Lying in ambush

Lying in ambush

HUMANITY seems to be losing the war against tuberculosis (T13).The picture is unnerving - eight million new victims and 2.9million deaths every year; dilapidated national TB programmes; emergence of multi -drug-resistant strains; prohibitive costs of treating the burden of excess cases; receding hopesof new drugs as research budgets shrink; the HIV epidemic andthe resurgence of veteran diseases such as malaria cutting intostatic health budgets. The disease is credited with killing overone million women (leading single infectious cause for femaledeaths in the world) and 1700children every year. Besidesmore HIV-infected individuals die from TB than from any othercause.

Though the picture does not give much cause for optimismmany believe T13 can still be tamed with a concertedglobal effort. Having declared TB a global emergencytheWorld Health Organization (WHO)in collaboration withdonor agencies like the World Bank (W13)is helping developing countries mount a fresh attack on this diehard monster. Atthe same timethe developed world is putting together itsrusty anti-T13 apparatus to tackle the menace. The WHO's planof action - viewed sceptically by many experts - is based onthe wisdom that greater resources and shorter durationtreatment will lead to a greater cure-rate. DOTSor directlyobserved treatmentshort course - as the WHO strategy iscalled - is a combination of four drugs is kill the T13 bacteriaunder close surveillance by health workers.

The WHO's sudden interest in T13howeveris questionable.Says Mira Shiva of the Voluntary Health Association of India(VHAI)Had there not been increasing incidence Of T13 in the developed world because of its association with HIV, it is unlikely that the ongoing suffering and deaths due to it would have really mattered:.. It is in the interest of Western countries to prevent the increase Of TB in the Third World which will continue to be the biggest pool of infection.Indeedthecontinue to be the biWHO's statement on current cases smacks of self-righteousness: "One quarter of all T13 cases in the us are among foreign-born personsand the increasing travel and immigration fromsuch countries adds t6 the spread of the disease. TB cannot becompletely controlled in the industrialised world until it issharply reduced as a health threat in developing nations." Butwould somebody ask the WHO that over the last 15 yearswhenT13 was still raging mad in developing countrieswhy did itallow its tuberculosis unit to decline to the point that a singleprofessional remained in 1989?

A Gordian knot
TBcaused by the bacillus Mycobacterium tuberculosisis a complex ailmenta mlange of conditions rather than a single entity. Needless to sayits control requires a strategy that can cope up with its protean character. In order to control TBthereforeit is essential to map its natural course.

TB spreads when contagiouspatients cough TB bacteria outof their lungs; the infectionspreads through inhalation.Insidea host's bodythe bacteriamoves slowly; only five- 10 percentof infected people become ill.

In most cases the bacteriaattacks the lungs. Pulmonary TB(TB of the lungs) destroys thelung tissuerupturing blood vessels in the process. Victims arevirtually consumed by the diseasewhich was calledconsumptionbefore LaurentBayleendowed it with its presentappalation. TB has a tendency todecline if left alone. The basisfor this tendency is a processcrucial to its transmissioneach stage of which isinefficient. Itis this inefficiency that hasbeen both the strength and weakness and that gives scientiststhe hope that the disease can beeliminated from human society.

A case-management packageconsisting of multi-drugchemotherapydetection ofinfected patients and a smoothsystem of supplying drugs hasled to virtual transmission Of TBinfection in the generalpopulation; in manyindustrialisedcountries there exists today anentire TB-free generation.Prevention based on this case-managementhoweverhasinnate limitationsone of whichis the inevitable creation ofdrug resistance. An estimated 50million people worldwide areinfected with drug-resistant TBtoday.

Clinically significant drugresistance is always attributableto the incorrect use ofantibioticsusually because ofimproperclinical or programme managementand non-compliancewith prescribed treatment. Sincethere are presently only alimited number of antibioticsactive against TB and littleimmediate promise of new potentagents at an affordablepricethe period of grace inwhich to achieve control of thedisease is rapidly drawing to aclose. The advent of the HIV epidemic has greatly increased the efficiency of the cycle oftransmission of TBreducing even further this window ofopportunity. HIV plays havoc with an individual's immunesystemand can effectively speed Up TB sickness. In additionpoor case-management has actually enlarged the size of theinfectious pool in the community.

