Sarah Anwar

As researchers continue to make strides in learning more about the mosquito-borne viruses that have been plaguing Brazil, a new study has found that the next disease epidemic to hit the country could be Chikungunya.

According to the results of a recently published 

 in Sergipe State, Brazil, were found to be “naturally infected” with the East-Central-South-African (ECSA) Chikungunya virus genotype. Although there have been thousands of Chikungunya cases identified in Brazil, until now, they have all been identified as travel-related.

The researchers collected 248 mosquitoes from inside and outside of homes in the urban areas of the city. Four mosquito strains were collected, the most common of which were 

 (20.2%) mosquitoes. The mosquitoes were tested for Zika, Dengue, and Chikungunya using QuantiTect Probe reverse transcription-polymerase chain reaction (qRT-PCR) and Mastercycler Realplex 2 thermocycler.

Mosquitoes from Aracuja were tested for these viruses because the city is known to be endemic for Dengue, and because Zika and Chikungunya cases had been confirmed in the city in 2016. In addition, studies have shown that co-infection with Zika and Chikungunya may lead to complications.

Of the collected mosquito pools, all pools tested negative for Zika and Dengue (genotypes 1-4). One female pool of 

 mosquitoes (38 mosquitoes) tested positive for Chikungunya virus, although all male pools (12 mosquitoes) tested negative. When the female mosquitoes in the 

 pool were individually tested, only one mosquito was positive for Chikungunya. According to the Centers for Disease Control and Prevention, 

 mosquitoes.” The authors note that they did not identify any 

 mosquitoes “in the inspected houses, although this species is endemic in Aracuja city.”

“Our findings constitute the first description of 

-[Chikungunya] genotype ECSA interaction in Brazil. These results reinforce the role of this species as an important vector of [Chikungunya] in urban areas of northeast regions in Brazil,” stated the authors of the study.

 Previous studies have shown that co-infection with Chikungunya and Zika may result in prolonged Zika virus RNA shedding, which may increase the severity of infections. “There may be a trend between 

 Editorial Advisory Board member Marta G. Cavalcanti, MD, PhD back in February 2017, in a session at the First International Conference on Zika virus. In addition, Dr. Cavalcanti noted that higher morbidity rates were identified among those with Zika and Chikungunya co-infection

Additional research analyzing the impact of the Zika virus epidemic in Brazil was recently published in 

 study analyzed the effects of the Zika epidemic in the Brazil between November 2015 and 2016, one year after the Ministry of Health declared Zika a Public Health Emergency of International Concern.

After collecting data on cases of Zika virus infection and microcephaly between January 1, 2015 and November 12, 2016, the authors found that of the total 1,673,272 reported cases of Zika virus in the country, 41,473 (2.5%) were reported to be pregnant women. A total of 1,950 cases of microcephaly resulting from congenital Zika infection were also confirmed.

The researchers discovered that there were “two distinct waves of Zika virus infection” that impacted all regions of Brazil in 2015 and 2016, with most cases occurring in the northeast region of the country after the first wave of Zika. The second wave of Zika was reported to have impacts in all regions of Brazil, and occurred between September 2015 and September 2016. The authors concluded that “occurrence of microcephaly was much lower than that following the first wave of Zika virus infection, reaching epidemic levels in all but the south of Brazil, with estimated monthly peaks varying from 3.2 cases to 15 cases per 10,000 births.”

authors concluded, “The distribution of infection-related microcephaly after Zika virus outbreaks has varied across time and Brazilian regions. Reasons for these apparent differences remain to be elucidated.”

 may be over in Brazil, the news of the potential for a Chikungunya epidemic in the same region begs the question, what will the clinical signs be for those with Zika virus infections who also acquire Chikungunya?

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As researchers discover Chikungunya-carrying mosquitoes in Brazil, a new study analyzes the impact of the Zika virus on the area.

Will Brazil's Next Epidemic Come from Another Mosquito-Borne Virus?

