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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 4  |  Issue : 2  |  Page : 85-90

Relationship between the radiographic pattern of pulmonary tuberculosis and CD4 cell count in patients with human immune deficiency virus infection


1 Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria
2 Federal Teaching Hospital, Gombe, Nigeria
3 University of Maiduguri Teaching Hospital, Maiduguri, Nigeria

Date of Web Publication16-Oct-2014

Correspondence Address:
Philip O Ibinaiye
Department of Radiology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-9596.143084

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  Abstract 

Background: The chest radiographic appearances of human immunodeficiency virus (HIV)-seropositive patients presenting with pulmonary tuberculosis (PTB) are diverse, creating difficulty in diagnosis and treatment. This study determined the relationship between the degree of immunosuppression and the various radiological patterns of PTB in HIV-infected patients with TB.
Materials and Methods: Sixty consecutive patients with PTB, and positive for HIV antibodies as detected using enzyme-linked immunosorbent assay and confirmed by immunoComb 11 (IMMUNOCOMBFIRM), who presented at the infectious diseases clinic of University of Maiduguri Teaching Hospital, Maiduguri and fulfilled the inclusion criteria were included in to a prospective cross-sectional study after obtaining an informed written consent. CD4+ lymphocytes counts were obtained for all the patients. Posterior anterior and lateral chest radiographs were obtained. The chest radiographic images were evaluated for the presence of either typical or atypical patterns of PTB.
Results: The mean CD4 counts of those with typical and atypical PTB pattern were 339.8 ± 139.52 and 138 ± 41.78 cells/μl, respectively (P = 0.001). Majority of the patients with typical pattern had a CD4 count of ≥200 cells/μl and they belonged to the HIV/PTB on highly active antiretroviral therapy (HAART) group (56.3%) as against 21.4% of HIV/PTB antiretroviral (ARV)-naïve patients. More of HIV/PTB patient who were ARV-naïve and had CD4 count <200 cells/μl presented with atypical pattern (60.7%) as against 25% of HIV/PTB on HAART. None of the patients with HIV/PTB ARV-naïve with CD4 count <200 cells/μl presented with typical pattern.
Conclusion: We concluded that radiographic patterns of PTB in HIV varied over a spectrum and are related to HIV disease stage and that atypical radiographic pattern was a good predictor of low CD4 counts.

Keywords: CD4 cell counts, chest radiograph, human immunodeficiency virus, pulmonary tuberculosis


How to cite this article:
Ibinaiye PO, Tahir NM, Saad ST, Tahir A, Ahidjo A, Yusuf H, Mustapha Z. Relationship between the radiographic pattern of pulmonary tuberculosis and CD4 cell count in patients with human immune deficiency virus infection . Arch Int Surg 2014;4:85-90

How to cite this URL:
Ibinaiye PO, Tahir NM, Saad ST, Tahir A, Ahidjo A, Yusuf H, Mustapha Z. Relationship between the radiographic pattern of pulmonary tuberculosis and CD4 cell count in patients with human immune deficiency virus infection . Arch Int Surg [serial online] 2014 [cited 2020 Oct 24];4:85-90. Available from: https://www.archintsurg.org/text.asp?2014/4/2/85/143084


  Introduction Top


A series of studies suggest that the radiographic appearance of pulmonary tuberculosis (PTB) in human immunodeficiency virus (HIV)-infected patients varies with degree of immunosuppression. [1],[2] Patients with CD4 lymphocyte count above 200 cells/mm 3 more frequently have the postprimary pattern of TB, including cavitary consolidation in the upper lobes and frequently lymphadenopathy. A CD4 lymphocyte count below 200 cells/mm 3 is usually associated with a primary TB pattern including adenopathy, pleural effusion and areas of noncavitary consolidation, more frequent in the middle and lower lobes, but often randomly distributed in the lungs. [3] Miliary, atypical patterns, or normal chest radiographs are frequently observed in the patients with very advanced immunosuppression, demonstrated by a CD4 lymphocyte count below (50 cell/mm 3 ). [3] Highly active antiretroviral therapy (HAART) may significantly increase the CD4 lymphocytes number and function in a significant proportion of HIV-infected patients. Moreover, there is accumulating evidence that this therapy may reduce the risk of developing HIV-associated TB, although this continues to occur also in HIV-infected patients who are on HAART. [4],[5] Conventional chest X-ray and high resolution computerized tomography of the chest are the most common radiological methods of investigation that could be used to determine the relationship of CD4 counts to radiographic features of PTB in HIV-infected patients.

