Abstract
Background
Tuberculosis (TB) has resurfaced as the leading cause of death by an infectious agent after the COVID-19 pandemic. The fight against TB needs to consider factors associated with mycobacterial reactivation and treatment of TB disease. Recent findings showed that Schistosoma mansoni co-infection leads to a Th2/Th1 profile that results in an immune modulation that favors the escape of the Mycobacteria. Schistosoma mansoni may contribute to tuberculosis (TB) incidence in endemic regions. We aimed to determine the co-infection rate and treatment outcomes.
Methods
A prospective cohort study was conducted between 2020 and 2022 at the University Clinical Research Center (UCRC). We included culture-confirmed pulmonary TB patients who were tested for Schistosoma mansoni in stools using Kato-Katz. S. mansoni co-infection was determined at baseline. Patients were classified into two -groups: TB/S. mansoni co-infected and TB-mono-infected. Univariable and multivariable logistic regression were performed to identify factors associated with the co-infection.
Results
We analyzed data from 174 tuberculosis-confirmed patients tested with Kato-Katz technique. Schistosoma mansoni co-infection among TB patients was 28.7%. The death rate was 18.0% in the co-infection group versus 5.6% in TB-mono-infected. Death was associated with bilateral lung opacities [aOR = 4.29 (2.98–18.74), p = 0.038]. TB/S. mansoni co-infection represented a high risk of death [aOR = 4.31 (1.17–15.90), p = 0.029]. However, HIV infection was not associated with death [aOR = 1.29 (0.18–9.20), p = 0.799].
Conclusions
Schistosoma mansoni co-infection was found in one-third of active TB patients, 2.5-fold higher than that of HIV. The co-infection was associated with death, and bilateral lung opacities were associated with a higher risk of death.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12879-026-12738-4.
Keywords: Tuberculosis, Schistosoma mansoni, Death, Associated factors, Mali
Background
Tuberculosis (TB) was the leading cause of death worldwide due to a single infectious agent before the COVID-19 pandemic. In 2022, 10.6 million people became ill with TB of whom 1.3 million (15%) died (~ 4384 per day) [1]. For the same year, TB killed more than HIV/AIDS by 2.5-fold (650,000) and malaria by 2.6-fold (619,000) [1, 2]. The new goals of the World Health Organization (WHO) to end TB are to reduce its mortality and incidence by 95% and 90%, respectively by 2035 [3].
Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis (Mtb) antigens without evidence of clinical manifestations of active TB. About one-third of the world’s population lives with TB bacteria [4, 5]. LTBI is controlled by a T-helper 1 (Th1) inflammatory reaction that results in formation of granulomas which inactivates the bacteria. It involves several immune cells such as macrophages, dendritic cells, lymphocytes, and cytokines, including interleukins (IL)-12, 17, 23, and interferon-gamma (INF-ɣ). Despite the granulomas being established, 5–10% of people with LTBI will reactivate to active TB during their lifetime. Despite improved diagnostic tools and treatment strategies, TB incidence remains high in low- and middle-income countries, particularly in Africa, Southern-East Asia, and the Western Pacific. Reactivation of TB bacteria can be caused by phenomena that induce immune depression such as malnutrition, HIV/AIDS, cancer, diabetes, smoking, alcohol, etc [4, 5]. HIV/AIDS is one of the main risk factors of LTBI reactivation, it increases the risk by 20 to 30-fold due to depletion of lymphocyte TCD4 + cells [6]. In Canada, smokers had a 1.8-fold increased risk of LTBI and a 2.3-fold risk of reactivation [7]. Recent studies brought immunological evidence that Schistosoma mansoni (S. mansoni) co-infection with LTBI promotes TB bacteria reactivation by modulating the type Th1 immune response. Unlike the type Th1 in LTBI, there is a proliferation of eosinophil cells and cytokines (IL-4, 5, 10,13)), and immunoglobulin E (IgE) [8]. The coexistence of the type Th2 immune response modulates the type Th1, thus, promoting the escape and multiplication of the bacilli towards active TB [9].