A recent study from the Centers for Disease Control and Prevention (CDC) reports on the prevalence of 

, shares data collected between 1995 and December 2016, reporting an 

 in southern US states. Findings show that 38 new counties in the south are reporting 

 presence — a 21% increase from the previous report – and 127 counties are reporting 

 presence (10% increase). This information is essential as this can help scientists estimate the spread of mosquito-borne viruses such as Chikungunya, Dengue, and Zika, the latter of which has been a cause for alarm among pregnant women and their families, as local transmission of the virus is expected to increase with the start of the summer. In fact, the CDC recently published a new article highlighting findings from 7 infants who died with congenital 

 infection shortly after birth, in their journal 

The infants examined in the article were from a northeastern state in Brazil, Ceará, who were most likely infected during the first trimester in 2015. Zika virus infection was diagnosed in all infants after real-time reverse transcription PCR (RT-PCR) of cerebrospinal fluid and tissue tested positive for the mosquito-borne virus. The infants were also tested for Dengue virus infection, which was diagnosed in just 1 infant.

Five of the mothers had Zika-like symptoms during the first trimester of pregnancy. Of these infants, 3 were female, and one of the males had “ambiguous genitalia” that was characterized after autopsy showed undescended testes. The gestational age for these infants “ranged from 30 to 42 weeks (median 37 weeks),” with “body weight within reference range for gestational age in all except neonate 6.” In addition, all infants presented with “remarkably decreased” brain weight which emphasizes “the neurotropism of Zika virus.”

The researchers reported that these findings are in-line with those from previous cases of congenital Zika virus infection. In addition, they noted that “the constellation of neuropathologic features (ventriculomegaly, mineralized neurons, and dystrophic calcification with band-like subcortical distribution) differs” from those observed in infants who present with other congenital infections, and warrants the suspicion of a Zika virus infection.

Although microcephaly was diagnosed in 6 of the 7 infants, only 1 with seemingly normal head circumference also had “morphologic changes typical of microcephaly.” The longest-surviving infant lived for 6 days, the second longest for 48 hours, while the rest lived for less than an hour. In addition, the researchers report that a major factor in mortality was pulmonary hypoplasia “defined as lung weight:body weight ratio of 

The authors conclude, “Our report confirms not only the neurotropism of the virus but also the occurrence of pathologic changes consistent with viral infection in multiple organs: liver (Councilman bodies and periportal lymphocytic infiltration), lungs (interstitial lymphocytic pneumonitis), and bladder (lymphocytic cystitis). PCR detection of Zika virus in liver, lung, and kidney tissue also strengthened our hypothesis that Zika virus can infect multiple tissues.”

Zika virus continues to be a threat to pregnant women and their developing fetuses. The CDC stresses the need for continued efforts for vector surveillance, urging state and local health departments to collaborate with “mosquito control districts” to control and prevent the spread of 

 mosquitoes, to curb the spread of Zika and other mosquito-borne viruses.

The CDC just released a study outlining areas where an increase of Aedes mosquitoes was observed in 2016. In addition, researchers report on Zika-related complications observed in 7 infants, postmortem.

CDC Reports Increase of Zika Vector in Some US States

As more and more bacteria become resistant to first-line antibiotics, the development of new agents is becoming increasingly important. Now, new research, published in 

, outlines how “commercial chemicals” found in researchers’ laboratories at Yale University can be used to synthesize “molecules related to the natural product 

This antibacterial is a fungal byproduct, the antibacterial qualities of which were first discovered in the 1950s. Through semisynthesis, researchers have been able to create thousands of derivatives of pleuromutilin. In addition, in the past decades, pleuromutilin was approved for treatment of “gram-positive bacterial skin infections,” according to the researchers. Nonetheless, many of the pleuromutilin derivatives “only vary at a single position in the molecule,” according to a 

. However, fully synthesizing pleuromutilin would allow for the development of new antibiotic agents, and this is what the Yale researchers set out to do.

Seth Herzon, PhD, professor of chemistry at Yale University, and member of the Yale Cancer Center, explained that he first tried to tackle this issue in 2008. He said, “We worked on this project for a few years when I started at Yale, but didn’t record much success. The pharmaceutical industry has historically been the driving force behind antibiotics development. However, antibiotics are essentially at the bottom of the list in terms of investment return. Consequently, most major pharmaceuticals have walked away from this area.”

