Outbreak of Severe Fungal Eye Infections Linked To IV Opioid Epidemic

MedicalResearch.com Interview with:
Aubrey Tirpack, PGY3

New England Eye Center
Tufts Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Intravenous drug abuse is a known risk factor for the development of endogenous fungal endophthalmitis (EFE), a severe intraocular infection cause by the seeding of mycotic organisms to the eye.

Our institution noted a marked increase in cases of EFE beginning in May 2014, which correlates to increasing rates of opioid abuse throughout the New England region. Ten patients were found to have intravenous drug abuse related EFE over the two year time period studied. The most common presenting symptoms were floaters, decreased vision, and pain. All patients were treated with systemic antifungals and nine patients underwent intravitreal antifungal injection. All patients were ambulatory at presentation and the majority were without systemic signs of infection.

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Rapid Tests For Foodborne Infections Can Provide Faster Treatment But Curtail Important Outbreak Data

MedicalResearch.com Interview with:

Ms. Ellyn Marder MPH</strong> Surveillance Epidemiologist, CDC Centers for Disease Control and Prevention Atlanta, Georgia

Ellyn Marder

Ms. Ellyn Marder MPH
Surveillance Epidemiologist, CDC
Centers for Disease Control and Prevention
Atlanta, Georgia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CDC’s Foodborne Diseases Active Surveillance Network (FoodNet) report provides the most up-to-date information about foodborne illnesses in the United States. Each year, FoodNet publishes a report that includes preliminary data compared with data from the previous three years. FoodNet has been monitoring illness trends since 1996 and collects data on about 15 percent of the U.S. population.

Campylobacter and Salmonella caused the most reported bacterial foodborne illnesses in 2016, according to preliminary data. FoodNet sites alone reported 24,029 foodborne infections, 5,512 hospitalizations, and 98 deaths in 2016. The numbers of reported illnesses by germ are: Campylobacter (8,547), Salmonella (8,172), Shigella (2,913), Shiga toxin-producing E. coli (1,845), Cryptosporidium (1,816), Yersinia (302), Vibrio (252), Listeria (127) and Cyclospora (55).

This is the first time the report also includes in the total number of infections those foodborne bacterial infections diagnosed only by rapid diagnostic tests in FoodNet sites. Previously, the report counted foodborne bacterial infections confirmed only by traditional culture-based methods in the total numbers.

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Low CD4 Count Linked To Heart Failure in HIV Patients

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Associate Professor of Medicine, Division of Cardiovascular Medicine
Vanderbilt Translational and Clinical Cardiovascular Research Center

MedicalResearch.com: What is the background for this study?

Response:  HIV infected people are living longer and are at risk for cardiovascular diseases. While acute myocardial infarction has been studied and the increased risk of Acute Myocardial Infarction (AMI) among HIV+ people compared to uninfected people is well documented, there are less data describing the risk of HIV and different types of heart failure, including reduced and preserved ejection fraction heart failure. Understanding more about the link between HIV and different types of HF is important because reduced and preserved ejection fraction heart failure differ with respect to underlying mechanism, treatment, and prognosis. Moreover, as cardiovascular care has improved, HIV infected people who experience an AMI are likely to survive but may live with a damaged heart. Understanding more about the link between HIV and heart failure may help providers and their patients prevent or reduce the impact of HF on the HIV community.

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Potential Drug-Binding Site Against Zika Virus Identified

MedicalResearch.com Interview with:

Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside.

Dr. Jikui Song

Dr. Jikui Song PhD
Assistant professor of biochemistry
University of California, Riverside.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV.

The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.

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Antibiotics in Pregnancy Increase Children’s Risk of Otitis Media and Ventilation Tubes

MedicalResearch.com Interview with:
Hans Bisgaard, MD, DMSc

Professor of Pediatrics
The Faculty of Health Sciences
University of Copenhagen
Copenhagen University Hospital, Gentofte
Copenhagen, Denmark

MedicalResearch.com: What is the background for this study?

Response: The consumption of antibiotics is increasing worldwide. Antibiotics alter the maternal bacterial colonization and by vertical transmission this can affect the offspring. An unfavorable microbiome may increase the disease propensity of the offspring.
Otitis media is one of the most common infections in early childhood. We hypothesized that antibiotic consumption in pregnancy can increase the children’s risk of otitis media.
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Promising New Drug Can Stop Malaria After Mosquito Bite

MedicalResearch.com Interview with:

Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany

Dr Mihály Sulyok

Dr Mihály Sulyok MD
Eberhard Karls University
Institute of Tropical Medicine,
Tübingen, Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: New antimalarials are desperately needed, not just for treatment, but also for prophylaxis. DSM265, a novel antimalarial compound that selectively inhibits the plasmodial dihydroorotate dehydrogenase has a promising pharmacokinetic profile characterized by a long elimination half-life.

