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Operational research on tuberculosis control in Malawi
Banerjee, A.
Publication date
2003
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Citation for published version (APA):
Banerjee, A. (2003). Operational research on tuberculosis control in Malawi.
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1.. INTRODUCTION
1.1.1.1.1.1. Extent of the TB/HIV problem
AA third of the world population has been estimated to be infected with
MycobacteriumMycobacterium tuberculosis (M. tuberculosis). There were an estimated eight million neww tuberculosis (TB) cases with 8% of the new cases co-infected with human
immunodeficiencyy virus (HIV) and 1.87 million TB deaths in 1997 [1]. Of the global totall of 42 million people estimated to be living with HIV/AIDS (PLWH) at the end of 2002,, 29.4 million (70%) are in sub-Saharan Africa [2]. In eight countries, all in Southernn Africa, the adult HIV seroprevalence rate is above 15% [3]. Of the 36.1 millionn PLWH worldwide at the end of 2000 about a third were co-infected with M.
tuberculosistuberculosis with 68% of those co-infected living in sub-Saharan Africa. Escalating tuberculosiss case rates over the past decade in many countries in sub-Saharan
Africaa are largely attributable to the HIV epidemic [4-14]. Since the mid-1980s, in manyy African countries, including those with well-organised programmes [15,16], annuall tuberculosis case notification rates have risen up to fourfold, reaching peaks off more than 400 cases/100,000 population [17]. More than 70% of patients with sputumm smear-positive pulmonary tuberculosis are HIV-positive in some countries in sub-Saharann Africa [8-10,12,16,18-21].
1.1.2.1.1.2. TB control
Tuberculosiss is caused by M.tuberculosis and is mainly spread through droplet infection.. Disease may present as i) smear-positive pulmonary TB (PTB) whereby bacillii are visible on direct microscopy of sputum, as ii) smear-negative PTB whereby noo bacilli are detected under sputum microscopy and as iii) Extra Pulmonary TB. Smear-positivee patients are the most infectious and can infect 1 0 - 1 4 other persons in aa year [22-24]. TB control programmes therefore emphasize the detection and cure of smear-positivee cases. The overall objectives of TB control are 1) to reduce mortality, morbidityy and transmission of TB and 2) to prevent the development of drug resistance. .
Case-findingg and treatment to ensure cure are the core tuberculosis control activities.. The currently recommended approach to case-finding involves detecting casess among people presenting with symptoms (most importantly chronic cough) to generall health services [25]. It has been shown that from a TB control point of view poorr treatment is worse than no treatment, resulting in more transmission and an increasedd risk of developing drug resistance [26]. Hence, achieving a high cure rate
iss of vital importance. To ensure relapse-free cure while preventing the emergence off drug resistance the strategy is to provide short course chemotherapy under direct supervisionn at least during the initial phase of treatment to at least all identified smear-positivee TB cases. As M. tuberculosis is a slow growing aerobic organism whichh can remain dormant for a prolonged period, prolonged treatment with multiple drugss is required [27-34], As rifampicin is the major sterilizing drug and the basis for modernn short course chemotherapy [35-39], directly observed therapy (DOT) was introducedd to prevent the emergence of resistance to rifampicin [37,40]. Intermittent regimenss have been shown to be as highly efficacious as daily regimens [41-50] and greatlyy facilitate direct observation of drug-intake [33] and ambulatory treatment. Ambulatoryy treatment has been shown to be highly effective without increasing the riskk of infection for close family contacts as multiplication of susceptible organisms stopss during the first days of effective treatment [35,42,43,51-56].
Forr the control of TB the World Health Organization (WHO) formulated a policy packagee called the DOTS (directly observed therapy, short course chemotherapy) strategyy based on previous experience in TB control [57,58], and comprising five elementss :
1.. political commitment to TB control at all levels
2.. case detection through case-finding by sputum smear microscopy examinationn of TB suspects in general health services
3.. standardised shorfecourse chemotherapy to at least all smear-positive TB casess under proper case management conditions, i.e. DOT when rifampicin iss used [25,59]
4.. regular, uninterrupted supply of all essential anti-TB drugs and diagnostic materials s
5.. a standardised monitoring system for programme supervision and evaluationn using treatment outcomes such as cure, death, smear positivity att 5 months indicating the efficacy of the regimen used, default reflecting the organizationn of services, and transfer outs
Thee targets set are :
-- to detect 70% of estimated new sputum smear-positive TB cases [60]
too cure 85% of the detected new cases of sputum smear-positive TB resultingg in immediate decrease in TB prevalence and rate of transmission, graduall decrease in TB incidence and reduction in acquired resistance [25,61,62] ]
Thee DOTS strategy has led to improved TB control in a number of countries [15,44, 48,60,62-75]] and has shown to be cost-effective [60,63-89]. Coverage globally was stilll only 32% in 2001 [90]. To achieve worldwide coverage accelerated expansion is neededd and will need to be based on a multi-sectoral approach building on national andd global partnerships to maintain commitment and resources [56].
