News Scan for Jul 31, 2014

Spread of resistant malaria
Chikungunya in Florida
Vaccine-narcolepsy study retraction
Pertussis outbreak recap

Study: Drug-resistant malaria spreading in Southeast Asia

Resistance to artemisinin, the main drug for treating malaria, has now spread throughout Southeast Asia, including critical border regions, and a genetic mutation in the Plasmodium falciparum parasite that causes the disease may be the culprit, according to a study today in the New England Journal of Medicine.

On the positive side, the large international team conducting the study, called the Tracking Resistance to Artemisinin Collaboration, also found that a 6-day course of medication instead of the standard 3-day course of artemisinin combination therapy (ACT) was almost 98% effective in treating drug-resistant malaria.

The team enrolled 1,241 adults and children infected with acute, uncomplicated P falciparum malaria at 15 sites in seven Southeast Asian and three African nations from May 2011 through April 2013. Patients received 3 days of artesunate, an artemisinin derivative, followed by a standard 3-day ACT course.

The researchers then assessed the rate of parasite clearance from the patients' blood. They found that median parasite clearance half-life varied from 1.9 hours in the Democratic Republic of the Congo to 7 hours at the Thailand-Cambodia border, where artemisinin resistance has been known since 2005. The proportion of patients with parasites in their blood 72 hours after treatment ranged from 0% in Kenya to 68% in Eastern Thailand.

The investigators found that artemisinin resistance is now firmly established in western and northern Cambodia, Thailand, Vietnam, and eastern Myanmar. They also noted signs of emerging resistance in central Myanmar, southern Laos, and northeastern Cambodia. They found no resistance at the three African sites studied.

Further, the team found that P falciparum with a mutant version of a gene called K13-propeller in western Cambodia corresponded with the recent spread of drug resistance among malaria patients. In addition, patients who had slow-clearing infections were more likely to have parasites at the stages in which they can infect mosquitoes, which suggests a transmission advantage.

"Frontline ACTs are still very effective at curing the majority of patients. But we need to be vigilant as cure rates have fallen in areas where artemisinin resistance is established," said lead author Elizabeth Ashley, MB BS, PhD, of the University of Oxford in a Wellcome Trust news release.

Wellcome Trust Director Jeremy Farrar, PhD, added, "If resistance spreads out of Asia and into Africa, much of the great progress in reducing deaths from malaria will be reversed."
Jul 31 N Engl J Med study
Jul 31 Wellcome Trust news release
Jul 31 N Engl J Med editorial on the study


Florida reports two more local chikungunya infections

Florida health officials yesterday announced two more locally acquired chikungunya cases, lifting the total to four.

One of the cases is the first to be reported in St Lucie County, in an adult who lives in a residential area north of Dan McCarty School in Fort Pierce, the Florida Department of Health (FDH) said in a statement. The patient did not need to be hospitalized and is recovering. The county's mosquito control department launched aggressive efforts on Jul 27 in response to the new case.

The other case is Palm Beach County's second, according to a separate FDH statement. No details were available about the patient. The confirmation of the second infection prompted the county to raise the mosquito warning level from "advisory" to "alert," signifying that the virus is likely in the mosquito population.

On Jul 17 the FDH announced its first locally acquired chikungunya cases, the first such infections on the US mainland. One was in Dade County, in addition to Palm Beach County's first case.

Florida also has reported 115 travel-related cases, most of them linked to destinations in the Caribbean region, which is experiencing a large epidemic. At the national level, 398 travel-linked cases have been reported to the US Centers for Disease Control and Prevention.
Jul 30 FDH statement on St Lucie County case
Jul 39 FDH statement on Palm Beach County case


Researchers retract H1N1 vaccine narcolepsy study

Scientists who in December published a study suggesting an immune system mechanism that could explain narcolepsy in some European children who received a 2009 H1N1 influenza vaccine have retracted their findings, according to a report yesterday in Science Translational Medicine (STM).

The team had published its initial findings in the Dec 18, 2013, edition of the journal. They looked at CD4+ T-cell activity in 39 narcoleptic children, plus their siblings who were also vaccinated but did not develop the condition. In youngsters with narcolepsy, CD4+ cells reacted to both hypocretin, a neurotransmitter that carries a "waking" signal, and the hemagglutinin surface protein on the 2009 H1N1 virus.

The researchers originally said the findings suggested that immunity to the 2009 H1N1 virus protein, from the vaccine or from the virus itself, affected hypocretin production, and that the adjuvant in the vaccine didn't appear to have contributed to the problem, aside from boosting the immune response.

According to the retraction, scientists weren't able to replicate the results of a test used to measure how immune system cells respond to foreign protein fragments. Lead author Emmanuel Mignot, MD, PhD, of Stanford University, told Science magazine that while trying to develop a diagnostic test for narcolepsy, his lab couldn't make the test (ELISpot assay) work.

Researchers who commented for Science's story on the retraction said there were some red flags in the study; for example, the group studied only one aspect of T-cell response to hypocretin. However, Katrina Kelner, STM's editor, told Science that the paper was reviewed with rigorous standards and that it reported replication of the finding in three independent groups of patients.
Jul 30 STM retraction (behind paywall)
Jul 30 Science story (intro only without pay)


Almost a third of students at low-vaccine school got pertussis

A 94-case outbreak of pertussis (whooping cough) a year ago at a charter school in a large religious community averse to vaccinations highlighted the challenges of outbreaks in undervaccinated populations, Florida health officials report today in Morbidity and Mortality Weekly Report (MMWR).

The first case was confirmed on Aug 30, 2013, at a 316-student pre-K-through-eighth-grade school in Columbia County. School records indicated that only 5 of 34 kindergartners (15%) and 1 of 22 seventh-graders (5%) were fully immunized against pertussis. Of the students who were not fully immunized in those two grades, 84% had religious exemptions.

The Florida Department of Health in Columbia County declared a communicable disease emergency on Sep 12, and sick children with a cough were excluded from school until evaluated by a healthcare provider. Pertussis vaccine was offered for free at the local health department, but "fewer than five persons from the community used this opportunity for vaccination," according to the report.

All told, 109 pertussis cases were identified in the community: 8 confirmed, 61 probable, and 40 suspected. Ninety-four were students from the school, and 14 cases, including 3 in infants, were in household contacts of ill students. The final case was in a teacher at the school, which had 16 teachers. Only one case involved a fully vaccinated person.

Attack rates were highest among the youngest students—57% among pre-kindergarteners—and decreased with increasing age, to 14% among eighth-graders.
Aug 1 MMWR report

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