Background: Despite increased deliverance of antiretroviral therapy (ART), morbidity and mortality from TB are still predominant among HIV/AIDS infected patients in Ethiopia. Thus, current study aimed to determine magnitude and predictors of tuberculosis among cohort of HIV infected patients at Arba Minch General Hospital, Ethiopia, 2015. Methods: Hospital based retrospective follow-up study was conducted among study population which was HIV/AIDS infected individuals registered from September 2007 to 2013. The data were collected using structured data abstraction form and four ART trained nurses were used to abstract the data. The data were checked for completeness, cleaned and entered into Epi Info 7.0 and analyzed using SPSS version (IBM-21). Results were summarized by using table of frequency, graph, and measure of central tendency. Statistical significance was inferred at P-value ≤ 0.05. Adjusted odd ratio (AOR) with 95% confidence interval (CI) was used to determine predictors. Result: Four hundred ninety six patient’s charts were abstracted. Cumulative and incidence density of tuberculosis were 21.4% (95% CI: 21.3, 21.44) and 5.36 per 100 person year respectively. Cigarette smokers (AOR: 2.82, 95% CI (1.27 - 6.27)), household with family size of 3 - 4 (AOR: 2.26, 95% CI (1.14 - 4.50)), baseline WHO clinical stage III (AOR: 20.26, 95% CI (7.09 - 57.6)) and IV (AOR: 22.9, 95% CI (6.91 - 76.4)) and heamoglobin level of <10 (AOR: 2.56, 95% CI (1.22 - 5.33)) were important predictors (risk factors) of tuberculosis among HIV infected patients. Conclusion and recommendation: Relatively high incident tuberculosis cases were established among HIV infected patients and history of cigarette smoking; family size; hemoglobin level and base line WHO clinical stage were responsible for this incidence. Therefore; early initiation of HAARTas per current guideline should get stressed, and the finding that smoking was important predictors for TB in Ethiopia had obvious TB control implication which required high attention focused on fighting against cigarette smoking among HIV infected cohort.
Tuberculosis (TB) remains one of the world’s deadliest communicable diseases. In 2013, an estimated 9.0 million people developed TB and 1.5 million died from the disease [
Tuberculosis has been recognized as a major public health problem for more than five decades in Ethiopia. Ethiopia is one of the 22 high burden countries (HBCs) and TB remains one of the leading causes of mortality. According to the 2014 WHO report, the prevalence and incidence of all forms of TB are 211 and 224 per 100,000 of the population, respectively. About 13% of all new TB cases are also HIV co-infected. Moreover, Ethiopia is one of the high TB/HIV and multidrug resistant TB (MDR TB) burden countries. Among TB patients with known HIV status, about 11% were HIV co-infected. [
Despite increased deliverance of antiretroviral therapy (ART), morbidity and mortality from TB are still predominant among PLHIV. Among 33.2 million individuals acquiring human immune deficiency virus (HIV), one-third of them are concomitantly infected with Mycobacterium tuberculosis [
The TB/HIV co-infection results derangement of quality of life, poor physical health than HIV infected individuals and has a greater risk of common mental disorders [
Moreover, the management of a TB and HIV co-infected individual is challenging because of frequent oral drug intake which can cause different problem [
The risk of tuberculosis among PLHIV is 20 times higher than HIV negative people [
Many efforts have been made to integrate TB diagnosis and treatment with HIV care in order to prevent, diagnose and manage TB among HIV infected individuals, though TB still occur in HIV patients who are on HAART receiving individuals [
Furthermore, adequate understanding of the specific situation through follow-up research should be done to provide baseline finding to program designing for respective organization. Therefore, this study aimed to determine the incidence and predictors of TB among PLHIV registered at Arba Minch General Hospital.
This study was conducted at the government owned General Hospital located in Arba Minch town, Southern Ethiopia. The town is 500 km south of Addis Ababa. In the hospital all HIV positive people from any service area were enrolled in ART clinic for comprehensive HIV care. There are multidisciplinary professional’s team that includes physicians, nurses, public health professionals, laboratory technologists, pharmacists, data clerks and volunteer adherence supporters. ART is being provided for HIV infected adult patients according to CD4 count and WHO clinical stage.