Alsothe necessity of maintaining efficient case-management for the full life-span of the last generationheavily infected with M tuberculosisespecially as thedisease becomes restricted to the marginalised and inaccessible sub-groups of the populationthreatens to ensure that thepriority Of TB disappears long before the disease itself. TBwould then rest as a circumscribed epidemic in this sector ofthe populationwaiting for the first opportunity to break outonce again.

Developed world: a death wish
This is what seems to be happening in the industrialisedworld. The incidence Of TB rose by 12 per cent in the usbetween 1986 and 1991; Italy reported a 28 per cent jumpbetween 1988 and 1990; Switzerlanda 33 per cent increasefrom 1986 to 1990. Experts have attributed this upward trendto changes in the social structure of citiesthe Hiv epidemicand a failure in certain regions to improve public treatmentprogrammes.

In the usseveral researchers have attributed a significantportion of TB outbreaks to immigrants; this is a fallacy. Of theexcess cases in 1990only 31 per cent could be traced to foreign-born individuals.

Case numbers tell only part of the story; the resurgenceof TB is severely complicated by emerging resistanceto powerful drugs like isonidazid and rifampicin. A Centerfor Disease Control (us) survey of drug resistance from1982to 1986 showed that isolates from nine per centof patients who were never previously treated wereresistant to one or more drugsand that 22.8 per centof isolates from previously treated patients were resistant.

The economic burden of the failure to get overthis pioblem could be enormous. For the us alonethedirect and indirect treatment costs of the excess cases Of TBthat were a result of increased active transmission from1985equal $640 million. If cases continue to rise atthe current rateit is estimated that by the end of this decadethe direct treatment costs of these cases would total $2.2billionand the indirect costs would add up to $1.9 billion.In addition to depreciating infrastructuredeclining budgetsand a patient population that is becoming more difficult totreatthe us is also faced with a generation of lost researchexpertise.

Developing nations: programmed to fail
The problem has assumed a far more fearsome aspectin developing nations. In factTB owes much of its successto the dismal performance of national tuberculosispro:grammes (NTPS) in the developing world. WHOestimates that only 30 per cent of all NTPs are applyingthe measures required to control the epidemic. Asiahometo majority of the world's TB-infectedcould very wellbe sitting on a drug-resistant powder keg waiting to beignited by the exploding number Of HIV-POSitiVe cases in thecontinent.

There are several reasons for the failure Of NTPS -inadequate funds and infrastructureexpensive drugsirrational drug prescriptionspoor adherence to therapycreationof multi - drug- re sis6nt strains and their transmission touninfected bodies and the advent Of HIV. Besideshindrancessuch as corruptionlack of commitmentmisperceptions andilliteracy have further weakened the programmes. Expertshave worked out that to make TB programmes successfulanadditional us $100 million per year needs to be provided bydonor nations to poot countries for medicinesmicroscopesand a modest infrastructure.

At home: disaster stalks
India's NTP is a case in point. The 1962-born programmehas come a cropper. The number of new TB cases detectedper 10population under the NTP has increased from 1.13in 1981 to 1.80 in 1991. It is estimated that annually TBafflicts about two-2.5 million new victims and kills 4200Itclearly indicates the programme has not functioned asexpected.

The NTP was envisaged as an integral part of the generalhealth services (GHS). Over the timethe GHs has beendestroyed and needs to be resurrected. To put the NTP back onthe tracksthe Indian government has revised its programmewith financial help of about Rs 700 crore from the WB. Thegovernment has also increased the funds for TB Control fromRs 150 million per annum three years ago to Rs 460 million in 1995.

