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Thursday, January 28, 2016

ZIKA VIRUS & microcephaly





Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015

On January 22, 2016, this report was posted as an MMWR Early Release on the MMWR website (http://www.cdc.gov/mmwr).
Lavinia Schuler-Faccini, PhD1; Erlane M. Ribeiro, PhD2; Ian M.L. Feitosa, MD3; Dafne D.G. Horovitz, PhD4; Denise P. Cavalcanti, PhD, MD5; André Pessoa2; Maria Juliana R. Doriqui, MD6; Joao Ivanildo Neri, MD7; Joao Monteiro de Pina Neto, PhD8; Hector Y.C. Wanderley, MD9; Mirlene Cernach, PhD10; Antonette S. El-Husny, PhD11; Marcos V.S. Pone, PhD4; Cassio L.C. Serao, MD12; Maria Teresa V. Sanseverino, PhD13; Brazilian Medical Genetics Society–Zika Embryopathy Task Force14 (View author affiliations)
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Summary

What is already known about this topic?An outbreak of Zika virus infection, a flavivirus transmitted by Aedes mosquitoes, was first recognized in northeastern Brazil in early 2015. In September, a sharp increase in the number of reported cases of microcephaly was reported in areas affected by the outbreak.
What is added by this report?The Brazil Ministry of Health developed a case definition for Zika virus–related microcephaly (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth). A task force and registry were established to investigate Zika virus–related cases of microcephaly and to describe the clinical characteristics of cases. Among the first 35 cases of microcephaly reported to the registry, 74% of mothers reported a rash illness during pregnancy, 71% of infants had severe microcephaly (>3 SD below the mean), approximately half had at least one neurologic abnormality, and among 27 who had neuroimaging studies, all were abnormal. Cerebrospinal fluid from all infants is being tested for Zika virus; results are not currently available.
What are the implications for public health practice?The increased occurrence of microcephaly associated with cerebral damage characteristically seen in congenital infections in Zika virus-affected areas is suggestive of a possible relationship. Additional studies are warranted to confirm the association and to more fully characterize the phenotype. In addition to removing potential breeding areas for mosquitoes, pregnant women in Zika-affected areas should wear protective clothing, apply a U.S. Environmental Protection Agency (EPA)-approved insect repellent, and sleep in a screened room or under a mosquito net.

In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August–October 2015 in eight of Brazil’s 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.
An outbreak of Zika virus infection was recognized in northeast Brazil in early 2015 (1). In September 2015, health authorities began to receive reports from physicians in this region of an increase in the number of infants born with microcephaly. In October, the MoH confirmed an increase in birth prevalence of microcephaly in northeast Brazil, compared with previously reported estimates (approximately 0.5/10,000 live births), which are based on review of birth certificates and include descriptions of major congenital anomalies. The MoH rapidly established a microcephaly registry in Brazil. On November 17, 2015, the MoH reported the increase in microcephaly cases, and possible association of microcephaly with Zika virus infection during pregnancy on its website;* and the Pan American Health Organization (PAHO) published an alert regarding the increase in occurrence of microcephaly in Brazil (2). In December, PAHO reported the identification of Zika virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in amniotic fluid samples from two pregnant women whose fetuses were found to have microcephaly by prenatal ultrasound, and the identification of Zika virus RNA from multiple body tissues, including the brain, of an infant with microcephaly who died in the immediate neonatal period (3). These events prompted new alerts from the MoH, the European Centre for Disease Prevention and Control (4), and CDC (5) concerning the possible association of microcephaly with the recent outbreak of Zika virus infection.
A comprehensive protocol for notification and investigation of all infants with microcephaly and all women with suspected Zika virus infection during pregnancy was developed by the MoH and implemented nationwide. In addition, the Brazilian Society of Medical Genetics established the Zika Embryopathy Task Force (SBGM–ZETF), which includes clinical geneticists, obstetricians, pediatricians, neurologists, and radiologists, to review all incident cases of microcephaly as well as all infants born to mothers with suspected Zika virus infection during pregnancy. Task force members collect data concerning the pregnancy (including exposure history, symptoms, and laboratory testing), physical examination of the infant, and any additional studies using a standardized spreadsheet. Microcephaly was defined as neonatal head circumference ≥2 SD below the mean for gestational age and sex of the infant at birth. Infection with Zika virus is difficult to confirm retrospectively because serological immunological tests might cross-react with other flaviviruses, especially dengue virus (6). Therefore a mother’s report of a rash illness during pregnancy was used as a proxy indicator of potential Zika virus infection.
Although 37 infants with microcephaly were evaluated, only 35 cases are included in this report. Two infants with microcephaly were excluded from the original cohort of 37 babies: one had autosomal recessive microcephaly with sibship recurrence, and one had cytomegalovirus infection. Overall, 26 (74%) mothers of infants with microcephaly reported a rash during the first (n = 21) or second (5) trimester (Table). Residence in or travel during pregnancy to areas where Zika virus is circulating was confirmed for all mothers, including women without a history of rash. Twenty-five (74%) infants had severe microcephaly (head circumference >3 SD below the mean for gestational age). Computed tomography scans and transfontanellar cranial ultrasounds showed a consistent pattern of widespread brain calcifications, mainly in the periventricular, parenchymal, and thalamic areas, and in the basal ganglia, and was associated in approximately one third of cases with evidence of cell migration abnormalities (e.g., lissencephaly, pachygyria). Ventricular enlargement secondary to cortical/subcortical atrophy was also frequently reported. Excessive and redundant scalp skin, reported in 11 (31%) cases, also suggests acute intrauterine brain injury, indicating and arrest in cerebral growth, but not in growth of scalp skin. Four (11%) infants had arthrogryposis (congenital contractures), indicative of central or peripheral nervous system involvement (7). All 35 infants in the cohort tested negative for syphilis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus infections. CSF samples from all infants enrolled in the cohort were sent to a reference laboratory in Brazil for Zika virus testing; the results are not yet available.

