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

1 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. 2 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 3 CONTENT CONTENT PAGE TITLE 1 ABSTRACT 2 ABBREVIATIONS 4 INTRODUCTION AND BACKGROUND 5 LITERATURE REVIEW 6 Problem statement 9 Rationale 9 Aims 10 SUBJECTS AND METHODS 11 Study area 11 Health care system 12 Programme for care and treatment of HIV/AIDS patients 12 Programme for care and treatment of tuberculosis and leprosy patients 14 Study design 18 Study population 18 Sampling procedure 18 Sampling method 19 Measure instruments 19 Data collection 19 Statistical analysis 19 Ethical issues 20 RESULTS 20 DISCUSSION 27 CONCLUSION 30 ACKNOLEDGEMENTS 30 REFERENCES 31 APPENDIX I: Questionnaire: English version 35 4 ABBREVIATIONS ABBREVIATION IN PLAIN TEXT AIDS Acquired Immunodeficiency Syndrome ARV Antiretroviral ART Antiretroviral therapy CTC Care and Treatment Clinic DMO District Medical Officer DOT Directly Observed Therapy (Short course) GUT Genital Urinary Tract FDC Fixed Dose Combination 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 PI Protease Inhibitor PMORALG Prime Minister’s Office for Regional Administration and Local Government TBL Tuberculosis and Leprosy TB Tuberculosis UN United Nations WHO World Health Organization 5 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) 6 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) 7 • 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). 8 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). 9 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. Rationale The Millennium Development Goal number 6 aims at combating HIV/AIDS, malaria and other diseases by 2015. In this regard, TB is one among other diseases. The Stop TB strategy of global TB control (launched by the Stop TB Partnership in 2006) aims at reducing by 50% of the global 10 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 [...]... 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... 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,... DISCUSSION Tuberculosis remains to be a major opportunistic infection in patients with HIV infection The overall prevalence of pulmonary TB was found to be 35%, followed by 26% of herpes zoster and other skin manifestations of HIV infection (Table 8) The results are consistent with a study done in Kagera, Tanzania which demonstrated a high prevalence of pulmonary TB, herpes zoster and other skin manifestations... Booster Vaccine Trial J Infect Dis 2007;195:118-123 McMurray DN Recent progress in the development and testing of vaccines against human tuberculosis International Journal for Parasitology 33:2003: 547–554 Ministry of Health and Social Welfare (MoHSW) National Aids Control Programme (NACP).2008.Pages 1–312 Dar es Salaam, Tanzania Ministry of Health, United Republic of Tanzania Ministry of Health and... 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... 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. .. The reduction in the prevalence of TB in HIV infected patients after the introduction of HAART has demonstrated remarkable changes towards improving the management of HIV patients 27 The greatest proportion of HIV associated TB was observed at the CD4 Count ≤200 cells/µl (Table 10) the results which were similar as previous studies done in Abidjan, Cote d’Ivoire which has shown similar findings (Ackah... that more strategic preventive measures are highly need especially in poor and limited resources Countries in order to tackle the problem of TB among HIV patients as well as to the whole community Limitations (1) The study period was short It is difficult to investigate the trend of effect of HAART on the development of TB and other co-morbidity among HIV patients when the study period is short (2) Small... and patients co -infected with TB/HIV (4)A cohort study of HIV patients on HAART is highly recommended in order to assess the effect of HAART on development of TB as well as risk factors associated with development of TB 29 CONCLUSION The results from this study indicate that the prevalence of pulmonary Tuberculosis before initiation is higher than after initiation of HAART among HIV patients Despite... 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 . PULMONARY TUBERCULOSIS AMONG HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTED PATIENTS IN THE ERA OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN DAR. scale industries. The main business activities include insurance, travel, clearing and forwarding agencies, hoteliers, printing press to distributors of industrial