Predictors of therapy failure in newly diagnosed pulmonary tuberculosis cases in Beira, Mozambique
Pizzol et al. BMC Res Notes
Predictors of therapy failure in newly diagnosed pulmonary tuberculosis cases in Beira, Mozambique
Damiano Pizzol 3
Nicola Veronese 2
Claudia Marotta 1
Francesco Di Gennaro 0 6
Jorge Moiane 5
Kajal Chhaganlal 5
Laura Monno 0
Giovanni Putoto 4
Walter Mazzucco 1
Annalisa Saracino 0
0 Department of Infectious Diseases, University of Bari “Aldo Moro” , P.zza G Cesare 3, Bari , Italy
1 Department of Science for Health Promotion and Mother to Child Care “G. D'Alessandro”, University of Palermo , via del Vespro, 133, Palermo , Italy
2 Department of Medicine (DIMED)-Geriatrics Section, University of Padova , Padua , Italy
3 Research Unit , Doctors with Africa-CUAMM, Beira , Mozambique
4 Research Section , Doctors with Africa CUAMM, Padua , Italy
5 Faculty of Health Sciences, Catholic University of Mozambique, Center for Research in Infectious Diseases , Beira , Mozambique
6 Doctors with Africa-CUAMM , Padua , Italy
Objective: Tuberculosis (TB) remains a major global health issue, ranking in the top ten causes of death worldwide. A deep understanding of factors influencing poor treatment outcomes may allow the development of additional treatment strategies, focused on the most vulnerable groups. Aims of the study were: (i) to evaluate the treatment outcome among TB subjects followed in an outpatient setting and (ii) to analyze factors associated with treatment failure in newly diagnosed patients with pulmonary TB in Beira, the second largest city of Mozambique. Results: A total of 301 TB adult patients (32.6% females) were enrolled. Among them, 62 (20.6%) experienced a treatment failure over a 6 months follow-up. On multivariate model, being males (O.R. = 1.73; 95% CI 1.28-2.15), absence of education (O.R. = 1.85; 95% CI 1.02-2.95), monthly income under 50 dollars (O.R. = 1.74; 95% CI 1.24-2.21) and being employed (O.R. = 1.57; 95% CI 1.21-1.70), low body mass index values (O.R. = 1.42; 95% CI 1.18-1.72) and HIV status (O.R. = 1.42; 95% CI 1.10-1.78) increased the likelihood of therapy failure over 6 months of follow-up. In this study, patients who need more medical attention were young males, malnourished, with low income and low educational degree and HIV positive. These subjects were more likely to fail therapy.
Tuberculosis; Mozambique; Therapy failure
Tuberculosis (TB) remains a major global health issue,
ranking in the top ten causes of death worldwide [
2015, 10.4 million people were estimated as newly
diagnosed with TB and 1.8 million deaths were registered
], not equally distributed all over the world.
Particularly, over 90% of global TB cases and deaths
occurs in low and middle income countries, and
especially in fragile states [
]. Moreover, despite effective
anti-tuberculosis chemotherapy, case-fatality rates of up
to 25% are described in both industrialized and
resourcepoor settings [
Mozambique is ranked 19th among the 22 TB High
Burden Countries in the world, with an estimated TB
incidence rate of 551/100.000 population in 2015 [
However, TB treatment covers only 38% of the
population, and an increasing rate of TB–HIV co-infection
is usually documented (49% of TB patients were
]. In Mozambique, the treatment success rate
among new sputum smear-positive cases has increased
from 76% in 2003–79% in 2007 and 87% in 2015 [
In this African Country, among the many challenges
dealing with TB control, both ensuring proper TB
diagnosis and treatment as well as implementing the one-stop
model for TB care have been regarded as national
] Worryingly, recent data from Manhiça, a district
located in southern Mozambique, show an alarming
mortality rate among TB adult cases co-infected with HIV
]. The potential threat of increasing multi-drug
resistance (MDR) cases in the country—the latest national
survey documented a MDR incidence of about 3.5% among
new TB cases—could jeopardize the achievement of the
treatment success targets set in the strategic plan 2014–
2018 of the National TB Control Programme (NCTP) [
A deep comprehension of factors influencing poor
treatment outcome may allow the development of
additional treatment strategies, focusing on the most
vulnerable groups. Unfortunately, very few data are available
addressing this issue, particularly in Mozambique. In
general, predictors for unsuccessful treatment are
considered socio-demographic, behavioral, disease-related
and treatment-related factors [
]. In Mozambique, only
one study conducted in the country highlighted
factors associated with a higher risk of death during the TB
treatment: HIV status, being male and lack of
laboratory confirmation [
]. For these reasons, the aims of our
study were (i) to evaluate the treatment outcomes among
TB subjects followed in an outpatient setting and (ii) to
analyze factors associated with treatment failure in newly
diagnosed cases with pulmonary TB in Beira, the second
largest city of Mozambique.