Hospital based retrospective follow up study was employed from December 2014-January 2015.
All HIV infected patients attending ART clinic of Arba Minch General Hospital and HIV infected individuals registered between September 2007 and August 2013 were source and study population respectively.
Inclusion criteria: All PLHIV aged 15 years and above and were enrolled into the adult chronic HIV care at the Arba Minch general Hospital were included in the study
Exclusion criteria: An individual with incomplete chart and diagnosed clinically without sputum examination, culture and chest X-ray were excluded from the study.
Sample size was determined for first specific objective by using StatCalc program of Epi Info, with the assumption of Z-score corresponding to 95% confidence interval, 28.9% proportion of tuberculosis among HIV positive patients, 4% degree of precision, ten percent of non-response rate and total enrolled patients (6015) in Arba Minch general hospital which resulted 502 samples.
Sample size was also calculated for second specific objective from the study conducted in Gondar University hospital and Felege-Hiwot Referral Hospital [
Simple random sampling was used through randomly generated number from patient’s data of 2007-2013. Despite, charts were organized on the shelf according to the hospital card number, which is given in chronological (sequential) order. Some of charts in the hospital were not arranged in numerical order, so new numbering started from 1 up to 2000 were assigned to charts of two thousand patients registered between 2007 and 2013. After a number was assigned to each chart, investigator draw 502 sample charts and among them 496 that fulfilled the inclusion criteria was reviewed one by one and the information was transcribed to the pre-structured data abstraction form.
Structured data abstraction form was prepared and used for chart review. Four ART nurses abstracted the data from ART registry book of HIV infected patients who had follow up starting from 2007 up to 2013 under supervision of medical doctors who were got trained for this purpose. Principal investigator rechecked if there is incomplete and inconsistent abstraction from the chart at every day, if incomplete checklist was found, he sent back to data collectors for correction.
Incident TB case: which was defined in this study, as an event, diagnosed with Sputum smear (+) (at least two), chest X-ray (suggestive of TB finding) and culture positive during follow-up, which was ascertained retrospectively?
Cumulative Incidence of TB: It was calculated by dividing total new occurrence of Tuberculosis to all total sampled patients.
Variables | CI | Power | OR | Ratio | Percent in unexposed | Lost to follow up | Sample size |
---|---|---|---|---|---|---|---|
Functional status/Working group | 95% | 90% | 2.67 | 1 | 23.1% | 10% | 242 |
WHO stage IV/Stage I/II | 95% | 90% | 10.3 | 1 | 10.4% | 10% | 57 |
CD4 count >200 | 95% | 90% | 2.13 | 1 | 21% | 10% | 396 |
Body mass index | 95% | 90% | 8.2 | 3.8% | 10% | 127 |
Incidence rate of Tuberculosis: Incidence rate in this research was calculated by dividing all new occurrence of Tuberculosis to total follow up time of patients in year.
TB diagnosis: TB was diagnosed using microscopic examinations of sputum smears, chest radiology, fine- needle aspiration of lymph-adenopathy, cytology with very high clinical grounds and mycobacterium culture.
Data was coded manually, entered and cleaned using Epi-Info 7 and exported to SPSS version 21 for descriptive and inferential analyses. Frequencies and cross tabulations were used to check for missed values and variables. Data was presented by using frequency, tables, and summarized by using mean and standard deviation. Back ward Logistic regression analysis was conducted to see the effect of explanatory variables on TB incidence and Statistical significance was inferred at P-value <0.05. Adjusted odd ratios with 95% confidence interval (CI) were used to determine predictors.
The study was approved by the institutional review board of Addis continental institute of Public health which was coordinated by Arba Minch University/CMHS. Additional written permission to conduct the study on medical records of patients was obtained from the Arba Minch General hospital. Personal identifiers were excluded during data abstraction. Since it is secondary data obtaining informed consents from the participants was not possible, but the confidentiality of information was maintained by not recording their name from the chart and keeping the data anonymous.