1.2.1.1.2.1. Difficulties in TB control
CaseCase detection
Earlyy case detection is important in order to reduce the transmission of TB. However,, early diagnosis is often difficult to achieve due to several months of patient andd health services delay. Patients are usually diagnosed as a consequence of the interactionn between their active efforts in seeking health and the passive case-findingg activities of health care workers in health centres. Several factors cause the delays.. First, since people live in a pluralistic medical society they make their own choicess oh where to seek treatment (traditional versus allopathic), depending in part onn their cultural beliefs regarding disease and of being at risk for disease [92]. Some mayy not be worried about a persisting cough until haemoptysis appears [93-97], Otherss may reject treatment based on allopathic medicine completely [98].
Second,, as TB is a contagious disease, it is a stigmatising condition that may elicit fearr and avoidance rather than sympathy. This results in patient isolation during treatmentt by the community and sometimes the family in view of the risk of infection [95,, 97,99-103] or may lead to self-stigmatisation and self-ostracism by the patient forr fear of being blamed for spreading the disease [104]. As a consequence it will preventt them from seeking health care and social services [94,96,97,104-106]. Third,, time constraints due to a heavy workload (often higher for women) may delay healthh seeking till the illness becomes more serious [95,107-110]. Fourth, factors affectingg accessibility to public health services may include limited accessibility geographicallyy [111] (and therefore incomplete coverage by the services), inconvenient clinicc times and fixed clinic days [112,113]. Access to services may be more difficult for womenn [114-117]. Fifth, the perception of quality of services provided is important as well.. Lack of drugs and diagnostic supplies, poorly trained staff resulting in diagnostic delayss [113,118,119], and frequent referrals to other facilities reduce its credibility [95-97].. Lack of attention and poor communication by staff to the patient [112], whether duee to socio-economic, educational, cultural or linguistic differences [120,121], also affectss the perceived quality. Sixth, services provided by the private sector are often perceivedd to be of better quality as patients often have little faith in the drugs providedd by the public health services. The private sector is however also often
poorlyy trained to diagnose and treat TB [95, 104,112,122-126,] and when the informall unqualified private sector is initially approached, this often causes additional delayss [127]. Finally, economic costs involved in seeking health care, whether direct orr indirect costs (i.e. transport, lost wages), will play a role in when and where to seekk services [128].
CaseCase holding
Prematurelyy interrupting or stopping treatment is the most serious impediment to the controll of TB. Among patients with active disease who do not adhere to treatment sputumm conversion to smear-negative will be delayed, relapse rates will be higher andd drug resistance may develop [129-133]. Other consequences of non-adherence includee the need for additional treatment leading to additional expense and possibly deathh [134,135].
Patientss have their own ideas about taking medications and evaluate the doctor's recommendationss with what they themselves know about disease and medication. Ass they need to manage their daily existence of which medical regimens are only a partt [136] they weigh up the costs, like the stigma of having to take drugs or attendingg the clinic, and the benefits of taking particular medications, like improvementt in symptoms or the promise of relief in the longer term, as they perceivee them within the contexts and constraints of their everyday lives and needs [137].. Drugs are taken on trial and patients adhere with medical advice when it makess sense to them and their own lay beliefs [138]. Often a pragmatic decision is takenn [139,140].
Reasonss for dropping out are several. First, reasons at a personal level are feeling symptomm free (usually after one or two months of effective chemotherapy [141]), loss of faithh in the therapy and the unwillingness to accept the unpleasantness of the therapy [142].. Second, there are social reasons such as the stigma attached to being a TB patientt or lack of social support [93,100]. Third, factors relating to public health services ass mentioned above remain valid for case holding [142]. Fourth, economic reasons, eitherr due to direct cost of treatment or the indirect costs of transport and lost wages, whetherr in the public or private sector, force patients to interrupt treatment [85,93,97,100,104,112,142].. And fifth, there are no defaulter retrieval systems in place inn the private sector [143,144].
