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PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 Tuberculosis treatment outcomes in patients with resistant
tuberculosis at a district hospital in Kwazulu-Natal Province of
South Africa
Ntambwe Malangu1 and Modinat O. Ibrahim2
Abstract
This study purported to investigate factors associated with treatment outcomes among MDR-
TB and XDR-TB patients treated at Greytown hospital. This was a cross-sectional study
based on a review of medical records of patients that have been treated at Greytown hospital
for drug resistant tuberculosis from January 2011 to December 2012. A data collection form
designed for the study was used. The data that was collated included socio-demographic
variables, clinical data including details of treatment given and adverse effects as well as
outcomes of treatment. Descriptive and inferential statistics were calculated. Overall, 127
records were found that met the inclusion criteria for this study during the study period. The
mean age of patients was 36.9±11.9 years, ranging from 12 to 82 years. Based on the median
age of 34 years, 54.3% were over 34 years old. The majority of patients were females
(56.7%), unemployed (89.8%) and the marital status of (78.7%) patients was not recorded
in the files. Overall, 55.1% were females aged 34 years and older. The majority of patients
suffered from pulmonary tuberculosis; only 3 cases (2.4%) were extra-pulmonary, while 72
(56.7%) suffered from multi-drug resistant tuberculosis (MDR-TB), and 55 (43.3%) had
extended drug-resistant tuberculosis (XDR-TB). They took their treatment fairly well as
about 70% of them adhered to treatment. Overall, the outcomes of treatment success was
poor as only 29.9% had completed the treatment and confirmed cured, while 18.1% had died.
In addition to being unemployed, clinical factors associated with being cured were namely,
taking the treatment for the correct duration and adhering to treatment. On the contrary,
failing to take the treatment correctly was associated with death. In conclusion, the treatment
success among patients with resistant tuberculosis was 29.9%. Adherence to treatment for
the correct duration of treatment was significantly associated with the success of treatment.
Key words: tuberculosis, resistant, treatment outcomes, risk factors
1 School of Public Health, Sefako Magkatho Health Sciences University, email: [email protected] 2 School of Public Health, Sefako Magkatho Health Sciences University, email: [email protected] PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 Background
Resistant tuberculosis (TB) is a worldwide problem. It is known that over 90 countries have
reported cases of multi-drug resistant tuberculosis (MDR-TB). In Sub-Saharan Africa, it is
now considered as a serious challenge due to the fact that it is strongly associated with
HIV/AIDS pandemic (Zignol et al, 2006; Bantubani et al, 2014). An estimated 1.1 million
(13%) of the 8.6 million people who developed TB in 2012 were HIV-positive. In 2012, an
estimated 450 000 people developed MDR-TB and there were 170 000 deaths from MDR-
TB (WHO, 2013). South Africa ranks as the third highest country in the world in terms of
TB incidence and the one with the highest number of MDR-TB and extended drug-resistant
tuberculosis (XDR-TB) in the African region (Bantubani et al, 2014; WHO, 2013). Though
several cases of resistant-TB have been reported throughout South Africa, the highest
prevalence of MDR-TB and XDR-TB has been recorded in Kwazulu Natal province,
especially Umzinyathi and Umkhanyakude districts (Gandhi et al., 2006; Wallengreen et al,
2011). This explains why a specialized unit for treating MDR-TB was established at
Greytown hospital.
Some studies have reported that MDR- TB patients were not effectively treated and this has contributed to the rise in the number of XDR-TB (Holtz et al, 2006; Mlambo et al,
2008). Between 2009 and 2010, the number of cases of XDR-TB diagnosed in South Africa
by the National Health Laboratory Services increased from 594 to 741; while the treatment
success rate has been reported to be below 50%, with a default rate of 30% (Shean et al,
2008; Shah et al, 2011; NDoH, 2011). These negative statistics necessitate the evaluation of
possible related factors. The association between the treatment outcomes and factors relating
to the patients circumstances and clinical status needs to be assessed in order to identify areas
to be targeted with interventions in order to improve the outcomes of treatment in patients
with MDR and XDR-TB. Hence, this study purported to investigate factors associated with
treatment outcomes among MDR-TB and XDR-TB patients treated at Greytown hospital. It
is hoped that the findings from the study could be used by clinicians, decision-makers, and
institutional managers to design and implement relevant interventions.

Methods
Study design and setting
This cross-sectional study based on a review of patients' medical records was conducted at
Greytown Hospital. This is a district hospital located in the south of the Kwazulu-Natal
province of South Africa. This province is one of the most affected by the double epidemic
of tuberculosis and HIV. The study was conducted by reviewing the records of patients
treated at this facility from first November 2013 to the end of January 2014. Data were
collected using a data collection form designed for the study. The data collated included
socio-demographic variables, clinical data including details of treatment given, adverse
effects, as well as outcomes of treatment.
PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 Population
The study population comprised of medical records of TB patients registered as MDR and
XDR cases in the TB register at Greytown Hospital. Records of all patients that were treated
at the health care facility during the study period, from January 2011 to December 2012, were
included in this study irrespective of age and sex.
Ethical considerations
Ethics approval for the study was obtained from the Medunsa Research Ethics Committee.
Permission to conduct, retrieve, and access patients' records was obtained from institutional
managers.
Data analysis
Data were double captured into a Microsoft Excel spreadsheet and imported into STATA 10
for data analysis. Descriptive and inferential statistics were calculated. For the comparison
of categorical variables, cross-tabulation was performed in order to assess the association
between variables; the Pearson's chi-square test was calculated to determine the statistical
significance of relationships between variables. The level of statistical significance was set
at <0.05 (Somekh and Lewin, 2005).

Results
Sociodemographic profile of patients
The mean age of patients was 36.9±11.9 years, ranging from 12 to 82 years. Based on the
median age of 34 years, 54.3% (69 cases) were over 34 years old. The majority of patients
were females (56.7%), unemployed (89.8%), and the marital status of (78.7%) patients was
not recorded in the files. Overall, 55.1% were females and aged 34 years and older (Table 1).
Table 1: Socio-demographic characteristics of patients
Variables
Frequency
Sex
Age category
34 years and older Employment status
Marital status
PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 Clinical profile of patients
The majority of patients suffered from pulmonary tuberculosis; only 3 cases (2.4%) were
extra-pulmonary; two of the three cases affected lymph nodes, and one case affected the
spine. Based on the reports on drug sensitivity testing, 72 (56.7%) patients in the sample had
MDR tuberculosis; while 55 (43.3%) had XDR tuberculosis. Although not statistically
significant, XDR-TB affected more females than males (62.3% versus 37.7%, p=0.13); more
patients aged 34 years old and older than the younger ones (56.4% versus 43.6%, p=0.69);
slightly more of those unemployed than those with employment (90.9% versus 9.1%,
p=0.81).
The majority of patients (91.7%) were co-infected with HIV; few patients suffered also from diabetes (3.7%), hypertension (3.7%) and alcohol abuse (0.9%) as co-morbidities. In addition, some of these patients were obese. The percentage of patients who were obese increased from 11.8% at the start of the treatment to 18.9% some months later after the treatment. Table 2 presents types of documented common adverse drugs reactions. The results indicate that adverse effects of drugs prescribed were documented in 61(48.4%) patients; among them, 32 (52.5%) patients had MDR-TB; the remaining suffered from XDR-TB. The most common ADR documented were vomiting, anemia and peripheral neuropathy. Of the ADRs documented, the majority (71.7%) was graded as not serious or mild; 13.3% were of moderate severity; while 15% were severe. Table 2: Adverse drug reactions documented
Adverse effects
Frequency
Peripheral Neuropathy Psychiatric conditions PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 There was no statistically significant difference with regard to severity based on the types of TB; ADR of moderate severity were documented almost equally in both groups (12.5% in MDR-TB versus 14.3% in XDR-TB, p=0.75). Of the 9 severe ADRs, 7 (5.5%) led to hospitalisation, 2 (1.6%) to some disability and 2 (1.6%) to treatment interruption in patients affected. Other reasons for treatment interruption were loss to follow-up (4 cases), poor adherence (3 cases), planned interruption (1 case), treatment failure (1 case), and death (1 case). The initial regimen for tuberculosis treatment was prescribed to 97.7% (124 cases) of patients. The MDR-TB regimen was made of kanamycin, ethionamide, ofloxacin, pyrazinamide, cycloserine or ethambutol. The standard regimen containing ethambutol was used in 69 cases (54.3%). Up to the time of data collection, some 53.5% of MDR-TB patients had received treatment for 6 months, 32.3% for 18 months. Before being transferred, XDR-TB patients were prescribed a regimen made of moxifloxacin, terizidone, pyrazinamide, ethionamide, and para-aminosalicylic acid (PAS). About 69.3% and 72.2% of patients achieved at least an 80% adherence with regard to the initial and MDR regimens respectively. Overall, in 12 patients' records (9.4%), it was recorded that these patients had been taking unspecified traditional medicines. Outcomes of treatment
Overall, the treatment success was 29.9% as 28.3% and 1.6% of patients respectively were
confirmed cured and had completed the treatment. However, the cure status was not known
of about half of the patients because they were either transferred out (33.1%) or undetermined
(15.7%) as they were still on treatment. Of those who defaulted, only 3 cases were traced
(3.2%), and one case was confirmed as a failed treatment (Table 3).
The reason for transferring patients was that they had XDR-TB, therefore, they
needed to be attended by a specialist facility. A case fatality of 18.1% was reported; the two
recorded causes of death were tuberculosis in 17 cases (13.4%) and co-morbid conditions in
6 cases (4.7%).