In Mali, two cross-sectional studies were included in a systematic review on schistosomiasis with a focus in Africa.The prevalence of S. mansoni was 17.3% in 2004 and 12.7% in 2011 [10]. In Tanzania, a study found a prevalence of 6.7% of S. mansoni coinfection among TB patients; 41.2% was reported in Kenya among TB/HIV-infected patients. A recent Systematic literature review found variation between 4 and 34% and the co-infection was found to be associated with low bacterial load at sputum microscopy and less cavities in chest radiography [11–13]. Schistosomiasis is a neglected tropical disease, Schistosoma mansoni is one of the 5 species that cause the disease. For many years, mass treatment has been implemented to eradicate the disease, but it continues to spread. In Mali, the co-infection TB/ S. mansoni has not been studied yet. The two studies reported the prevalence of S. mansoni infection among people living in rural areas, but not in TB patients. However, in Kenya, the co-infection rate was found to be relatively high in TB patients. The study was conducted in Kisumu County, located near the Lake Victoria. The study aimed to investigate if S. mansoni infection matters in TB in endemic areas. The prevalences of the co-infection reported in the systematic review show an increasing association in a context where actions are separately implemented to eliminate both (TB and schistosomiasis) infections that could be combined for a significant impact.
To achieve the WHO End TB goals, efforts must be placed on the identification and management of known and unknown risk factors of LTBI reactivation to reduce TB incidence and break transmission. Each potential risk factor must be considered in its epidemiological context. Schistosoma mansoni infection occurs through contact with stagnant water such as backwaters, or rice fields. Thus, this study aimed to investigate the co-infection of S. mansoni in active pulmonary TB patients in Mali, a country where many people are farmers, breeders, and fishers. Our hypothesis was that S. mansoni infection is high among TB patients with or without HIV infection and the coinfection is associated with poor TB treatment outcomes.
Methods
Study design and setting
This was a prospective cohort study over 30 months from January 1, 2021, to June 30, 2023 (2.5 years). The study was conducted at the University Clinical Research Center (UCRC) of the University of Sciences, Techniques and Technologies of Bamako (USTTB) in Mali. Patients were enrolled and followed in the 6 district TB Diagnostic and Treatment centers (DTC) of Bamako and the Department of Pneumophtisiology of the Hospital of Point-G. Bamako is the capital city of Mali, it has six (6) district hospitals, and each has a center for TB diagnostic and treatment with laboratory and clinic components. The DTC receives all TB-suspected patients referred by the different units of the hospital for tests. Once the diagnosis is established and drug-sensitive, the treatment is initiated and followed during the 6-month treatment course. We decided to enroll patients in all six DTCs for fast recruitment and the generalizability of the data.
Study population, inclusion, and exclusion criteria
All microscopy-positive pulmonary TB patients starting TB treatment were considered for this study. We included both male and female patients, aged 12 years or above, diagnosed with rifampicin-sensitive TB by GeneXpert/RIF® and confirmed by a positive Mycobacterial culture who were naïve to anti-TB drugs and permanent residents in Mali for > 5 years. Consent was obtained from patients ≥ 18 years and assent from participants between 12 and 17 years. We excluded patients with sputum cultures negative for Mycobacterium tuberculosis (Mtb) or positive for nontuberculous mycobacteria or rifampicin-resistant and/or multidrug-resistant tuberculosis. Patients under 12 years were excluded because of the difficulty of collecting sputum samples for TB confirmation. Following WHO TB guidelines adopted by the Malian national guidelines, Xpert MTB/RIF® test should be used to screen for TB in suspected patients, it has a good sensitivity between 95 and 99%. In this study, mycobacterial culture was used as the gold standard of TB confirmation. We only analyzed data of patients with baseline sputum culture positive for Mycobacterium tuberculosis.
