Research Article: Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin
Research Article: Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin
Research Article: Characteristics and Treatment Outcomes of Retreatment Tuberculosis Patients in Benin
Research Article
Characteristics and Treatment Outcomes of
Retreatment Tuberculosis Patients in Benin
Serge Ade,1,2,3 Omer Adjibod,1 Prudence Wachinou,1
Narcisse Toundoh,1 Brnice Awanou,1 Gildas Agodokpessi,1 Dissou Affolabi,1
Gabriel Ad,1 Anthony D. Harries,3,4 and Sverin Anagonou1
1
1. Introduction
Patients with retreatment tuberculosis (TB) represent those
who have been treated previously for one month or more with
anti-TB drugs and who have been diagnosed once again with
the disease. These patients mainly include relapses, treatment
after failure, or loss to follow-up on a first-line treatment
regimen [1]. The number of these patients is not negligible.
In 2014, of the 6.3 million TB cases that were notified
by National TB Programmes (NTPs) to the World Health
Organization (WHO), approximately 700,000 patients were
already previously treated [2].
Interest in this category of TB comes from the fact that
patients are known to have a higher risk of drug resistance
compared with new cases. Therefore, in addition to recommendations that all TB patients be screened for Human
Immunodeficiency Virus (HIV) coinfection, NTPs have been
advised since 2010 by WHO to systematically test at diagnosis
all retreatment TB patients for culture and drug susceptibility
(DST with genotypic and/or phenotypical methods), in order
to detect resistance to rifampicin which is usually synonymous with multidrug resistance (MDR, strictly defined as
resistance of Mycobacterium tuberculosis to both rifampicin
and isoniazid) [3, 4]. Unfortunately, there is concern about
implementation of this recommendation as only 58% of all
retreatment TB patients in the world were tested for drug
resistance in 2014 [2]. Improving this proportion in the future
requires an analysis of the situation at country levels.
2
In Benin, a sub-Saharan country that reports approximately 40 incident TB cases per 100,000 people per year,
retreatment patients account for less than 10% of all notified
TB cases. Unfortunately, there is dearth of information
on the epidemiological characteristics and HIV status of
these patients in annual reports in the country [5]. Two
previous studies, which were only conducted in Cotonou,
the economic capital, and which had included retreatment
patients diagnosed in the periods of 19922001 and 2005
2009, respectively, reported a high loss to follow-up of 12%,
with a treatment success of retreatment cases significantly
lower than new cases. Moreover, the majority of these patients
recorded as loss to follow-up during the retreatment initially had also defaulted from their first-line treatment [6, 7].
DST in retreatment cases was also only performed in early
2003 in those patients registered in Cotonou that also houses
the Laboratoire de Reference des Mycobacteries (LRM).
The current study was therefore undertaken in the whole
country to determine the principal characteristics of retreatment patients, to assess how well DST was performed in
this category of patients and whether there was any change
in their treatment outcomes. Specific objectives were to
determine among retreatment TB patients diagnosed and
treated in 2013 in Benin: (i) the epidemiological, clinical and
geographical characteristics and HIV status of these patients
and compared to those registered with New Pulmonary
Bacteriologically Confirmed TB (NPBCT); (ii) the proportion with DST results available along with the proportion
showing resistance to rifampicin; (iii) treatment outcomes of
these patients compared with NPBCT cases; and (iv) factors
associated with a successful treatment outcome.
Table 1: New category of patients and treatment outcomes recommended by the WHO [1].
