Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase–polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.)

The safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants. Within 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth. A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan–Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two- and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P<0.001 for both comparisons with the other groups). In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two- or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)

Symptomatic Zika virus (ZIKV) infection of pregnant women is characterized by an acute illness with fatigue and malaise, arthralgia, conjunctivitis, and most characteristically a pruritic rash.^1-4 Similar symptoms also occur in other mosquito-borne flavivirus infections, such as dengue or chikungunya. Differential diagnosis requires real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assays performed on blood, urine, or both during the acute period of illness.⁵ Serologic testing often poses problems in areas where Zika and dengue viruses cocirculate due to serologic cross-reactivity.

During the Zika virus (ZIKV) epidemic in Rio de Janeiro from September 2015 through June 2016, a prospective cohort study involving symptomatic pregnant women who had ZIKV infection confirmed by reverse-transcriptase–polymerase-chain-reaction assay was established.¹ The study was approved by the institutional review boards at Fundação Oswaldo Cruz in Rio de Janeiro and the University of California, Los Angeles, and all the women provided written informed consent for themselves and their children.

The 2017–2018 yellow fever virus (YFV) outbreak in southeastern Brazil marked a reemergence of YFV in urban states that had been YFV-free for nearly a century. Unlike earlier urban YFV transmission, this epidemic was driven by forest mosquitoes. The objective of this study was to evaluate environmental drivers of this outbreak. Using surveillance data from the Brazilian Ministry of Health on human and non-human primate (NHP) cases of YFV, we traced the spatiotemporal progression of the outbreak. We then assessed the epidemic timing in relation to drought using a monthly Standardized Precipitation Evapotranspiration Index (SPEI) and evaluated demographic risk factors for rural or outdoor exposure amongst YFV cases. Finally, we developed a mechanistic framework to map the relationship between drought and YFV. Both human and NHP cases were first identified in a hot, dry, rural area in northern Minas Gerais before spreading southeast into the more cool, wet urban states. Outbreaks coincided with drought in all four southeastern states of Brazil and an extreme drought in Minas Gerais. Confirmed YFV cases had an increased odds of being male (OR 2.6; 95% CI 2.2–3.0), working age (OR: 1.8; 95% CI: 1.5–2.1), and reporting any recent travel (OR: 2.8; 95% CI: 2.3–3.3). Based on this data as well as mosquito and non-human primate biology, we created the “Mono-DrY” mechanistic framework showing how an unusual drought in this region could have amplified YFV transmission at the rural-urban interface and sparked the spread of this epidemic. The 2017–2018 YFV epidemic in Brazil originated in hot, dry rural areas of Minas Gerais before expanding south into urban centers. An unusually severe drought in this region may have created environmental pressures that sparked the reemergence of YFV in Brazil’s southeastern cities. In 2017–2018, cities in southeastern Brazil experienced an unusual outbreak of yellow fever virus. In the early 20^th century, these cities had large outbreaks of yellow fever, spread by Aedes mosquitoes. But until this recent outbreak, they had been free of yellow fever for nearly a century. While this outbreak was spread by Haemagogus forest mosquitoes, the reemergence of yellow fever in densely populated urban areas raises serious concerns about it reestablishing ongoing transmission in cities, spread by urban Aedes mosquitoes. Our study sought to understand how and why yellow fever virus remerged in this area. We traced the outbreak, finding that it started in hot, dry, rural areas and spread south into cool, wet urban areas. The epidemic coincided with a severe drought, particularly in Minas Gerais where the epidemic started. Individuals with outdoor or rural risk factors were at highest risk, especially when the epidemic started. Therefore, this severe drought may have promoted the spread of yellow fever at rural-urban boundaries. To further explore this idea, we developed a unique framework based on forest mosquito and Howler monkey biology. Our framework, “Mono-DrY,” shows how severe drought could have increased mosquito and monkey densities, promoting the spread of yellow fever.