Data and sample collection
Data were collected through a direct interview using a structured questionnaire built for the purpose of this study. It is administered sooner after the participants give consent for participation. At the day 0 (D0) visit, we collected socio-demographic parameters such as age, sex, profession, permanent residence, living near river; medical histories such as history of TB contact, HIV, diabetes, and cancer; clinical parameters such as symptoms, body mass index (BMI), blood pressure, and heart rate. Two sputum samples on 2 consecutive days (D0 and D1) and 5 mL blood sample were obtained. Chest X-ray results were collected, and findings were classified into unilateral infiltrate, bilateral infiltrate, and the presence of a cavity. All patients enrolled in this study underwent 6 months of TB treatment. They were monitored for 6 months to record outcomes. The TB treatment regimen used in Mali is 2 months of Rifampicin (R), Isoniazid (H), Pyrazinamide (Z), and Ethambutol (E) and 4 months of Rifampicin (R), Isoniazid (H) [2RHZE/4RH]. Treatment was monitored during the six-month for standard TB treatment period. The final microscopy test was assessed at M5 and M6 for treatment outcomes.
Sputum microscopy, mycobacterial culture and identification
The UCRC Biosafety Laboratory Level-3 (BSL-3) laboratory performed all the sputum tests for the study. The algorithm used at the UCRC BSL-3 for TB diagnosis begins with sputum smear microscopy using Auramine Rhodamine staining. The Xpert MTB/RIF® is used for the fast detection of Mycobacterium tuberculosis complex (MTBC) genome. Mycobacterial culture and identification of MTBC sub-species from non-tuberculosis. Microscopy was performed at D0 M5 and M6, and culture was done at baseline (D0). At each visit, 3–5 mL of sputum were collected and underwent the following procedures: decontamination, digestion, and centrifugation for concentration. The pellet was used for microscopy using Auramine /Rhodamine staining (BBL™ Becton Dickinson, Sparks MD, USA) and fluorescence microscope for reading the acid-fast bacillus (AFB). GeneXpert MTB/RIF® was performed to confirm the presence of Mycobacterium tuberculosis complex (MTBC) and determine rifampicin susceptibility. Mycobacteria culture was performed by inoculating both media, liquid Mycobacterium Growth Incubator Tube (MGIT), BD, USA, and solid (Middlebrook 7H11 agar and selective 7H11 agar). The Capilia test was used to identify MTBC strains from non-tuberculosis bacteria (NTM).
Blood HIV and glucose tests
Each patient was tested for Human Immunodeficiency Virus (HIV) at following the UCRC immunology Laboratory algorithm for HIV test. The screening was performed using a discriminatory rapid test The SDBioline® and patients with HIV-positive results were later confirmed by the Enzyme-Linked Immuno-Sorbent Assay (ELISA). A random blood glucose test was performed using Accu-Chek rapid test to screen for diabetes and all patients with blood glucose levels above 2.0 g per liter were retested the next day after 8 h of diet for confirmation. Diabetes is one of the 5 attributable risk factors for tuberculosis. Thus, a screening was done to assess its proportion.
Kato-Katz test for Schistosoma mansoni
One stool sample was obtained from each participant at D1 or during the first week of the recruitment. The Kato-Katz test is a qualitative and semi-quantitative technique, recommended by the WHO for areas where the prevalence of schistosomiasis is between 10 and 50% [14]. Stools were tested at the clinical laboratory of the Hospital of Point-G. The co-infection rate was only determined at the baseline visit.
Sample size calculation
To determine the proportion of S. mansoni infection in TB patients, the proportion method was used to calculate the sample size. We estimated the proportion (P) of TB/S. mansoni co-infection to be 12% [10], with a precision (I) of 5% at 95% confidence interval (CI). The following formula was used [Z² (95%z_score) x P x Q (1-P)/ (I)²]. Our minimum sample size was (n)= (1.96)² x 0.12 × 0.88/(0.05)² = 0.405673/0.0025 = 162.3; n = 162 patients. To test the hypothesis that TB/S. mansoni co-infection is associated with increased risk of death compared to TB-mono-infected patients. An appropriate sample size was calculated to perform the multivariable logistic regression. We assumed that the ratio (r) TB/S. mansoni co-infected over the TB-mono-infected individuals to be 2.5. The following formula was used: N2 = (Zα/2 + Zβ)². [P1* (1-P1) + P2* (1-P2) /r] (P1-P2)²; N2 = sample size of patients TB/S. mansoni co-infected; N1 = sample size of TB-mono-infected patients = r*N2; r: Ratio between TB-mono-infected and TB/S. mansoni co-infected patients; r= N1/N2 = 2.5. Z_α/2 = 1.96 (for 95% confidence interval); Z_β = 0.84 (for 80% power); P1: Proportion of deaths in TB-mono-infected patients was based on the national TB cohort death rate in 2021 = 7% [15]; P2: Proportion of death in TB patients co-infected with S. mansoni = 22%; N2 = 46.60 = 47 patients co-infected with S. mansoni; N1 = r * N2 = 2.5 * 47 = 118 patients mono-infected with TB. The total sample size was N = N1 + N2 = 47 + 118 = 165 patients.
