News Scan for Sep 13, 2017

News brief

Malaria drug AQ-13 shows promise in test against established treatment

An experimental malaria drug called AQ-13 compared well with an established combination treatment in a non-inferiority trial in Malian men with non-severe malaria, according to a report yesterday in The Lancet Infectious Diseases.

AQ-13 is one of a class of compounds called 4-aminoquinolines with modified side chains, which are active against resistant malaria parasites, the report says. Chloroquine was used to treat Plasmodia falciparum malaria until resistant strains emerged more than 50 years ago.

In the randomized trial, 66 men in two areas of Mali who had uncomplicated malaria were randomly assigned to receive either artemether plus lumefantrine or AQ-13 for 3 days and then were monitored for clearance of the infection and adverse events for several weeks.

All participants had clearance of asexual parasites by the end of the first week, and there were no serious adverse events in either group. A total of 453 less-severe adverse events were reported, with 214 in the combination treatment group and 239 in the AQ-13 group. Two members of the combination treatment group had recurrence of their infections.

In the per-protocol analysis, the cure rates were similar for the two groups: 28 of 28 (100%) for AQ-13 and 31 of 33 (93.9%) for artemether plus lumefantrine. AQ-13 therefore met the preset non-inferiority criterion.

In the intention-to-treat analysis, the cure proportions were 28 of 33 (84.8%) for AQ-13 and 31 of 33 (93.9%) for the combination treatment. By this measure, AQ-13 failed to show non-inferiority, but the authors attributed this to the fact that two AQ-13 recipients dropped out and three others were lost to follow-up. They noted that there were no treatment failures with AQ-13.

The authors said their results indicate that the safety and efficacy of AQ-13 for uncomplicated malaria are similar to those of artemether plus lumefantrine in Malian men. "However," they added, "because semi-immune participants, such as those included in our study, might clear parasites resistant to the drugs being tested, additional studies in non-immune individuals, such as children, are needed before deciding whether to recommend the widespread use of aminoquinolines such as AQ-13."

In a Tulane University press release, senior author Donald Krogstad, MD, called the trial "extraordinarily encouraging," adding, "Compared to the current first-line recommendation for treatment of malaria, the new drug comes out very well." He is a professor of tropical medicine at Tulane's School of Public Health and Tropical Medicine.
Sep 12 Lancet Infect Dis report
Sep 12 Tulane press release
Related Sep 12 Lancet Infect Dis commentary

 

Annual report: Global Fund efforts saved 22 million lives in 15 years

Programs supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria have saved 22 million lives since 2002, according to a Global Fund annual report released today.

In addition to the estimated 22 million lives saved, the report estimates that that Global Fund efforts have led to a decline by a third in the number of people dying from HIV, tuberculosis (TB), and malaria in countries where the Global Fund invests; 11 million people on antiretroviral therapy for HIV (more than half the global total); 17.4 million people received TB treatment; and 795 million mosquito nets distributed through malaria programs.

As a result of prevention and control interventions in more than 100 countries, the Global Fund's target of averting 140 million to180 million infections by the end of 2016 was met in 2015. Malaria saw a 50% drop in global deaths from 2000 to 2015, and the number of malaria cases treated through Global Fund–supported programs rose 15% in 2016 alone, to reach a cumulative total of 668 million by the end of last year.

Through 2016, the Global Fund spent $32.6 billion to support programs for HIV, TB and malaria. In addition, countries have committed an additional $6 billion to their health programs for 2015 through 2017 compared with 2012 through 2014, a 41% increase, the report said.

"Investing in global health is a highly cost effective way to achieve greater security and stability, to protect communities worldwide from infectious disease and to halt emerging health threats," said Marijke Wijnroks, Interim Executive Director of the Global Fund. "This report highlights outstanding achievements, and also how much more there is to do."
Sep 13 Global Fund news release
Sep 13 full report
Sep 13 summary of findings

Stewardship / Resistance Scan for Sep 13, 2017

News brief

Study finds no link between US antibiotic prescribing, resistant gonorrhea

Although overuse of antimicrobials is a known contributor to antimicrobial resistance in general, researchers reported yesterday they could find no association between numbers of US antimicrobial prescriptions during a recent 8-year period and resistance in the bacteria that causes gonorrhea.

The researchers, from the Centers for Disease Control and Prevention (CDC) and several other institutions, note that Neisseria gonorrhoeae has developed resistance to every antimicrobial prescribed for it over the years and has been declared an urgent resistance threat by the CDC.

Writing in Emerging Infectious Diseases, the team said it is unclear to what extent antimicrobial use contributes to the emergence of gonococcal resistance in the United States.

To investigate the question, they gathered county-level antimicrobial susceptibility data from the CDC's Gonococcal Isolate Surveillance Project (GISP), county-level antimicrobial consumption data from the private company IMS Health, and demographic data from the US Census Bureau. The study covered the years 2005 to 2013.

The research included susceptibility test results for 43,852 N gonorrhoaea isolates taken from men treated for gonococcal urethritis at clinics for sexually transmitted infections. The isolates were tested against azithromycin, ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and tetracycline. The IMS Health data covered more than 70% of all outpatient prescriptions during the study period.

Using multivariable statistical models, the team found no associations between N gonorrhoeae susceptibility and the numbers of prescriptions of any of the studied drugs.

Writing on what might explain the results, the authors speculated that factors other than population-level prescribing rates, such as importation of resistant strains, might contribute to gonococcal resistance. Or, they said, their data sources or methods might not have been sensitive enough to detect a relationship between prescribing and resistance.

The findings "suggest that population-wide domestic antimicrobial drug prescribing rates might not play a prominent role in the emergence of gonococcal resistance in the United States," they conclude. "Other means, such as importation from other countries, might play larger roles. Through this lens, enhanced surveillance for and public health capacity to respond to imported resistant strains are important strategies."
Sep 12 Emerg Infect Dis report

 

High levels of resistant bacteria found in Tanzanian street children

A study yesterday in PLoS One found a high incidence of fecal carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae among street children in Mwanza city, Tanzania, a port city of almost 3 million people.

The researchers analyzed stool samples obtained from 107 street children in 2015 and found ESBL-producing Enterobacteriaceae (EPE) in 34 of them (32%). Out of 36 isolates from the 34 children, 36 (100%), 35 (97%), 25 (69%), and 16 (44%) were resistant to tetracycline, trimethoprim-sulfamethoxazole, ciprofloxacin, and gentamicin, respectively.

The CTX-M-15 ESBL gene was detected in 27 isolates, or 75%. About 83% of the resistant pathogens were Escherichia coli.

The authors say their study "highlights the need for multidisciplinary approaches to understand the epidemiology and drivers of antimicrobial resistance in low-income countries."
Sep 12 PLoS One study

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