Four hundred ninety six records of HIV Infected patients were analyzed. Their mean age was 33.8 (±8.89 SD) years and almost half, 235 (47.4%), of them were in the age group of 25 - 34 years. Over half (58.1%) of the PLHIV were females and the majority (73.4%), of them were urban dwellers.
Almost all (99.8%) patients disclosed their HIV status, to their brothers/sisters/parents. Forty three (8.7%) of them were cigarette smokers (see
One hundred seventeen nine (36.1%) of them were at WHO clinical stage 3 during enrolment. Three hundred twenty five (65.2%) of the participants were on working status at baseline. The median CD4 count during enrollment was 221 (IQR: 125 - 340.7).
The predominant regimens initially prescribed were a combination of (TDF + 3TC + NBC) and (3TC + EFV + NVP) (38.3%), followed by Staudinger, Lamivudine and, Nevirapine (17.8%).
One hundred thirteen (22.8%) patients had changed their initial regimen during the follow up period mainly to (TDF + 3TC + NVP) + (3TC + EFV + NVP) 45 (9.6%), and ten (8.85%) patients were switched to second line HAART.
For 105 (92.9%) and 3 (2.65%) patients, regimens were changed due to drug side effect and TB occurrence respectively, while the reasons for changing the initial regimen were not recorded for 4 (3.54%) patients (see
Cumulative incidence and incidence rate of tuberculosis among PLHIV patients was 21.4% (21.3, 21.44) and 5.36 per 100 persons year respectively (see
Bivariable logistic regression analysis of socio-demographic and Behavioral variables on incidence of TBC revealed that age, sex, disclosure of HIV status to one of family member, history of cigarette smoking and household family size were predictors of incidence of TB, but all other variable like educational status, marital status,
Variable | Frequency | (%) |
---|---|---|
Sex | ||
Male Female | 208 288 | 41.9 58.1 |
Age (33.2 + 8.89) | ||
15 - 24 25 - 34 35 - 44 ≥45 | 66 235 137 58 | 13.3 47.4 27.6 11.7 |
Marital status | ||
Married Single Divorced Separated Widowed | 321 60 54 29 32 | 64.7 12.1 10.9 5.8 6.5 |
Residence | ||
Urban Rural | 364 132 | 73.4 26.6 |
Religion | ||
Orthodox Muslim Protestant | 334 21 141 | 67.3 28.4 4.2 |
Level of educational | ||
No education Primary Secondary Tertiary | 116 169 158 53 | 23.4 34.1 31.9 10.7 |
Occupation | ||
Farmer Government employ Housewife Merchant Private gainful work Others (unspecified job) | 24 72 158 44 67 131 | 4.8 14.5 31.9 8.9 26.4 13.5 |
Addiction | ||
Addicted Not addicted | 39 457 | 7.9 92.1 |
Family size | ||
≤2 3 - 4 ≥5 | 127 221 148 | 25.6 44.6 29.8 |
Cigarette smoking | ||
Yes No | 43 453 | 8.7 91.3 |
and other analyzed were not predict Incidence of Tuberculosis among HIV infected patients (see
In multivariable logistic regression analysis, Family size, History of cigarettes smoking, Baseline WHO clinical
Variables | Frequency | % |
---|---|---|
ART intervention Pre-ART HAART | 137 359 | 27.6 72.6 |
