The Observatory

July 20, 2016

Infectious Diseases

Monkey study shows Zika infection prolonged in pregnancy. University of Wisconsin–Madison researchers studying monkeys have shown that one infection with Zika virus protects against future infection, though pregnancy may drastically prolong the time the virus stays in the body. The researchers published a study describing their work establishing rhesus macaque monkeys as a model for studying the way Zika virus infections may progress in people.

The researchers infected monkeys with the type of Zika virus causing an epidemic that first became apparent in South America in 2015, and found that those monkeys resisted infection by the same Zika strain 10 weeks later.

But their findings also uncovered a stark contrast in the length of infection of pregnant monkeys versus males and non-pregnant females. Though non-pregnant animals in the study were found to be free of Zika virus within 10 days of infection, the virus persisted in the blood of pregnant monkeys for 30 days to 70 days. The prolonged infection has implications for the severe impacts of Zika virus during pregnancy. One possible explanation for the persistence of the virus in pregnancy is that the immune systems of mothers-to-be are compromised, and they aren’t able to clear the virus as fast.

Though the researchers have been performing ultrasounds on Zika-infected pregnant monkeys and collecting fluid from their wombs, they can’t yet say whether the still-growing fetuses themselves are infected or whether any of them are developing microcephaly.

New study sheds light on how some survive Ebola. A first-of-its-kind Ebola study has yielded clues to how some people are able to survive the deadly virus and suggests possible avenues for treatments that could save more lives. Researchers at the U.S. Centers for Disease Control and Prevention (CDC), Emory University School of Medicine, and University of Nebraska Medical Center analyzed the immune responses of Ebola patients treated in the United States. Their study was recently published online in the Clinical Infectious Disease Journal.

This is the first time researchers have been able to study Ebola virus disease (EVD) using samples taken from patients during both their illness and recovery. In the seven U.S. patients, researchers tracked 54 different markers of immune-system activity from hospital admission until the day of discharge. Among the seven patients, five had moderate EVD and two had severe EVD requiring mechanical ventilation and dialysis.

“We were able to identify the particular components of patients’ immune systems that successfully fought off the virus,” says lead author Anita McElroy, MD, PhD. “These are the parts of the immune system that we need to tap into to develop new therapies.”

The results show patients with severe EVD had high levels of virus in their blood and out-of-control immune responses, leading to destruction of healthy tissues, multisystem organ failure, shock, and, in most cases, death. In contrast, patients with moderate EVD had strong, healthy immune responses that were able to control the virus. All patients with moderate illness and one patient with severe illness survived.

It is unclear why some people’s immune systems respond more effectively to viruses. Possible contributing factors include genetics and whether or not a person has other illnesses or conditions. Identifying which parts of the immune system malfunction in severe EVD cases as well as the parts that function well in moderate cases could lead to the design of therapies that might theoretically inhibit the disease’s progression.


HPV vaccine reduced cervical abnormalities in young women. Young women who received the human papillomavirus (HPV) vaccine through a school-based program had fewer cervical cell anomalies when screened for cervical cancer, found a new study in CMAJ (Canadian Medical Association Journal).

“Eight years after a school-based HPV vaccination program was initiated in Alberta [Canada], three-dose HPV vaccination has demonstrated early benefits, particularly against high-grade cervical abnormalities, which are more likely to progress to cervical cancer,” writes study co-author Huiming Yang, MD.

Alberta has both a school-based HPV vaccination program and a population-based screening program for cervical cancer. In 2008, the province introduced HPV vaccination for Grade 5 girls (aged 10-11) and a three-year catch-up program for Grade 9 girls (aged 14-15); in 2014, it was expanded to include boys. The program provides three doses of the vaccine that protects against two strains of HPV, which account for 70 percent of all cases of cervical cancer.

To determine whether HPV vaccination had an impact on Papanicolaou (Pap) test results, researchers looked at data on the first cohort of women who participated in both the school vaccination program and cervical cancer screening. Of 10,204 women born between 1994 and 1997, 1,481 (14.5 percent) were cases—that is, they had cervical anomalies detected during screening —and the remaining 8,723 (85.5 percent) were controls—with no cervical abnormalities detected. Among cases, most (1,384, 93.5 percent) had low-grade cervical abnormalities, and the remaining 97 (6.5 percent) had high-grade abnormalities.