DirectlyDirectly observed treatment
Off the 5 elements of the DOTS strategy directly observed treatment (DOT) is the controversiall one. On the one hand, in western countries such as The Netherlands where,, with the exception of high risk groups, self administered treatment (SAT) is applied,, treatment success rates are reportedly high and drug-resistant levels low. It is arguedd that DOT may have benefits but that it may not be needed universally [145-147] andd that DOT should be accompanied with other inputs such as incentives and enablerss [90,134,148-156]. On the other hand, identification of likely defaulters is difficultt as other studies have shown that age, gender, ethnicity, racial origin, occupation,, socio-economic status, educational level, marital status, cultural backgroundd and religious beliefs are not helpful in identifying who will or will not be compliantt with treatment [90,156-159]. DOT has therefore been advocated as a fundamentall part of the DOTS strategy, in particular to prevent multi-drug resistance [61,160].. This can be provided by a health worker in hospital or at a clinic [161,162], but hass posed problems of coverage in developing countries. There has been a shift to involvee trained lay people such as household members, community health workers, communityy health volunteers [153,163], community leaders, storekeepers [59,164], religiouss leaders, peer groups [143,165] and others [99,166]. Lay workers have shown too be at least as effective in observing treatment resulting in high treatment success ratess among patients [99,164,167-179].
Randomlyy controlled trials looking at DOT have shown mixed results. While some didd not show additional benefit to DOT [180-184] another study did [171].
1.2.2.1.2.2. Difficulties in TB control in high risk populations
Inn settings where people at higher risk for TB and HIV are concentrated, intensified case-findingg will lead to detecting more cases with on average a shortened duration off infectivity. High risk populations for tuberculosis include the homeless, migrants, thosee living in refugee camps [185,186] and captive populations such as in prisons, policee stations, remand centres, penal colonies, prisoner of war camps, detention centress for asylum seekers and secure hospitals.
Prisonerss often belong to disadvantaged groups in which TB and HIV incidence is higherr than in the average population [187]. Though few prisons systematically reportt tuberculosis case-finding and treatment outcomes [188], TB incidence in prisonss can be as high as 7000 per 100,000 population [189-195]. Increased transmissionn of TB in prisons can be attributed to [196-199]:
latee case-finding through delays in diagnosis due to failure of medical servicess in remand custody or holding centres to refer tuberculosis suspects forr diagnosis or to initiate treatment and provision of sub-standard treatment resultingg in failure to cure patients and prolonged infectiousness
transferr of prisoners with infectious tuberculosis between and inside prisons andd failure to separate the infectious cases from other prisoners
overcrowdingg (limited cell space per person and prolonged confinement insidee cells), poor ventilation, poor nutrition and poor hygiene
Sexx between men and use of drugs by injection are common and may promote the transmissionn of HIV infection. Prison conditions therefore promote tuberculosis transmissionn within the prison directly and indirectly through facilitating HIV transmissionn and to the community at large as the prison population is a fluid one [200]. .
Intensifiedd case-finding for TB may involve screening all for a chronic cough of more thann three weeks or less [201] and examining their sputum [202] or include CXR screeningg in some settings and has proven to be valuable in prisons [203].
1.2.3.1.2.3. Difficulties due to the HIV epidemic
HIVV infection results in the decrease of CD4 cells with a progressive loss of immune functionn and appearance of opportunistic infections [204,205]. HIV promotes progressionn to active tuberculosis in people with recently acquired M. tuberculosis infectionss [206] and is the most powerful known risk factor for reactivation of latent tuberculosiss infection to active disease [10,207]. The annual risk of developing tuberculosiss in a PLWH who is co-infected with M. tuberculosis ranges from 5-15% [10]. .
Sincee the mean CD4 cell count is around 300/mm3 in HIV-infected tuberculosis patientss [208], tuberculosis often occurs after PLWH have already suffered from severall different illnesses [209]. Also, increasing tuberculosis cases in PLWH pose ann increased risk of tuberculosis transmission to the general community, whether or nott HIV-infected [6,210]. TB however also alters the course of HIV infection as it inducess cell mediated immunity and therefore more HIV viral replication and more rapid progressionn to AIDS [211-214]. TB/HIV co-infection has caused the following problemss in relation to TB control:
1.. Increase in cases: Since the mid-1980s, in many African countries, annual tuberculosiss case notification rates have risen up to fourfold [7-9,11-17].
