Context: The burden of TB in Africa tends to be exacerbated by the socio-economic situation and the high prevalence of intercurrent infections such as HIV, malaria and non-specific bacterial infections. These factors often result in anemia, making patients at high risk for anemia. Objective: We aimed to gain insights into the characteristics of anemia, hematologic variations and socio-economic status in untreated pulmonary TB patients (PTB) in Kinshasa, the Democratic Republic of Congo. Methods: We conducted a cross-sectional analysis of 200 smear-positive pulmonary TB patients (PTB) recruited at the initiation of TB treatment. Complete Blood Count, Iron profile, BMI, CRP and albuminemia were assessed. Data were analyzed using Student t or Mann Whitney tests as appropriate, and logistic regression was performed to assess the strength of associations. Results : Anemia was a regular finding in (69%). This anemia was mostly moderate (92.2%) and with iron deficiency pattern (48%). Hypoalbuminemia was observed in half of the subjects and appears to be correlated with the severity of anemia. Surprisingly, the severity of inflammation, as reflected by the CRP, was inversely correlated with the anemia. In the multivariate analysis, alcohol intake (OR: 2.38; IC 95%: 1.05 - 5.38), hypoalbuminemia (OR: 1.98; IC 95%: 1.02 - 3.82) and CRP rate were significantly associated with the presence of anemia among pulmonary tuberculosis at the diagnostic. Conclusion: This study demonstrates the heavy burden of the iron responsive anemia and risky life conditions in newly diagnosed TB patients, and underscores the potential usefulness of iron supplementation in the Congolese context.
More than 130 years after the identification of Mycobacterium tuberculosis and 60 years after the first discovery of anti-tuberculous antibiotics, tuberculosis (TB) remains a public health concern, especially in developing countries. TB is still a major cause of mortality in the world, after HIV/AIDS. The World Health Organization reported an estimate of 1.4 million TB deaths for 2015 [
Anemia is widely recognized as a common TB-associated morbidity [
Besides iron assessment, a full characterization of anemia should be recommended since other hematologic modifications affecting platelets, leucocytes or proteins can inform about the disease prognostic. Results from leucocytes and platelet lineages assessment in TB are variable in that both leukocytosis and leukopenia are reported, as well as both thrombocytosis and thrombocytopenia [
A better understanding of the causes and types of TB-associated variations would pave the way for the implementation of efficient management strategies in DRC. This study aimed at gaining insights into the characteristics of anemia, hematologic variations and socio-economic status in untreated pulmonary TB patients (PTB) in Kinshasa, the Democratic Republic of Congo.
This study was conducted in 5 centers fully dedicated to the diagnostic and treatment of TB in Kinshasa (DTC) between June and October 2015. These DTC were selected based on their geographical accessibility and the high number of treated patients. In each of these centers, we systematically recruited all adult TB patients (aged at least 15 years) newly diagnosed and naïve of any TB treatment. The diagnostic was considered positive upon the detection of acid fast bacilli (AFB) on 2 consecutive sputum smears stained by Ziehl-Neelsen. In addition to patients previously under TB treatment, we also excluded patients with comorbidities (a disease with significant impact of hematologic parameters) or other treatment with potential impact on hematological parameters, with exception for HIV. HIV screening was performed on whole blood sample. A total of 200 patients were recruited and from each of them we collected anamnestic (previous exposure contact, alcohol and/or tobacco use), demographic information (age, sex, gender) and anthropometric data (weight and height for BMI calculation). The time interval between the onset of symptoms and diagnosis of tuberculosis, and the social and economic level (SEL) according to the scale of the Ministry of plan in DR Congo, were also recorded.
Blood sample was drawn from each participant both in a dry tube and in an EDTA coated tube, and these tubes were transported in a cool box to the laboratories. The complete blood count was performed at the Monkole Hospital using the sample in the coated tube on a Sysmex XN-1000 PLC sysmex corporation japan Kobe 2012), within 6 hours after the collection, and following the manufacturer’s procedure. This PLC delivered the hemoglobin (Hb) level and hematocrit (Ht), white blood cell total and differential counts, platelets and red blood cell counts, as well as the reticulocyte count.