We performed a study at the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany) to investigate safety, tolerability and efficacy of DSM265 using controlled human malaria infection. In the first cohort, 400mg of DSM265 was administered orally to five healthy, malaria naive individuals one day before direct venous inoculation of an established infective dose of P. falciparum sporozoites (PfSPZ Challenge). Placebo was administered to two volunteers. The study was randomized and double blinded. In this cohort all placebo participants developed malaria, whereas all DSM265 participants were protected.

In a second cohort, 400mg DSM265 was administered 7 days before the sporozoite inoculation for six participants, two participants recieved placebo. In this cohort, the two placebo and three of six DSM265 volunteers developed thick blood smear positive malaria. The remaining three DSM265 volunteers developed transient submicroscopic parasitemia without symptoms or thick blood smear positivity. The only possible DSM265-related adverse event was a slight transient elevation in serum bilirubin in one volunteer.

The study was funded by the Global Health Innovative Technology Fund, Wellcome Trust, Bill & Melinda Gates Foundation through Medicines for Malaria Venture, and the German Center for Infection Research.

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Comparison Zika Outbreaks in French Polynesia, Colombia and the State of Bahia in Brazil

MedicalResearch.com Interview with:

Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China

Dr. Daihai He

Daihai He PhD
Department of Applied Mathematics
The Hong Kong Polytechnic University
Hung Hom, Kowloon
Hong Kong (SAR), China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.

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Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes

MedicalResearch.com Interview with:
Anders Hviid

Senior Investigator, M.Sc.,Dr.Med.Sci.
Department of Epidemiology Research
Division of National Health Surveillance & Research

MedicalResearch.com: What is the background for this study?

Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.
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Patients With Clostridium difficile Infections Should Have Need For Gastric Acid Suppression Reassessed

MedicalResearch.com Interview with:

Sahil Khanna,

Dr. Sahil Khanna

Sahil Khanna, M.B.B.S. MS
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, Minnesota

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and has recently shown increasing incidence especially in the community. Novel risk factors for CDI development include the use of gastric acid suppression medication, presence of systemic comorbid conditions, C difficile carriage in water and food sources, amongst others.

Gastric acid suppression medications such as proton-pump inhibitors (PPIs) and histamine-2 receptor blockers (H2Bs) are commonly prescribed and consumed over the counter for gastroesophageal reflux disease, peptic ulcer disease, or functional dyspepsia, but they are also sometimes prescribed for unnecessary indications, which leads to overuse of these medications. Recurrent CDI after a primary infection is a major problem, with the risk being as high as 50% to 60% after 3 or more Clostridium difficile infections. Data on the association between acid suppression and recurrent CDI are conflicting and therefore we performed a systematic review and meta-analysis to study the association between the use of gastric acid suppression medications and the risk of recurrent CDI.

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Adolescents Perinatally Infected with HIV Are At Increased Risk of Serious Physical and Mental Health Problems

MedicalResearch.com Interview with:

Anne M Neilan, MD,MPH Assistant In Medicine, Massachusetts General Hospital Research Fellow, Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114

Dr. Neilan

Anne M Neilan, MD,MPH
Assistant in Medicine and Pediatrics
Massachusetts General Hospital
Instructor at Harvard Medical School
Department: Medicine Service
Division: Infectious Disease
Department: Pediatric Service
Massachusetts General Hospital
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect. This study found that U.S. youth infected with HIV around the time of their birth are at higher risk throughout their adolescence and young adulthood for experiencing serious health problems, poor control of the HIV virus (having high levels of HIV virus in their bodies and fewer CD4 immune cells which protect the body from infection), or death. The study also found that among those with good HIV control, serious health problems are rare.

By combining data from two large, long-term U.S. studies – the Pediatric HIV/AIDS Cohort Study (PHACS, www.phacsstudy.org) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT, www.impaactnetwork.org) Network – we were able to study the health of more than 1,400 perinatally HIV-infected children, adolescents and young adults ages 7 to 30 years between 2007 and 2015. The study found that youth ages 13 to 30 were most likely to have poor HIV control AIDS-related illnesses, and death compared to younger participants. Among 18 – 30 year-olds, the study found that poor control of the HIV virus – meaning higher levels of HIV virus and lower levels of CD4 immune cells which protect the body from infection –35 percent of the time, increasing the risk that these youth would stop responding to certain HIV medications and could transmit HIV to others. These findings are consistent with other U.S. and European reports. Despite being engaged in health care, the number of deaths among youth born with HIV in the U.S. is 6 to12 times higher than for youth without HIV of the same age, sex and race.

