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Study here points to antibiotic resistance from malaria drug

Health Ministry says never approached for permission

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.

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6 Responses to “Study here points to antibiotic resistance from malaria drug”

Berkeley Van Bowen
on July 24th, 2008 7:56 am

A worldwide alert was publicized sometime ago that extreme caution should be taken when using drugs manufactured in India. The South Asian country has been accused of dumping cheap compromised drugs on the world market that have a disproportionate affect on poor countries. Because the drugs are not able to affectively cure/treat the diseases for which they are created, the consequence is often patient deaths.

[Reply to this]
La vie est bonne!
on July 24th, 2008 9:45 am

Not only was the caution about drugs manufactured in India, but also from China.
Quality control is no existent or it is not seriously taken at these locations.
North America has had many instances of “bad pharmaceuticals” slipping into the mainsteram pharmacare.

[Reply to this]
Chemist
on July 24th, 2008 10:57 am

Unfortunately the correct channels were not sought prior to carrying this study for whatever reasons, but as word of caution the Minister should take heed and do further investigations on this finding. The current Tx. using Cholroquine should be revisited as parts of Guyana was part of the Variable to low risk areas for chloroquine resistance 2003-2004 which by now may have changed either positively on negatively. It is likely to develop Quinolone resistance easier after the use or exposure to chloroquine as a result of a cross effect due to a similarity of the two types of drugs in their mechanism of action in the bacterial cell with the micro oragnism showing easier resistance to chloroquine due to its non-specific effect over the quinolone that is more specific resulting in the bacteria developing a ‘memory response’ (resistance) initially to chloroquine generating greater to become resistance to quinolones(ciprofloxacin). To address Mr. Berkley Van Bowen’s concerns, pleease be specific, a lot of manufacturers in India have been producing quality drugs at a fraction of the cost of similar drugs for years, almost all of which has passed assays and quality control tests some of which I have personal knowledge of with good results, thanks to India a lot can afford Chemotherapeutics, antiretrovirals among others.

[Reply to this]
ankoko
on July 24th, 2008 12:23 pm

Chemist - you are on to something no question. Lots of times the interaction of drugs change due to many factors. Good one day bad the next!
Question/Suggestion to the administration: Is it possible to have an independent screening of the manufacturing processes and properties of drugs imported before they are bought to ensure quality?
I know that Guyana doesn’t have the wherewithal to do so at this time but couldn’t these services be obtained internationally at no or nominal charge?
Could the information available from the US Food and Drug Administration be used to assist in this respect?

[Reply to this]
Chemist
In reply to the above comment on July 24th, 2008 1:14 pm:
In the Caribbean there is randon batch testing of drugs originating from companies manufacturing and supplying drugs without previous previous consistent quality control and proven track records, not sure if Guyana is privy to such services, buy in the past the Pharmacy and Poisons Board had the responsibility for assaying drugs used in Guyana, not sure how functionable they are today might some guidance in that respect.

[Reply to this]
Brainstorm
on July 24th, 2008 3:25 pm

There are also companies working round the clock to find a vaccine for Malaria. If you want to support them so we no longer need to worry about drug resistence you can do that with a necklace designed to show support for Malaria that donates 25% to finding a cure as well as providing nets and medicines. Visit Linkedforacause.com if you are interested.

[Reply to this]