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WHILE the World Health Organization (WHO) indulges in endless prolatives of achieving "Health for All" by 2000 AD, the global disease burden is on the boil, especially in developing countries. According to the Organization's World Health Report, 1996, infectious and parasitic diseases killed about 17 million people in 1995 - almost one-third of all deaths due to illnesses reported in that year; over 99 per cent of these deaths were from developing countries. Tuberculosis (TEI), which claims over three million lives a year globally topped the list, while malaria, with a toll of'2.7 million, stood a close second - mainly due to the emergence of virulent, multiple- drug-resistant forms and the lack of effective new drugs or vaccines to combat them. Moreover, TB being the most common opportunistic infection in AIDS patients, the advent Of HIV has contributed further to its expansion.
India has its unenviable share of global incidences Of TB and malaria. Every year, of the over 10 million cases Of TB, 2.5 million turn out to be infectious. With about five lakh deaths per year, India contributes almost 17 per cent of the global deaths due to TB. The case of malaria is no better. Almost 2.5 million cases are reported every year, of which the fatal falciparum or cerebral malaria claims over 1 000 lives. India contributes about 40 per cent of all malaria cases in the world outside Africa.
These figures do not reveal the entire picture, though; the virtual collapse of health surveillance and information systems in India has led to gross manipulation and under-reporting of data by concerned authorities. Lack 6f surveillance has also affected the management of disease-control. This is especially true for malaria and TB, which require prolonged multi-drug therapy for complete cure and prevention of relapse. For example, lack of epidemiological information regarding the type of malarial parasite, vector species and the level of drug resistance in a particular area leads to the choice of wrong drugs/insecticides and doses.
Surveillance, however, is only one of the many problems. The dismal condition of our primary health care centres, total neglect of preventive measures, shrinking health budgets, liberalisation of drug policy, irrational drug use, excessive privatisation of health care delivery, increasing poverty and malnutrition have all contributed to the present situation.
An important aspect that is often missed while discussing the growth of these diseases is their correlation with our unsustainable and inequitable development patterns. It is now widely recognised that the growth of malaria is directly related to the creation of malariogenic conditions through neglected inland water bodies, irrigation and construction projects etc. On its part, TB is a common occupational health problem along with silicosis and other respiratory disorders among workers of industries such as mining, iron and steel, glass, cement and asbestos.
Our disease control programmes - 'vertical' approach ones like the national malaria eradication programme, which runs parallel to the general health services (GHs), as well as 'horizontal' approach types like the national tuberculosis control programme, which is totally integrated within the GHS - have failed to achieve their goals. One reason for this is their dependence at the peripheral level on rural primary health care centres and multipurpose health workers. This is unlike in the '60s (the golden era of the Indian public health system) when there were separate malaria and T13 workers. Another major problem is the fund sharing between the Central and state governments, beset by non-compliance on both sides. A general decline in health budgets has further compounded the problem.
Tackling the two maladies is as much a scientific challenge as one of public health. The age of triumphant chemical warfare against them is pass6. Drug resistance is on the rise and new vaccines are still non-existent. In the case Of TB, the BCG vaccine is already proving ineffective for adults.
Obviously, there are no short-cuts. A strong public health network, better infrastructure, a reliable and prompt health surveillance system, better living and working conditions, stress on prevention, health education, community participation, higher health budgets, focussed research, and above all, strong social commitment and political will for the proper implementation of the stated programmes are all equally important if results are to be achieved and sustained.
ALMOST 100 years after the discovery of the mosquito-bornemalarial parasite by Sir Ronald Ross in 1897scientists andpublic health experts are still grappling with ways to tackle thekiller disease. According to World Health Organization (WHO)estimatesmalaria afflicts about 500 million people annuallythe world over; 90 per cent of the cases occur in Africa aloneand the rest mainly in India (40 per cent of all malaria casesoutside Africa)BrazilSri LankaAfghanistanThailandVietnam and Colombia. The disease claims about 2.7 millionlives annuallyincluding an estimated one million Africanchildren under five.
According to V P Sharma, several states have reported
instances of falciparum with advanced resistance to chloroquine. Resistance to sulphalene / sulphadoxine and pyrimethamine groups of drugs, amodiaquine, mefloquine, a banned
drug sold unofficially, and quinine, the ultimate choice in
complicated cases, is also on the rise.
Resistance to insecticides like DDT is common; malathion
and dieldrin have joined the list as well. Recent reports in the
Indian Journal of Malariology reveal that resistance to even
multiple insecticide combinations is developing. Synthetic
pyrethroids (insecticides which do not have long-term residual
effects) such as lambdacyhalothrin are known to be more
effective and environmentally safer than insecticides in use,
but their cost is prohibitive. Chemical larvicides such as paris green, temephos or fenthion and
biological larvicides such as
the bacteria, Bacillus
thuringenesis and B sphericus
can also be
sprayed over water bodies.