Discussion

Microcephaly usually results from abnormal brain development. The long-term consequences of microcephaly depend on underlying brain anomalies and can range from mild developmental delays to severe motor and intellectual deficits, like cerebral palsy. In addition to congenital infections, microcephaly can result from chromosomal abnormalities; exposure to drugs, alcohol, or other environmental toxins; premature fusion of the bones of the skull (craniosynostosis); and certain metabolic disorders. The sudden increase in the number of infants born with microcephaly associated with cerebral damage characteristically seen in congenital infections in a region where an outbreak of a newly circulating virus has recently occurred is suggestive of a possible relationship. The association between maternal infections and congenital anomalies has long been recognized, especially when infection occurs during the first 12 weeks of pregnancy (8). Brazil’s vaccination program has eliminated some infections that result in congenital anomalies, such as rubella. Congenital infections can affect multiple organ systems, and many are associated with specific brain damage, including microcephaly, calcifications (predominantly periventricular, but also in the basal ganglia and in cerebral parenchyma), ventriculomegaly, neuronal migration disorders (pachygyria, polymicrogyria, lissencephaly, and schizenchephaly), cerebellar hypoplasia, and white matter anomalies (8). Ongoing surveillance and evaluation of new cases are important to describe the phenotypic spectrum of potential Zika virus-associated congenital infections. In addition, special studies, including case-control studies, are needed to confirm the association, determine the magnitude of the potential risk, and identify other possible risk factors.
CDC recently tested samples from two pregnancies that ended in miscarriage and from two infants with microcephaly who died shortly after birth. All four cases were from Brazil and were positive for Zika virus infection, indicating that the infants had become infected during pregnancy. Zika virus was present in the brain of the full term infants, and genetic sequence analyses show that the virus in all four cases was the same as the Zika virus strain currently circulating in Brazil. All four mothers reported having experienced a febrile rash illness during their pregnancies.
Prevention strategies established by the MoH include aggressive efforts to eliminate mosquito breeding areas by removing standing water containers, as well as recommendations for personal protective measures, including preventing mosquito bites among pregnant women by applying insect repellents, wearing long-sleeved shirts and long pants, and using mosquito nets, as well as risk communication and community mobilization (3). Pregnant and lactating women can use all EPA-registered insect repellents according to the product label.
This findings in this report are subject to at least four limitations. First, historical birth prevalence of microcephaly in Brazil, approximately 0.5 cases per 10,000 live births, calculated from birth certificates, was lower than expected estimates of 1–2 cases per 10,000 live births (9), which might indicate general underascertainment of microcephaly in Brazil. However, during the second half of 2015 alone, >3,000 suspected cases of microcephaly (approximately 20 cases per 10,000 live births) were reported to the MoH through the special notification protocol, suggesting a sharp increase in birth prevalence, although the special notification protocol might have also increased case reporting. Second, before the November MoH alert, although descriptions of congenital anomalies were reported, infant head circumference was not routinely recorded. Hence, it is possible that mild cases of microcephaly might not have been reported. Since the MoH alert and the attendant media coverage of the outbreak, surveillance for microcephaly and physician reporting of suspected cases have increased. Third, because Zika virus infection was not laboratory-confirmed in infants or their mothers, the history of a nonspecific rash illness during pregnancy is subject to recall bias and might have resulted in misclassification of potential Zika virus exposure. Finally, this report does not comment on other features characteristic of intrauterine infections such as hepatosplenomegaly, rash, and chorioretinitis, or on some features that have been reported in cases with presumed Zika including hearing loss, pale maculas, and swallowing difficulties.
As of January 2016, there has been confirmed autochthonous transmission of Zika virus in 19 countries in the Americas outside Brazil (10). Although other countries in the Americas, including Uruguay and Argentina, have not reported autochthonous Zika virus, the presence of a competent vector, Ae. aegypti, in these countries poses a potential risk for further spread of the virus.