Definitions
Category of TB patients
New pulmonary bacteriologically confirmed patients
Previously treated patients
Relapse patients
Treatment after failure patients
Treatment after loss to follow-up patients
Other previously treated patients
Patients with unknown previous TB treatment history
Patients never treated for TB (or treated for less than 1 month) and whose
sputum is positive by smear microscopy, culture, or WHO-approved Rapid
Diagnostic (such as Xpert MTB/RIF)
Patients have received 1 month or more of anti-TB drugs in the past
Patients have previously been treated for TB, were declared cured or treatment
completed at the end of their most recent course of treatment, and are now
diagnosed with a recurrent episode of TB
Patients have previously been treated for TB and failed treatment during or at
the end of their most recent treatment course
Patients have previously been treated for TB and were declared lost to
follow-up during or at the end of their most recent course of treatment
Patients have previously been treated for TB but their outcome after their
most recent course of treatment is unknown or undocumented
Patients do not fit into any of the categories listed above
Treatment outcomes
Cured
Treatment completed
Treatment failed
Died
Loss to follow-up
Not evaluated
Treatment success
3. Results
In 2013, 241 retreatment TB patients were diagnosed and
treated in Benin on the basis of a positive result for acidfast bacilli using sputum smear microscopy. They represented
6% of the 3957 total TB cases notified in the country in
the same time-period. Demographic characteristics and HIV
status of these patients were compared to those reported from
NPBCT and are shown in Table 2. There were significantly
more males ( = 0.04), patients from the AtlantiqueLittoral ( = 0.006), patients aged between 45 and 64
years ( = 0.007), and HIV-positive patients ( = 0.04)
among retreatment TB cases compared to NPBCT patients.
On the other hand, patients younger than 24 years were
Table 2: Demographic characteristics and HIV status of new pulmonary bacteriologically confirmed and retreatment tuberculosis
patients, Benin, 2013.
NPBCT
3129
Total
Sex
Male
2063 (65.9)
Female
1066 (34.1)
Age (years)
0024
600 (19.2)
2544
1705 (54.5)
4564
676 (21.6)
65 and above
148 (4.7)
Region
Atacora-Donga
199 (6.4)
Borgou-Alibori
231 (7.4)
Zou-Collines
416 (13.3)
Mono-Couffo
486 (15.5)
Oueme-Plateau
708 (22.6)
Atlantique-Littoral 1089 (34.8)
HIV status
HIV positive
396 (13.5 )
HIV negative
Unknown
Retreatment TB
241
value
175 (72)
67 (28)
0.04
0.04
21 (8.7)
136 (56.6)
70 (28.9)
14 (5.8)
0.00005
0.55
0.007
0.43
14 (5.8)
13 (5.4)
33 (13.7)
29 (12)
47 (19.5)
105 (43.6)
0.72
0.24
0.86
0.14
0.26
0.006
43 (18.2 )
193 (82)
5 (2.4)
0.04
Of the 236 retreatment tuberculosis patients who underwent the HIV test,
43 were found positive.
4. Discussion
The main findings of this study were the predominance of
males, adults aged between 45 and 64 years, and HIV-positive
status among retreatment TB cases compared with NPBCT
patients. Most of these previously treated TB patients were
reported from Atlantique-Littoral where there were also
predominately relapse cases. The large majority of patients
who were reported from Oueme-Plateau were recorded as
lost to follow-up prior to treatment, which is a department
close to Atlantique-Littoral in the southern part of the
Table 3: Demographic characteristics and HIV status of the different types of retreatment tuberculosis patients, Benin, 2013.
Total
Sex
Male
Female
Age (years)
0024
2544
4564
65 and +
Regions
Atacora-Donga
Borgou-Alibori
Zou-Collines
Mono-Couffo
Oueme-Plateau
Atlantique-Littoral
HIV status
HIV positive
HIV negative
Unknown
Relapse
147
Failure
78
value
102 (69.4)
45 (30.6)
56 (71.8)
22 (28.2)
16 (100)
0.03
0.03
10 (6.8)
86 (58.5)
42 (28.6)
9 (6.1)
10 (12.8)
42 (53.8)
22 (28.2)
4 (5.1)
1 (6.3)
8 (50)
6 (37.5)
1 (6.3)
0.29
0.69
0.74
8 (5.4)
7 (4.8)
16 (10.9)
16 (10.9)
27 (18.4)
73 (49.7)
6 (7.7)
6 (7.7)
16 (20.5)
12 (15.4)
10 (12.8)
28 (35.9)
0
0
1 (6.3)
1 (6.3)
10 (62.5)
4 (25)
0.09
0.46
0.00002
0.04
27 (18.4)
116 (78.9)
4 (2.7)
14 (17.9)
63 (80.8)
1 (1.3)
2 (12.5)
14 (87.5)
0
0.84
0.70
Table 4: Retreatment tuberculosis patients, drug susceptibility testing achieved, and bacilli sensitivity to rifampicin, Benin, 2013.