However, we decided to make use of conventional chest X-ray to carry out this study, because it is readily available, affordable, and more importantly delivers less radiation dose to patient when compared to computerized tomography and they can be reproduced in most hospitals in developing countries. The aim of this study was to determine the relationship between the degree of immunosuppression and the various radiological patterns of PTB in HIV-infected patients with TB.


  Materials and Methods Top


This study was carried out at the University of Maiduguri Teaching Hospital, Maiduguri, Nigeria between March 2010 and February 2013. Maiduguri is the capital of Borno State in North-Eastern Nigeria with a population of about 0.7 million. A total of 60 consecutive patients with PTB, and positive for HIV antibodies as detected by enzyme-linked immunosorbent assay and confirmed by immunoComb 11 (IMMUNOCOMBFIRM), who presented at the infectious diseases Clinic of University of Maiduguri Teaching Hospital, Maiduguri and fulfilled the inclusion criteria were included in to a prospective cross-sectional study after obtaining an informed written consent.

Inclusion criteria are adult patients (>15 years) with confirmed HIV-infection and PTB (the PTB is defined by the presence of at least two of the following criteria one of which must be "a"); (a) presence of acid fast bacilli (AFB) in the sputum, (b) clinical features (cough >3 weeks, night sweat, fever, and weight loss), (c) chest X-ray features suggestive of PTB and (d) positive Mantoux reaction. Exclusion criteria are patients on immunosuppressive drug therapy, patients on anti TB therapy for more than 1 month, patients who did not give their consent and patients with diabetes mellitus, chronic renal failure, nephrotic syndrome, sickle cell disease, and widespread malignancies. On entering the study, a questionnaire was administered to each patient and details regarding demographic data, CD4 T-lymphocytes count and radiographic patterns were documented.

Posterior anterior (PA) and lateral chest radiographs were obtained with film screen at 50-70 kVp in majority of the patients. The obtained chest radiographic images were reviewed by three consultant radiologists to arrive at consensus diagnosis. Where there were uncertainties in the imaging findings, the cases were not included in the study. For descriptive purposes, both lung fields were divided in to three zones by two horizontal lines through the anterior ends of the second and fourth ribs anteriorly. [6] Findings were classified as consolidation, cavitations, reticular changes, nodular opacities, reticulonodular opacities, mediastinal/hilar-adenopathy, pleural effusion, lung collapse and miliary pattern. Where all such features were absent the radiograph was classified as normal. Furthermore, the chest X-ray pattern of TB was classified as typical TB if upper zone consolidation, reticular changes or cavitations were present including pleural effusion, and they were classified as atypical if reticular changes and cavities were present predominantly in the lower zones, and if intra-thoracic adenopathy, and miliary disease was present, or if the chest X-ray was normal.

The CD4+ lymphocyte count of all the patients was grouped in to two (<200 cells/μl and >200 cells/μl) because a series of studies suggest that the radiographic appearance of PTB in HIV-infection varies with degree of immunosuppresion. HAART may significantly increase the CD4 lymphocyte count and function in significant proportion of HIV-infected patients. [4] Furthermore, the Centers for Disease Control and Prevention (CDC) 1993 expanded surveillance definition for acquired immunodeficiency syndrome (AIDS), a CD4+ T-lymphocyte count of <200 cells/μl was selected as a marker of significant immunosuppression and a logical cut-off between those subjects who may respond in a typical versus an atypical manner to Mycobacterium tuberculosis.

Statistical methods

The data obtained were entered in to a computer to generate a computerized database for subsequent analysis using statistical package for social sciences (SPSS) for window 11.0 (SPSS inc Chicago, Illinois, USA). Values were expressed as mean ± standard deviation (M ± SD). Chi-square and Student's t-test were used to analyze the data. A P < 0.05 was considered as significant. Tables and diagrams were used for illustration as and when appropriate. Primary outcome measures are CD4+ cell counts and chest radiographic patterns.