Data analysis
The questionnaire used in this study was developed for this study [Supplementary file 1]. Data were entered into Excel 2013, cleaned, and analyzed by SPSS software version 25.0 for Windows. Continued values such as age, temperature, and BMI were categorized based on common classifications. The patients were classified as TB/S. mansoni co-infected and TB-mono-infected. Temperature values were categorized into normal (temperature below 37.6 °C), low-grade fever or Feverishness (temperature 37.6–38.0 °C), and fever for a temperature above 38.0 °C. We performed descriptive analyses and compared means for age and body mass index (BMI), the cut-off value for BMI was 18.5 kg/m². The normal value (BMI between 18.5 and 24.9 kg/m²) and Underweight (BMI < 18.5 kg/m²) [16]. A comparison was made between TB/S. mansoni coinfected and TB mono-infected patients using independent sample T-tests. Univariable and multivariable logistic regression analyses were performed for associations between TB/S. mansoni co-infection and sociodemographic and clinical characteristics of patients. The assumption of the model was to measure the association between TB/S. mansoni co-infection and every single co-variable of the patients to remove the confounding effects. TB treatment outcomes were divided into two groups. Patients were classified as cured (if the smear microscopy tests were negative at months 5 and 6) and as unfavorable treatment outcomes if the treatment failed (smear microscopy test was positive at month 5 or 6) or lost-to-follow-up (patient not seen at the treatment center at month 5 or 6) or death (occurred anytime during TB treatment). Death was also analyzed as an independent variable to check if the TB/S. mansoni coinfection was associated with a high risk of death. Any difference observed with a p-value < 5% at a 95% confidence interval (CI) was considered significant. Between groups heterogeneity of the sample was assessed using the non-parametric two-independent samples test of U de Mann-Whitney. We compared means of age between the TB/ S. mansoni co-infected and TB-mono-infected groups. The significance level was p = 0.594 which means we accept the null hypothesis that the means of age are identical between the two groups. The model’s fitness R-Square of Nagelkerke was 0.30 (30%) for multivariable logistic regression.
Results
Sociodemographic characteristics
In total, 302 patients suspected of pulmonary TB were included, 204 (67.5%) males and 98 (32.5%) females. Among them, 128 (42.4%) were excluded for culture negative for MTBC or positive for Non-Tuberculous Mycobacteria (NTM) and/or Kato-Katz test not performed and data from 174 (57.6%) patients were analyzed in this study (Fig. 1). Males were more predominant with 62.6% with a sex ratio of 1.7. The mean age was 34.9 ± 13.8 years with extremes of 14 and 76 years. The age groups [25–34] and [14–24] years were most represented with 32.8% and 25.9%, respectively. The most common occupations were housewives (27.0%) and laborers (19.5%). Bamako (39.1%), Mopti (12.6%), and Kayes (10.9%) were the most predominant cities of residence and 55.2% lived near a watercourse (Table 1).
Fig. 1.
Patients’ flow chart. SM= Schistosoma mansoni
Table 1.
