HIV/AIDS and Tuberculosis Coinfection in Rural Northern Tanzania. Epidemiology, clinical presentation and impact on CD4 T cell counts

Abstract

Tuberculosis (TB) and HIV/AIDS are the main causes of morbidity and mortality in adults aged 15-49 years in Sub Saharan Africa (SSA). The interaction between tuberculosis and HIV/AIDS makes the diagnosis and management of the coinfection difficult. A cross sectional hospital based study was conducted at Haydom Lutheran Hospital (HLH) to assess the interaction between tuberculosis, HIV/AIDS and tuberculosis HIV/AIDS coinfection in relation to the CD4 T cells. Furthermore, CD4 T cell counts in healthy subjects in different age groups were determined for the purpose of establishing reference values. Study subjects were recruited from • People living with HIV/AIDS • Tuberculosis clinic • HIV Voluntary counselling and testing clinic (VCT). Physical examination and investigation including sputum for fluorescence microscopy and culture, tuberculosis drugs susceptibility testing and Chest X-Ray (CXR) were done for all tuberculosis and HIV/AIDS patients. Sputum samples were stained using auramine and examined by fluorescence microscopy. Sputum culture was done using Lowenstein Jensen media and sensitivity to the first line TB drugs was tested. HIV test was done using 2 different rapid antibody tests, Determine HIV-1/2 (Abbott laboratories, Abbott Park, IL, USA) and Capillus HIV-1/2 (Trinity Biotech, Bray, Co Wicklow, Ireland). Discordant samples were sent to the regional hospital for confirmatory test using ELISA; Enzygnost anti-HIV 1+2 Plus ELISA (Behring, Marburg, Germany) and Wellcoenzyme HIV recombinant ELISA (Murex, Dartford, England). Complete blood cells (CBC) count was done using Sysmex Kx-21 (Sysmex Corporation; Kobe Japan). CD4 T cells were analyzed using a FACSCount flow cytometer (Becton Dickinson Immunocytometry Systems, San Jose, Calif.) We enrolled 440 subjects (102 healthy subjects, 105 newly diagnosed tuberculosis patients with unknown HIV status, and 233 people living with HIV/AIDS). Males were 158 (35.9 %) and 282 (64.1 %) were females. The overall HIV/AIDS and tuberculosis coinfection prevalence was 34/338 (10.1 %). For the newly diagnosed tuberculosis patients 14/105 (13.3%) were HIV/AIDS coinfected; and for the people living with HIV/AIDS 20/ (8.5 %) were coinfected with tuberculosis. Sixty three out of 92 (68.5%) sputum specimens from newly diagnosed tuberculosis patients were culture positive and 66/92 (71.7%) were smear positive for acid fast bacilli (AFB). Out of 66 culture positive specimens, 58 (92.1%) isolates were susceptible to the first line tuberculosis drugs. Twenty (8.5%) sputum samples from people living with HIV/AIDS were culture positive. Eight of the culture positive samples (40%) were smear positive AFB. Fifteen (75%) of these patients neither had clinical symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates (95%) were susceptible to the first line tuberculosis drugs. In groups, (newly diagnosed tuberculosis and PLWHA coinfected with tuberculosis) there were no cases of multi-drug resistant tuberculosis. For the healthy subjects recruited for the establishment of reference values, the mean absolute CD4 T cells was 745.9 + 256.6, and the mean absolute CD8 T cells was 504 + 218.4. Females had significantly higher mean CD4 T cells (802 + 250) than males (665 + 247, t=2.7, df =89, p=0.007) and higher mean absolute CD8 T cells (551.0 + 215.4) than males (438.2+208.4, t=2.7, df =90, p=0.009). The mean haemoglobin level was 13.6+ 2.4 (males 14.1+ 2.7, females 12.6+1.9. Females had significantly lower mean haemoglobin level than males, (t=3.2, df =68, p=0.03) For the newly diagnosed tuberculosis patients; tuberculosis patients had statistically significant lower mean CD4 T cells (559 + 238) than healthy subjects (746 + 257, t=5.3, df =190, p<0.01). Tuberculosis patients had significantly lower haemoglobin level (10.9 + 2.4) than healthy subjects (13.2 + 2.4, t=6.5, df =188, p<0.01) and HIV/AIDS patients (11.6 + 2.2, t=2.4, df =152, p=0.02). Tuberculosis patients were significantly more malnourished (BMI 15.6 + 2.3) than healthy subjects (BMI 23.4 + 3.4, t=18.8, df=178, p<0.01), HIV/AIDS patients (BMI 19.4 + 3.4, t=11.5, df=241, p<0.01) and HIV/AIDS tuberculosis coinfected patients (BMI 16.7 + 2.8, t=2 df =50, p=0.04). We found high prevalence of HIV/AIDS and tuberculosis coinfection as compared to the HIV prevalence in the general population in this setting. Half (17/34) of the sputum samples from HIV/AIDS coinfected patients were smear positive AFB by fluorescence microscopy. About 90% of the mycobacteria isolated from these patients were sensitive to the first line tuberculosis drugs. Chest radiograph suggestive of tuberculosis and clinical symptoms of fever and cough were uncommon findings in HIV/AIDS and tuberculosis coinfected patients. Irrespective of the HIV status tuberculosis was significantly associated with lower mean CD4 T cells, malnutrition and anaemia when compared to healthy subjects, indicating that tuberculosis may cause a reduction in CD4 T cells independent of HIV infection. The immunohaematological values we found were different from standard values for western countries. Females had significantly higher mean CD4 T cell counts and lower mean haemoglobin levels than males. This raises the issue of the appropriateness of the present reference values and guidelines for monitoring HIV/AIDS patients in Tanzania. We recommend active detection of tuberculosis among PLWHA patients and also HIV infection among tuberculosis patients; this will improve clinical staging of HIV and AIDS disease and also help to scale up anti-retroviral therapy (ARV), cotrimoxazole preventive therapy (CPT) and isoniazid preventive therapy (IPT) to those in need, provided that there is no contraindications to ARV, CPT and IPT. The screening for tuberculosis among PLWHA by smear microscopy and/or culture (if available) can be done at inclusion of the patient to care and treatment and during the routine follow up. Screening for HIV among tuberculosis patients is recommended to be done on a routine basis once the diagnosis of TB is made. We also recommend reviewing published reports to establish local immunohaematological reference value for the Tanzanian population.