According to Joseph Larsen, PhD, Director of the Biomedical Advanced Research and Development Authority (BARDA) with the US Department of Health and Human Services, developing 

 can take years, and only become profitable after an average of about 23 years. In addition, in an 

®, Robert W. Malone, MD, MS, CEO/CSO of Atheric Pharmaceuticals, LLC, mentioned that getting a new drug or vaccine on the market takes around $1 billion and approximately 10 years. However, there is less incentive in creating new antibiotics because of revenue. According to Dr. Larsen, “for the last 6 antibiotics approved in the United States, the projected first 2 years’ sales ranged between $30 million to $80 million, which is not much when compared to medications used to treat more chronic diseases, which routinely have first 2 years’ sales in excess of a billion dollars.”

In their most recent study, Dr. Herzon and his colleagues were able to “prepare an isomer of pleuromutilin — a compound that has the same connectivity, but with a different arrangement of atoms – and rearrange it in the final steps of the synthesis to pleuromutilin.” With this, the research group was able to fully synthesize pleuromutilin, which may allow for the development of more antibiotics. The group outlined their complete synthesis methods in their study.

The authors concluded, “We can envision adapting the strategy outlined herein to create additional derivatives with optimized structures (ring sizes, atomic substitution, and/or substitution patterns) that may further address constraints inherent to semisynthetic approaches and may be accessible by shorter, higher-yielding sequences. Recent successes in the development of convergent routes to tetracycline and macrolide antibiotics underscore the potential to generate new clinical antibacterial candidates by total synthesis.”

Researchers from Yale University have come up with a new “chemical process” that may aid in the development of a new class of antibiotics.

Yale Researchers Pave the Way for Development of New Antibiotics

In late April 2017, 2 adults in the MidCoast area in Maine were hospitalized due to infection with Powassan encephalitis.

According to the Centers for Disease Control and Prevention (CDC), patients infected with 

 do not usually exhibit symptoms. However, when they do, the symptoms are usually fever, headache, vomiting, weakness, confusion, loss of coordination, difficulty speaking, and sometimes seizures. The CDC notes that infection with Powassan virus can cause meningitis as well as encephalitis (inflammation of the brain). Encephalitis resulting from a Powassan virus infection is fatal in about 10% of cases.

 was the first human in the state to be diagnosed with Powassan virus. The patient developed severe complications, including seizures “that included rightward eye deviation and right arm stiffening,” for which he was hospitalized. According to the infant's physicians, MRIs showed signs consistent with encephalitis. After the infant was treated for the seizures, he was released from the hospital, only to develop other complications 1 month later. Researchers reporting on this case strongly recommended that, in areas endemic for ticks, patients presenting with encephalitis be tested for Powassan virus.

The 2 most recent cases were reported to the Maine Centers for Disease Control and Prevention in late May 2017, one month after patients were hospitalized. The patients were diagnosed based on testing conduced at the CDC in Fort Collins, Colorado; they have since been release from the hospital and are now recovering. There have only been 7 cases of Powassan virus reported in Maine since 2000 (not including these 2 most-recent cases).

Powassan virus is transmitted by infected 

 ticks that are not known to bite humans. Maine State Epidemiologist, Siiri Bennett, MD, said in a 

, “Powassan, although rare, can be serious, so it is important to be aware of your surroundings and take steps to avoid being bitten by ticks. Ticks are found in wooded and bushy areas, so use caution if you go into these areas.” She then went on to note that using the “No Ticks 4 Me approach,” can lower the risk of tick exposure as well as the risk for tick-borne diseases.

The No Ticks 4 Me approach includes wearing light-colored clothing that leaves ticks visible if they are on clothes, and wearing long-sleeve shirts and long pants so as to reduce the amount of exposed skin. The approach also includes using United States Environmental Protection Agency (EPA)-registered tick-repellent or Permethrin-treated clothing. Ticks can also hide on pets. Although 

-based products are safe to use in dogs, it is recommended to avoid their use in cats, as it can be poisonous to them.

As part of the approach, individuals are also urged to avoid “wooded and bushy areas with high grass.” It is recommended that those who do go into nature “stay in the middle of trails whenever possible,” and check their bodies for attached ticks, daily, especially once out of tick-endemic areas. In addition, showering immediately after returning from such areas is also highly recommended so as to remove ticks from the body, and protect from disease.

Two adults were hospitalized in Maine as a result of Powassan virus encephalitis.

Two Powassan Encephalitis Cases Reported in Maine

University of Nebraska Medical Center (UNMC) researchers recently conducted a single center, prospective, controlled trial to establish whether the use of a Steripath initial specimen diversion device (ISDD) decreased contamination of blood cultures in emergency department patients.

