The Observatory

Sept. 22, 2016

was the year ZIKV was isolated from a sentinel rhesus monkey in the Zika Forest of Uganda.

was the year human illness was first confirmed due to ZIKV infection in Nigeria.

of the population in French Polynesia had symptomatic ZIKV infection from October 2013 to February 2014.

of individuals with ZIKV infection are asymptomatic, and may transmit the virus sexually for an unknown duration of time, up to six months or longer.

of blood collected in 2016 from asymptomatic donors in Puerto Rico tested positive when screened for ZIKV.

days is the time period that whole blood had detectable viremia in patients after ZIKV symptom onset when compared to serum.

8.1 million
is the number of viral copies per milliliter in serum ZIKV infection in non-pregnant individuals that may be produced, which lasts about one to two weeks, though duration of viremia may be longer.

of all donated whole blood and blood components should be tested for ZIKV in the U.S. The FDA advises a blood screening test authorized for use by the FDA under an IND application, or a licensed test when available. Alternatively, an FDA-approved pathogen-reduction device may be used for plasma and certain platelet products.

Source: Revised Recommendations for Reducing the Risk of Zika Virus Transmission by Blood and Blood Component, from the FDA in August 2016. Visit the FDA for the guidance at


FDA advises ZIKV testing for all donated blood and components in United States. As a further safety measure against the emerging Zika virus outbreak, the U.S. Food and Drug Administration (FDA) has issued a revised guidance recommending universal testing of donated whole blood and blood components for Zika virus in the U.S. and its territories.

The FDA first issued guidance on Feb. 16 recommending that only areas with active Zika virus transmission screen donated whole blood and blood components for Zika virus, use pathogen-reduction devices, or halt blood collection and obtain whole blood and blood components from areas of the U.S. without active virus transmission. The revised guidance recommends that all states and U.S. territories screen individual units of donated Whole Blood and blood components with a blood screening test authorized for use by the FDA under an investigational new drug (IND) application, or a licensed test when available. Alternatively, an FDA-approved pathogen-reduction device may be used for plasma and certain platelet products.

The FDA has updated its guidance after careful consideration of all available scientific evidence and consultation with other public health agencies, and taking into consideration the potential serious health consequences of Zika virus infection to pregnant women and children born to women exposed to Zika virus during pregnancy. Testing of donated blood had already been underway in Florida and Puerto Rico, as well as in other areas, and it had shown to be beneficial in identifying donations infected with Zika virus. Expanded testing will continue to reduce the risk for transmission of Zika virus through the U.S. blood supply and will be in effect until the risk of transfusion transmission of Zika virus is reduced.

Female mosquitoes can transmit ZIKV to their eggs and offspring. New research reveals that female mosquitoes can pass the virus on to their eggs and offspring, bolstering the need for larvicide use as an integral part of the effort to stop the spread of the virus.

“The study connects to two important things,” says Stephen Higgs, PhD, president of the American Society of Tropical Medicine and Hygiene. “One is the science: how Zika and other mosquito-borne viruses can survive in the tropics during the dry season. The second is the need for a U.S. federal funding system that adequately plans for and addresses infectious disease outbreaks.”

To determine whether female mosquitoes that carry Zika virus pass it on to their offspring, researchers injected laboratory-reared Ae. Aegypti with the virus. The mosquitoes were fed, and within the next week they were laying eggs. The researchers collected and incubated the eggs and reared the hatched larvae until adult mosquitoes emerged. Culture of these adults found Zika virus in one of every 290 mosquitoes tested.

Mosquitoes are known to pass other viruses on to their offspring, including dengue and yellow fever, both of which are also transmitted by Ae. Aegypti. West Nile and St. Louis encephalitis viruses can also be passed on in eggs of Culex mosquitoes. The authors note that vertical transmission appears to provide a survival mechanism for the virus during adverse conditions: cold periods in temperate regions and hot dry seasons in tropical zones, or when many people become immune because of prior infection or vaccination.

“Now we need to show that vertical transmission occurs in nature,” study co-author Robert Tesh says. To do that, “researchers need to collect larvae in areas where the virus is actively circulating—Latin America and the Caribbean, and now the Miami area. Finding infected larvae in an abandoned tire or water container would be evidence of vertical transmission.”

NIH collaboration helps advance potential Zika treatments. Researchers at the National Center for Advancing Translational Sciences (NCATS) recently identified compounds that potentially can be used to inhibit Zika virus replication and reduce its ability to kill brain cells. These compounds now can be studied by the broader research community to help combat the Zika public health crisis. NCATS is part of the National Institutes of Health (NIH).

Using NCATS’ drug repurposing screening robots, researchers identified two classes of compounds effective against Zika. One is antiviral, and the other prevents Zika-related brain cell death. The compounds include emricasan, an investigational drug currently being evaluated in a clinical trial to reduce liver injury and fibrosis, and niclosamide, a U.S. Food and Drug Administration-approved drug for use in humans to treat worm infections. In addition, the researchers identified nine cyclin-dependent kinase (CDK) inhibitors. CDK usually is involved in regulation of cellular processes as well as normal brain development, but the Zika virus can negatively affect this process.

NCATS researcher Wei Zheng, PhD, and his team led the drug repurposing screen to test three strains of Zika: Asian, African, and Puerto Rican. The scientists first developed an assay using caspase 3, a protein that causes brain cell death when infected by the virus. The next step was screening 6,000 FDA-approved and investigational compounds, which resulted in the identification of more than 100 promising compounds. The team then evaluated the protective effect of these compounds in brain cells after Zika virus infection. Three lead compounds, emiracsan, niclosamide, and a CDK inhibitor known as PHA-690509, were identified as reducing neuronal cell death caused by Zika virus infection. These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. For example, emricasan prevents cell death, and niclosamide and the nine CDK inhibitors stop the virus’s replication.

