PULMONARY TUBERCULOSIS AMONG HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED PATIENTS IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN DAR ES SALAAM MUNICIPAL, TANZANIA pdf

PULMONARY TUBERCULOSIS AMONG HUMAN IMMUNODEFICIENCY VIRUS HIV INFECTED PATIENTS IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY HAART IN DAR ES SALAAM MUNICIPAL, TANZANIA Author: V

PULMONARY TUBERCULOSIS AMONG HUMAN

IMMUNODEFICIENCY VIRUS (HIV) INFECTED PATIENTS

IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN DAR ES SALAAM MUNICIPAL,

TANZANIA

Author: Veneranda Masatu Bwana

(MPH 2009) Supervisor: Associate Professor Lennarth Nyström

Umeå International School of Public Health, Umea University,

Sweden

ABSTRACT

Aim: The aim of this study is to estimate the prevalence of pulmonary Tuberculosis (TB) among

HIV-infected patients and to estimate the effect of HAART on the development of pulmonary

TB

Subjects and Methods: During February 2009 a cross-sectional study of 174 HIV positive

patients on HAART 15-49 years old was performed in Dar es Salaam, Tanzania Information was collected at exit interviews and from the patients’ case files using a questionnaire Data

analysis was done using SPSS

Results: There were 102 males (59%) and 72 females (41%) The median age was 37 years

(Range: 16-49 years) All but three was in first line of HAART treatment and good adherence was reported by 80% The prevalence of TB before HAART initiation was found to be higher than after HAART initiation (29 % vs 6.0 %; p< 0.0001) Among those diagnosed with TB after HAART the median time between TB diagnosis and at HAART initiation was 146 days (Range 14-1481 days) The median CD4 Count at time of TB diagnosis was 111cells/µl (Range: 6-418 cells/µl)

Conclusion: HAART has largely contributed to the reduction of prevalence of TB among

people living with HIV However more strategic preventive measures that enhance body

immunity among HIV patients are highly needed as early as possible before they develop active

TB A sustainable effective intervention especially through vaccination is highly recommended

Keywords: Pulmonary Tuberculosis, Prevalence, HIV infection, HAART, Dar es Salaam,

Tanzania

CONTENT

CONTENT PAGE TITLE 1 ABSTRACT 2

Programme for care and treatment of HIV/AIDS patients 12

Programme for care and treatment of tuberculosis and leprosy patients 14

ABBREVIATIONS

ABBREVIATION IN PLAIN TEXT

AIDS Acquired Immunodeficiency Syndrome

ARV Antiretroviral

DMO District Medical Officer

DOT Directly Observed Therapy (Short course)

HAART Highly Active Antiretroviral Therapy

HIV Human Immunodeficiency Virus

MDH Muhas Dar es Salaam City Harvard Collaborative Project MoHSW Ministry of Health and Social Welfare

MUHAS Muhimbili University of Health and Allied Sciences

NACP National AIDS Control Programme

NMCP National Malaria Control Programme

NRTI Nucleoside Reverse Transcriptase Inhibitor

PMORALG Prime Minister’s Office for Regional Administration and Local

Government TBL Tuberculosis and Leprosy

TB Tuberculosis

WHO World Health Organization

INTRODUCTION AND BACKGROUND

Tuberculosis (TB) is an infectious disease caused by the bacteria Mycobacterium

tuberculosis.TB is a major disease burden globally In 2006 it was estimated that there was 9.2

million incident cases, and among these 0.7 million cases were HIV-positive The HIV

prevalence in TB patients is less than 1% in the Western Pacific but 22% in Africa, however, in countries with the highest HIV prevalence; more than 75% of cases of TB are HIV-associated Southern Africa has the highest prevalence of HIV infection and had the highest incidence of TB before the HIV/AIDS era (Badri et al, 2002; WHO, 2008)

Tuberculosis commonly present with atypical symptoms Mycobacterium tuberculosis was

isolated from 9% of adults with acute pneumonia in Kenya (Scott et al, 2000) and 23% of febrile hospitalized HIV-infected in Dar es Salaam, Tanzania (Archibald et al, 1998) Besides that, Kwesigabo and co-workers (1999) showed that the prevalence of pulmonary TB among HIV-1 patients was 59% among hospitalized patients in Kagera region, Tanzania