Ethical consideration

All aspects of the study were reviewed and authorized by the Ethical Committee of the University of Maiduguri Teaching Hospital before initiation. Patients had the unlimited liberty to deny consent for, or opt out of the study at any stage without any consequences.


  Results Top


Sixty patients with positive sputum AFB smear and HIV antibodies were enrolled in to a prospective cross-sectional study between March 2010 and February 2013. Of these, 32 (53.3%) were on HAART for duration ranged between 6 and 18 months (M ± SD: 9 ± 2.61) and 28 (46.7%) were not. All the patients had plain PA and lateral chest radiographs and CD4+ T-lymphocyte count determination. Thirty eight (63.3%) patients were females and 22 (36%), were males. Their ages ranged between 19 and 50 years (M ± SD: 32.9 ± 7.15).

[Table 1] shows the frequency of HIV/PTB in the different age groups and sexes. The most prone sex and age groups occurred in females between 25 and 34 years.
Table 1: Age and sex distribution of the patients studied

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[Figure 1] shows the frequency of HIV/PTB in the different marital status groups. Married men and women were the majority in the study representing 61.7%.
Figure 1: Distribution of marital status among the patients studied

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[Figure 2] shows the distribution of occupation of the patients. Significant number of patients in the study was made up of either full time house wives or students, representing 25% and 23.3%, respectively.
Figure 2: Distribution of occupation among the subjects studied

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The mean CD4 counts of those with typical and atypical PTB pattern were 339.8 ± 139.52 and 138 ± 41.78 cells/μl, respectively (P = 0.001).

[Table 2] is the summary of CD4 counts of the patients studied. A total of 68.7% of HIV/PTB on HAART patients had a CD4 counts of ≥ 200 as against 39.3% of antiretroviral (ARV)-naïve HIV/PTB patients (P = 0.00). Also, 60.7% of HIV/PTB ARV-naïve patients had CD4 counts <200 cells/μl as against 31.3% of HIV/PTB on HAART patients (P = 0.00).
Table 2: Summary of CD4 counts of the patients studied


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[Table 3] shows the relationship between chest radiographic pattern and CD4 counts. Majority of the patients with typical pattern had a CD4 count of ≥200 cells/μl and they belonged to the HIV/PTB on HAART group (56.3%) as against 21.4% of HIV/PTB ARV-naοve patients. More of HIV/PTB patient who were ARV-naïve and had CD4 count <200 cells/μl presented with atypical pattern (60.7%) as against 25% of HIV/PTB on HAART. None of the patients with HIV/PTB ARV-naïve with CD4 count <200 cells/μl presented with typical pattern.
Table 3: Relationship of chest radiographic pattern with CD4 counts

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[Figure 3], [Figure 4], [Figure 5], [Figure 6] are some of the chest radiographic findings in the patients studied.
Figure 3: Chest radiograph of patient with CD4 count of 230 cells/μl, showing homogenous opacity with background cavitary changes in the right upper zone

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Figure 4: Chest radiograph of patient with CD4 count of 150 cells/μl, showing homogenous opacity in the right lower zone in keeping with consolidation. There is widening of the right superior mediastinum with lobulated outline suggesting mediastinal adenopathy. Right axillary curvilinear calcification also suggests axillary adenopathy

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Figure 5: Chest radiograph of patient with CD4 count of 205 cells/μl, showing streaky opacities in the right upper zone. There is a homogenous opacity in the left lower zone obliterating both diaphragmatic and cardiac outline with tracking along the lateral chest wall. In keeping with right upper zone fibrosis with right hilar adenopathy and left pleural effusion

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Figure 6: Chest radiograph of patient with CD4 count of 80 cells/μl, showing marked right hilar adenopathy. Reticulonodular changes are also seen in the remaining lung fields bilaterally

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  Discussion Top


The age distribution among HIV-associated PTB patients reported by other workers, [5],[7] and Mankatittham et al. [8] in Thailand, is similar to this study. This corroborates the fact that HIV is more common in people in their reproductive and sexually active age groups. The male:female ratio reported by authors in other parts of the world [9] and Nigeria [5],[7],[10],[11] either found a male preponderance or an even sex distribution. This is in contrast to the female preponderance in this study. The reason for this could be either due to polygamy, early marriages, and freedom to remarry after divorce or death of a spouse, which is the order of the day in this part of the country. A remote possibility could be that more women may be presenting to the hospital than men. Most of the patients in the study were married men and women followed by singles and widows. This may be due to high rates of extra marital affairs in our society. Majority of the patients were low income earners as most of them were full time house wives, students, civil servants, and farmers. The rest of the patients were petty traders or unemployed and therefore belong to low socioeconomic stratum of the society. This, coupled with poverty, ignorance and disease further assist the spread of HIV/PTB in these patients.