Formulations of biolarvicides,
developed and field-tested by
the MRc and NMEP, were recently
cleared for use in mosquito
control.
Experts attribute malaria's
resurgence mainly to the failure
of
peripheral public health
institutions. About 40 per cent
of
posts in India's health care
centres lie vacant, according to
V P
Sharma. NMFP officials say that
most primary health care centres (PHCS) do not have
microscopes in working order.
Even in
fully functional PHcs, blood
slides accumulate for four-six
weeks, delaying diagnosis and
radical treatment. In most villages, the drug distribution
centres and fever treatment
depots
for malaria care are either
non-existent or defunct.
Insecticide spraying operations
are either not conducted,
or are incomplete or ineffective
in terms of the choice of the
insecticide, area covered,
number of required rounds and
adulteration. The collapse of
the health surveillance system
has
resulted in adhocism. Funding
for malaria research is in a
worse bind. Under the NMEP'S
modified plan of operation
(1977), malaria control costs
came to be shared equally by the
Centre and the states.
The subsidy cuts under the
structural adjustment programme brought budgetary
allocation down to Rs 72.45 crore
in 1991-92, and to Rs 50 crore
in 1992-93. Subsequently, the
allocation was increased to Rs I
10 crore, but included programmes for kala azar, filaria,
Japanese encephalitis and
guinea worm as well. The Union
government is currently
negotiating a us $140 million
World Bank loan to fight malaria in the metros and tribal
areas.
D Banerjee, public health expert
and professor emeritus at
the Centre for Social Medicine
and Community Health,
Jawaharlal Nehru University, New
Delhi, says,Unpardonableacts of omission and commissionby the political leadership ...have led to a sharp decline inthe quality of public healthservices... When there was anoutbreak of malaria in Rajasthanin 1994the malaria controlmachinery of the state wasalmost non-existent in theaffected villages... theafflictedpeople had to Cry Out to NGOSfor help." VHAi activists pointout that health officials tendto suppress malaria incidencefigures (during the 1994Rajasthan epidemicthe officialfigureof annual parasite index was0.59independent surveys'showed this to be above 5.0).
A country-wide review of malariacontrol strategies wasundertaken in 1995followingwhich a Malaria ActionProgramme (MAP) was launched.Under MAP'high risk' ruraland urban areas were identifiedfor accelerated control measuresdrug policies andtreatment schedules. Vectorcontrolmeasures were revisedwithemphasis on appointment of voluntary link workers at thevillage levelupgradation offacilitiesand intersectoral coordination.But experts point out thatmany of the changes - selectiveinsecticide sprayingfor one- suggested under MAP aretechnical and shortsighted.
In keeping with India'scommitment to the October 1992WHO global malaria controlstrategythe government draftedanational malaria controlstrategy in 1995. The newstrategyemphasises decentralisationepidemiological approaches in malaria controlcommunity participationmanagementinformation systems and health educationamong other things.
Till datethe responsibility for malaria control in the entirecountry had mostly rested with the NMEP. Under the proposednew strategythe financialtechnical and administrativeresponsibilities will be shared by major establishments in- theprivate and public sectorssuch as megaprojectstea / coffeeplantationsirrigation projects or railways / airports / seaports. The NMEP and MRc directors and V S Orlov of the WHO hadjointly recommended in 1994 that health impact assessmentbe made an integral part of the environmental impact assessment of all developmental projects.
Malaria research has several aspects: developing newdrugsvaccinessimple diagnostic methodsinsecticides andlarvicidesmethods of sterilising mosquitoesepidemiologicaland entomological studieshost-parasite interactionsimmunology of the disease andfinallyecology.
Experts strongly argue for bio -environmental control ofmosquito breeding by spraying larvicidal microbesorthrough fish species such as gambusia or the gupp MRC Scientists have identified at least four other species of fishtheDanio rerioAplocheilus panchaxOryzias melastigma andAapia mossambica which are known to feed on mosquito tar -vae. Combining mosquito control with rearing fish for consumption and profit has yielded encouraging results.Moreoverthe estimated cost of biocontrol could be as low asRs 4.97 per capita per yearas compared to Rs 6 using chemical insecticides.
Impregnated bednets are being increasingly recommendedfor malaria controlfollowing encouraging results in Orissaand the north-east. These bednets are impregnated twice ayear with synthetic pyrethroidsoffering effective protectionfor six-eight months from mosquitoesbedbugs and headlice.
Among the new drugs waiting to be introduced in themarket is a Chinese herb derivativeArtemisia annuapopularly known as Qinghaosu in China. Artemisinthe raw material.was identified as a potent antimalarial and analysed in Chinain 1972. Introduced by WHO in VietnamThailand and Cambodiait successfully curedmulti- drug- resistant malariacases. Another Chinese herbaldrugPyronaridinehas beenfound to be 100 per centeffective in the early stages ofmalariaaArding to a report in TheLancet (January 1996).