In Tanzania, the HIV prevalence among new smear-positive TB patients increased from 28% in 1991-1993 to 40% in 1994-1998 (Range et al, 2001) The largest increase was observed in the youngest birth cohorts suggesting ongoing HIV transmission Furthermore it was estimated that 86% of new smear-positive TB in patients with HIV infection was directly attributable to HIV

The advent of highly active antiretroviral therapy (HAART) has greatly contributed to the reduction of the severity of HIV infection and in one way or another will consequently reduce the susceptibility of opportunistic infections among HIV patients The therapy involves a

combination of protease inhibitors taken with nucleoside reverse transcriptase inhibitors (NRTI) which are used in treating AIDS and HIV The usual HAART regimen combines three or more different drugs from different classes such as

• two NRTIs and one Protease Inhibitor (PI)

• two NRTIs and two PIs

• two NRTIs and one non-NRTI (MoHSW.URT NACP.2008)

Basically there are two types of TB: pulmonary TB (whereby the bacteria Mycobacterium

tuberculosis typically affects the lungs) and extra pulmonary TB (whereby the bacteria affect

other organs) According to the Tanzania national tuberculosis and leprosy (TBL) program policy guidelines, the disease in adults is classified into three categories: smear-positive

pulmonary TB, smear-negative pulmonary TB and extra-pulmonary TB TB may arise at a time when body immunity is low and conditions like HIV infection, diabetes, malnutrition, recurrent infections are known to be an important cause of reactivation of the TB infection In recent years

TB has become prevalent among people living with human immunodeficiency virus (HIV) which poses a major public health problem especially in Sub-Saharan Africa including Tanzania (MoHSW.URT NTLP 2006; WHO, 2008)

Tuberculosis continues to be among the major public health problems in Tanzania The number

of cases has increased six-fold between 1983 and 2006 and the majority of the cases appear in young adults (15-44 years), the same age group which is mostly affected by HIV/AIDS

(MoHSW URT.NTLP 2006) This study aims at estimating the prevalence of pulmonary TB (all patients diagnosed by attending Medical Officer as TB case) among HIV patients and to estimate the effect HAART on pulmonary TB in order to improve the survival among patients with HIV associated TB

LITERATURE REVIEW

Literature search

A literature search was performed using PubMed, WHOs website Hinari, and specific journals (Clin Infect Dis, BMC Oral Health, Emerging Infectious Diseases, Int J Tuberculosis Lung Dis,

Am J Resp Critical Care Med, Science, BMJ, J Acquir Immune Defic Syndr and AIDS) The

following keywords were used in PubMed:

• HIV infection and TB and opportunistic infection and Sub-Saharan Africa (5 articles, 1 review)

• Tuberculosis and HAART and HIV infection and Africa (3 articles, 1 review)

• Tuberculosis and HIV infection and mortality and Sub-Saharan Africa (4 articles)

• Antiretroviral adherence and East Africa (No articles)

• Antiretroviral adherence and Tanzania (2 articles)

• HIV infection and TB and Tanzania (2 articles)

Antiretroviral treatment

The major goal of antiretroviral treatment scale-up is to reduce HIV-associated morbidity and mortality Tuberculosis case-fatality rates (proportion of patients dying while on antituberculous treatment) in Africa are 16–35% in HIV-positive cases not receiving antiretroviral treatment and 4–9% in HIV-negative cases (Mukadi et al, 2001) Increased mortality during the first month of treatment seems largely attributable to the TB itself (Mukadi et al, 2001) The greatest proportion

of HIV positive associated TB patients are found at CD4 count <200 cells/µl and they also have the highest mortality rates (Ackah et al, 1995) (CD4 cells are type of lymphocyte cells (white blood cells) that form an important part of the immune system Human Immunodeficiency virus most often infects these cells) (MoHSW URT NACP 2008)

Several studies from different countries have showed that antiretroviral drugs reduce the

incidence of TB in HIV-infected people by 80% or more, with the greatest effect at the lowest CD4 counts (Badri et al, 2002; Girardi et al, 2000) However, clinically, immune dysfunction persists even during successful antiretroviral treatment and the TB incidence remains high, even

at high CD4 counts (Girardi et al, 2000) The risk of recurrent disease in patients with previous HIV-related TB is also high, suggesting a need for secondary prevention.Furthermore the risk of active TB after HAART initiation was significantly higher in patients with a previous history of

