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Typhoid, kala-azar drugs fail in India

NEW DELHI: About three-fifths of Kala Azar patients in India are failing to respond to conventional first-line drugs and three inexpensive typhoid drugs, highly effective in curing the life-threatening disease in the capital a decade ago as they have become largely ineffective, according to World Health Organisation (WHO).

In a recent report titled "Overcoming Anti-Microbial Resistance", who said about 70 per cent of Kala Azar cases in Bihar are non-responsive to current treatment regimens.

Till 1972, chloramphenicol was the choicest drug for typhoid in the Indian subcontinent. But by 1992, two-thirds of thypoid patients were resistant to it that gave way to treatment with expensive quinolones, that are themselves losing effectiveness, the report said.

In 1990, almost all cholera isolates gathered around New Delhi were sensitive to cheap drugs furazolidone, ampicillin, cotrimoxazole and nalidixic acid. Now they are mostly useless.

Resistance to drugs has become a global problem covering a variety of diseases including pneumonia, malaria, hepatitis, diarrhoeal diseases, tuberculosis (TB), AIDS, gonorrhea and even hospital-acquired infections.

Though vaccination is the ultimate weapon against infectious diseases, no vaccines are currently available against five of the six major infectious killers. "Today the situation in developing nations remains as grim as that of previous generations in industrialised nations," it said.

Moreover, as research funding for major infectious diseases is woefully inadequate worldwide, there are no new drugs or vaccines ready to emerge from the research pipeline, the report said.

Increasing resistance of microbes to drugs has resulted in a small, but growing, number of HIV-infected patients showing primary resistance to zidovudine (AZT) and other new Anti-HIV therapies.

AIDS, which claimed about 2.6 million lives last year, is a particularly insidious disease as those infected become reservoirs for TB, kala azar, pneumonia and other infections some of which have themselves developed resistance.

About 98 per cent of gonorrhea strains in South-East Asia have become resistant to penicillin. Newer expensive drugs like ciprofloxacin are also showing a rising failure rate in treating gonorrhea, resistant strains of which along with other sexually transmitted diseases (STDs) have become a driving force in HIV epidemic, the WHO report said.

Nearly one-third of patients taking lamivudine -- a drug developed only a few years back to treat hepatitis-B -- are showing resistance to therapy after the first year of treatment. Lamivudine, though eliminates about four-fifths of the virus, rebounds more vigorously when treatment stops.

Despite availablity of vaccines against hepatitis, lack of committment by governments is responsible for the growing rate of infection.

Malaria, a major killer in Asia and Africa, is reappearing in areas earlier deemed disease-free. Resistance to chloroquine, the treatment of choice earlier, is widespread in four-fifths of the 92 countries including India, where the disease continues to be a major killer.

Unfortunately, many new drugs for malaria are expensive and have serious side effects. Resistance to mefloquine, another malaria drug, emerged soon after its introduction in south-east asia. Thailand has completely lost the means of using three popular anti-malarials, the report said.

TB, another ancient killer, is staging a major comeback with increased resistance to anti-TB drugs. Recent reports of global trends in multi drug-resistant (MDR) TB are particularly chilling keeping in view that TB is transmitted by tiny particles suspended in the air.

Non-compliance to WHO-recommended directly observed treatment, short-course (DOTs) regimen for TB and poor quality drugs are two important factors contributing to resistance.

"The ability of HIV to accelerate the onset of acute MDR TB has serious implications for humanity," the report warned.

Increase in the number of HIV-infected is also resulting in rise in MDR leishmaniasis (whose visceral form is called kala azar) cases in developed mediterranean nations.

Resistant strains of Leishmaniasis flourish in areas with high poverty, low surveillance and inconsistent treatment due to limited medical access, availability of spurious drugs and political discord.

Leishmaniasis is now resistant to drugs containing toxic antimony compounds in about two-thirds of cases in some developing nations, the report pointed out.

Widespread confusion worldwide over the difference between viral and bacterial respiratory infections, which often show the same clinical symptoms, has led to 70 per cent of chest infections becoming resistant to one of the first-line drugs.

With the onset of resistance, newer treatments for respiratory infections are proving too costly for the poor. Laboratory tests for the diagnosis of these diseases are expensive too, the report said.

Recent W.H.O. studies have shown four-fifths of patients with respiratory infections worldwide are unnecessarily treated with antibiotics which also led to drug resistance.

Ten years ago, a shigella dysentery epidemic could be easily controlled with cotrimoxazole, a drug cheaply available in generic form. Nearly all shigella bacteria strains are not responding to the drug any more. Resistant to ciprofloxacin, the only viable medication left, is just round the corner.

As shigella dysentery is rare in developed countries, it is not a pressing concern to pharma companies favouring higher returns on research and development, the report noted.

Among the bacteria causing hospital-acquired infections, salmonella, pseudomonas and klebsiella are showing high levels of resistance in developing nations.

In the 1960s, most staphylococcus infections were pencillin-sensitive. Now they are not only resistant to it, but increasingly impervious to each successive drug developed.

Economic and social patterns have a crucial role to play in this trend. The economic consequences of anti-microbial resistance can be staggering, the report warns. The cost of treating a patient with multidrug-resistant (MDR) TB is a hundred times more than that needed for treating a non-resistant case.

New York City spent nearly one billion -- a cost beyond the reach of most of the world's cities -- to control an outbreak of MDR TB in the early nineties.

Under-use of drugs in poor nations and overuse of drugs in rich nations -- two diametrically opposite trends -- are fuelling growth of anti-microbial response, which is paradoxical, the report noted.

Overuse of anti-microbials by wealthy countries in food production, treating sick animals and promoting livestock and poultry growth is also contributing to increased drug resistance. About half of the antibiotic production worldwide is currently used for these purposes.

Dispelling a common misconception that pharma companies are frequently making new drugs to replace the ineffective ones, it said while newer versions of older drugs are being developed, there is a dearth of new class of anti-microbials.

After a flurry of discoveries between 1930 and 1970, the past 30 years have witnessed fewer discoveries in the fight against infectious killers, the report added. PTI

The important point is that kala azar is preventable by use of vector control. "An ounce of prevention is worth a pound of cure." is very applicable in the case of kala azar, which is a deadly disease, treatable only with highly toxic drugs, that is preventable by regularly conducted vector control. DDT works for this purpose. Typhoid is also eminently preventable by simple sanitation measures.

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