Regimen change during follow up Yes No | 113 383 | 22.8 77.2 |
New regimen First line 2nd line | 103 10 | 91.2 8.85 |
Reason for switch first regimen Side effect Pregnancy Tuberculosis Others | 105 1 3 4 | 92.9 0.88 2.65 3.54 |
Past TB treatment history Yes No | 68 428 | 13.7 86.3 |
Functional status Working Ambulatory Bed redden | 325 134 37 | 65.5 27.0 7.5 |
---|---|---|
CD4 count <50 50 - 100 101 - 200 200 | 35 58 127 276 | 7.1 11.7 25.6 55.6 |
Hemoglobin <10 ≥10 | 17 479 | 3.4 96.6 |
Year of follow up ≤1 1 - 3 ≥3 | 16 129 351 | 3.2 26.0 70.8 |
Variable | Incidence of tuberculosis | COR (95% CI) | |
---|---|---|---|
Yes (%) | No (%) | ||
Age 15 - 24 25 - 34 35 - 44 ≥45 | 8 (12.1) 46 (19.6) 33 (24.1) 19 (32.8) | 58 (87.9) 189 (80.4) 104 (75.9) 39 (67.2) | 1 1.76 (0.78, 3.95) 2.30 (0.99, 5.31) 3.53 (1.41, 8.87) |
Sex Male Female | 55 (26.4) 51 (17.7) | 153 (73.6) 237 (82.3) | 0.59 (0.39, 0.92) 1 |
Marital status Divorced Married Single Separated Widowed | 14 (25.9) 69 (21.5) 13 (21.7) 3 (10.3 7 (21.9) | 40 (74.1) 252 (78.5) 47 (78.3) 26 (89.7) 25 (78.1) | 1.25 (0.44, 3.52) 0.98 (0.40, 2.36) 0.41 (0.09, 1.77) 0.99 (0.35, 2.79) 1 |
Religion Muslim Orthodox Protestant | 6 (28.6) 69 (20.7) 31 (22.0) | 15 (71.4) 265 (79.3) 110 (78.0) | 1 0.65 (0.24, 1.74) 0.70 (0.25, 1.97) |
Level of educational No education Primary Secondary Tertiary | 29 (25.0) 30 (17.8) 34 (21.5) 13 (24.5) | 87 (75.0) 139 (82.2) 124 (78.5) 40 (75.5) | 1.03 (0.48, 2.18) 0.66 (0.32, 1.39) 0.84 (0.40, 1.75) 1 |
Occupation Farmer Government employ Housewife Merchant Private gainful work Others (unspecified Job) | 5 (20.8) 21 (29.2) 30 (19.0) 8 (18.2) 15 (22.4) 27 (20.6) | 19 (79.2) 51 (70.8) 128 (81.0) 36 (81.8) 52 (77.6) 104 (79.4) | 1 1.56 (0.52, 4.74) 0.89 (0.31, 2.57) 0.84 (0.24, 2.94) 0.98 (0.34, 2.88) 1.09 (0.35, 3.43) |
Addiction Addicted Not addicted | 15 (38.5) 91 (19.9) | 24 (61.5) 366 (80.1) | 2.51 (1.27, 4.98) 1 |
Family size ≤2 3 - 4 ≥5 | 19 (15.0) 55 (24.9) 32 (21.6) | 108 (85.0) 166 (75.1) 116 (78.4) | 1 1.88 (1.06, 3.35) 1.57 (0.84, 2.93) |
Cigarette smoking status Yes No | 20 (46.5) 86 (19.0) | 23 (53.3) 367 (81.0) | 3.71 (1.95, 7.06) 1 |
Disclosure status Disclosed Not disclosed | 106 (21.5) 0 (0.0) | 386 (78.5) 4 (100) | 1 2.51 (1.27 - 4.98) |
stage and hemoglobin level were important risk factors for incidence of TB among HIV infected patients.
Thus, an individual who live in the family size of 3 - 4 was two times (AOR: 2.26, 95% CI (1.14 - 4.50)) at risk of developing Tuberculosis among HIV than an individual who live in the family of less than or equal to two.
WHO clinical staging is Predictor for incidence of Tuberculosis among HIV patients; accordingly HIV patients with clinical stage III 20 times (AOR: 20.26, 95% CI (7.09 - 57.6)) and stage IV 22 times (AOR: 22.9, 95% CI (6.91 - 76.4)) were more likely to develop tuberculosis than an individual who were enrolled to ART clinic on the first WHO clinical stage.