Study population and design
An observational study was implemented.
All cases of pulmonary TB diagnosed between
January and August 2016 were recruited in this observational
study from three urban outpatient health-care centers of
Beira district, namely Ponta-Gea, Munhava and
Macurungo, the largest in Sofala’s Province, involved in the
National Tuberculosis Control Programme (NCTP).
Inclusion criteria were to be a subject aged ≥ 18 years,
having a confirmed TB diagnosis (positive sputum smear
result, GeneXpert positive result, culture positive result
or Positive chest X-ray) [
] and able to undergo anti-TB
treatment, not having any anti-TB treatment or TB
treatment started within the previous 2 months.
Anti-TB treatment was prescribed according to the
Mozambique National Tuberculosis and Leprosy
Control Programme guidelines [
]. So, when GeneXpert
was negative for resistances, patients underwent an
initial phase of therapy with Isoniazid, Rifampin,
Pyrazinamide and Ethambutol lasting the first 2 months and then
a continuation phase with Isoniazid and Rifampin for
the next fourth months. While, when GeneXpert
documented a resistance to Rifampin a second line therapy
At the end of therapy every patient underwent a
general visit, X-rays and/or sputum smear, and diabetes
A face-to-face interview conducted by a trained nurse
encompassed questions about demographic
characteristics (age, residence, education, occupation, marital
status, monthly income), pregnancy, behaviours (sexual
behaviour, concurrent sex partners, condom use, smoke
and alcohol abuse, etc.) and medical history, including
TB and diabetes symptoms. A basic physical examination
(vital signs, weight, height, waist circumference, blood
pressure and general appearance) was performed. The
body mass index (BMI) was calculated. Moreover,
subjects with unknown HIV status received a pre-HIV test
or a rapid HIV test, if not done before.
Each participant, during two consecutive clinic visits,
underwent two fasting blood glucose tests to investigate
on diabetes: according to WHO guidelines, patients were
considered as non-diabetic if both measurements were
≤ 110 mg/dl, and as diabetic if both measurement were
above 126 mg/dl. If at least one value was between 110
and 126 mg/dl, the Oral Glucose Tolerance Test (OGTT)
was further performed: patients were considered
diabetic when plasma glucose at 2 h was ≥ 200 mg/dl [
TB-diabetic patients underwent assessment of diabetic
Treatment outcomes were defined according to WHO
]. Successful treatment outcome was defined
as a clinical and radiological improvement in a patient
with a baseline smear positivity and evidence of at least
two negative sputum smears, the first during the
maintenance period, and the second as the treatment was
completed. Treatment failure was defined as the detection of
positive sputum smear in a patient at month 5 or later of
Data were reported as mean and standard deviations for
continuous variables. Absolute and relative frequencies
(percentages) were used for categorical variables.
Independent T-test was used to compare groups for
continuous variables, whilst a Chi square test (with the
Fisher’s correction if less than 5 cases were present in a
cell) was applied for categorical variables.
A logistic regression model was implemented as
follows. Treatment failure was considered as
dependent variable and each one of the available factors at the
baseline evaluation as independent variables (univariate
analysis). In the multivariate analysis all the factors with
a p-value < 0.10 at the univariate analyses were included.
Multicollinearity among covariates was assessed through
the variance inflation factor (VIF), taking a value of 2 for
excluding a covariate. However, no variable was excluded
according to the previous criterion.