, blood cultures are usually collected to test for bacterial and fungal infections, as well as to “guide specific antimicrobial therapy.” Rates of blood culture contamination can range anywhere between 0.6% and 6% contamination in US healthcare facilities. It is believed that blood cultures become contaminated when skin fragments contaminated with bacteria are “dislodged with venipuncture,” according to the authors. This contamination can result in additional laboratory and treatment expenses; more specifically, tests that yield false-positives, potentially due to this contamination, can result in around 20% increase in lab charges, as well as about a 40% increase in antibiotic costs, due to unnecessary prescribing. Furthermore, a patient can spend up to 5 additional days in the hospital, experience toxicity, drug interactions, and negative side effects, all from false blood culture results. According to a 

 on the study, false cultures subsequently “contributes to antibiotic resistance and undermines nationwide efforts to improve antimicrobial stewardship.”

Because the authors hypothesized that contamination occurs as a result of contaminated skin fragments mixing with the sample during venipuncture, the authors set out to “test a device that diverts and sequesters the first 1.5—2 mL portion of blood, which presumably carries the contaminating skin fragments, from the culture specimen to determine whether blood culture contamination is diminished.”

The study included 2 blood cultures collected from each of 904 patients who “require[ed] phlebotomy for blood culture due to clinical suspicion of serious infection.” The majority of the study subjects were male (55%), with an average age of 59 years.

Samples were collected between November 2014 and October 2015. The authors compared standard blood culture collection procedures with that of the Steripath ISDD. Patient skin was disinfected with 2% chlorhexidine gluconate and 70% alcohol for 30 seconds and left to dry before samples were collected. The culture vials were properly disinfected using “70% isopropyl alcohol pads before inoculation.” The first sample from each patient was acquired through a syringe and inserted into a blood culture vial—standard blood culture collection procedures. For the second sample, after the syringe was inserted, the Steripath ISDD separated the first 1.5-2.0 mL of blood into a “holding chamber” and directed the remainder of the blood into the collection vial.

According to the study parameters, a blood culture sample was found to be contaminated if coagulase-negative staphylococci, 

 sp. was identified in one of the cultures. The researchers found that the “most common cause of true bacteremia were the 

 (20.7%).” Sixteen samples collected through the standard procedure showed contamination. More than half of these were caused by coagulase-negative staphylococci (51%), followed by 

 sp. (19%). On the other hand, 2 samples collected through the Steripath ISDD procedure showed contamination.

The authors wrote, “Discordance between the 2 methods of phlebotomy with regard to detection of true bacteremia was essentially equal. In 12 instances, the standard procedure yielded a true pathogen while the ISDD was sterile, and in 11 instances, the ISDD yielded a true pathogen while the standard procedure was sterile.” According to the authors, these findings stress the need for 2 blood cultures in order to effectively identify true bacteremia; the incidence of detecting of true bacteremia with a single blood culture was 73%.

The authors concluded that use of the Steripath ISDD significantly decreased the number of false positive results. Contamination rates went down from 1.78% to 0.2%, which was observed to be an 88% reduction.

In comparing the number of contaminated blood cultures obtained 6 months before and 6 months after the study, the authors noted that the use of both blood culture collection procedures resulted in the prevention of 373 contaminations. They write, “The costs associated with blood culture contamination range from $1000 (1998) to $8700 (2009) per case. If a midpoint cost estimate is used ($4850), and the added cost of the device is not taken into account, it equates to a cost avoidance of $1.8 million per year at our institution.”

Commenting on the study’s findings in a press release, Mark Rupp, MD, professor and chief of the UNMC Division of Infectious Diseases and medical director of the Department of Infection Control and Epidemiology at Nebraska Medicine said, “The 1.78% baseline rate of contamination may seem small, but we should strive to decrease adverse events to the lowest possible level because of the impact to the patient and the burden to our healthcare system. We quite clearly showed the rate of contamination was significantly reduced, and that decrease has a very big impact.”

Researchers from the University of Nebraska Medical Center conducted a trial to measure if using a specific device for blood collection would reduce the rate of culture contamination.