Fifty-six percent of study participants were unvaccinated, and 44 percent had received one or more doses of the HPV vaccine before being screened for cervical cancer. Of the women who had been vaccinated, 84 percent received three or more doses. Among the unvaccinated women, 16.1 percent had cervical abnormalities, compared with 11.8 percent in the fully vaccinated group.


Blood coagulation detector may help in monitoring stroke risk. Researchers at Tokyo Medical and Dental University have shown that an analyzer recently developed to measure blood coagulability has the sensitivity to detect hypercoagulatibility associated with stroke risk in those without atrial fibrillation (AF), a common risk factor for stroke. The study was reported in PLOS ONE.

To estimate the risk in AF patients and determine the requirement for anticoagulation therapy, the CHADS2 predictive score was used. Because some parts of this score are also associated with atherosclerosis risk and increased blood coagulability, a high score has been proposed as linked to hypercoagulability (an increased tendency for blood clotting) in both AF and non-AF patients. However, this association has not been fully investigated, partly owing to the lack of a sensitive means of detection. The researchers used a highly sensitive technique to measure small changes in blood coagulation, and found hypercoagulability in non-AF patients with high CHADS2 scores.

Several physical and chemical factors affect blood clotting; some can be measured over time to determine blood coagulability and likelihood of clot formation. Dielectric blood coagulometry (DBCM) is a recently developed test that measures changes in the dielectric permittivity of whole blood, representing clumping of red blood cells. The researchers used DBCM to detect changes in the dielectric permittivity of whole blood at 10 MHz. Comparisons between untreated blood and that with added heparin (a blood thinner) or tissue factor (a blood-clotting accelerator) enabled derivation of a coagulability index.

“We calculated the end of acceleration time (EAT) as an index of coagulability from temporal changes in dielectric permittivity,” coauthor Satomi Hamada says. “This value reduced when tissue factor was added, and increased with heparin present. It was sensitive enough to detect small changes in coagulability, particularly in hypercoagulability.”

The researchers found that patients receiving warfarin had a significantly longer EAT than those without, confirming the anticoagulation effect. They also showed that patients with high CHADS2 scores had a significantly shorter EAT that represented hypercoagulability compared with patients with lower scores.


Women with BRCA1 gene mutation at higher risk of deadly uterine cancer. Women who carry the BRCA1 gene mutation that dramatically increases their risk of breast and ovarian cancers are also at higher risk for a lethal form of uterine cancer, according to a study led by a Duke Cancer Institute researcher.

This newly defined risk, the first to show a conclusive link between the BRCA1 gene mutation and a small but significant chance of developing an aggressive uterine cancer, could become a consideration in weighing treatment options.

Currently, women with the BRCA1 mutation often have preventive surgeries to remove both breasts, as well as their ovaries and fallopian tubes, based on studies showing that the gene mutation elevates their risk for cancers in those organs. But conflicting evidence has created controversy over the need to remove the uterus. Smaller studies identified a link between the gene mutation and uterine cancer, but a larger study had been lacking until now.

Says lead author Noah D. Kauff, MD, “Our study presents the strongest evidence to date that women with this genetic mutation should at least discuss with their doctors the option of having a hysterectomy along with removal of their ovaries and fallopian tubes.”

In the research, published in JAMA Oncology, Kauff and colleagues from nine other institutions analyzed data from 1,083 women. All had BRCA1 or BRCA2 genetic mutations, had undergone removal of their ovaries and fallopian tubes, and were followed for a median 5.1 years. Incidences of uterine cancer in the BRCA-positive women in the study were compared to the rates that would be expected in the general population, based on data from the U.S. government’s Surveillance, Epidemiology, and End Results program.

