News Scan for Nov 07, 2017

News brief

Most MDR-TB isolates in central China resistant to key MDR-TB drug

Chinese scientists have found that 62% of multidrug-resistant tuberculosis (MDR-TB) isolates they tested were also resistant to pyrazinamide (PZA), a key drug in treating MDR-TB, according to a study published yesterday in BMC Infectious Diseases.

The researchers analyzed 133 MDR-TB isolates collected from TB patients in Chongqing province in central China. They assessed for PZA resistance using a Bactec MGIT 960 system and then sequenced genes that conferred PZA resistance.

They found that 83 (62.4%) of the 133 isolated were PZA-resistant. In addition, resistance to streptomycin, ofloxacin, kanamycin, amikacin, and capromycin were more frequently observed among PZA-resistant isolates compared with PZA-susceptible isolates. And sequence analysis revealed that 73 (88.0%) of the MDR strains harbored a mutation located in the pncA gene.

PZA is typically subscribed in both first- and second-line treatments of MDR-TB.
Nov 6 BMC Infect Dis study

Madagascar's plague outbreak still slowing but tops 1,900 cases

Though the number of pneumonic plague infections and hospitalization are declining in Madagascar's outbreak, the World Health Organization (WHO) Regional Office for Africa said 146 more confirmed or suspected cases were reported since its last update on Oct 31, raising the total to 1,947.

Also, 16 more deaths were reported, putting the fatality number at 143. The outbreak's case-fatality rate held at 7%.

Plague is endemic and seasonal in Madagascar, with the bubonic form most common.The country, however, has been experiencing an unusual surge in the more deadly pneumonic plague, accounting for 74% of cases. Some of its biggest cities are among the hardest-hit areas. The pace of pneumonic cases has been declining since the middle of October, but the WHO has warned that new cases are likely through April, when Madagascar's plague season typically winds down.

Response efforts are still ramping up, with 346 health workers having been trained on infection prevention and control measures, and more medical staff have been hired for six treatment centers in Antananarivo, the country's capital, along with centers in Tamatave and Fenerive East.

The WHO estimates that $9.5 million is needed for the joint response, but so far only 26% of the total has been funded, and money received so far has already been spent on the response. Private-sector contributions such as broadcasting services, storage facilities, and personal protective equipment are increasing, the agency added. On Oct 31 the WHO and national authorities meet with Chinese experts to discuss collaboration and response support. As of Nov 6, the WHO and its partners have 151 experts deployed to Madagascar.
Nov 6 WHO situation update

Nigeria's monkeypox total climbs to 38 confirmed cases

Nigeria's number of lab confirmed monkeypox cases has jumped from 9 to 38 from eight states and the Federal Capital Territory (FCT), where the country's capital Abuja is located, though the number of cases reported over the last 2 weeks shows signs of slowing, the Nigeria Center for Disease Control (NCDC) said in its latest update.

Over the course of the outbreak, which began in late September, 116 suspected cases from 20 states and the FCT have been reported. Rapid response teams have been deployed to four states: Akwa Ibom, Bayelsa, Delta, and Enugu.

The epidemiologic investigation has found that twice as many males as females have been infected, and patients ages 21 to 40 years are the most affected age-group. States with the highest numbers of suspected and confirmed cases are in the southern part of Nigeria. So far no deaths have been reported.

As of late last week, 103 patient samples have been collected and sent for testing to the country's national laboratory in Lagos. Authorities are following 145 contacts, and 59 contacts have already completed their 21-day monitoring period.
Nov 3 NCDC monkeypox outbreak situation report

Takeda's dengue vaccine performed well in phase 2 trial

An 18-month interim phase 2 trial of Takeda's TAK-003 dengue vaccine proved to be safe and immunogenic in children ages 2 to 17. The results of the trial were published today in The Lancet Infectious Diseases and presented today at the American Society of Tropical Medicine and Hygiene's annual meeting.

The double-blind study looked at TAK-003's performance in 1,794 children living in the Dominican Republic, Panama, and the Philippines in both one-dose and two-dose schedules. Study subjects received either one primary dose of TAK-003, two primary doses of TAK-003 administered 3 months apart, one primary dose of TAK-003 followed by a booster dose 1 year later, or a placebo.

The results support a two-dose regimen administered 3 months apart. Participants who received the vaccine had a relative risk of symptomatic dengue of 0.29 (95% confidence interval, 0.13 to 0.72) compared with controls. Immunogenicity was achieved for all four dengue subtypes regardless of previous dengue virus exposure or infection.

"We are seeing an acceptable safety profile and sustained antibody responses out to 18 months in this trial. These data are an important step in the development of our dengue vaccine candidate," said Derek Wallace, MBBS, the global dengue program lead at Takeda, in a company press release. "The reduced incidence of dengue in children and adolescents receiving TAK-003 is encouraging."