TB than in those with no TB history (Churchyard et al, 2003; Seyler et al, 2005)

Tuberculosis

Tuberculosis is an aggressive opportunistic infection that arises at higher median CD4 count compared with other AIDS-related diseases conditions In Cote d’Ivoire smear-positive TB patients presented with a median CD4 count of 257 cells/µl (Range: 200-500 cells/µl) (Ackah et

al, 1995) However, WHO current guidelines recommend treatment for patients with

symptomatic HIV or a CD4 count of <200 cells/µl for resource-poor settings (WHO, 2008)

Therefore, the potential effect of antiretroviral treatment on the TB incidence is reduced because many HIV-infected patients with TB present before antiretroviral drugs are prescribed

In contrary, Lawn et al (2005) showed that TB developed also among individuals who were responding to HAART They also demonstrated that among 27 patients who developed TB, the median plasma viral load at the time TB was diagnosed (2.98 log10copies/ml) was twice as low

as that at enrolment (5.38 log10copies/ml) and the median CD4 cell count at time of TB

diagnosis (198 cells/µl) was significantly higher than at baseline (112 cells/µl) This suggests that TB incidence and mortality will be reduced if antiretroviral drug coverage is high, start early and is combined with TB preventive treatment (Williams et al, 2003)

Opportunistic infections

Opportunistic infections continue to cause morbidity and mortality in patients with HIV-1

infection throughout the world However, HAART potent combination has reduced the incidence for certain patients with access to care Hamza and colleagues (2006) showed that oral

candidiasis was the commonest oral lesion accounting for 24% among HIV-associated oral lesions, followed by mucosal hyper pigmentation (4.7%) Ravera and co-workers (1999) showed that 91% of the participants (42 females, 35 males) had both oral and oesophageal candidiasis and 47% (n=40) had oesophageal symptoms and all had oesophageal candidiasis at endoscope Furthermore, Kwesigabo et al (1999) showed that the prevalence of herpes zoster and other skin manifestations was 86% among HIV-1 infected patients

Adherence to antiretroviral treatment

Treatment of patients already on HAART for TB is complex because of the high number of drugs administered simultaneously which poses practical problems related to adherence and side-effects (Bonnet et al, 2006) Adherence levels in Africa have been found to be better than in the United States However, at all the facilities studied in Botswana, Tanzania and Uganda, around one out of four antiretroviral users failed to achieve optimal adherence, risking drug resistance and negative treatment outcomes, which make them more susceptible to other infections (Hardon

et al, 2007)

In a study done in Botswana 54% (59/109) of patients reported optimal adherence (defined as completing ≥95% of prescribed doses) (Weiser et al, 2003) In contrast, in Tanzania 84%

(126/150) patients reported complete adherence and 16% (24/150) patients reported incomplete adherence (incomplete adherence was defined as self reported adherence completing <100% of the prescribed doses) (Ramadhani et al, 2007) In comparable studies conducted in developed countries, rates of incomplete self-reported adherence ranged from 40% to 70% (Incomplete adherence was defined as self reported adherence completing < 80% of the prescribed doses) (Chesney et al, 2001)

Thus TB is a major public health problem, which poses the greatest burden among HIV positive patients suggesting the need for further studies to estimate the prevalence of pulmonary TB as well as to estimate the effect of HAART on the development of pulmonary TB among HIV infected patients

Problem statement

The prevalence of TB is increasing in many countries and is the leading infectious cause of death worldwide Infection with HIV, likewise increasing in prevalence, has emerged as the most

important predisposing factor for developing TB in people co-infected with Mycobacterium

tuberculosis In Africa, TB is often the first manifestation of HIV infection, and it is the leading

cause of death among HIV-infected patient (MoHSW.URT.NTLP 2006; WHO, 2008)

Archibald et al (1998) showed in a study done in Dar es Salaam, Tanzania that Mycobacterium

tuberculosis was isolated from 23% of febrile HIV-infected hospitalised patients In addition

Kwesigabo et al (1999) showed that the prevalence of pulmonary TB among HIV-1 patients was 59% among hospitalized patients and Range et al (2001) estimated that 86% of new smear

positive TB in patients with HIV infection was directly attributable to HIV

burden of TB (per capita prevalence and death rates) by 2015 and reducing the global incidence

of active TB by less than 1 case per million per year by 2050 Tanzania among other countries has also made efforts through its national tuberculosis and leprosy program (NTLP) towards achieving this goal in line with the MDGs