Conversely, the dry tube was centrifuged at 5000 rpm on a KOKUSAN H-36 centrifuge (Kokusan corporation japan Tokyo) and the plasma was collected and stored at −20˚C for the following analyzes: C-Reactive Protein (CRP, mg/l), albumin (µg/l), iron (g/dl), transferrin (mg/dl), creatinine (mg/dl), and HIV serology.
The dry tube was transferred upon collection to the University Hospitals of the University of Kinshasa (CUK) where serum iron was assayed by spectrophotometry as previously described [
The measurement of serum albumin was done at the CUK on a photometric colorimetric test based on the previously described principals [
The socioeconomic level was evaluated by scoring the assets in the household and the accommodation characteristics, and the classification was made based on the total score:
・ Low socioeconomic level, when the score is ≤ 5.
・ Average socioeconomic level, when the score is between 5 and 11.
・ High socioeconomic level, when the score is above 10 [
Undernutrition was defined as a BMI < 18.5 kg/m2 [
Anemia was defined as Hb > 13 g/dl for men or Hb < 12 g/dl for women [
- moderate between 8 - 12 g/dl (for women) and 8 - 13 g/dl (for men)
- severe below 8 g/dl
The microcytic Anemia was defined by a value of VGM < 80 μ3, the macrocytic anemia by a value of MCV > 100 μ3, and the hypochromic anemia by a value of MCHC less than 32% [
We used Microsoft Excel 2010 and SPSS version 21.0 to store and compute our data. Tables or graphics were used, as appropriate, for the presentation of results. Continuous quantitative variables with Gaussian distribution were expressed as mean ± standard deviation, whereas those with abnormal distribution were presented as median (extremes). Qualitative variables were described as relative frequency (%). Comparison of means or medians of two groups was made, as appropriate, using the Student t test or Mann Whitney U test. One-way ANOVA test was used to compare the means of more than 2 groups, the Pearson chi-square test or Fisher exact test was used to compare proportions. Factors associated with the blood count disorder were sought through logistic regression, odds ratio and 95% confidence intervals were shown. For all statistical tests the level of significance was p < 5%.
This study was conducted with the approval of the National Tuberculosis Program. Oral consent was obtained after oral explanation of the study aims and methods. The confidentiality was guaranteed by De-anonymizing data. The results were returned to those patients after appropriate counselling.
The general characteristics of the study population are summarized in
The mean age was 30.1 years for the 200 patients, and there were more males (65%) than females. Married and single represented respectively 34% and 58.5%. The vast majority of our patients (80%) received at least the secondary school education and 19% were pursuing their studies at the time of recruitment. However, 40% were unemployed. About 93% had a low socioeconomic level.
Regarding patient’s lifestyle and history, 29% were alcohol consumers while 27.5% were current smokers. Previous contact with TB patients was reported in 16% of cases and 6.5% had a positive HIV status. Half of patients were malnourished (51%) and the median duration of the disease since diagnostic was 4 weeks. About 58% of patients presented with hypoalbuminemia and the median CRP was 24 mg/dl.