An exhaustive 1996 study (Tackling TB: The Search forSolutions) by the Mumbai-based Froundation for Research inCommunity Health points out that although 60 per cent of thecountry's TB patients seek treatment at private clinicsthe NTPremains out-of-bounds for the private medical sector. Thestudy lists lack of awareness about TBinfrastructuralbottlenecks and non-adherence to sustained treatmentamong othersas the major causes behind the failure of theNTP to control the disease.

Through the revised programmethe government hopesto achieve a cure rate of about 85 per centand treat at least100infectious patients per 1000population. But manyexperts believe that the RNTP - the revised programme -suffers from the same drawbacks as NTP: no efforts being madeto strengthen primary health care and GHS; no foolproofsolution being suggested to ensure adequate production andsupply of anti-TB drugs; the high costs involved in supervisedscc (shorter course chemotherapy) compared to domiciliarytreatment; Indian experts and scientists not consulted in planning and revising programmes; and NTP being revised as perthe dictates of the WB.

MoreoverTB enthusiasts have expressed concern at thefate Of NTP in the rest of the country where RNTP is not beingimplemented. They fear that the whole machinery being preoccupied with RNTPthe ongoing programme might be neglected.

SCC seems to be the major plank for RNTP (see box: A tale oftwo treatments). For scc as envisaged under RNTPit isestimated that the cost for treatment will come to Rs 1500perpatient; to treat 10 lakh sputum positive casesthe cost will bean estimated Rs 150 crore per year; this exceeds the entire TBprogramme budget. With financial institutions like the WBincreasingly influencing global and national health and drugpoliciesit remains to be seen as to whose interests willprimarily be safeguarded - that of the Bank's shareholdersand the Northern countries'or that of the powerless millionsof the South?

Science says
Given the dir'e straits of global TB eradication programmescanbasic science offer any solace to the victims of this marauder?

Scientists have gained a fair amount of knowledge of themechanisms of resistance to antitubercular drugsan important step forward as it allows appropriate regimen changes incases of suspected resistancewhich should result in betterprognosis and subsequent reduction in the risk of transmission of disease. Improved ways to detect drug resistance couldalso help in monitoring the efficacy of control programmes.

There are several reasons for the rapid rise of multi-drug-resistant TB; and foremost among these are poor complianceand inadequate drug regimens. The former is often a result ofthe length of treatmentwhich could be improved by shortening the duration of chemotherapyalthough this wouldrequire the availability of longer-acting or more powerfuldrugs. Several new drug targets have been discovered; theseinclude enzymes involved in synthesising components of thecell wall.

Vaccination is undoubtedly the most cost-effective meansof preventing diseasewith the Basille Calmette-Guerin (BCG)vaccine BCG being a front-ranker. Much current research isaimed at improving the BCGwhich till date has demonstratedlittle evidence of having made any significant dint in TB'Sarmour. Further understanding of protective immunity andpathogenesis may be obtained from comparing pairs of virulent and avirulent strains. The recent demonstration that theadministration of thalidomide leads to striking clinicalimprovement in patients infected with M tuberculosis couldalso help strengthen the arsenal against TB.

Afterword
The effectiveness of standard six-month chemotherapy is substantially reduced when the drugs are delivered or taken inappropriately. This is the case with many patients in developingcountries and for those of developed countries who live insocio-economic conditions close to those prevailing in thedeveloping world - the unemployed and homelessthe HIV-infectedthe drug addicts and recent immigrants who havepoor access to medicare.

in the world of infectious diseasesthere is nothingfrom which we are remote or disconnected. We will continueto be challenged by emergent threats to healthnew agentsand vectors and new evolutionarily selected and human-made variants. We know how to cure and preventconventional TB; we must earnestly and with all haste developthe capacity to prevent the spread of drug-resistant TB. If wedo not take the current TB outbreaks seriouslywe may losethe las t opportunity to defeat one of the greatest killers inhuman history.

With inputs from Souparno Banerjee