Zika: an ongoing threat to women and infants

Santos, Beatriz Macedo Coimbra dos; Coelho, Flávio Codeço; Armstrong, Margaret; Saraceni, Valéria; Lemos, Cristina

doi:10.1590/0102-311x00038218

Cited by 11 publications

(16 citation statements)

References 13 publications

(13 reference statements)

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“…Figure 5 shows the ratio ARW(120)/ARM(120) in terms of the intensities of both sexual and vectorial transmission. This effect has been observed in Zika incidence data [14,17,26,27], but it was frequently confounded with gender-related underreporting; however, from our estimates of the male underreporting, we conclude that underreporting can account for only a 20% drop, with the rest of the difference being explained by the excess in female cases due to sexual transmission.…”

Section: Discussionsupporting

confidence: 58%

See 1 more Smart Citation

Sex-Specific Asymmetrical Attack Rates in Combined Sexual-Vectorial Transmission Epidemics

Barros¹,

Santos²,

Massad³

et al. 2019

Microorganisms

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In 2015–2016, South America went through the largest Zika epidemic in recorded history. One important aspect of this epidemic was the importance of sexual transmission in combination with the usual vectorial transmission, with asymmetrical transmissibilities between sexual partners depending on the type of sexual contact; this asymmetry manifested itself in data as an increased risk to women. We propose a mathematical model for the transmission of the Zika virus including sexual transmission via all forms of sexual contact, as well as vector transmission, assuming a constant availability of mosquitoes. From this model, we derive an expression for R 0 , which is used to study and analyze the relative contributions of the male to female sexual transmission route vis-à-vis vectorial transmission. We also perform Bayesian inference of the model’s parameters using data from the 2016 Zika epidemic in Rio de Janeiro.

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Section: Discussionsupporting

confidence: 58%

“…Any point to the right of this curve has R0>1. It is worth noticing that the reported excess cases reported for Zika in women are possible both during epidemics and off-season [26].…”

Section: Figurementioning

confidence: 99%

Sex-Specific Asymmetrical Attack Rates in Combined Sexual-Vectorial Transmission Epidemics

Barros¹,

Santos²,

Massad³

et al. 2019

Microorganisms

View full text Add to dashboard Cite

show abstract

“…It remains unknown when the next outbreak of ZIKV will occur, yet we know through past devastating epidemics, in which millions of individuals, including women and children, were affected by this virus that we still have an urgent need for effective therapies against ZIKV infection (16,53,54). Despite current potential protection due to herd and selfimmunity, environmental factors, and host-vector-virus interactions that keep ZIKV at low incidence (1,55,56), preventing ZIKV and other arbovirus infections should be a priority.…”

Section: Discussionmentioning

confidence: 99%

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

Kottkamp

Jesus

Grande

et al. 2019

J Virol

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Arthropod-borne viruses represent a significant public health threat worldwide, yet there are few antiviral therapies or prophylaxes targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy-acceptable antiviral compounds is to repurpose well-known and widely used FDA-approved drugs. In this study, we addressed the antiviral role of atovaquone, an FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides, indicating that atovaquone functions through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner, providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women and children.IMPORTANCE The ability to protect vulnerable populations such as pregnant women and children from Zika virus and other arbovirus infections is essential to preventing the devastating complications induced by these viruses. One class of antiviral therapies may lie in known pregnancy-acceptable drugs that have the potential to mitigate arbovirus infections and disease, yet this has not been explored in detail. In this study, we show that the common antiparasitic drug atovaquone inhibits arbovirus replication through intracellular nucleotide depletion and can impair ZIKV infection in an ex vivo human placental explant model. Our study provides a novel function for atovaquone and highlights that the rediscovery of pregnancy-acceptable drugs with potential antiviral effects can be the key to better addressing the immediate need for treating viral infections and preventing potential birth complications and future disease.

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“…It remains unknown when the next outbreak of ZIKV will occur, yet we know through past devastating epidemics, in which thousands of women and children were affected by this virus that we still have an urgent need for effective therapies against ZIKV infection [11], [50], [51]. Despite current potential protection from herd and self-immunity, environmental factors, and host-vector-virus interactions that keep ZIKV in the low incidence figures [1], [52], [53], [54], [55], preventing ZIKV and other arbovirus infections should be a priority.…”

Section: Discussionmentioning

confidence: 99%

The antiparasitic drug atovaquone inhibits arbovirus replication through the depletion of intracellular nucleotides.

Kottkamp

Jesus

Grande

et al. 2018

Preprint

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Arthropod-borne viruses represent a significant public health threat worldwide yet there are few antiviral therapies or prophylaxis targeting these pathogens. In particular, the development of novel antivirals for high-risk populations such as pregnant women is essential to prevent devastating disease such as that which was experienced with the recent outbreak of Zika virus (ZIKV) in the Americas. One potential avenue to identify new and pregnancy friendly antiviral compounds is to repurpose well-known and widely used FDA approved drugs. In this study, we addressed the antiviral role of atovaquone, a FDA Pregnancy Category C drug and pyrimidine biosynthesis inhibitor used for the prevention and treatment of parasitic infections. We found that atovaquone was able to inhibit ZIKV and chikungunya virus virion production in human cells and that this antiviral effect occurred early during infection at the initial steps of viral RNA replication. Moreover, we were able to complement viral replication and virion production with the addition of exogenous pyrimidine nucleosides indicating that atovaquone is functioning through the inhibition of the pyrimidine biosynthesis pathway to inhibit viral replication. Finally, using an ex vivo human placental tissue model, we found that atovaquone could limit ZIKV infection in a dose-dependent manner providing evidence that atovaquone may function as an antiviral in humans. Taken together, these studies suggest that atovaquone could be a broad-spectrum antiviral drug and a potential attractive candidate for the prophylaxis or treatment of arbovirus infection in vulnerable populations, such as pregnant women.

show abstract

Zika: an ongoing threat to women and infants

Cited by 11 publications

References 13 publications

Sex-Specific Asymmetrical Attack Rates in Combined Sexual-Vectorial Transmission Epidemics

Sex-Specific Asymmetrical Attack Rates in Combined Sexual-Vectorial Transmission Epidemics

Atovaquone Inhibits Arbovirus Replication through the Depletion of Intracellular Nucleotides

The antiparasitic drug atovaquone inhibits arbovirus replication through the depletion of intracellular nucleotides.

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