Treatment with a common malaria drug could be the reason why residents of some Amerindian villages show high levels of resistance to a widely used class of antibiotics known as fluoroquinolones, despite never taking the drugs, a recently published study by Canadian researchers have said.
The study suggested that treating malaria with the cheap, widely used drug chloroquine – a drug close to fluoroquinnolones – may increase the risk of resistance to the antibiotics.
Heading the study, which was done between 2002 and 2005, was Dr Michael Silverman of Lakeridge Health Centre in Oshawa, Ontario.
The study was conducted in Bartica and six villages along the Mazaruni River, Jawalla, Kako, Kamarang, Phillipai, Waramadong and Quebanang. The villages were surveyed for the presence of rectal carriage of ciprofloxacin-resistant Gram-negative bacilli (GNB) and it also included testing the drinking water of the villages.
Stabroek News had been seeking a comment from Health Minister Dr Leslie Ramsammy on the study since Tuesday but none had been forthcoming. Last evening, the Government Information Agency (GINA) issued a statement on the study reporting Dr Ramsammy as saying he was unable to pronounce on the findings of the study because an investigation by the Ministry has to be conducted.
Minister Ramsammy said, according to GINA “We have no evidence that there has been an increasing incidence of and greater difficulty in treating e-coli infection either in the malaria regions of Guyana or anywhere else in the country.”
He said that the Ministry of Health was never approached for permission to conduct this study. He noted also that the journal. PLoS ONE where the study appeared is not an approved one.
“That doesn’t mean that the findings may not be interesting. However, unless the Ministry is provided with the information much cannot be said on the issue,” Minister Ramsammy said.
He explained that if there is any truth to the findings of the research it is not a reflection about Guyana’s system since drug use worldwide can result in changes in the genetics of organisms. He reiterated that permission for such studies has to be obtained from the ethics committee of the ministry. The study does say that permission was obtained from local Amerindian leaders and the Guyana government. It didn’t indicate who in the government provided approval.
Remote villages
According to the study in the very remote villages, 4.8% of the patients carried ciprofloxacin-resistant E. Coli despite no local availability of quinolones. However, the study said there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic. No antibacterial agents were found in the drinking water, but chloroquine was demonstrated to be present. The researches concluded in the remote communities, the heavy use of the malaria drug likely selected for ciprofloxacin resistance in E. Coli.
“This may be an important public health problem in malarious areas,” the study said. It was stated that in Guyana, “fever with no obvious anatomic source is empirically treated with choroquine until malaria smears have been completed,” the study said while adding that in most malarious countries the particular drug is still an important component in the treatment. Despite resistance to falciparum, the study said recurrent empiric treatment with the malaria drug several times a year is widespread in the tropics, primarily due to its low cost.
To arrive at their findings the researchers collected a total of 535 rectal swabs during the four-year period but only 15.4% of individuals reported antibiotic exposure in the previous five years. It said that no patients received antibiotics within 30 days of the sampling while all denied the use of fluoroquinolone.
And the study revealed that only one of the 24 water samples collected in 2004 yielded a single isolate of ciprofloxacin-resistant E. coli, isolated from Bartica river water.
Meanwhile one of the 13 water samples collected in 2005, river water from Kamarang, was found to contain chloroquine at a concentration of 4.7.
The researchers said to their knowledge they are the first to report implicating quinoline anti-malarial use in the development of bacterial quinolone resistance in the tropics. It said that the resistance mutations that were found in the local samples, and selected in vitro by chloroquine exposure, result in cross resistance to all quinolone antibiotics.
Antibiotic resistance
Importantly, the study said that antibiotic resistance has become a global crisis as a result of widespread use of antibiotics in medical and agricultural practice even though there is limited access to antimicrobials in the villages from which samples were taken in Guyana.
“Moreover there are geographical barriers limiting travel in and out of the region [from which the samples were taken],” the study said.
But the researchers acknowledged that they cannot with certainty dismiss the possibility that a few individuals may have travelled outside of the villages and become exposed to fluoroquinolones and transmitted the resistant organisms of their neighbours. “However, this hypothesis is unlikely not only because of the isolation of these communities, and thus rarity of outside travel, but also because the resistant E. coli were primarily polyclonal and the strains were widely distributed among inhabitants of different villages,” the study said.
It said that the fact that 24 different clones of quinolone resistant E. coli were found is evidence that an occasional traveller would be an unlikely source of the multiple resistant strains and therefore there must be a local factor selecting for resistance.
And chloroquine found in the drinking water in Kamarang may have been as a result of contamination by human waste and as such suggests widespread exposure to chloroquine, even in the absence of individual malaria treatment.
And while some residents may have acquired the resistance to the drug from exposure to contaminated water the fact that 24 distinct isolates of the strain were found suggests that single point source of water contamination would not be able to explain the multiple circulating strains.