2.. Higher risk of nosocomial transmission: In high HIV prevalence settings over 50% off admissions may be HIV sero-positive and up to 25% may have TB [215]. Due to thee delay in diagnosis of TB in hospital [216], HIV sero-positive patients and staff are att great risk of acquiring new TB infection and subsequent disease [206,217-222] 3.. Difficult diagnosis : In early HIV infection with mild to moderate immunodeficiency, TBB disease resembles that seen in those without HIV infection. However, many programmess have reported an increase in smear-negative TB and EPTB [7,13,223-225].. This is because more advanced immunodeficiency is associated with an increasedd frequency of pulmonary disease resembling primary pulmonary tuberculosiss and of extrapulmonary (including disseminated) disease [48,217,226]. Inn these patients, the bacillary load in sputum samples may not be representative of thee actual number a patients harbours [10]. These smear-negative PTB patients can posee diagnostic problems as chest X - Rays (CXR) become more atypical with decliningg CD4 cell count. For instance, the CXR may be normal in some patients with disseminatedd disease. Further, a number of patients will be wrongly diagnosed as TB patientss [227,228].
4.. Higher mortality and shorter survivah Although HIV-infected TB patients respond as welll as HIV-negative TB patients to anti - tuberculous chemotherapy [10,217,229,230], att the level of immunodeficiency at which PLWH develop tuberculosis, susceptibility too a range of diseases is associated with high case fatality rates by the end of tuberculosiss treatment, typically about 20% for new sputum smear-positive and up to 50%% for new sputum smear-negative cases. Many deaths take place early in treatmentt and 2 year survival is low [10,19-21,208,229-239]
5.. Higher risk of side effects of drugs : HIV-infected patients are more likely to experiencee toxic and sometimes fatal side reactions to medications, in particular cutaneouss hypersensitivity to thiacetazone [217,223,236,238,240-245]. Thiacetazonee has been replaced with ethambutol in most TB programmes for this reason.. Ethambutol is well tolerated and has similar efficacy.
6.. Increased risk for recurrence : Relapse following cessation of chemotherapy due too exogenous re-infection, appears to be more frequent among HIV-infected comparedd to non-HIV-infected individuals [20,47,209,217,238,246-250].
7.. Community perception that TB is HIV: In those countries with a high HIV prevalence thee community starts perceiving TB and HIV to be the same disease. This might influencee treatment seeking behaviour and adherence to treatment and makes DOT evenn more important in HIV-infected TB patients [67,226],
1.2.4.1.2.4. Interventions to control TB In high HIV prevalence
populations populations
HIVV fuels the tuberculosis epidemic. To control TB, firstly expansion of the DOTS strategyy is needed as it is thought that the DOTS strategy has reduced the increase inn TB cases due to HIV [251]. Second, HIV prevention will have a major impact on TBB control. Highly active antiretroviral therapy (HAART) has also shown to prevent orr delay the emergence of TB in HIV-infected and thereby transmission of TB [252,253].. Whether funds should be spent on prevention only or on HAART as well inn poor resource countries is still a matter of debate [254,255,256]. Third, intensified casee finding will be efficient in groups of people with a higher likelihood of having TB orr HIV such as people with respiratory symptoms attending general health service providerss in the public, private and non-governmental organisation (NGO) sectors (out-patients,, in-patients and health care workers [257]), people attending sexually transmittedd disease (STD) clinics, centres for voluntary counselling and testing (VCT)) for HIV [258] and household contacts of HIV-positive index infectious tuberculosiss cases [259]. Whether or not intensified case finding is worth undertakingg in these groups depends on factors such as the TB prevalence/incidence,, the cost of screening and, the adequacy of passive case findingg which may vary from setting to setting. Fourth, in view of the high mortality andd low survival of TB patients, even with TB treatment [248], interventions such as isoniazidd (INH) prophylaxis, cotrimoxazole prophylaxis and possibly HAART should bee included in the package of services to be delivered to TB patients as well [251].