In Indiaclinical trials ofArteethera derivative developedby the Central Drug ResearchInstitute (CDRI)Lucknowarecurrently underway. The CentralInstitute of Medicinal andAromatic Plants (CIMAP)again inLucknowhas successfullyadapted the plant for cultivationin Indiaand also developedan improved method for extractingarternisinic acid and converting it into artemisinpavingthe way for its indigenouscommercial production. A WHOcommittee has recommendedthat in order to avoiddevelopment of resistance toartemisinits use should be restricted toonly those regions where multiple drug resistance is rampant.
Indigenous production and sale ofmefloquin was clearedby the government in March thisyear. The technology for theproduction of the drug is alreadyavailable with the IndianInstitute of Chemical TechnologyHyderabad.
The MRC is currently conductingclinical trials for a drugdeveloped by the CDR1. The drugcodenamed Compound80has been found to beeffective in curing monkey malaria; the results of human trialsare awaited. MRC scientists arealso assessing the antimalarialproperties of a wild herb fromBastarMadhya Pradeshlocallycalled bhuineem. The Centrehas applied remote sensing andgeographical information systems to identify malariatransmission conditions inGujarat's Kheda district.
Indian Council of MedicalResearch scientists at Port BlairAndaman & Nicobar Islandshaverecently found a plant thatis used by the local Onge tribeand could provide yet anotherweapon to fight malaria. -But thecontroversy on intellectualproperty rights over the plantproduct is likely to delay itsinduction into the antimalariaprogramme.
Scientists at the IndianInstitute of ScienceBangaloreareworking on a drug which attacksthe heme biosynthetic pathway of the P berghei which causesmouse malaria. According todirector G Padmanabhanthefinding may help in fightinghuman malaria too. Ais team hasalso developed a diagnostickit in collaboration with AstraResearch CentreBanglorebased on non-radioactivedetection Of DNA of the parasiteinblood samples without amicroscope.
Bangalore University's Centre for Applied Geneticsresearchers have taken adifferent route to beat malaria -bygenetically modifying mosquitoesso that they cannot breed.According to director N J Shettythey have already succeededin inducing genetic sterility inthe male Anopheles (Anstephansi and An fluviatilis).The researchers have alsoidentified a strain of femaleAnopheles that is resistant to themalarial parasiteand the genethat imparts this resistance.
The idea of controlling malariathrough genetically engineered mosquitoes dates back toChris Curtis' (of the LondonSchool of Hygiene and TropicalMedicine) efforts in the '60s.Laboratories in many countriesare still pursuing the idea.Howeverscientists such asAndrew Speilman of HarvardUniversityUSAfeel that suchhi-tech approaches divertmoney and attention from the lessglamorous conventionalmethods. Indian scientists alsopoint out that research intoepidemiologyvector behaviourecology and public health arenot receiving adequate attention.
There are three major stages inthe life-cycle of the parasite which are targets for vaccine development:
• A vaccine based on sporozoites is designed to preventinfection.
• Vaccines based on the asexual blood stages of the parasite(merozoites) will not prevent infectionbut can reduce oreliminate parasites in the blood.
• Vaccines directed at the sexual stages of the parasite (gametocytes) aim to interfere with the ability of the parasite toinfect mosquitoes and thereby prevent transmission of thedisease.
Ideallya vaccine aprist malaria should contain all threefeaturesbut since the cell surface characteristics of each stageof the parasite are differentthat would be possible only froma 'cocktail' of antigens (cell surface proteins) of all stages. About 45 different proteins of the parasite have been identified so farof which about 15 are considered potential targetsfor vaccine development. A vaccine developed by a group ofAustralian researchers is undergoing trials since 1994 in USAand Africa.
According to V S Chauhanconventional vaccinesdesigned to generate antibodies against the parasite are notlikely to provide full protection. They also need to activate the'killer cells' (T-cells) of the human immune system.Fortunatelythe parasite does carry some markers on its cellsurface which can also activate these T-cells. Identifying andincorporating them into the 'final cocktail' will get the bestresults. Chauhan's team has identified some such markers. Asimilar strategy is being followed by researchers led by AdrianHill at the Institute of Molecular MedicineOxfordUK.
There are no magic bullets to beat malaria as yet. Settingaside eradicationbetter public health management practicesstrong primary health care infrastructure and emphasis onpreventive measures and community participation have thepotential to reduce malaria incidence and make the WHO'sdream of a one-fifth reduction in malaria incidence by 2000 AD- in at least 75 per cent of the affected countries - a reality.
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.
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.
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.
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.
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?
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.
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