Socio-demographic characteristics of the study patients
| Settings | Frequency | Percentage | |
|---|---|---|---|
| Age (Years) | 14–24 years old | 45 | 25.9 |
| 25–34 years old | 57 | 32.8 | |
| 35–44 | 32 | 18.4 | |
| 45 and over | 40 | 23.0 | |
| Mean of age (Years): 34.9 | Standard deviation: 13.8 | ||
| Gender | Female | 65 | 37.4 |
| Male | 109 | 62.6 | |
| Marital status | Married | 100 | 57.5 |
| Single | 74 | 42.5 | |
| Level of Education | No formal conventional education | 76 | 43.7 |
| Primary | 31 | 17.8 | |
| Secondary | 48 | 27.6 | |
| University | 19 | 10.9 | |
| Occupation | Civil servants | 31 | 17.8 |
| Housewives | 47 | 27.0 | |
| Students | 19 | 10.9 | |
| Trader | 27 | 15.5 | |
| Laborers | 34 | 19.5 | |
| Farmers/breeders | 11 | 06.3 | |
| Others | 5 | 02.9 | |
|
Permanent residence †Patient with other country origin (Burkina Faso, Guinea Conakry) |
Bamako | 68 | 39.1 |
| Kayes | 19 | 10.9 | |
| Koulikoro | 14 | 8.0 | |
| Sikasso | 10 | 5.7 | |
| Segou | 16 | 9.2 | |
| Mopti | 22 | 12.6 | |
| Toumbouctou | 9 | 5.2 | |
| Gao | 3 | 1.7 | |
| Kidal | 2 | 1.1 | |
| Other countries† | 4 | 2.3 | |
| Residence near a watercourse | No | 78 | 44.8 |
| Yes | 96 | 55.2 | |
Patients were relatively young, males, married, primary or lower than secondary education level, informal occupation, and living near a river
Patients’ clinical, bacteriological characteristics and chest X-ray findings
Smoking and alcohol consumption were found in 29.9% and 13.8% of cases, respectively. HIV co-infection was 11.5% and diabetes (6.3%). History of TB contact was found in 26.4%. Undernourishment (BMI < 18.5 kg/m2) was found in 55.7%. Low-grade fever (temperature 37.6–38.0 °C) was found in 17.2% and 7.5% had fever (> 38.0 °C). Lung lesions were bilateral in 51.1% and cavity in 41.2%. Most patients, 71.9%, had positive sputum with a high bacterial load of more than 10 bacilli/High Power field (HPF) on microscopy. S. mansoni co-infection rate was 28.7% (Table 2).
Table 2.
Clinical characteristics of the study patients
| Clinical and paraclinical parameters | Frequency | Percentage | |
|---|---|---|---|
| Current Tobacco Smoking | Yes | 52 | 29.9 |
| No | 122 | 70.1 | |
| Alcohol consumption | Yes | 24 | 13.8 |
| No | 150 | 86.2 | |
| Contact with a tuberculosis patient | Yes | 128 | 73.6 |
| No | 46 | 26.4 | |
| Comorbidities with TB | Diabetes | 11 | 06.3 |
| Sickle Cell Disease | 2 | 01.1 | |
| HIV | 20 | 11.5 | |
| Hypertension | 4 | 02.3 | |
| None | 137 | 78.7 | |
| Clinical symptoms | Cough | 174 | 100 |
| Dyspnea | 13 | 07.5 | |
| Chest Pain | 19 | 10.9 | |
| Hemoptysis | 6 | 3.4 | |
| Body temperature | Normal (≤ 37.5 °C) | 131 | 75.3 |
| Feverishness (37.6–38.0 °C) | 30 | 17.2 | |
| Fever (> 38.0 °C) | 13 | 7.5 | |
| BMI (Kg/m²) | Less than 18.5 | 97 | 55.7 |
| 18.5–24.5 | 72 | 41.4 | |
| 25 and over | 5 | 2.9 | |
| Lesions on Chest X-ray (n = 131) | Bilateral | 67 | 51.1 |
| Unilateral | 64 | 48.9 | |
| Cavity | 54 | 41.2 | |
| Not Performed | 43 | 24.7 | |
| Bacterial load at sputum microscopy (AFB) | Few (1–10 bacilli/ 100 HPF) | 7 | 4.0 |
| Moderate (1–10 bacilli/ HPF) | 39 | 22.4 | |
| High (> 10 bacilli/ HPF) | 125 | 71.9 | |
| Negative | 3 | 1.7 | |
| Proportion of Schistosoma mansoni co-infection | Positive | 50 | 28.7 |
| Negative | 124 | 71.3 | |
Smoking was found in 30%, HIV in 11.5%, undernourishment in 55.7%; 71.9% had a high sputum bacteria load, and 28.7% were co-infected with S. mansoni
Tuberculosis treatment outcomes and associated factors
The overall TB treatment success was 83.9%, the mortality was 09.2% (16 cases), including 18.0% (9/50) in the co-infected group and 5.6% (7/124) in the TB-mono-infection group. The cure rate was higher in the TB mono-infected group (75.3%) compared to the TB/S. mansoni co-infected group (24.7%). The mortality was higher in the TB/S. mansoni co-infected group (56.3%) than the TB mono-infected group (43.7%) (Table 3). The univariable analysis found that High education level was associated with low risk of death [OR = 0.20 (0.45–0.93), p = 0.030] but the coinfection was associated with high risk of death [OR = 3.67 (1.28–10.48), p = 0.018]. The multivariable logistic regression has identified that death was associated with bilateral lung opacities [aOR = 4.29 (2.98–18.74), p = 0.038]. TB/S. mansoni co-infection represented a high risk of death [aOR = 4.31 (1.17–15.90), p = 0.029]. However, HIV infection was not associated with death [aOR = 1.29 (0.18–9.20), p = 0.799] (Table 4).