Monitoring of the preventive programmes to ensure that they reach the global targets for TB control is crucial especially in Africa with limited resources Consequently a comprehensive study that estimate the effect of HAART on development of pulmonary TB among HIV infected patients is important so that preventive measures can be instituted and eventually improve the

management of HIV patients in a comprehensive manner

In Tanzania TB continues to be among the major public health problems Furthermore, the

distribution of TB in the country varies e.g the Dar es Salaam Region with 6% of the population contribute about 24% of all cases of TB (MoHSW.URT NTLP 2006) Therefore TB is still a major global public health problem and there is a need to allocate more resources and to establish more sustainable preventive strategies especially in poor resource and developing countries

Aims

The aim of this study is to estimate the prevalence of pulmonary TB among HIV-infected

patients The specific aims are that among HIV-positive patients on HAART:

• To estimate prevalence of TB by age and sex

• To estimate the effect HAART on TB disease

• To estimate duration between TB diagnosis and at initiation of HAART

• To estimate effect of TB on the CD4 Count level at TB diagnosis, HIV diagnosis and at initiation of HAART

• To assess adherence to ARV drugs by age, sex and co-morbidity

SUBJECTS AND METHODS

Study area

The study was conducted in the capital of the United Republic of Tanzania, Dar es Salaam situated on the East coast of Tanzania It includes the municipalities of Ilala, Temeke, and Kinondoni and borders the Indian Ocean to the East and the Coastal region on all other sides (Pwani) The climate is typically tropical, with hot weather throughout the year (Range: 26°–35°C) and two rainy seasons, short rains in November–December and long rains in March–May Kiswahili is the most spoken language and is the national language

The main productive economic activities include agriculture, livestock, natural resources, fishing and large and small scale industries The main business activities include insurance, travel, clearing and forwarding agencies, hoteliers, printing press to distributors of industrial

commodities and petty traders

Some demographic and public health indicators for Dar es Salaam and the whole country are presented in Table 1 The main health problems in the region are malaria, diarrhoeal diseases, upper respiratory tract infections, pneumonia, anaemia, intestinal worms, sexual transmitted

diseases and HIV/AIDS (MOH, Health Statistics Abstract URT.1999; Kitua et al, 2008)

Table 1 Some demographic characteristics for Tanzania and Dar es Salaam by sex (M=Males, F=Females)

Source: MOH, Health Statistics Abstract, Dar es Salaam June 1998 and November, 1999

Source: National Bureau of Statistics, Dar es Salaam-Tanzania, NBS 2007

Demographic and public health indicators Tanzania (Year) Dar es Salaam (Year) Population size 39,394,223 (2007) 2,497,940 (2002) Life expectancy at birth (years) for both sex 51 (2007) -

Life expectancy at birth (years) M: 49, F: 52 (2007) -

Crude birth rate 36/1000 (2007) 28.6/1000 (1999)

Maternal mortality rate/100,000 live births 578/100,000 (2005) 669/100,000 (1999)

Infant mortality rate/ 72/1000 (2007) -

Under-five mortality rate/ 112/1000 (2005) -

Total fertility rate (children/15-49 year) 6 (2002) -

(2002)

M: 92%, F: 69% (1998)

The health care system

The government is the main provider of health services in Tanzania The health care system in Tanzania is fairly well distributed, about 80% of the population has access to health services and over 90% of the population live within 10km The Ministry of Health and Social Welfare

(MoHSW) and the Prime Minister’s Office for Regional Administration and Local Government (PMORALG) are jointly responsible for the delivery of public health services The national health system is based on decentralising services to Local Government Authorities

The health care system is operating at three levels, central, regions and districts The MoHSW plays a role at central level as it is responsible for policy formulation and develop guidelines in order to facilitate the implementation of that policy Regional Health Management Teams in mainland Tanzania, headed by a regional medical officer, are responsible to interpret these policies into actions and monitor their implementation in their districts The regional medical officer report through the Regional Administrative Secretary to the MoHSW on issues related to technical management and to the PMORALG on issues related to health administration and management of health services The Council Health Management Teams, headed by a district medical officer, are responsible for Council health services at dispensaries, health centres, and district hospitals The district medical officer is in charge of all district health services and is answerable to the local government authority and is responsible to the regional medical officer (MoHSW URT National Health Policy 2003)