With respect to the thresholds applied during this study, anemia was present in 139/200 subjects (69.5%). The characteristics of anemia are shown in details in
Serum transferrin assessed in 62 patients presenting with the lowest Hb values (≤5.8 to 10.6 gr/%) allowed the distinction of two groups: the first group had anemia associated with low or normal serum transferrin values (48.4%) whereas
Variables | N = 200 | % |
---|---|---|
Age, means ± SD, years | 30.1 ± 11.8 | |
Gender | ||
Male | 130 | 65.0 |
Female | 70 | 35.0 |
Profession | ||
Unemployed | 79 | 39.5 |
Independent | 64 | 32.0 |
Student | 38 | 19.0 |
Driver | 11 | 5.5 |
Stateworker | 8 | 4.0 |
Marital status | ||
Single | 117 | 58.5 |
Married | 68 | 34.0 |
Divorced | 9 | 4.5 |
Widow(ed) | 6 | 3.0 |
Education | ||
None | 2 | 1.0 |
Primary | 38 | 19.0 |
Secondary or higher | 160 | 80.0 |
SES | ||
Low | 185 | 92.5 |
Middle | 14 | 7.0 |
High | 1 | 0.5 |
Alcohol intake | 58 | 29.0 |
Tobacco | 55 | 27.5 |
Median disease duration (Q1-Q3), in weeks | 4 (3 - 6) | |
History of tuberculosis | 32 | 16.0 |
HIV status | 13 | 6.5 |
BMI, mean ± SD, (kg/m2) | 18.0 ± 2.4 | |
BMI < 18.5 | 102 | 51.0 |
BMI ≥ 18.5 | 98 | 49.0 |
Albumin | ||
Hypoalbuminemia | 115 | 57.5 |
Normal | 85 | 42.5 |
CRP | 24 (3.6 - 192) |
SES: socio-economic status; SD: standard deviation.
Variables | n | % |
---|---|---|
Severity | ||
Moderate | 131 | 92.2 |
Severe | 8 | 5.8 |
Central or peripheral | ||
Regenerative | 119 | 92.2 |
Non regenerative | 10 | 7.8 |
RBC mean volume and Hb concentration | ||
Hypochromic microcytic | 73 | 52.5 |
Hypochromic normocytic | 66 | 47.5 |
RBC: Red blood cells.
the second had anemia with high serum transferrin values (51.6%). Iron deficiency anemia suggested by a high serum transferrin is present in slightly more than 1 out of 2 patients.
Normal or low transferrin was significantly associated with inflammation expressed by CRP rate (p = 0.024) in the sub-cohort of 62 patients (
The cell count in white lineage was within the normal range in the vast majority of patients (80%), whereas hyperleukocytosis was observed in 11% and leukopenia in only 9% (
The platelet count was normal in 65.5% of cases, and thrombocytosis or thrombocytopenia was observed respectively in 25.5% and 8% of subjects (
Anemia was more frequent in the hypo-albuminemia context. Hypo-albuminemia was twice more associated with anemia than normo albuminemia (OR: 1.98; IC 95%: 1.02 - 3.82). The CRP was more elevated in patient with anemia (36.4 vs 24.4).
In this study, we prospectively recruited newly diagnosed PTB patients from treatment centers across Kinshasa and investigated their general characteristics, anemia as well as other hematologic changes. The mean age of patients was around 30 years and male patients were predominant in this study. Similar trend has been previously reported from the Sub-Saharan Africa sub-continent and elsewhere [
Transferrin | p | ||
---|---|---|---|
elevated (n = 30) | normal or low (n = 32) | ||
CRP, mean ± SE | 30.7 ± 5.0 | 50.2 ± 8.2 | 0.052 |
CRP grouped | 0.024 | ||
- ≤6 | 7 (87.5) | 1 (12.5) | |
- >6 | 23 (42.6) | 31 (57.4) | |
Creatinine, mean ± SE | 0.85 ± 0.04 | 0.91 ± 0.04 | 0.366 |
history of smoking and alcohol intake.