Blood Culture Collection Device Significantly Reduces Contamination Rates

The Centers for Disease Control and Prevention (CDC) just published a

) highlighting data on the largest number of completed pregnancies with lab-confirmed Zika virus infection. In addition, during a telebriefing, CDC Acting Director, Anne Schuchat, MD, shared the CDC’s stance on the end of the Zika epidemic in Puerto Rico.

 report is the first of its kind from US territories, including the Federated States of Micronesia, American Samoa, the Republic of Marshall Islands, the US Virgin Islands, and the Commonwealth of Puerto Rico.

The report reflects data collected between January 1, 2016 and April 25, 2017, and includes data on 2,549 completed pregnancies, 1,508 of which had lab-confirmed Zika virus infection. Of the completed pregnancies, 122 infants (5%) exhibited Zika-related birth defects, with 5% of afflicted infants born to symptomatic mothers and 4% born to asymptomatic mothers. The CDC notes that this number does not constitute a clinical significance in terms of risk of infants born to symptomatic mothers developing complications versus those born to asymptomatic mothers.

Zika lab testing results were reported for only 59% of liveborn infants included in the registry. Of those, 52% received neuroimaging and 79% had hearing tests. The CDC stresses the importance of performing head ultrasounds on infants born to mothers with confirmed Zika infection, as these tests can show abnormalities that aren’t apparent after birth.

The report also highlights that the greatest incidence of Zika-associated birth defects was apparent among infants born to mothers infected during the first trimester: the results showed that 8% of infants born to Zika-infected mothers in US territories developed complications compared with 15% of those born in US states. According to a press release, “these estimates are based on relatively small numbers and are not statistically different.” Infection during the second trimester resulted in the second highest incidence of complications (5%), and infection during the third trimester was found to have the lowest incidence of complications (4%). On average, the CDC estimates that 1% to 13% of Zika infections that occur during the first trimester of pregnancy lead to microcephaly. However, this 

 report is the first to identify “preliminary estimates of risk for each trimester.”

Another important finding that Peggy Honein, PhD, co-lead on the Pregnancy and Birth Defects Task Force for CDC Zika Response, shared during the telebriefing, is that these findings are consistent with a previous 

, published in early April 2017, which noted that, of completed pregnancies with a possible Zika virus infection, 5% may result in Zika-related complications.

 At the moment, the CDC acknowledges that congenital Zika virus infection can cause brain abnormalities and vision problems. Some infants may even have trouble swallowing and sitting up due to constricted joints, while others may cry continuously and appear to be inconsolable. Although much is known about Zika-associated complications there is still much to be discovered, especially in infants who are seemingly healthy upon birth. This makes follow-up care even more crucial, since it can also inform management strategies.

During the telebriefing, Dr. Schuchat and Dr. Honein commented on surveillance efforts in US territories, noting that previously, US territories did not follow a standard case definition. However, now, all US states and territories are reporting using the CDC’s standard case definition, which can be found online.

During the telebriefing, the CDC acknowledged the gap in Zika case reporting that was occurring in 

 last year. Those on the call were assured that health authorities in Puerto Rico are now doing a “very good job” in terms of evaluating and reporting Zika infection cases, specifically among pregnant women.

In addition, Puerto Rico recently declared the Zika virus epidemic over on the island. Health officials made this announcement after assessing the situation and finding that there has been a sharp drop in the number of reported cases of Zika virus infection. The CDC is “very pleased the incidence is low;” however, they continue to advise pregnant women against travel to areas with Zika transmission, including Puerto Rico, especially in the coming months. When asked if the CDC acknowledges the epidemic to be over in Puerto Rico, CDC officials stated that they believe there are “low levels of transmission in some areas.”

According to Dr. Schuchat, this report indicates that Zika is a “very serious virus when acquired during pregnancy,” regardless of when the mother was infected during pregnancy. CDC officials also acknowledge that Zika has taken an economic toll on both families with infants who have Zika-related complications, and on tourism to areas where the virus is endemic. However, the CDC is working with the Centers for Medicare and Medicaid Services to reduce the economic burden of care for these infants.

Based on past experience with Dengue and Chikungunya outbreaks, the CDC reports that the Zika virus is an ongoing threat in Puerto Rico and other areas. The CDC recommends that individuals living in areas with active Zika virus transmission take the necessary precautions to avoid mosquito bites.

In the most recent MMWR, the CDC released data indicating the risk of Zika congenital infection resulting into complications based on trimester of infection. 

Sarah Anwar

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