Acknowledgments

Patricia S. Sousa, Luciana S.S. Melo, Elza C.C.S. Barros, Brazilian Medical Genetics Society–Zika Embryopathy Task (SBGM–ZETF), Maranhão; Tirzah Lajus, SBGM–ZETF, Rio Grande do Norte; Bethânia F.R. Ribeiro, SBGM–ZETF, Acre; Luiz Carlos Santana da Silva, Gloria Colonelli, SBGM–ZETF, Pará; Larissa S.M. Bueno, Angelina X. Acosta, Joanna G.C. Meira, Manoel Sarno, SBGM–ZETF, Bahia; Liane Giuliani, SBGM–ZETF, Mato Grosso do Sul; Cynthia A.M.S. Pacheco, Claudia N. Barbosa, Sheila M. Pone, Patricia S. Correia, SBGM–ZETF, Rio de Janeiro; Antonio F. Moron, Amelia M.N. Santos, Ana Beatriz Alvarez Perez, Rayana E. Maia, Victor E.F. Ferraz, SBGM–ZETF, São Paulo; Tani M.S. Ranieri, Andre A. Silva, Fernanda S.L. Vianna, Alberto Abeche, Julio Cesar L. Leite, SBGM–ZETF, Rio Grande do Sul; Mariela Larrandaburu, SBGM–ZETF, Uruguay.

Corresponding author: Lavinia Schuler-Faccini, lavinia.faccini@ufrgs.br, 55-51-9975-6770.
1Universidade Federal do Rio Grande do Sul, Brazil; 2Hospital Infantil Albert Sabin, Fortaleza, CE, Brazil; 3Universidade Federal de Pernambuco, Brazil; 4Fundação Oswaldo Cruz, Rio de Janeiro, Brazil; 5University of Campinas, Sao Paulo, Brazil; 6Hospital Infantil Juvencio Mattos, Maranhao, Brazil; 7Universidade Potiguar, Rio Grande do Norte, Brazil; 8University of Sao Paulo, Ribeirao Preto, Brazil; 9Secretaria de Estado da Saúde do Espírito Santo, Brazil; 10Universidade Federal de Sao Paulo, Brazil; 11Centro Universitário do Estado do Pará, Brazil; 12Universidade do Estado do Rio de Janeiro, Brazil; 13Hospital de Clinicas de Porto Alegre, Brazil; 14Brazilian Medical Genetics Society–Zika Embryopathy Task Force.