Table 3.
The outcomes of patients followed during six (6) months of treatment
| Outcomes | S. mansoni | Total n (%) |
||
|---|---|---|---|---|
| Negative n (%) |
Positive n (%) |
|||
| Anti-tuberculosis Treatment | Cured | 110 (75.3) | 36 (24.7) | 146 |
| Failure | 4 (57.1) | 3 (42.9) | 7 | |
| Lost-to-follow-up | 3 (60.0) | 2 (40.0) | 5 | |
| Death | 7 (43.8) | 9 (56.2) | 16 | |
| Total | 124 | 50 | 174 | |
The treatment success rate was higher in TB mono-infected group (75.3%) versus TB/S mansoni co-infected patients (24.7%). The mortality was higher in TB/S. mansoni 9/16 (56.2%) coinfection versus TB mono-infected 7/16 (43.8%). Five patients were lost-to-follow-up, 2 were TB/S. mansoni co-infected and 3 in the S. mansoni negative group
Table 4.
Univariable and multivariable logistic regression for factors associated with death
| Parameters | Death | Odds Ratio (OR) OR (95% IC), P-Value |
Adjusted Odds Ratio (AOR) AOR (95% IC), P-Value |
||
|---|---|---|---|---|---|
| Yes | No | ||||
| Age (Years) | Age < 35 | 8 | 94 | 0.68 (0.24–1.91), p = 0.596 | 0.42 (0.10–1.73), p = 0.231 |
| Age ≥ 35 | 8 | 64 | |||
| Sex | Male | 7 | 103 | 0.42 (0.15-1,18), p = 0,10 | 0.60 (0.13–2.75), p = 0.515 |
| Female | 9 | 55 | |||
| Marital Status | Married | 13 | 87 | 3.53 (0.97–12.89), p = 0.062 | - |
| Single | 3 | 71 | |||
| Education level | ≥ 10 years | 2 | 65 | 0.20 (0.45–0.93), p = 0.030* | 0.12 (0.01–1.2), p = 0.07 |
| < 10 years | 14 | 93 | |||
| TB contact person | Yes | 4 | 42 | 0.9 (0.28–3.01), p = 1,0 | - |
| No | 12 | 116 | |||
| Smoking | Smoker | 3 | 49 | 0.51 (0.14–1.88), p = 0,39 | 0.28 (0.03–3.07), p = 0.296 |
| Non-smoker | 13 | 116 | |||
| Alcohol consumption | Yes | 2 | 22 | 0.88 (0.19–4.16), p = 1.0 | 1.47 (0.07–31.17), p = 0,803 |
| No | 14 | 136 | |||
| HIV Infection | Positive | 3 | 17 | 1.91 (0.49–7.40), p = 0.40 | 1.29 (0.18–9.20), p = 0.799 |
| Negative | 13 | 141 | |||
| Living near a water course | Yes | 5 | 91 | 0.34 (0.11-1.0), p = 0.063 | - |
| No | 11 | 67 | |||
| Body temperature | Fever | 4 | 39 | 1.0 (0.31–3.31), p = 1.0 | - |
| Normal | 12 | 118 | |||
| Mody Mass Index (Kg/m²) | Low BMI < 18.5 | 10 | 89 | 1.27 (0.44–3.68), p = 0.79 | 1.16 (0.29–4.67), p = 0.836 |
| Normal BMI ≥ 18.5 | 6 | 68 | |||
| Lung Opacities (n = 131) | Bilateral | 9 | 58 | 3.16 (0.81–12.23), p = 0.13 | 4,29 (2.98–18.74), p = 0.038* |
| Unilateral | 3 | 61 | |||
| Lung Excavations (n = 131) | Absence | 5 | 49 | 1.02 (0.31–3.40), p = 1.0 | - |
| Presence | 7 | 70 | |||
| Grade of smear microscopy | Positive < 3+ | 6 | 43 | 0.62 (0.21–1.82), p = 0.39 | 0.88 (0.20–3.85), p = 0.864 |
| Positive at 3+ | 10 | 115 | |||
| S. mansoni Co-infection | Yes | 9 | 41 | 3.67(1.28–10.48), p = 0.018* | 4.31 (1.17–15.90), p = 0.029* |
| No | 7 | 117 | |||
Death was associated bilateral lung opacities and TB/S. mansoni co-infection