Programme for care and treatment of HIV/AIDS patients

The main purpose of antiretroviral care and treatment programme is to provide care to HIV patients Attention is paid to a number of issues including aggressive efforts to identify HIV-

positive individuals, developing a team approach to treatment, strict observation of standard

protocols by clinicians, and strict application of patient classification and treatment schedule

models (MoHSW URT.NACP, 2008)

Care and Treatment Clinics (CTC) have been established at selected health care facilities to

provide HIV care and treatment services Once enrolled, every CTC clients are also linked to a

wide range of other services including reproductive health and family planning, social and

spiritual support and home-based care services Since TB and HIV services have been integrated

in every CTC and TB screening has become a routine for all HIV patients during their follow up

visit (MoHSW URT.NACP, 2008)

Outline of care and treatment

The main aim of the care and treatment is to improve the overall health and to reduce

transmission and to slow down the progression of disease on individual and population level In

addition to routine clinical care, each patient may fall into three categories with specific clinical

goals of treatment (Table 2):

Table 2 Determination of CD4 Count patient category

Category HIV/AIDS CD4 cell count/µl CD4 determined

Moderately immuno-suppressed HIV+ 200-350 4 month

Antiretroviral therapy

Antiretroviral drug treatment in Tanzania started in 2004 and all services including ARV drugs

are provided free of charge in every CTC Currently the following drugs that are available in

Tanzania: Drugs under the class NRTIs are Zidovudine, Stavudine, Lamivudine, Abacavir,

Emtricitabine, Didanosine; Non NRTIs are Nevirapine and Efavirenz; and PIs are

Lopinavir/Ritonavir and Atazanavir.The first line recommended regimen in Tanzania is

Zidovudine/Lamivudine/Nevirapine or Zidovudine/Lamivudine/Efavirence Also alternatives

regimes are available in specific situations Patients with severe anaemia will receive Stavudine

instead of Zidovudine ande non-pregnant patients who cannot tolerate Nevrapine will receive Efavirence Also patients who develop TB while on antiretroviral therapy will receive Efavirence instead of Nevirapine (MoHSW.URT NACP, 2008) According to the WHO clinical stages for HIV positive patients, there are four stages based on clinical symptoms Based on the WHO clinical staging for adults and adolescents the eligibility criteria for initiation of ARV are

grouped into three (Table 3)

Table 3 Clasification of the patients by eligibility criteria to start antiretroviral therapy

Patient category with Antiretroviral treatment

WHO stage 4 Eligible regardless of CD4 count

WHO stage 3, CD4 ≤350 Eligible

CD4 ≤200 Eligible regardless of WHO clinical stage

Special categories for considerations of antiretroviral therapy (ART) in TB and HIV co-infected patients according to Tanzania National AIDS Control Programme, 2008 Tanzania

Antiretroviral therapy improves the quality of life and greatly improves survival of people living with HIV/AIDS It is a lifelong treatment requiring a high adherence rate to achieve long term benefits and minimize the development of drug resistance ART should be offered to all eligible TB/HIV positive patients (Table 4)

Table 4 Special categories for considerations of ART in TB and HIV co- infected patients

Patient category with Consideration for antiretroviral therapy

CD4> 350 Treat TB first, re-assess for ART after completion of TB treatment CD4 200-350 Treat TB first for two months before starting ART

CD4 <200 or WHO stage 4 Begin ART as 2 weeks after TB treatment initiation

Programme for care and treatment of tuberculosis and Leprosy (TBL)

At national level the TBL central unit is responsible for coordination of all activities pertaining

to TBL in the country including policy formulation, planning, monitoring, evaluation, resource mobilization and coordination of drugs and supplies procurement and distribution It is also

responsible for giving primary health education; provide preventive and curative and

consultation to the patients At regional level a regional TBL coordinator work under the

regional medical doctor and at district level a district TBL coordinator is responsible to the district medical officer for the implementation and coordination of TBL control activities within the district The national TBL programme has extended its activities up to the village level to involve the community in treatment

Community-based direct observation treatment involves village health workers, village leaders, religious people and community members These were well trained by ommunity Health