Other factor that affect TB incidence among PLHIV was level of hemoglobin. According to this study an individual with hemoglobin level of less than 10 mg/dl was 2.5 times ((AOR: 2.56, 95% CI (1.22 - 5.33)) highly acquire TB than an individual with hemoglobin level of greater than ten (see
Other socio demographic and clinical characteristics like; Age in group (≥45), addiction (Addicted), sex of respondent, CD4 count, ART intervention(HAART), type of initial regimen and history of past TB treatment
Variables | Incidence of TBC | COR (95% CI) | AOR (95% CI) | P-Value | |
---|---|---|---|---|---|
Yes | No | ||||
Age 15 - 24 25 - 34 35 - 44 ≥45 | 8 (12.1) 46 (19.6) 33 (24.1) 19 (32.8) | 58 (87.9) 189 (80.4) 104 (75.9) 39 (67.2) | 1 1.76 (0.78, 3.95) 2.30 (0.99, 5.31) 3.53 (1.41, 8.87 | - | |
Disclosure status Disclosed Not disclosed | 106 (21.5) 0 (0.0) | 386 (78.5) 4 (100) | 2.51 (1.27-4.98) 1 | - | |
Family size ≤2 3 - 4 ≥5 | 19 (15.0) 55 (24.9) 32 (21.6) | 108 (85.0) 166 (75.1) 116 (78.4) | 1 1.88 (1.06, 3.35) 1.57 (0.84, 2.93) | 1 2.26 (1.14 - 4.50) 1.76 (0.83 - 3.69) | 0.02 0.14 |
Cigarette smoking Yes No | 20 (46.5) 86 (19.0) | 23 (53.6) 367 (81.0) | 3.71 (1.95, 7.06) 1 | 2.82 (1.27 - 6.27) 1 | 0.011 |
ART intervention Pre-ART HAART | 16 (11.7) 90 (25.1) | 121 (88.3) 269 (74.9) | 1 2.53 (1.43, 4.49) | - | |
Type of initial regimen 1a 1b 1c 1d 1e + 1f | 19 (11.7) 19 (29.7) 5 (8.3) 13 (23.6) 34 (24.3) | 121 (88.3) 45 (70.3) 21 (52.5) 55 (91.7) 42 (76.4) | 1.32 (0.68, 2.55) 2.82 (1.36, 5.85) 0.28 (0.11, 0.76) 0.96 (0.46, 2.00) 1 | - | |
Past TB treatment history Yes No | 22 (32.4) 84 (19.6) | 46 (67.6) 344 (80.4) | 1.96 (1.12, 3.43) 1 | - | |
WHO clinical stage I II III IV | 7 (6.1) 6 (3.5) 76 (43.9) 17 (44.7) | 108 (93.9) 164 (96.5) 97 (56.1) 21 (55.3) | 1 0.56 (0.18, 1.72) 12.0 (5.31, 27.5) 12.5 (4.61, 33.8) | 1 0.33 (0.06 - 1.86) 20.26 (7.09 - 57.6) 22.9 (6.91 - 76.4) | 0.21 <0.001 <0.001 |
CD4 count <50 50 - 100 101 - 200 200 | 20 (57.1) 23 (39.7) 38 (29.9) 25 (9.1) | 15 (42.5) 35 (60.3) 89 (70.1) 251 (90.9) | 13.4 (6.10, 29.4) 6.59 (3.38, 12.8) 4.28 (2.44, 7.50) 1 | ||
Hemoglobin <10 ≥10 | 24 (48) 82 (18.4) | 26 (52) 364 (81.6) | 1 3.46 (1.30, 9.18) | 1 2.56 (1.22 - 5.33) | 0.012 |
Note: significant ≤ 0.05.
(treated) were significant predictors of tuberculosis among HIV infected patients in bivariable analysis, but the association was diluted in multivariable analysis.
Since the introduction of HIV infection in the world, TB is one of common opportunistic infection and Persons co-infected with TB and HIV were 21 - 34 times more likely to develop active TB disease than persons without HIV [
In this study, cumulative incidence and overall incidence rate of TB were 21.4% and 5.36 per 100 PY respectively.