References

  1. Campos GS, Bandeira AC, Sardi SI. Zika virus outbreak, Bahia, Brazil.Emerg Infect Dis 2015;21:1885–6. CrossRef PubMed
  2. Pan American Health Organization. Epidemiological alert. Increase in microcephaly in the northeast of Brazil—epidemiological alert. Washington DC: World Health Organization, Pan American Health Organization; 2015. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=32636&lang=en.
  3. Pan American Health Organization. Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas—epidemiological alert. Washington DC: World Health Organization, Pan American Health Organization; 2015. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=32405&lang=en.
  4. European Centre for Disease Prevention and Control. Rapid risk assessment: microcephaly in Brazil potentially linked to the Zika virus epidemic. Stockholm, Sweden: European Centre for Disease Prevention and Control; 2015. http://ecdc.europa.eu/en/publications/Publications/zika-microcephaly-Brazil-rapid-risk-assessment-Nov-2015.pdf.
  5. CDC. Recognizing, managing, and reporting Zika virus infections in travelers returning from Central America, South America, the Caribbean, and Mexico. CDC Health Advisory. Atlanta, GA: US Department of Health and Human Services, CDC; 2016. http://emergency.cdc.gov/han/han00385.asp.
  6. Hall JG. Arthrogryposis multiplex congenita: etiology, genetics, classification, diagnostic approach, and general aspects.J Pediatr Orthop B 1997;6:159–66. CrossRef PubMed
  7. Lanciotti RS, Kosoy OL, Laven JJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007.Emerg Infect Dis 2008;14:1232–9. CrossRef PubMed
  8. Silasi M, Cardenas I, Kwon JY, Racicot K, Aldo P, Mor G. Viral infections during pregnancy.Am J Reprod Immunol 2015;73:199–213. CrossRef PubMed
  9. EUROCAT European Surveillance of Congenital Anomalies. Prevalence tables. Ispra, Italy: EUROCAT European Surveillance of Congenital Anomalies; 2015. http://www.eurocat-network.eu/accessprevalencedata/prevalencetables.
  10. Hennessey M, Fischer M, Staples JE. Zika virus spreads to new areas—region of the Americas, May 2015–January 2016.MMWR Morb Mortal Wkly 2016;65(3).
Return to your place in the textTABLE. Main phenotypical findings of the first 35 patients enrolled in the Brazilian Society of Medical Genetics–Zika Embryopathy Task Force Registry — Brazil, 2015
Characteristicn (%)
Reported maternal rash during pregnancy
First trimester21 (57)
Second trimester5 (14)
Not reported9 (26)
Sex
Female21 (60)
Male14 (40)
Gestational age at birth (34)*
Term31 (91)
Preterm3 (9)
Weight
≥2,500g26 (74)
<2,500g9 (26)
Defect
Head circumference >3 SD25 (71)
Head circumference >2 SD to 3 SD10 (29)
Excessive and redundant scalp skin11 (31)
Talipes (clubfoot)5 (14)
Arthrogryposis (contractures)4 (11)
Other defects (microphthalmia)1 (3)
Abnormal funduscopic examination (11)2 (18)
Neurologic examination
Any abnormality17 (49)
Hypertonia/Spasticity13 (37)
Hyperreflexia7 (20)
Irritability7 (20)
Tremors4 (11)
Seizures3 (9)
Neuroimaging (27)
Any abnormality27 (100)
Calcifications20 (74)
Ventricular enlargement12 (44)
Neuronal migration disorders (lissencephaly, pachygyria)9 (33)
Abbreviation: SD = standard deviations.
* Number of patients sampled was less than total (35).
Suggested citation for this article: Schuler-Faccini L, Ribeiro EM, Feitosa IM, et al. Possible Association Between Zika Virus Infection and Microcephaly — Brazil, 2015. MMWR Morb Mortal Wkly Rep 2016;65:59–62. DOI: http://dx.doi.org/10.15585/mmwr.mm6503e2.
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Friday, January 22, 2016

ENFERMEDADES DEL ESOFAGO / OTROS

Enfermedades del Esófago / Otros: Ulceras Esofágicas por Liquen Plano o Dermatitis Liqueniforme

Diagnóstico: BIOPSIA. CLINICA.

Las ulceras o lesiones de la mucosa del esófago, causadas por activación de Liquen Plano son frecuentes, como en el la boca, encias, lengua, estómago y el resto del tracto digestivo. No deben confundirse con Helicobacter Pylori y pueden coexistir con el Helicobacter. Tener presente qwue la Dermatitis por Liquen Olano, activada, es una enfermedad de PIEL y MUCOSAS como bien la describió Erasmus Wilson, en Inglaterra. La BIOPSIA de piel hace el diagnostico. ES FRECUENTE EN NIÑOS Y EN ADULTOS. SE HEREDA DE LOS PADRES O ABUELOS, Puede afectar los genitales.




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El esófago es el tubo que transporta alimentos, líquidos y saliva desde la boca al estómago. Es posible que no esté consciente de su esófago hasta que trague algo demasiado grande, demasiado caliente o demasiado frío. También puede notarlo cuando algo anda mal.
El problema más común con el esófago es la enfermedad por reflujo gastroesofágico (GERD, por sus siglas en inglés). Ocurre cuando un anillo muscular que se encuentra al final del esófago no cierra adecuadamente. Eso permite que el contenido del estómago vuelva o haga reflujo, hacia el esófago y lo irrite. Con el tiempo, la GERD puede causarle lesiones en el esófago. Otros problemas incluyen acidez y cáncer.
El tratamiento depende del problema. Algunas personas mejoran con medicinas sin receta médica o con cambios en la dieta. Otras, pueden necesitar medicinas con receta o cirugía.

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Sunday, January 17, 2016

Discurso impecable - Fidel Castro INVASOR DE VENEZUELA desde 1999.




FIDEL CASTRO AUSENTE DEL ASALTO AL MONCADA

TRAIDOR DE LA CARTA DE JAMAICA DE SIMON BOLIVAR

TRAIDOR DE LA REVOLUCION CUBANA

INVASOR DE VENEZUELA DESDE 1999 APOYADO POR HUGO CHAVEZ, UNASUR, PAISES BRICS Y EL VATICANO.