Along with HIV-related health problems, the most commonly reported health conditions concerned mental health and brain and nervous system development. Many women in the study also had sexually transmitted infections, which was found to be associated with lower CD4 immune cell counts. This may suggest a biological mechanism or may reflect that patients who have difficulty with their medications are also engaging in more frequent risky sexual behaviors.

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High Risk Individuals Are Testing For HIV More Frequently

MedicalResearch.com Interview with:
Qian An, PhD

Division of HIV/AIDS Prevention

MedicalResearch.com: What is the background for this study?

Response: Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended HIV testing for all persons aged 13-64 years old. Persons at high risk for HIV infection should be tested more frequently. Among sexually active men who have sex with men (MSM), repeat testing is recommended at least annually. An analysis in 2011 suggested that MSM might benefit from more frequent than annual testing.(1)

Among non-MSM, repeat testing is recommended at least annually for persons at high risk, including persons who inject drugs (PWID) and their sex partners, those who have sex in exchange for money or drugs, heterosexuals who have had more than one sex partner since their most recent HIV test, and those whose partners are living with HIV..

Using statistical models based on renewal theory, we estimate the mean HIV inter-test interval (ITI) — meaning the average time period (in months) between two successive HIV tests — to describe temporal trends in HIV testing frequency among MSM, PWID and high-risk heterosexuals (HRH) and differences in testing frequency by age and race/ethnicity. A decrease in ITI means individuals are testing more frequently.

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Human Placenta May Be Most Vulnerable To Zika In First Trimester

MedicalResearch.com Interview with:

R. Michael Roberts

Dr. R. Michael Roberts

R. Michael Roberts PhD
Curators’ Distinguished Professor
240b Bond Life Sciences Center
Columbia, Missouri 65211-7310

MedicalResearch.com: What is the background for this study?

Response: My background in placental biology and in communication between the embryo and the mother in early pregnancy made me curious about how the zika virus (ZIKV) crossed the placenta in early pregnancy to cause microcephaly. My group had been working on a laboratory model for placental trophoblast for over 10 years. We generate trophoblast from human pluripotent cells (embryonic stem cells and induced pluripotent stem cells) by exposing them to the growth factor BMP4 and two pharmaceuticals that inhibit the signaling pathways necessary to maintain pluripotency. I was curious to determine whether or not ZIKV could infect these cells, replicate, and release infectious virus, because work from my collaborator Yoel Sadovsky at the University of Pittsburgh indicated that the mature placenta was likely to be resistant to infection.

MedicalResearch.com: What are the main findings?

Response: There are, I believe two striking outcomes from this work.

One is that the results indicate that the human placenta is likely most vulnerable to infection by Zika during the first trimester. We also suggest that women whose fetus is affected from an infection occurring later in pregnancy likely had a past dengue infection. The second striking result is that the African strain of Zika may have greater virulence towards early placenta than the Asian strains, such as the ones that have spread in the New World.

The work with the virus only began when we realized that term trophoblasts lacked expression of the genes that encode the protein factors that promote flavivirus infection (ZIKV is a flavivirus, like dengue, West Nile virus), e.g. TYRO3, AXL, MERTK, and also had a poised innate immune system that would counteract virus replication. Conversely, the trophoblasts we create from embryonic stem cells had the factors that would promote virus uptake, but seemed ill-prepared to counteract virus replication once infection occurred. In other words, the early placental trophoblasts were potentially more susceptible to infection. We confirmed this hypothesis with two strains of ZIKV (an Asian strain related to the one encountered in Brazil, and an African strain often considered to be relatively benign). What was unexpected was the African strain appeared to be more virulent than the Asian strain.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Whether the early placenta could be protected by some sort of immune therapy or by prior vaccination of the mother is clearly uncertain at present. Vaccination programs have not been altogether successful when used to protect against Dengue, which is a virus related to ZIKV.

There is evidence that the early placenta is also permissive to other viruses, such as Rubella. Also there is a very interesting paper in the Journal of the American medical Association by Honein et al. that was published on December 15, 2016. In this study, the overall risk for microcephaly and other brain abnormalities in infants born to a large cohort of U.S. women exposed to ZIKV while traveling (n = 442) was 5.9 % (18), and, of these, there were no cases noted among the women known to have been infected during their second or third trimesters. In Brazil, women appear to be at risk for fetal infections by ZIKV throughout their pregnancies but this may be because they had experienced an earlier infection by Dengue. I have discussed this puzzle in the paper.

I have no disclosures to make, nor conflicts of interest regarding the research or this response to your queries.


PNAS Plus – Biological Sciences – Applied Biological Sciences:
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts
Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; published ahead of print February 13, 2017, doi:10.1073/pnas.1616097114

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