This study used cumulative incidence of TB as outcome variable. Thus, cumulative incidence of Tuberculosis (21.4%) reported in this study was lower than study done in former capital of Tanzania, Dares Salaam (27.1%) and study done in North west Ethiopia (Debre Markos hospital) (44%) [
In multivariable analysis; Family size, History of Cigarettes smoking, WHO Baseline clinical stage and hemoglobin level were important predictors of incidence of Tuberculosis among HIV infected patients.
This study could establish association between TB and number of people in the household. Thus, an individual who live in the family size of 3 - 4 was two times at risk of developing Tuberculosis than an individual who live in family with <2 children. It is consistent with Studies, which have shown that risk of TB was associated with the number of people living together in the household (overcrowding) [
Others predictors associated with incidence of tuberculosis was history of cigarette smoking, thus cigarette smoker were 3 times at higher risk of developing TB than non-smokers. The finding was consistent with study done in Taiwan [
Baseline WHO clinical staging was strong predictor for Incidence of Tuberculosis; accordingly HIV patients with clinical stage III and IV were 20 and 22 times more likely develop tuberculosis than an individual who was started follow up on the first WHO clinical stage. The finding was supported by different study done in Ethiopia [
In addition, patients having a hemoglobin level of <10 mg/dl have 2.5 times higher risk of developing TB than those patients having hemoglobin level 10.0 mg/dl, the finding was similar to other study findings in south west Ethiopia [
Other factors like; Age in group, addiction, sex of respondent, CD4 count, ART intervention, type of initial regimen and past history of TB treatment were significant predictors of incidence of tuberculosis among HIV infected patients in bivariable analysis, but the effect of this socio demographic and clinical characteristics were diluted in multivariable analysis.
Analysis of the past history of TB after adjustment, that it was a TB risk factor among PLWHAs, which is in agreement with a number of previous studies [
Many studies have used the patients’ CD4 cell counts to assess association between CD4 Count and TB incidence and found that a lower CD4 cell count was associated with a higher risk of TB infection [
The main limitation of our study was the retrospective nature of the cohort. The study individuals whose charts were lost not included in the study, which could undermine the result if the charts excluded were related to incidence of TB.
Cumulative and overall incidence rate of tuberculosis were found to be 21.4% and 5.36 per 100 PY respectively, which one was the highest. Family size, history of cigarettes smoking, heamoglobin level and WHO baseline clinical stage were important predictors of incidence of tuberculosis among HIV infected patients.
Finding that smoking is important predictors for TB in Ethiopia has obvious TB control implication which requires high attention focused on fighting against cigarette smoking in HIV infected populations.
The health institutions particularly work on lifestyle modification specifically on halting cigarette smoking habit through counseling. Early initiation of HAART as current guideline should get emphasis and behavioral education that discourages addiction is important to reduce the risk of TB infection. Furthermore, concomitant infections and risk factors for anemia among HIV patients should get managed and prevented.
The authors are very grateful to Arba Minch General Hospital, for its administrative and technical assistance. Data collectors, supervisors and Arba Minch University deserves especial acknowledgement for data abstraction, care full supervision and provide ethical clearance to conduct this research work respectively.
The authors declare that there is no competing interest
1MD was the primary researcher, conceived the study, designed, participated in data collection and quality assurances, conducted data analysis, drafted and finalized the manuscript for publication. 2AT was assisted in data collection and analysis and reviewed the initial and final drafts of the manuscript
Mulugeta Dalbo,Alemu Tamiso, (2016) Incidence and Predictors of Tuberculosis among HIV/AIDS Infected Patients: A Five-Year Retrospective Follow-Up Study. Advances in Infectious Diseases,06,70-81. doi: 10.4236/aid.2016.62010
AGH: Arba Minch General Hospital; AIDS: Acquired Immuno Deficiency Syndrome; ART: Active Antiretroviral Therapy; AZT: Zidovudine; EFV: Efavirenz; HAART: Highly Active Antiretroviral Therapy; IRIS: Immune Reconstitution Inflammatory Syndrome; NVP: Nevirapine; OIs: Opportunistic Infections; PY: Person Years; SPSS: Statistical Package for Social Science; TB: Tuberculosis; 3TC: Lamuvudine; WHO: World Health Organization.