KARACHI: After conducting a series of research projects for five years, doctors at the Aga Khan University (AKU) have found a diverse group of drugs effective against Naegleria fowleri (N. fowleri), a deadly pathogen that has claimed many lives over the past five years, it emerged on Tuesday.

The research team was led by Dr Naveed Ahmed Khan and Dr Abdul Mannan Baig, senior experts at the department of biological and biomedical sciences at the AKU. The drugs tested to tackle N. fowleri are already in use for other illnesses.

“We had tested several Food and Drug Administration-approved drugs to check their efficacy against N. fowleri. Of them, three have been found to be effective,” said Dr Khan, adding that the drugs would hopefully be used to treat humans infected with N. fowleri next year.

According to Dr Khan, the problem with the conventional medicine being used to counter N. fowleri is that the drug does not reach the brain easily to kill the residing pathogen.

“The drug doesn’t go directly to the brain that has been infected by the germ. Rather, it circulates in the blood and ends up in tissues primarily, resulting in side-effects. By the time, it gets to the brain its effect has significantly been diluted,” he told Dawn.

“It’s idiotic that we have been using the same drug and the same mode of delivery for the past five to six decades, though we couldn’t save a single life, at least in Pakistan,” he added.

“If we keep doing the same thing, we will keep getting the same result. There is a need for innovative thinking,” he said.

Nasal rinsing

The researchers not only envisage using different drugs for the deadly infectious agent, but also a novel way to deliver them; the plan is to administer the drugs through nasal cavity so it reaches the brain directly.

“With the help of a nebuliser, the drugs will be administered in vapourised form to get to the infected area, the site where N. fowleri reaches and concentrates as its natural course of the disease, before spreading to the rest of the central nervous system,” said Dr Khan explaining the rationale behind using the new method to administer the drugs.

The other reason for this approach lies in the fact that the so-called ‘brain-eating amoeba’ also uses the nasal cavity to invade the brain (when contaminated water goes into the nostrils deeply); an effort seemed to outsmart the pathogen.

The next step for the team is to administer the drugs to animals before applying them to humans. “We need approval from relevant authorities before administering them to patients,” Dr Khan said while expressing the hope that everyone would understand the urgency in the matter and accord approval to the drugs without wasting too much time.

The fatality rate of Primary Amoebic Meningoencephalitis (PAM), a rare disease caused by N. fowleri, has so far remained more than 95pc all over the world (and 100 pc in Pakistan) despite advances in antimicrobial chemotherapy and supportive care.

A recent paper published by the AKU team indicated that although recreational activities are likely contributing to PAM cases, reports from Pakistan suggest that the victims habitually didn’t have a history of swimming but yet succumbed to the disease.

“While cleaning the nose in ablution, many people push water forcefully up the nostrils, even though this is not a mandatory part of the ablution. The process has tremendous health benefits only if water supplies are free of pathogenic microbes,” the study states.

It also identifies excessive reliance on water tanks as a major risk factor for PAM as, according to the study, these tanks are the breeding grounds for the propagation of these free-living amoebae.

“There is a need for awareness to take measures to make water safer for ritual nasal rinsing. Using sterile water that is boiled for at least one minute and left to cool or water filtered to remove small organisms or water disinfected properly using recommended concentrations of chlorine together with careful ablution (not pushing water inside nostrils aggressively) should minimize the risk in contracting PAM infection,” it says.

Loss of smell

Describing the disease as devastating as there was no cure for the infection, Dr Khan said that majority of the victims in Pakistan were young men who were often the sole breadwinners for their families. Hence, it’s not a case of one death but countless families being affected.

In his opinion developed countries that report very few cases of PAM won’t invest in discovering an effective drug for the disease. It’s the developing countries having the most burden of the disease that have to come up with solutions.

Doctor Khan and doctor Baig said that one of the challenges in treating PAM had been the way the disease presented itself that had been often overlooked.

One of the initial classic symptoms of the disease, these experts pointed out, was parosmia (a distorted sense of smell) that swiftly progressed to anosmia (loss of sense of smell) and severe headache (the symptoms that are not present in other cases of bacterial meningitis).

Other indications of PAM are stiff-neck, fever, altered mental status, seizures and coma, leading always to death.

“A high mortality in PAM is attributed to delayed diagnosis, a factor directly linked to the fact that most of our health facilities are poorly equipped,” Dr Khan said.

“My laboratory is the only health facility that uses advanced molecular tools including polymerase chain reaction and immunodiagnostics to diagnose PAM and lab results are available within three hours while other laboratories rely on an old method that takes 72 hours to produce results,” he said adding that time factor was crucial since a PAM patient could die within five to six days.

Dr Khan believes that thousands of people in Pakistan are dying of PAM but only a few cases are reported as people and medical practitioners are generally unaware of the disease.

In coming years, he warned the number of reported cases would vary but the number of incidence would increase due to global warming as the lethal amoeba grows in warm temperatures.

“With temperatures reaching up to 50 degrees centigrade and water temperatures being recorded at 30-35 degrees centigrade, millions of people facing prolonged water cuts turn to freshwater lakes, ponds, standing water, etc, for a relief.

“The presence of N. fowleri in such waters, lack of awareness and/or control measures, poor health infrastructure, unavailability of drugs to counter this infection present a major health hazard for communities,” he concluded.

Published in Dawn, July 22th, 2015

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