Prevalence, Immunological and Clinical Factors Associated with Malaria Among Patients with Tuberculosis in Mulago Hospital
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Background: Uganda is among the 30 most TB/HIV burdened countries. Similarly, Uganda ranks 9th among the 15 countries that contribute 80% of the global malaria deaths. There is a possibility of a dual infection of malaria and TB. Malaria and TB reduce CD4+, CD8+ cells and CD4:CD8 ratio independent of each other and a co-infection would be expected to exacerbate this problem. The result would be impaired TB containment thus increasing mortality and morbidity of TB patients. An attendant problem to malaria and TB dual infection is the overlap of symptoms and complications that would hamper early diagnosis of malaria in TB patients. Despite all this, the prevalence of malaria among TB patients, T-cell counts and associated factors are unknown in the Uganda setting. The objectives of this study were to determine the prevalence of Malaria among TB patients, compare CD4+, CD8+ counts and CD4:CD8 ratio among TB patients with malaria and those without malaria and to determine clinical factors associated with malaria among patients with TB in Mulago Hospital. Methods: A cross-sectional study design was used to recruit 363 bacteriologically confirmed TB adult patients by consecutively sampling patients presenting at the TB treatment unit at Mulago hospital. Structured questionnaires were administered to study participants to gather demographics and medical history. A general physical examination was performed on study participants and 5mls of blood were drawn for malaria typing and parasite density, rapid malaria diagnostic test (RDT) for those with a negative smear, HIV testing, CD4 & CD8 cell counts, complete blood count and a hematological film analysis. Data was entered using EpiData and exported to STATA for analysis. We determined malaria prevalence as a proportion of participants with a positive RDT or malaria blood smear. Median CD4, CD8 counts and CD4:CD8 ratios were compared between participants with malaria and those without. Multivariate logistic regression was used to establish factors associated with malaria in patients with TB. Results: The study participants were mostly male (61.4%), with a median (IQR) age of 31(25-39) years and 35.81% were HIV positive. We found a prevalence of malaria of 2.2 % (8/363) of all study participants, 5.17% (3/58) of participants with rifampicin resistance and Malaria/HIV/TB triple infection was found in 0.83% (3/363) of all study participants. Participants with malaria had mild anemia with higher median (IQR) red blood cell counts than those without malaria (5.42 (5.03-5.955) X 109/l compared to 4.69 (3.97-5.38) X 109/l p=0.032). They also had higher median (IQR) white cell counts than participants without malaria (11.425 (7.63-17.22) X 109/l compared to 6.69 (4.77-9.22) X 109/l) p=0.031). Participants with malaria and TB had a higher median (IQR) CD4 count of 864 (257-1281) cells/µl and a higher CD4:CD8 ratio of 1.82 (1.51-1.99) compared to those with TB alone (495 (269-796) cells/µl and 1.54(1.11-2.21) respectively). A median (IQR) CD8 count of 527 (443-740) cells/µl was observed among participants with malaria that was lower than that of participants with TB alone (595.5 (403.5-831) cells/µl). However the differences in T cell counts and ratio were not statistically significant. We coincidentally found a high prevalence of anemia of 58% among all participants. In a multivariate logistic regression model that controlled for Age, Sex, Smoking and HIV status, having malaria was associated with having a CD4 count within the normal range for Ugandans (418 – 2015 cells/µl) (aOR: 9.074 (CI: 1.05-77.84 p=0.044)), Hypochromia (aOR: 59.176 (CI:3.11-1122.50) p=0.007)) and a very low bacillary load (aOR: 33.331 (CI:1.76-628.49) p= 0.019). Conclusions: The prevalence of malaria is low among TB patients generally but higher among those with rifampicin resistance. Patients with Malaria and TB have non-statistically significant higher median CD4 counts and CD4:CD8 ratios when compared to those without malaria and a slightly lower CD8 count. Albeit with a small number of study outcomes, there is a trend towards an association of Malaria with hypochromia, very low bacillary load and a normal CD4 count among patients with TB. There is a high prevalence of anemia among TB patients. Recommendations: We recommend further characterization of malaria in patients with Drug resistant TB. We propose screening for anemia among all patients with TB in Uganda and formulation of guidelines for screening and treatment of anemia among TB patients in Uganda.