores in children with smaller head circumferences.

    Recently, Zika virus has been identified as a possible pathogen that has the potential to cause brain injury and microcephaly in the fetus. This association was based on a microcephalic infant where blood and tissue samples obtained after death were found to have Zika virus present. This, in conjunction with an unprecedented number of infants born with microcephaly in northern Brazil, has led to calls for additional research regarding the effects of Zika virus on pregnant women and fetus.

    Zika virus RNA can be isolated in amniotic fluid, suggesting it crosses the placental barrier and may affect the fetal brain. While it is too early to definitely establish a link between Zika virus and the dramatic increase in microcephaly in Brazil, it must be noted that the incidence of microcephaly in northern Brazil since July far exceeds what would be expected from a presumably normally distributed anthropomorphic measurement. Clearly more intensive monitoring and microbiologic studies by public health officials are urgently needed.

    Jonathan M. Davis, MD
    Department of Pediatrics
    The Floating Hospital for Children
    Tufts Medical Center

    Peter D. Murray, MD, MSM 
    Department of Pediatrics
    The Floating Hospital for Children
    Tufts Medical Center

    References:

    Ashwal S, et al. Neurology. 2009;doi:10.1212/WNL.0b013e3181b783f7.

    Avery GB, et al. Am J Dis Child. 1972;123:214-217.

    Deloison B, et al. Prenatal Diag. 2012;doi:10.1002/pd.3923.

    Natale V, et al. BMJ Open. 2014;doi:10.1136/bmjopen-2013-003735.

    http://portalsaude.saude.gov.br/index.php/o-ministerio/principal/secretarias/svs/noticias-svs/20929-ministerio-divulga-boletim-epidemiologico-sobre-microcefalia. Accessed December 3, 2015.

    Volpe, Joseph. Neurology of the Newborn, 5th edition. Philadelphia: Saunders Elsevier, 2008.

    Von der Hagen M, et al. Dev Med Child Neurol. 2014;doi: 10.1111/dmcn.12425.

    Disclosures: Davis and Murray report no relevant financial disclosures.

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