Saturday, January 16, 2016

ZIKA VIRUS ON THE RUN!












LEA DENGUE Y VIRUS CON FIEBRES HEMORRAGICAS EN ESTE BLOG

LLAMENOS O CONTACTENOS SI NECESITA AYUDA: +58 412 3932265 carlosmixares@gmail.com




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Aedes aegypti mosquitoes at a lab of the Institute of Biomedical Sciences of the Sao Paulo University. The species is known to carry Zika virus, which has been connected to birth defects. CreditNelson Almeida/Agence France-Presse — Getty Images

The first case of brain damage linked to the Zika virus within the United States was reported on Friday in Hawaii.
The Hawaii State Department of Health said that a baby born in an Oahu hospital with microcephaly — an unusually small head and brain — had been infected with the Zika virus, which is believed to have caused the same damage in thousands of babies in Brazil in recent months. The presence of the virus was confirmed by the Centers for Disease Control and Prevention.
The child’s mother had lived in Brazil in May last year and probably was infected by a mosquito then, early in her pregnancy, the health department said. The virus presumably reached the embryo and damaged its developing brain.
“We are saddened by the events that have affected this mother and her newborn,” Dr. Sarah Park, Hawaii’s state epidemiologist, said in a statement. “This case further emphasizes the importance of the C.D.C. travel recommendations released today.”


Also on Friday, the C.D.C. recommended that pregnant women consider postponing travel to any countries or regions with active Zika virus transmission.
As of Saturday, those included 17 Latin American and Caribbean countries and territories: Brazil, Colombia, Ecuador, El Salvador, French Guiana, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Saint Martin, Suriname, Venezuela and the Commonwealth of Puerto Rico. The list of countries with transmission has been steadily growing; on Saturday, Barbados reported its first cases.
Women considering becoming pregnant were advised to consult doctors before going to Zika-infested areas, and all travelers headed to such areas were urged to take vigorous measures to avoid mosquito bites.
There have been no confirmed cases of Zika virus transmission within Hawaii, Dr. Park said. Six Hawaii residents are known to have had the virus since 2014, but all picked it up through travel elsewhere. Nevertheless, Hawaii is undergoing an outbreak of dengue fever, and the same mosquitoes that transmit it also can transmit Zika.
A C.D.C. epidemiologist recently predicted that Zika would follow the same pattern that dengue has, with local transmission during hot weather in tropical parts of the country, including Florida, the Gulf Coast and Hawaii.
In Washington, administration officials said the decision to issue a travel alert developed quickly at the end of the week and triggered a flurry of diplomatic contacts with the countries named in the alert, given the potential economic and tourism impact that the decision could have. Officials said that notification effort delayed the C.D.C. announcement for several hours on Friday.
Scientists do not yet know how the Zika virus damages fetal brains. It is related to the dengue, yellow fever and West Nile viruses, which normally do not cause such damage; it is not closely related to rubella orcytomegalovirus, which are known to cause microcephaly.
The virus was first discovered in monkeys in the Zika Forest in Uganda in 1947. It is widespread in Africa and Southeast Asia but had never been seen as a major threat because the disease it causes is usually mild. About 80 percent of people who get the virus show no symptoms; those who do usually get a fever, rash and red eyes, but they rarely require hospitalization.
In 2007, the Asian strain of the virus was detected moving across the South Pacific; it caused a large outbreak on Yap Island that year. By late 2014, it had reached Easter Island, off the coast of Chile.
The connection to microcephaly was not made until late last year in Brazil. The virus first appeared in the country in May, and epidemiologists estimate that more than 1.5 million Brazilians have been infected.
In October, doctors in Pernambuco State noticed a surge in cases of microcephaly. Normally, about 150 cases of the birth defect are reported in Brazil each year. Since October, more than 3,500 have been reported there.
It is also not known whether the virus alone causes microcephaly or if it happens only if the mother has a previous infection, such as with dengue virus.
Dengue is unusual in that a first infection is rarely life-threatening, but a subsequent infection with a different strain can trigger dengue hemorrhagic fever, which can be fatal.
Hawaii is conducting a “Fight the Bite” campaign intended to stop its dengue outbreak. Residents have been urged to get rid of all standing water on their properties, to apply mosquito repellents and to try to avoid being bitten.
The Zika and dengue viruses — like virtually all mosquito-borne diseases — do not occur in mosquito larvae. Adult female mosquitoes pick them up by biting one infected human, and then, some days later, after the virus has traveled from their gut to their salivary glands, they infect another human. Dr. Park said neither the mother nor the baby in Hawaii is still infectious.