There is a surprising contrast between the higher number of patients with at least secondary education (80%) and the particularly high number of patients with low socio-economic situation (SES) (92.5%). The higher education rate is compatible with the urban setting where this study was conducted. In contrary, the lower SES overserved here supports the known correlation between TB and poverty [
Half of patients presented with BMI below 18.5 and hypoalbuminemia, which corresponds to undernutrition. Such observation is not a surprisingin TB patients given the anorexia, the TNF-α related cachexia and other factors. TNF-α is abundantly produced during the macrophage invasion of bacilli [
The 6.5% rate of TB-HIV/AIDS co-infection in this study is significantly lower than the 15% DRC average or 31 African average reported in the WHO Global report 2016 [
Anemia | Crude OR brut (IC 95%) | p | adjusted OR (IC 95%) | p | ||
---|---|---|---|---|---|---|
yes (n = 139) | no (n = 61) | |||||
Age, mean ± SE | 30.4 ± 0.9 | 29.5 ± 1.5 | 1.01 (0.98 - 1.03) | 0.617 | 1.00 (0.97 - 1.03) | 0.906 |
Gender | ||||||
- Female | 49 (70.0) | 21 (30.0) | 1.04 (0.55 - 1.95) | 0.91 | 1.45 (0.72 - 2.94) | 0.303 |
- Male | 90 (69.2) | 40 (30.8) | 1 | 1 | ||
Alcohol | ||||||
- yes | 47 (81.0) | 11 (19.0) | 2.32 (1.11 - 4.87) | 0.026 | 2.38 (1.05 - 5.38) | 0.037 |
- no | 92 (64.8) | 50 (35.2) | 1 | |||
HIV status | ||||||
- yes | 11 (84.6) | 2 (15.4) | 2.54 (0.55 - 11.80) | 0.236 | 2.26 (0.45 - 11.36) | 0.321 |
- no | 128 (68.4) | 59 (31.6) | 1 | 1 | ||
Hypoalbuminemia albuminemia | ||||||
- yes | 90 (78.3) | 25 (21.7) | 2.65 (1.43 - 4.91) | 0.002 | 1.98 (1.02 - 3.82) | 0.042 |
- no | 49 (57.6) | 36 (42.4) | 1 | 1 | ||
CRP, mean ± SE | 36.4 ± 2.7 | 24.4 ± 2.2 | 1.02 (1.01 - 1.04) | 0.007 | 1.02 (1.00 - 1.03) | 0.029 |
SE: Standard error.
disparity could result from differences in study design and setting. It has been abundantly proven that many TB-HIV patients present with smear-negative or extra pulmonary TB [
Anemia of any severity was observed in more than two-third of patients (69.5%) in the current study. This is rather a common finding during TB [
Although majority of our patients have normal leucocyte count (80%) and platelet count (65.5%), some variations were observed included leukocytosis (11%), leukopenia (9%), thrombocytosis (25.5%) and thrombocytopenia (8%). Depending of studies, important variations of leukocytes, including leukocytosis in 3% to 28.63% and leucopenia in 2.20% to 24% of patients, have been previously reported [
In univariate analysis, alcohol consumption, HIV infection, hypoalbuminemia and CRP showed a significant association with anemia in the study population. This association remained significant in multivariate analysis only for alcohol intake (OR: 2.38; IC 95%: 1.05 - 5.38), hypoalbuminemia (OR: 1.98; IC 95%: 1.02 - 3.82), with an inverse correlation for CRP rate. The link between alcohol consumption and TB was previously reported and could be attributed to the immunosuppressive role of alcohol [
This is the first comprehensive study of hematologic variation in TB in Kinshasa. However, these results need to be interpreted with caution due to study limits, mostly attributable to the design of the study and to the limited resourced setting. The first one is inherent to the cross-sectional nature of the study and the small size of the sample which cannot allow generalization of data to the all population of Kinshasa. The second is the lack of validated reference values for blood counts related to race and socio-economic environment and the use of WHO recommended standards in this area. The third limitation is related to the semi-quantitative assay of CRP, which can introduce bias due to the visual assessment by a single individual. Main strengths are the assessment of anemia characteristic at TB diagnosis which can influence therapeutic strategies by the national TB program. Further studies will use these values to address longitudinal studies involving more patients.
Mulenga, C.M., Kayembe, J.-M.N., Kabengele, B.O. and Bakebe, A. (2017) Anemia and Hematologic Characteristics in Newly Diagnosed Pulmonary Tuberculosis Patients at Diagnosis in Kinshasa. Journal of Tuberculosis Research, 5, 243-257. https://doi.org/10.4236/jtr.2017.54026