1.3.1.1.3.1. Research questions for TB control in view of the impact of
HIV HIV
Thee dramatic increase in the tuberculosis burden over the past decade, related to thee HIV epidemic in many countries in sub-Saharan Africa has greatly increased the pressuree on existing government and NGO health services. It has become more difficultt for the public sector to provide diagnosis and treatment [210] and there is a needd to rethink the role of service delivery for TB [13,251]. Research questions may bee formulated, such as :
-- Can decentralization of DOT to the community [260] improve treatment outcomes andd reduce costs ? On the one hand, medical staff at busy clinics, who often are littlee aware of the social and economic situation of patients, may not be the best personss to encourage patients to complete their treatment. On the other,
community-basedd volunteers may lack the skills, authority, or financial incentives to ensuree treatment completion.
-- Can interventions such as HIV testing and subsequent provision of INH prophylaxis [20,209,261-267],, cotrimoxazole prophylaxis [20,21,235,264,266,268,269] and antiretrovirall treatment [165,252,264,270-272] to HIV-infected, successful under pilot conditions,, reduce HIV-associated mortality among TB patients and transmission of TBB under programme conditions ?
-- Can intensified case-finding to diagnose infectious cases in risk groups with high TB/HIVV prevalence reduce transmission of TB ?
-- Can improved collaboration between TB and HIV programmes contribute to decreasingg the tuberculosis burden, and, if so, how can this best be organised [57,251,264,273,274]? ?
-- Can collaboration with the private sector (both for profit and non-profit) increase casee finding, reduce the delay in diagnosis, and increase cure rates [57,124,275] ? Further,, the development of a more effective vaccine for TB [87,276,277] and a vaccinee for HIV [277,278], new diagnostic tools [87,277] and drugs and regimens [87,277,279,280]] and multi-drug resistance surveillance are needed.
ff .3.2. Operational research for TB control in Malawi
Operationall research is aimed at developing interventions that result in improved policyy making, better design and implementation of health systems, and more efficientt methods of service delivery. It offers relevant gains at low cost and in a shortt time frame by addressing the programme's priorities [281]. The national tuberculosiss programme (NTP) of Malawi carried out operational research in order to identifyy possible solutions to improve TB control and relieve the overburdened health servicess by looking at ways to increase the efficiency of tuberculosis management throughh simplification of tuberculosis control and decentralization of services to the community.. Results of the research justified the increase in resources for tuberculosiss control.
Researchh questions were formulated looking at the diagnostic pathway to identify reasonss for delay in diagnosis [282-286], proper categorization of patients [287] and initiationn of treatment [288], at the laboratory services provided [116,283,289-291], accuracyy of X-Ray diagnosis [282,292], the identification of initial defaulters and the needd for three sputa examinations [293], at diagnostic problems in sputum smear-negativee HIV-infected patients [227,228,294,295], at whether staff are following the nationall guidelines [294,296] and at the possibility to involve traditional healers
withinn the programme. Questions were also formulated around outcomes of the programmee such as the association between HIV and TB treatment outcomes [12,20,21,231,287,297-300]] and decentralization of services in view of the increase inn cases. Other topics were the prevalence of TB in hotspots such as prisons [201] andd health institutions (nosocomial transmission) [219,291], surveys of HIV infection amongg TB patients, provision of cotrimoxazole prophylaxis [301] and detailed monitoringg of the ongoing programme [302] and the changes implemented based on earlierr research [303].
1.3.3.1.3.3. Outlay of Ms thesis
Thiss thesis describes operational research carried out in Ntcheu district in Malawi withh regard to tuberculosis case detection and case holding and its impact on the policyy of the Malawi National TB Control Programme. Chapter 2 describes the TB/HIVV epidemic in Malawi and the national tuberculosis programme. The following threee chapters describe the research done to identify the extent of TB and TB/HIV co-infectionn in the district. Chapter 3 compares tuberculosis treatment outcomes of HIV-negativee and HIV-positive patients. Chapter 4 explores whether tuberculosis is moree common among urban than rural populations. Chapter 5 examine the prevalencee of tuberculosis as well as HIV and STDs among new prisoners in a districtt jail in Malawi. Chapter 6 and 7 look at perceptions of tuberculosis patients andd involvement of traditional healers in the programme. The next three chapters deall with the decentralization of care to the community and its evaluation. Chapter 8 andd 9 present TB treatment outcomes using a simplified regimen and community-basedd treatment. Chapter 10 examines whether DOT can be carried out by non-healthh workers. Finally, in chapter 11 the main findings of the studies and their limitationss are discussed, and recommendations are made for tuberculosis control andd further research.
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