Odds Ratios (ORs) as adjusted Odds Ratios (Adj–ORs)
with their 95% confidence intervals (CIs) were used to
measure the association between factors at the baseline
(exposure) and treatment failure (outcome).
All statistical tests were two-tailed and statistical
significance was assumed for a p-value < 0.05. Analyses were
performed by using the SPSS 21.0 for Windows (SPSS
Inc., Chicago, Illinois).
A total of 301 TB adult patients (32.6% females) were
enrolled in the study (Table 1), distributed among
the three outpatient health-care centers as follow:
132 (43.8%) Ponta-Gea, 63 (20.9%) Munhava and 106
(35.2%) Macurungo. The whole sample had a mean age
of 31 years (S.D.: 12.5). Nearly half of the participants
(48.2%) reported to have no education, 187 (62.0%)
participants were employed and only 83 (27.6%) had a
monthly income higher than 50 dollars.
With regard to participants’ lifestyle and behaviour
information, 25 participants (8.3%) reported to be
current smokers and 38 (12.6%) daily drinkers. The majority
of the participants reported to have one sexual partner,
whereas only 7 (4.7%) reported to have more than one,
and the remaining part (36.5%) had no partner.
According to medical history and examination, 56.0%
of participants presented a BMI (< 18.5) below the
healthy range, whereas arterial hypertension was found
just in only 1 patient (0.3%).
The HIV status was known to be positive in 131
patients (43.5%) and 93 (70.9%) of them were receiving
antiretroviral treatment (ART). Furthermore, diabetes
or impaired glucose tolerance (IGT) was diagnosed in 9
TB was diagnosed by a positive chest X-ray
examination in 148 patients (49.2%); 246 patients (81.7%) had a
positive sputum examination and 56 patients (18.6%) a
positive GeneXpert sputum test.
The most reported symptoms before the initiation of
treatment were cough (98.3%), loss of weight (86.7%),
asthenia (71.4%), night sweats (67.1%) and fever (57.8%).
A total of 62 patients (20.6%) experienced a treatment
failure over a 6-month follow-up.
No difference was documented between patients
experiencing treatment failure or success as regards
age (p-value: 0.84) and gender (p-value: 0.25). On the
contrary, employed subjects (93.1%; p-value < 0.0001),
with no education (71.7%; p-value < 0.0001) and with a
monthly income < 50 dollars (77.5%; p-value < 0.0001)
were more frequent in the success group, whereas daily
alcohol users (55.3%; p-value < 0.0001) and current
smokers (77.5%; p-value < 0.0001) exceeded in failure
The multivariate model considered the effects of
gender, BMI, education, alcohol use, being employed,
monthly income, smoking habits, HIV status, being
on ART, sputum examination and GeneXpert
positivity. Significant predictors of therapy failure over
6 months of follow-up are reported in Table 2: male sex
(O.R. = 1.73; 95% CI 1.28–2.15), absence of education
(O.R. = 1.85; 95% CI 1.02–2.95), monthly income under
50 dollars (O.R. = 1.74; 95% CI 1.24–2.21) and being
employed (O.R. = 1.57; 95% CI 1.21–1.70), low BMI
values (O.R. = 1.42; 95% CI 1.18–1.72) and HIV status
(O.R. = 1.42; 95% CI 1.10–1.78).
Very few data are available about the outcome of TB
treatment in high burden countries, leaving a lack of
important evidences for the implementation of future
public health and clinical strategies. In our sample of
patients referring to the three urban health centers of the
Beira District, a percentage of 20% of patients
experiencing a treatment failure over a 6 months follow-up was
In the present study these unsuccessful treatment
outcomes were found to be associated with a low education
level, low income and low BMI (< 18.5), resulting as the
most relevant predictors of therapy failure from the
In fact, in our sample nearly half of patients had no
educational degree and almost 70% had a monthly
income lower than 50 dollars, defining a low
socioeconomic status. This patients’ profile, according to the
], is more likely to have less awareness of
health issues, reduced access to health services, low
selfcare attention, resulting in delays in the TB diagnosis and
treatment. Also, patients with low education level will be
more likely to misuse and discontinue drug use during
Similarly more then half of our patients presented a
BMI below the healthy range, and it is well known that
malnutrition is associated with an increased risk of
mortality and relapse of active TB, whereas the use of
macronutrient supplementation during treatment with weight
gain at 2 months may result in improvement in physical
function, sputum conversion and treatment completion
In agreement with current literature, in our study, an
association of poor TB treatment outcome with HIV
infection was found [
]. HIV co-infection is the most
important risk factor for developing active TB, which
increases susceptibility to primary infection, re-infection
and/or reactivation of latent TB. TB also has a negative
impact on the immune response to HIV, increasing the
progression from HIV infection to acquired
immunodeficiency syndrome (AIDS) .