NCATS’ screening effort enabled the broader research team to quickly translate its earlier discoveries toward work to develop treatments for Zika virus infection. Johns Hopkins University is working on a mouse model to study the neuroprotective effects of the compounds identified from the screen and studying the mechanism of action of the lead compounds. Florida State University is testing the efficacy of these compounds in a Zika virus mouse model and is also studying the mechanism of action of the lead compounds.


WHO issues new treatment guidelines for chlamydia, gonorrhea, and syphilis. New guidelines for the treatment of three common sexually transmitted infections (STIs) have been issued by the Geneva, Switzerland-based World Health Organization (WHO) in response to the growing threat of antibiotic resistance.

Chlamydia, gonorrhea, and syphilis are all caused by bacteria and are generally curable with antibiotics. However, these STIs often go undiagnosed and are becoming more difficult to treat, with some antibiotics now failing as a result of misuse and overuse. It is estimated that, each year, 131 million people are infected with chlamydia, 78 million with gonorrhea, and 5.6 million with syphilis.

Resistance of these STIs to the effect of antibiotics has increased rapidly in recent years and has reduced treatment options. Of the three STIs, gonorrhea has developed the strongest resistance to antibiotics. Strains of multidrug-resistant gonorrhea that do not respond to any available antibiotics have already been detected. Antibiotic resistance in chlamydia and syphilis, though less common, also exists, making prevention and prompt treatment critical.

When left undiagnosed and untreated, these STIs can result in serious complications and long-term health problems for women, such as pelvic inflammatory disease, ectopic pregnancy, and miscarriage, and untreated gonorrhea and chlamydia can cause infertility in both men and women. Infection with chlamydia, gonorrhea, and syphilis can also increase a person’s risk of being infected with HIV two- to three-fold. An untreated STI in a pregnant woman increases the chances of stillbirth and newborn death.


Ebola virus lingers longer than expected in semen. Initial data from a Liberian public health program show about nine percent (38) of 429 male Ebola survivors had fragments of Ebola virus in their semen. Of those, 63 percent had semen samples that tested positive for Ebola fragments a year after recovering from the disease and, in one man’s case, at least 565 days after he recovered. Men older than 40 were more likely than younger men to have a semen sample test positive.

The report provides preliminary results from Liberia’s Men’s Health Screening Program (MHSP), the first national semen testing program for Ebola virus. It is the largest analysis to date to look at Ebola virus persistence in male survivors. The tests detect Ebola virus genetic material but cannot tell if live virus is present and capable of spreading disease.

As part of the Liberia MHSP, male Ebola survivors ages 15 and older can enroll and have their semen tested monthly. Men receive counseling on safe sex practices and receive condoms at each visit. Men who have two consecutive negative semen tests “graduate” from the program.

The potential role that sexual contact could play in sparking new outbreaks of Ebola in West Africa came to light in March 2015 when a woman from Monrovia, Liberia, became ill with Ebola and died. The nation had been declared free of Ebola at the time, and the woman’s only known exposure to Ebola was through unprotected sexual intercourse with an Ebola survivor. The man’s semen was tested and found to be positive 199 days after he first became ill with Ebola. Genetic analysis showed that the infections of the man and woman closely matched each other.

Scientists have long known that Ebola virus can survive in certain sites within the body that the immune system may have trouble reaching, including the testes and eyes. This report provides new understanding of how long virus fragments can persist in the body. It also is shedding light on the individual differences in the length of time that traces of Ebola can remain in survivors’ semen.

Drugs of Abuse

FDA announces Opioids Action Plan. After an extensive review of the latest scientific evidence, the FDA has announced it is requiring class-wide changes to drug labeling, including patient information, to help inform healthcare providers and patients of the serious risks associated with the combined use of certain opioid medications and a class of central nervous system (CNS) depressant drugs called benzodiazepines.

Among the changes, the FDA is requiring boxed warnings—the agency’s strongest warning—and patient-focused Medication Guides for prescription opioid analgesics, opioid-containing cough products, and benzodiazepines (nearly 400 products in total), with information about the serious risks associated with using these medications at the same time. Those risks include extreme sleepiness, respiratory depression, coma, and death.

The actions are among a number of steps the FDA is taking as part of the agency’s Opioids Action Plan, which focuses on policies aimed at reversing the prescription opioid abuse epidemic, while still providing patients in pain access to effective and appropriate pain management.

Given the importance of reaching healthcare professionals and the public with information about the risks of using these products together, the FDA also issued a Drug Safety Communication. Through the Drug Safety Communication and by requiring patient Medication Guides, the agency also provides information for anyone who is taking, or who knows someone taking, either of these types of medications and encourages them to better understand the risks of taking them together; and, when it is medically necessary, for healthcare providers, to remind them to be careful to prescribe them as directed, without increasing the dose or dosing frequency for either drug.

The FDA’s data review showed that physicians have been increasingly prescribing opioids and benzodiazepines together, and this has been associated with adverse outcomes. The agency concluded that from 2004 to 2011, the rate of ED visits involving non-medical use of both drug classes increased significantly, with overdose deaths (from taking prescribed or greater than prescribed doses) involving both drug classes nearly tripling during that period. Additionally, the number of patients who were prescribed both an opioid analgesic and benzodiazepine increased by 41 percent between 2002 and 2014, which translates to an increase of more than 2.5 million opioid analgesic patients receiving benzodiazepines.