Management Team (CHMT) who are involved in formulations of Guidelines for based direct observation treatment (MoHSW.URT.NTLP, 2006) Since AIDS and TB are closely related, they have integrated AIDS education together with TB and the district tuberculosis and leprosy coordinator continue to cooperate closely with the district AIDS control coordinator All TB/HIV services, including care and treatment of patients with TB/HIV co-infection, have been integrated together in every CTC and TB and antiretroviral drugs are provided in one section (MoHSW.URT.NTLP.2006)

community-Definition of TB patients’ category in adults according to National Tuberculosis and Leprosy Programme, Ministry of Health and Social Welfare, 2006.Tanzania

Smear positive pulmonary TB: “Tuberculosis in a patient with at least two initial smear

examinations positive by direct microscopy for Acid Fast Bacilli (AFB positive), or TB in a patient with one initial smear examination positive by direct microscopy and positive by culture for mycobacteria Or TB in a patient with one initial smear examination positive by direct

microscopy for Acid Fast Bacilli (AFB positive) and X-ray abnormalities suggestive of active tuberculosis as determined by the treating Medical Doctor.”

Smear negative pulmonary TB: “Tuberculosis in a patient with three initial negative smear examinations by direct microscopy for Acid Fast Bacilli (AFB negative) and non-response to a course of broad-spectrum antibiotics, and again three negative smear examinations by direct microscopy, and X-ray abnormalities suggestive of active TB as determined by the treating medical doctor Or TB in a patient with three initial smear examinations negative by direct microscopy but positive by culture for mycobacteria.”

Extra-pulmonary TB: “Tuberculosis in organs other than the lungs proven by one culture

positive specimen from an extra-pulmonary site or histopathological evidence from a biopsy

Or TB based on strong clinical evidence, including macroscopic evidence of specimen

inspection, consistent with active extra-pulmonary Tuberculosis and the decision by a medical doctor to treat with a full course of anti-tuberculous therapy” (MoHSW.URT.NTLP.2006)

Tuberculosis treatment regimens

The first short-course regimen of 8 months was introduced in Tanzania in 1987 for sputum smear positive patients only Since July 2001 non-infectious patients also receive a short-course regimen A six months short-course regimen for new smear-positive, smear-negative and extra pulmonary

TB was introduced in 2006 TB regimens are divided into the initial phase (intensive) and

continuation phase In the intensive phase the majority of TB bacilli are rapidly killed and infectious patients become non-infectious within one to two weeks Short-course chemotherapy has a very high success rate if properly applied in a patient with TB diagnosed in time The length of the regimen varies from 6 to 8 months depending on the patient’s category of disease The six months regimen, which contains rifampicin throughout, is slightly more effective in preventing re-activation of

dormant bacilli, reducing relapse especially in HIV positive tuberculosis patients Since 2006 the treatment of TB is available as a fixed dose combination (FDC) which contains 2, 3 or 4 drugs depending on the patients’ categories (either Smear-positive pulmonary TB or Smear-negative pulmonary TB or Extra-pulmonary TB) There are four essential first line drugs which are also available in combinations, and in line with WHO recommendations, these are isoniazid,

rifampicin, pyrazinamide, ethambutol Such combinations are 4 FDC (rifampicin, isoniazid, pyrazinamide, ethambutol), 3FDC (rifampicin, isoniazid, pyrazinamide), 2FDC (rifampicin, isoniazid) and 2FDC (ethambutol, isoniazid) All services for TB patients including anti TB drugs are provided free of charge in every health facility (MoHSW.URT.NTLP.2006)

Preventive treatment for tuberculosis

Isoniazid Preventive Treatment (IPT) in HIV positive patients: The aim of preventive treatment

is to prevent progression from TB infection to disease Isoniazid given at a dose of 5 mg/kg daily for 6 months has been recommended as an effective preventive treatment Currently, there is no enough evidence and experience of the impact of large scale preventive treatment in Tanzania

Furthermore, IPT is not an alternative for the DOTS strategy for controlling TB in Tanzania However, IPT is recommended in HIV positive patients who do not have active TB disease and who have an increased chance of contracting TB infection This will in one way or another

prevent many cases of active TB Therefore if IPT is given, active TB must always be excluded first (sputum examination, clinically, history, chest X-ray) (MoHSW.URT.NTLP.2006)