Total retreatment TB patients
Patients whose specimens were sent to the LRM for DST tests ()
MTB identification after culture and or Xpert MTB/RIF
Xpert (+) Culture (+) ()
Xpert (+) Culture () ()
Xpert () Culture (+) ()
Resistance to rifampicin ()
241
171 (71)
163 (95)
86 (50)
72 (42)
5 (3)
17 (10)
Note: TB: tuberculosis; LRM: Laboratoire de References des Mycobacteries; DST: drug susceptibility testing.
The percentage was derived from the total tuberculosis patients retreated.
The percentage was derived from the total tuberculosis patients whose sputa were sent and analysed in LRM.
Of the 17 patients with resistance to rifampicin, there were 9 multidrug resistant and 8 monoresistant.
Table 5: Treatment outcomes of new pulmonary bacteriologically confirmed and retreatment tuberculosis patients, Benin, 2013.
Total
Successful outcome
Cure
Completion
Unsuccessful outcome
Failure
Death
Loss to follow-up
Not evaluated
NPBCT
3124
2803 (89.7)
2587 (82.8)
216 (6.9)
321 (10.3)
91 (2.9)
170 (5.4)
45 (1.4)
15 (0.5)
Retreatment TB
224m
208 (92.9)
184 (82.1)
24 (10.7)
16 (7.1)
3 (1.3)
9 (4)
3 (1.3)
1 (0.4)
Of the 3129 new smear positive TB patients treated, treatment outcomes were assessed for 3124 patients in 2013.
m
Of the 241 retreatment tuberculosis patients treated, 18 were found multidrug resistant and did not continue the retreatment regimen.
value
0.12
0.79
0.03
0.13
0.16
0.37
0.83
0.72
Sex
Female
Male
Age group
0024
2544
4564
65 and +
Type of TB
NPBCT
Relapse
Failure
Treatment after loss to follow-up
HIV status
HIV negative
HIV positive
HIV status unknown
Region
Atacora-Donga
Borgou-Alibori
Zou-Collines
Mono-Couffo
Oueme-Plateau
Atlantique-Littoral
Successful outcome
Risk ratio
[95% CI]
value
60/62 (97.8)
148/162 (91.4)
1
0.94
0.881.01
0.24
19/19 (100)
117/124 (94.4)
60/67 (89.6)
12/14 (85.7)
1
0.94
0.90
0.86
0.900.99
0.830.97
0.691.06
0.59
0.34
0.17
2803/3124 (89.7)
133/140 (95)
63/69 (91.3)
12/15 (80)
1
1.06
1.02
0.89
1.021.10
0.951.10
0.691.15
0.04
0.67
0.19
169/181 (93.4)
38/39 (97)
1/4 (25)
1
1.04
0.27
0.981.11
0.051.46
0.47
0.001
13/14 (92.9)
9/11 (81.8)
28/30 (93.3)
27/28 (96.4)
40/42 (95.2)
91/99 (91.9)
1.01
0.89
1.02
1.05
1.04
1
0.861.18
0.671.10
0.911.14
0.961.15
0.951.13
1
0.26
1
0.68
0.72
5. Conclusion
In 2013, the proportion of retreatment TB patients tested for
culture and DST in Benin was 71%. Although the treatment
success of these patients was encouraging, there is room for
improvement. There is a need to increase the proportion of
patients having the last follow-up sputum examination and
to understand why one of the regions of the country has a
sizeable number of patients recorded as lost to follow-up.
Ethical Approval
The study was approved by the Benin NTP Coordination
and the Ethics Advisory Group of the International Union
against Tuberculosis and Lung Disease, Paris. Because of
its retrospective nature, approval from the national ethics
committee Comite National dEthique pour la Recherche en
Sante was not required according to the countrys recommendations.
Competing Interests
All authors declared no competing interests.
Acknowledgments
The authors thank all workers in the 57 health facilities
involved in tuberculosis management in the country for
their daily hard work. The authors also thank The Union for
technical and financial support in this study. S. Ade is partly
supported as a Union Operational Research Fellow.
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