Kolawole et al. [12] at, Ibadan Nigeria in 1975 showed that, the upper lobes were the most affected and there were also adults with the childhood pattern, probably due to failure of localization of the primary intrapulmonary parenchyma lesions with subsequent hematogenous spread. The Ibadan study was carried out before the era of HIV-infections suggesting that in the Nigerian population, other factors could account for atypical radiological features as seen in HIV related PTB. Nguyen et al., [13] Solomon and Rabinowitz [14] concluded that the high incidence of diabetes mellitus, malnutrition and other infections as well as environmental socioeconomic factors would account for the severity of PTB.

A series of studies including this study suggest that the radiographic appearance of PTB in HIV-infection varies with degree of immunosuppression. [1],[2] Using the guidelines of the CDC 1993 expanded surveillance definition for AIDS, a CD4+ T-lymphocyte count of <200 cells/μl was selected as a marker of significant immunosuppression and a logical cut-off between those subjects who may respond in a typical versus an atypical manner to M. tuberculosis and was shown in this study to reliably indicate those at risk for atypical radiographic manifestation of TB. Mean CD4− T-lymphocyte count of subjects presenting with radiographically atypical PTB and those with typical reactivation PTB were significantly different. These findings are in agreement with the work of Keiper et al. [15] who found the mean CD4 T-lymphocyte count of subjects presenting with typical versus atypical radiographic pattern to be 323 cells/μl and 69 cells/μl respectively. The higher rates in our study may be due to selection of the patients.

Studies [16],[17] suggest that the radiographic appearance of PTB in HIV-infected patients varies with the degree of immunosuppression. Patients with CD4 lymphocyte count above 200 cells/mm, more commonly have the postprimary pattern of TB, including cavitary consolidation in the upper lobe and infrequently lymphadenopathy. A CD4 lymphocyte count below 200 cells/mm is usually associated with a primary TB pattern including adenopathy, pleural effusion, and areas of noncavitary consolidation, more frequent in the middle-lower lobes but often randomly distributed in the lung. Miliary, atypical patterns, or normal chest radiographs are frequently observed in patients with very advanced immunosuppression, demonstrated by a CD4 lymphocyte count below 50 cell/mm. [3] In this study, miliary pattern and normal radiographs occurred at CD4 count of 80-120 cells/μl. This difference may be due to nutritional status of the patients or racial differences. Our data confirm the association between CD4 lymphocyte count and the chest imaging pattern.

In addition, our results suggest that the increased proportion of patients presenting with a postprimary pattern among those treated with HAART may be due to the fact that they are less immunosuppressed than untreated patients when they develop active PTB. The development of PTB despite HAART regimen probably reflects the fact that tuberculous infection is highly prevalent and that it may also produce low level immunosuppresion. Moreover, it has been suggested that the HAART-induced increase in the CD4 cell count does not restore comprehensive immune function. It is worth of note that CD4 count does not uniquely explain the host response to PTB in HIV-infected patients. Nutritional status and exposure to infection may contribute to this. Nevertheless, the overwhelming majority of patients presenting with atypical radiographic pattern have CD4 count of <200 cell/μl. These findings are in agreement with the work of Akinbami et al. [18]


  Conclusion Top


The radiographic patterns of PTB in HIV varied over a spectrum and are related to HIV disease stage and that atypical radiographic pattern was a good predictor of low CD4 count.