Discussion
Socio-demographic characteristics of tuberculosis patients
Males represented more than half with 62.6% of our study sample. The predominance of males in active TB patients has been consistently reported by WHO and many studies [1, 17–20]. The mean age was 34.9 ± 13.8 years and 62.7% were < 35 years. In the African region and most high-burden countries in the world, most of the TB cases are diagnosed among young populations [1]. In Mali, a study on TB in rural community settings found 79.2% of males [21]. In Côte d’Ivoire, 70% of TB patients were under 35 years with a mean of 31 years [22]. In the Central African Republic, where TB incidence reached 540/100,000 people, the mean age was 35.7 years and more than half were < 35 years [23]. Occupations exposed to inhaled particles and promiscuity increase the risk of acquiring TB infection [24]. This study found a predominance of housewives, laborers, civil servants, and traders. In Mali and most TB endemic countries, TB treatment is provided on an outpatient basis. Most of the patients in this study were permanent residents of four administrative regions including Bamako (39.1%), Mopti (12.6%), Kayes (10.9%), and Ségou (9.2%), all located in the south alongside the two main rivers in Mali named Niger and Senegal. The Niger crosses the country over 1750 km, 42% of its total length, bathing Bamako, Koulikoro, Segou, Mopti, Timbuktu, Gao, and Ansongo [25]. In this study, 55.2% of patients were living near a watercourse. These rivers serve fishing, rice cultivation, vegetable growing, and household work. In Mali, people in rural areas live in precarious hygiene due to poor socio-economic conditions. In 2020, the sanitation access rate was 39% [26]. A community-based TB study found that farmers and housewives were the most dominant occupations with 58.3% and 20.8%, respectively [21].
Clinical and bacteriological characteristics
In this study, our patients were characterized by undernourishment in more than half, smokers represented nearly one-third, and HIV infection was 11.5%. Chest X-rays found unilateral versus bilateral localization of TB bacteria in the lungs were similar (51.1% vs. 48.9%) with and cavities were present on less than half of them. In Mali, the national TB/HIV co-infection rate was 8% in 2021 [15]. Two studies reported similar proportions of diabetes among TB patients, 5.5% in 2019 and 5.2% in 2020 [27, 28]. In Senegal, smoking was found in 21.6% [29], and the HIV/TB co-infection was 13.1% [20]. In Congo Brazzaville, a study reported HIV/TB co-infection in 37.7%, smoking in 9.33%, and undernourishment 22.3%; chest X-ray showed bilateral lesions in 30% and cavity in 57% [30]. The differences between HIV coinfection among TB patients may be due to the national prevalence of HIV in the country and its testing rate among active TB patients.