An accompanying commentary in The Lancet Infectious Diseases said, "Overall, the interim results from this phase 2 trial are encouraging." TAK-003 is now being tested in a phase 3 trial.
Nov 7 Lancet Infect Dis study
Nov 7 Takeda press release
Nov 7 Lancet Infect Dis commentary

Long-term effects of West Nile virus seen on MRIs

Even patients who are symptom-free may have long-term brain damage from West Nile virus, according to a new study presented at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) yesterday.

The study, conducted at the Baylor College of Medicine in Houston, tracked 262 people in the Houston area with West Nile virus from 2002 and 2012, and recruited 117 of those patients to be tested extensively for signs of neurological deficits. About half of the 117 patients, (57 or 49%) showed neurological and physical symptoms. Seven of those patients had no symptoms of neurological damage, but test results that showed neurological deterioration. Of those 57, 30 agreed to undergo magnetic resonance imaging (MRI), which showed damage or thinning in different parts of the cerebral cortex.

"The issues we are seeing on the MRIs are consistent with what would occur from an infection that caused a lot of inflammation in the brain," said Kristy Murray, DVM, PhD, of Baylor's National School of Tropical Medicine and the lead author of the study, according to an ASTMH news release. "Inflammation can lead to scarring as the brain starts to heal, and that scarring can cause damage."
Nov 7 ASTMH press release

Zika Scan for Nov 07, 2017

News brief

Data from meeting indicate 2nd mosquito feeding key to Zika spread

The proportion of Zika virus–carrying Aedes albopictus and Aedes aegypti mosquitoes capable of transmitting the virus increased dramatically after a second blood meal, according to data presented today at the 66th annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).

US researchers fed both Ae albopictus and Ae aegypti mosquitoes blood containing the Zika virus and then fed them virus-free blood 2 days later.

"We found that if you gave these mosquitoes a second feeding a couple of days later—and with just regular blood that contained no virus—they became much more infectious," said lead author Doug Brackney, PhD, in an ASTMH news release. "The percentage of our Asian tiger mosquitoes [Ae albopictus] that were capable of transmitting virus jumped from 25% to 75%."

The effect was also noted in Ae aegypti, the most common Zika spreader. "We found that the second feeding not only increases the proportion of insects that are infectious, but also shortens the time it takes for the virus to reach their saliva," Brackney said. "It produces a lot of infectious mosquitoes very quickly."

A related study noted that Ae albopictus mosquitoes are expanding their range deeper into New England, according to the release.
Nov 7 ASTMH news release

EPA approves Wolbachia-infected mosquitoes to curb disease threat

Though it hasn't formally announced its decision, the US Environmental Protection Agency (EPA) has cleared the way for MosquitoMate to release its Wolbachia pipientis infected mosquitoes to battle Ae albopictus mosquitoes and combat diseases like Zika, dengue, and yellow fever, Nature News reported yesterday in a news story. It said the EPA notified the company of its decision on Nov 3, which will allow it to release the lab-infected male mosquitoes in 20 states and in Washington, DC.

According to the report, the EPA has restricted the release of the MosquitoMate mosquitoes to places with climates similar to where they were tested, which included Kentucky, New York, and California. Nature said the EPA's approval doesn't extend the use to southeastern states, which have large mosquito populations and longer mosquito seasons, because the company didn't do field trials there.

The company told Nature that it will start selling its mosquitoes in Lexington, Ky., its home base. Then as it scales up protection MosquitoMate will expand availability to other cities in the region, such as Louisville and Cincinnati. Potential customers include homeowners, golf courses, and hotels.

Male mosquitoes infected with naturally occurring Wolbachia bacteria don't bite, and when they mate with female mosquitoes, the eggs don't hatch, a tactic that helps drive down local mosquito populations.

In 2016 a World Health Organization expert group that assessed if any new mosquito control tools could be helped to curb the spread of Zika virus found that Wolbachia was one of only two methods that warranted careful pilot testing with rigorous monitoring.
Nov 6 Nature News story

Brazil study shows chikungunya spike as Zika outbreak wound down

Brazilian investigators writing yesterday in PLoS Neglected Tropical Diseases detail the waning of the Zika outbreak in Recife in the northeast, which was then replaced by a chikungunya outbreak.

The experts assayed acute and convalescent blood samples from 263 patients who had fever and other symptoms suggestive of an arboviral disease and attended an urgent care clinic in the Recife metropolitan area. The patients were in the clinic from May 2015 to May 2016.

Polymerase chain reaction testing determined that 26 (9.9%) were positive for Zika virus and 132 (50.2%) for chikungunya virus but none for dengue virus. This was at a time when there were many official dengue notifications in the area.

The authors concluded, "We show that when Zika cases started to decrease, chikungunya cases appeared and increased rapidly, remaining high until the end of the study. We also highlight the high levels of cross-reactivity on dengue serological assays with ZIKV-positive samples, emphasizing the importance of choosing appropriate tests in areas with simultaneous circulation of arboviruses."
Nov 6 PLoS Negl Trop Dis report