BCG Vaccination: BCG (Bacille Calmette-Guerin) is a live attenuated vaccine derived from

Mycobacterium bovis It was first used in 1921 The vaccine is given intra-dermally in the upper

part of the right arm at a dose of 0.05 ml to all neonates shortly after birth BCG protects young children and it has considered more effective by 80% against disseminated and severe forms of tuberculosis, e.g TB meningitis, miliary TB It has been observed that, BCG has little or no

protection against the development of TB in adults Furthermore, the WHO recommends that in

countries with a high prevalence of TB, like Tanzania, BCG should be given to all neonates, regardless of the HIV status, immediately after birth The possible benefits of BCG outweigh the possible disadvantages However, BCG should not be given to children who present with clear signs and symptoms of HIV-disease or AIDS due to higher risk of development of disseminated BCG (MoHSW.URT.NTLP.2006, Waddell et al 2001) Despite the widespread use of BCG, for more than half century, TB has been growing dramatically in the world, fueled by the increased susceptibility of HIV-infected people to TB The BCG vaccine for prevention of TB given in childhood in many countries ceases to be effective TB remains the largest cause of death worldwide which calls attention to scientists and researchers (Haile and Kallenius 2005, McMurray ND 2003, Matee et al 2007)

Mycobacterium vaccae vaccine: Mycobacterium vaccae vaccine is a whole inactivated

mycobacterium It has been in development for more than 16 years It had been tested for safety and immunogenicity in a variety of previous human studies in Europe, North America and Africa (Vuola et al 2003, Waddell et al 2000) Tanzanian and United State researchers have recently announced a discovery of a Mycobacterium vaccae vaccine that can reduce TB infections by almost 40 per cent among HIV infected people The vaccine was given to study volunteers in a five dose series over a period of 12 months in a large scale placebo-controlled randomized

clinical trial conducted in Tanzania This study was recently in phase three study designed to test

the safety and efficacy of a TB vaccine in a large population of HIV-positive people However there still remain questions to researchers about the true degree of efficacy of the vaccine (Von

The study population were non-pregnant HIV positive patients on HAART 15-49 years old

living in Dar es Salaam Children and pregnant women were not included as they follow a

special HIV programme Patients with chronic conditions like diabetes, chronic renal failure,

cancer and malnutrition were excluded

Sampling procedure

There are one national, three municipal-government hospitals, several dispensaries and several private hospitals in Dar es Salaam At some of these units there are government supported HIV clinics This study was conducted in government HIV clinics due to difficulties in accessing private facilities Presently there are 14 government HIV clinics in charge of the HAART

programme; six in Ilala district (Tabata, Amana, Buguruni, Infectious Disease Control,

Muhimbili National Hospital, Mnazimmoja), four in Kinondoni district (Sinza, Kimara,

Tandale, Mwananyamala) and four in Temeke district (Temeke, Mbagala, Vijibweni and

Kigamboni) The number of patients at each clinic varies The old clinics (Muhimbili National Hospital, Amana, Infectious Disease Control, Mwananyamala and Temeke) serve between 15,000 and 16,000 patients while the new serve between 1000 and 1200 patients.The study area was stratified by district Two HIV clinics were selected, one in Ilala district (Amana) and one in Kinondoni district (Mwananyamala).In every HIV clinic clients were conveniently selected from HAART and TB/HAART sections after their exit from Medical officer and having finished their daily normal follow up schedule

Sampling method

Convenience sampling method was the main method that was used during data collection in every CTC A total of 174 study subjects were enrolled in this study, 63 from Amana and 113 from Mwananyamala

Measure instrument

Questionnaire was used for data collection and it was structured based on knowledge background

of the HIV related infection as well as all co-morbidity associated with HIV infection The questionnaire contained question on basic socio-demographic characteristics, prior history of

TB, behavior on ART adherence and smoking, clinical diagnostic information of co-morbidity including TB, clinical stage of HIV; treatment of the patient, CD4 counts and sputum smear for AFB Questionnaire was translated from English to Swahili version It is the Swahili version that was used for data collection

Statistical analysis

All questionnaires were assigned a serial number Open ended questions were coded before computerisation using Epi Info Data cleaning and analysis was done using SPSS Pearson chi- square, Fisher’s exact test were used to compare group difference between categorical variables

A p value > 0.05 are considered as non significant Good adherence by self reporting was defined