Co-infection of tuberculosis and Schistosoma mansoni
In this study, 55.2% of patients live near a watercourse, which can increase the risk of schistosomiasis infection. In 2021, the incidence of TB was 52 per 100,000 people in Mali [1]. The TB/S. mansoni coinfection rate in this study is included in the range reported in a literature review that TB and S. mansoni co-infection vary between 4% and 34% depending on the prevalence in the country [13]. Considering S. mansoni infection as a TB reactivation risk factor, it stands at the 3rd rank after undernourishment and smoking. According to WHO, undernourishment ranks first place followed by smoking, HIV, alcoholism, and diabetes. The order in this study was undernourishment, smoking, S. mansoni infection, alcoholism, HIV, and diabetes. This proportion was higher than the traditional known risk factors of HIV, diabetes, and alcohol consumption [1]. The proportion of HIV infection in this study sample was 11.5% and that of S. mansoni was 28.7%, which is 2.5 times higher than that of HIV. The bivariate analysis did not observe any significant association between TB+/ S. mansoni co-infection and the socio-demographic, clinical, and radiological parameters. The multivariate logistic regression showed a significant association between the co-infection and the absence of cavities on chest X-ray. This observation of fewer cavities has been found in the Tanzanian study [11]. The sensitivity of the Kato-Katz depends on the density of eggs in the sample, repeated sample testing, and the prevalence of the parasite. In Ivory Coast, a study collected samples in 3 different areas and found a varying sensitivity between 47.1 and 70.2% for 1-sample to 90.7–95.2 for 4-samples [31].
Treatment outcomes
The overall treatment success rate was 83.9%. The cure rate was better in the TB mono-infected group (75.37%) compared to S. mansoni co-infected TB group (24.7%). This may be due to increasing drug side effects caused by the intestinal parasites as the clinical manifestations of the infection include abdominal pain, nausea, and vomiting. The overall death rate was 09.2% (16 cases), with 9 patients in the TB/ S. mansoni co-infected group (56.2%), and 7 in TB mono-infected patients (43.8%). There is a statistically significant association between TB/S. mansoni co-infection and death (p = 0.018). The mortality in this study was slightly higher than the 7% of the national TB cohort in 2021 [15]. During follow-up, 5 patients were lost to follow-up, including 3 in the TB/S. mansoni positive group and 2 in the S. mansoni negative. The reason for missing their visits for the 5 participants was that they had to travel to their home city before the end of the treatment.
Limitations: Our study shows a high S. mansoni co-infection rate among active TB patients and the level of factors associated with it. Despite the homogeneity of the two groups, the low sample size in the S. mansoni co-infected group limits the interpretation of the data.
Conclusions
S. mansoni co-infection was 28.7%, 2.47-folds higher than HIV (11.5%). The TB/S. mansoni co-infection was associated with less excavation on chest X-rays, unfavorable treatment, and death. Despite the low sensitivity of the Kato-Katz technique for a single sample, this study shows evidence that S. mansoni infection may play a role as a risk factor in LTBI reactivation to active TB.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
The authors to M. Soumaila Traore, Mme Oumou Niare, and Dr. Yeya dit Sadio Sarro for their contributions to the conduct of the study and the writing of the manuscript.
Author contributions
BB, BD, DKD, AS, SD, MM, AM, YT and RLM made concept of the study. BB, AM, DS, KO, TK and DG collected data & samples. BD, DKD, FGT, DK, MS and AM did the laboratory tests. BB, BD, DKD, AS, MM wrote the first draft of the manuscript. SD, SD, MM, YT, DS, KO, TK, RLM, DK, and AM made critical edits. All the authors approved the last version of the manuscript for publication.
Funding
Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number U54EB027049 and the Fogarty International Center of the National Institutes of Health under award number Building the Next Generation of Researchers in TB/HIV Diagnostics in Mali (B-NextGen) Mali, D43TW010350. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Data availability
All the data collected and included in this manuscript are available under the UCRC data repository.
Declarations
Ethics approval and consent to participate
The study was approved by the Ethics Committee of the University of Sciences, Techniques and Technologies of Bamako in Mali referenced Nº2020/22/CE/FMOS/FAPH dated February 06, 2020. Written informed consent was obtained from all the participants and from the legal guardians of the participants who were below 16 years of age. Samples were deidentified by assigning a unique protocol number. Patients with HIV and/or S. mansoni co-infection received appropriate management.
Consent for publication
All authors consented to the publication.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Supplementary Materials
Data Availability Statement
All the data collected and included in this manuscript are available under the UCRC data repository.