 
  References Top

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Kisembo HN, Boon SD, Davis JL, Okello R, Worodria W, Cattamanchi A, et al. Chest radiographic findings of pulmonary tuberculosis in severely immunocompromised patients with the human immunodeficiency virus. Br J Radiol 2012;85:e130-9.  Back to cited text no. 1
    
2.
Padmapriyadarsini C, Tripathy S, Sekar L, Bhavani PK, Gaikwad N, Annadurai S, et al. Evaluation of a diagnostic algorithm for sputum smear-negative pulmonary tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr 2013;63:331-8.  Back to cited text no. 2
    
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Chamie G, Luetkemeyer A, Walusimbi-Nanteza M, Okwera A, Whalen CC, Mugerwa RD, et al. Significant variation in presentation of pulmonary tuberculosis across a high resolution of CD4 strata. Int J Tuberc Lung Dis 2010;14:1295-302.  Back to cited text no. 3
    
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Bakari M, Arbeit RD, Mtei L, Lyimo J, Waddell R, Matee M, et al. Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: The role of chest X-ray and sputum culture. BMC Infect Dis 2008;8:32.  Back to cited text no. 4
    
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Girardi E, Antonucci G, Vanacore P, Libanore M, Errante I, Matteelli A, et al. Impact of combination antiretroviral therapy on the risk of tuberculosis among persons with HIV infection. AIDS 2000;14:1985-91.  Back to cited text no. 5
    
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Jones JL, Hanson DL, Dworkin MS, DeCock KM, Adult/Adolescent Spectrum of HIV Disease Group. HIV-associated tuberculosis in the era of highly active antiretroviral therapy. The Adult/Adolescent Spectrum of HIV Disease Group. Int J Tuberc Lung Dis 2000;4:1026-31.  Back to cited text no. 6
    
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Leung AN, Brauner MW, Gamsu G, Mlika-Cabanne N, Ben Romdhane H, Carette MF, et al. Pulmonary tuberculosis: Comparison of CT findings in HIV-seropositive and HIV-seronegative patients. Radiology 1996;198:687-91.  Back to cited text no. 7
    
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Mankatittham W, Likanonsakul S, Thawornwan U, Kongsanan P, Kittikraisak W, Burapat C, et al. Characteristics of HIV-infected tuberculosis patients in Thailand. Southeast Asian J Trop Med Public Health 2009;40:93-103.  Back to cited text no. 8
    
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Chaisson RE, Slutkin G. Tuberculosis and human immunodeficiency virus infection. J Infect Dis 1989;159:96-100.  Back to cited text no. 9
    
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Wokoma FS. HIV status of adult Nigerian patients suffering from pulmonary tuberculosis. Niger Med Pract 1997;34:22-4.  Back to cited text no. 10
    
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Haas DW, Des Prez RM. Tuberculosis and acquired immunodeficiency syndrome: A historical perspective on recent developments. Am J Med 1994;96:439-50.  Back to cited text no. 11
    
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Kolawole TM, Onadeko EO, Sofowora EO, Esan GF. Radiological patterns of pulmonary tuberculosis in Nigeria. Trop Geogr Med 1975;27:339-50.  Back to cited text no. 12
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Nguyen DT, Hung NQ, Giang LT, Dung NH, Lan NT, Lan NN, et al. Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam. Int J Tuberc Lung Dis 2011;15:1528-34, i.  Back to cited text no. 13
    
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Solomon A, Rabinowitz L. Primary cavitating tuberculosis in childhood. Clin Radiol 1972;23:483-5.  Back to cited text no. 14
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Mark D Keiper, Maria Beumont, Ashraf Elshami, Curtis P. CD4 T Lymphocyte count and the radiographic presentation of pulmonary tuberculosis. Dept. of radiology, Hospital of the University of Pennsylvania, 3400 spruce street, Philadelphia, PA 19104.  Back to cited text no. 15
    
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Moss AR, Bacchetti P. Natural history of HIV infection. AIDS 1989;3:55-61.  Back to cited text no. 16
    
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Yoo SD, Cattamanchi A, Den Boon S, Worodria W, Kisembo H, Huang L, et al. Clinical significance of normal chest radiographs among HIV-seropositive patients with suspected tuberculosis in Uganda. Respirology 2011;16:836-41.  Back to cited text no. 17
    
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Akinbami AA, Adegboyega AO, Oshinaike OO, Adebola PA, Enabulele C, Dosunmu OA, et al. Chest X-ray findings in HIV patients in relation to the CD4 count. Nig Q J Hosp Med 2011;21:306-11.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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