The risk of poor treatment outcome in that
particular subpopulation is higher. Hence, a particular
attention should be destined for HIV/TB-co-infected patients
whose TB treatment is burdened by frequency of drug
administration, pill burden, drug interactions, drug
toxicity and worse general health conditions, [
Instead, we did not find additional risk factors for
TB treatment default such as smoking and alcohol use
], probably because our data could be underreported
because they were not verified and were based on
This study has some limitations. First, no sufficient data
on MDR or XDR, no data on check at 2 month from start
therapy and delay in diagnosis. This points, together with
a deeper exploration of the role of comorbidities, such
as diabetes [
] should influence future research on this
field. On the contrary strengths are the high number of
patients and the data from country where there are few
notice about treatment outcome.
We describe the phenotype of patients that need more
medical attention: young, male, malnourished, with low
income and low educational degree, HIV positive. They
have more possibility to failure therapy and they need
close follow up. Counseling and education on TB is
always recommended in this more vulnerable patients
These considerations suggest that a drug approach is
not enough to treat tuberculosis and further policies will
have to take into account a multidisciplinary approach
including education and social equity. Moreover, it is
crucial to create a simple and effectiveness monitoring
system, allowing a national overview also on multi-drug
resistance and delay in diagnosis, in order to obtain
complete and quality data to guide public health actions.
In conclusion, this study underlines that only
pharmacological approach isn’t longer sufficient to guarantee a
reduction of TB burden. Social determinants of health
have a crucial role, and more work, more instruction,
in other words less poverty, HIV educational associated
with pharmacological approach and early diagnosis can
real improve TB patients outcomes and global TB
burden. We believe that this is the way forward.
TB: tuberculosis; WHO: World Health Organization; OR: odds ratio; BMI: body
mass index; HIV: human immunodeficiency virus; MDR: multi-drug
resistance; NCTP: National Tuberculosis Control Programme; OGTT: Oral Glucose
Tolerance Test; VIF: variance inflaction factor; Adj–ORs: adjusted odds ratios;
ART: antiretroviral treatment; IGT: impaired glucose tolerance; SDH: social
determinants of health.
All individuals listed as authors have contributed substantially to designing,
performing or reporting the study and every specific contribution is indicated
as follows. Conception and design of the study: DP FDG KC JM GP AS LM. Data
collection: KC FDG DP. Statistical analysis: NV JM. Interpretation of data: DP NV
CM FDG WM. Manuscript writing and drafting: DP FDG CM NV. Revision of the
manuscript: DP, NV, CM, FDG, CG, GP, LM, WM, AS. Approval of the final version
of the manuscript: DP, NV, CM, FDG, CG, KG, JM, GP, LM, WM, AS. The document
has been reviewed and corrected by a native English speaker with extensive
scientific editorial experience to ensure a high level of spelling, grammar and
punctuation. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Availability of data and materials
The data that supports the findings of this study are available on demand
from the authors upon reasonable request and with permission of Doctors
with Africa CUAMM.
Consent to publish
No individual consent for publication was required as all the analyses were
made on aggregated data.
Ethics approval and consent to participate
The study was approved by the Comité Nacional de Bioetica para a Saúde—
National Bioethics Committee for Health (protocol reference: 168/CNBS/15),
Mozambique. An informed consent was administered to all the enrolled
patients. Confidentiality was maintained keeping all the data in anonymity.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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