Among the BRCA-positive women, eight uterine cancers were reported within the study period—a rate that was slightly higher but not statistically different than the national norm. Of those cancers, however, five were of an uncommon, very aggressive subtype called serous endometrial cancer. All but one of the serous endometrial cancers occurred in women with the BRCA1 genetic mutation.

Given the incidence of this cancer in the wider population, only about .18 cases would be expected among women with the BRCA1 mutation over the time period analyzed, meaning the women with the BRCA1 trait were at significantly higher risk.

New Assays

FDA clears test for genetic markers for antibiotic-resistant bacteria. The FDA has cleared for marketing the Xpert Carba-R Assay, an infection control aid that tests patient specimens to detect specific genetic markers associated with bacteria that are resistant to Carbapenem antibiotics.

Carbapenem antibiotics are widely used in hospitals to treat severe infections. These resistant organisms are commonly referred to as Carbapenem-resistant Enterobacteriaceae, or CRE, and have been reported in almost all states within the United States.

Current methods to identify colonization with CRE or other resistant organisms rely on growing bacteria from fecal material in cultures, which are then subjected to antimicrobial susceptibility testing to determine in vitro susceptibility to antimicrobial agents.

The Xpert Carba-R Assay tests specimens directly taken from patients, which are usually obtained by rectal swabs, for the presence of five different genetic markers that are associated with carbapenemase, the enzyme produced by CRE.

The assay is intended as an aid in infection control and can be used in conjunction with other clinical and laboratory findings. Although it tests for the most prevalent carbapenemase genes associated with resistance to carbapenem antibiotics, it does not detect the bacteria, carbapenemase activity, or other possible non-enzymatic causes of carbapenem resistance. The Xpert Carba-R Assay tests only for genetic material.

The assay also does not detect all types of carbapenemase genes, and it is important to recover bacteria for accurately tracking the spread of carbapenem resistance. Labs should continue to perform standard bacterial culture in conjunction with it. In addition, concomitant cultures are necessary to recover organisms for epidemiological typing, antimicrobial susceptibility testing, and for confirmatory bacterial identification.

Lab-tested diagnosis needed when treating patients with persistent diarrhea. Persistent diarrhea, which is diarrhea that lasts at least 14 days, is an illness typically caused by parasites or bacteria and requires accurate diagnosis in order to determine what treatment to give, according to Herbert L. DuPont, MD, director of the Center for Infectious Diseases at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health.

In a literature review published recently in JAMA, DuPont advises medical practitioners to be alert when diagnosing persistent versus acute diarrhea in patients. It is common for doctors not to focus on how many days their patients have had diarrhea, he adds.

“I’d like to educate doctors about the importance of taking the history and assessing duration of illness,” DuPont says. For acute diarrhea, the lab has a minimal role, restricted to patients passing bloody stools. If a patient has had diarrhea for two weeks or more, the doctor should focus on the cause of the disease through laboratory testing, with an emphasis on parasites.”

Acute diarrhea lasts less than two weeks, and it is typically caused by viruses or toxins. Persistent diarrhea is most commonly caused by bacteria or parasites, including Giardia, Cryptosporidium and Cyclospora. Less common parasites include Entamoeba Cystoisospora belli, Dientamoeba fragilis, Strongloides stercoralis, and microsporidia. These parasites, all of which can be detected in laboratory testing, can be contracted through food or water or from other people, and are commonly picked up while traveling.

A new testing method called multiplex polymerase chain reaction (PCR) was developed within the past year. This simultaneous, single test identifies unique DNA sequences to detect a panel of causes of diarrhea. Two platforms have been approved by the U.S. Food and Drug Administration for use.

Previously, researchers would culture bacteria from a stool sample and examine it for isolated bacteria. For parasites, they would either look under a microscope or, for three of the parasites, use commercial enzyme immunoassays. Both methods were only able to identify a small number of parasites.

Clarification: The July 2016 Clinical Issues article, “Automated analyzers add efficiency to laboratory testing” by Maria Luz Rodriguez, PhD, incorrectly placed the subhead that read “Microarray-based technologies” on page 32. Liquid chromatography and mass spectrometry as well as laboratory automation for other fields are not under this subhead.