Table 3: Outcomes of treatment
Outcomes of treatment
Frequency
PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 With regard to factors associated with being cured, most of the clinical factors that were assesses were actually associated (Table 4). The factors significantly associated with being cured were not having interrupted treatment; taking the initial regimen for 6 months and the MDR regimen for 18 months, as well as achieving at least 80% adherence to both regimens. It is interesting to note that MDR-TB patients were more likely to be cured than those who suffered from XDR-TB. The only sociodemographic variable assessed that was significantly associated with being cured was being unemployed. Patients who were unemployed were about five times more likely to be cured than those who were employed (p=0.01). Table 4: Factors associated with being cured

OR (95% CI)
Over 34 years old versus younger 1.19 (0.55, 2.62) Females versus males 1.09 (0.49, 2.43) Not married versus others 1.93 (0.68, 6.23) Unemployed versus employed 4.75 (1.45, 15.88) MDR patients versus XDR patients 49.62 (7.44, 2052.81) Taking the initial treatment for 6 months versus not 5.2 (1.93, 15.39) Taking the MDR-TB treatment regimen for 18 months versus not 68.00 (7.32, 2954.47) Achieving at least 80% adherence to initial treatment versus not 4.76 (1.48, 19.91) Achieving at least 80% adherence to MDR-TB treatment regimen versus not 27.00 (3.30, 1184.96) Did not used Traditional medicines versus used 2.10 (0.41, 20.59) Did not interrupted versus those who interrupted 248.2 (30.84, 1994.00) ADR documented versus not 1.03 (0.43, 2.41) Suffered ADRs of mild severity versus those who suffered from severe ADRs 4.17 (0.84, 20.73)
Moreover, with regard to factors associated with dying, numerically the majority of
patients who died were younger than 34 years old and unemployed who suffered from MDR-
TB. However, upon assessment of factors significantly associated with dying, the factors so
associated were having suffered from severe ADRs, failing to take the initial regimen for 6
months and the MDR-TB regimen for 18 months as well as failing to achieve at least 80%
adherence to both regimens. Interestingly, having suffered from ADRs or having taken
traditional medicines did not show any association with dying in this study. Similarly, all
sociodemographic variables assessed were not significantly associated with dying. However,
it was found that 21 out 23 patients (91.3%) who died were also co-infected with HIV (Table
5).
PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014
Table 5: Factors associated with death among patients

OR (95%CI)
Patients younger than 34 years old versus older 2.17 (0.86, 5.47) Males versus females 1.28(0.46, 3.49) Married versus unmarried 2.69 (0.98, 7.38) Employed versus unemployed 2.90 (0.36, 23.51) Those who interrupted versus those who did not 2.5 (0.49, 10.45) Those who suffered severe ADRs versus those with mild ADRs 4.15 (1.06, 16.21) Did not take initial treatment for 6 months versus those who did 5.53 (1.77, 20.30) Did not take MDR treatment for 18 months versus those who did 160.00 (13.00, 688.68) Did not achieve 80% adherence to initial treatment versus who did 3.90 (1.4, 11.13) Did not achieve 80% adherence to MDR treatment versus who did 144 (13.08, 6267.99) Used traditional medicines versus who did not 0.89(0.09, 4.68)
Discussion
The findings from this study showed that the majority of patients who suffered from resistant tuberculosis at Greytown hospital were females and over 34 years old. The background of these patients could be described as disadvantageous as many of them were unemployed. This profile is similar to reports by Porwal and co-workers (2013) who found that more than a third of MDR-TB and XDR-TB patients were also female and from disadvantaged communities. Clinically, these patients suffered from some co-morbid conditions, of which, the most common was HIV. This finding concurs with several reports that have indicated that the HIV pandemic has exacerbated the incidence of tuberculosis (Shean et al, 2008; Otwombe et al, 2013). As reported in other settings, this study found also that the majority of patients were affected by adverse drug reactions of mild severity. Although the adherence rate was relatively high in comparison to reports from other settings, the outcomes of treatment were poor (Shean et al, 2013; Brust et al, 2013; O'Donnell et al, 2013). The overall cure rate was 28.3% while the case fatality rate was 18.1%. In these respects, the findings from this study concur with reports by other investigators who reported poor cure rates and high mortality in patients with resistant tuberculosis (Satti et al, 2012; O'Donnell et al, 2013). The success of treatment from this study setting is far less better as compared to what has been reported in Gauteng Province where it was about 49% (Marais et PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 al, 2014). Given the overall low cure rate, it seems that preventing the onset of MDR-TB and XDR-TB is a more effective strategy; hence, it is necessary that the national and provincial health care facilities should adopt new technologies for identifying resistance early. Moreover, drug regulatory authorities should ensure a mechanism for a quick phasing-in of new drugs that can help curtail the onset of drug resistance (Zumla et al, 2013). Among the factors associated with treatment outcomes, it is interesting to note that being unemployed appeared to be associated with being cured. This finding suggests that unemployed people adhered more to their treatment may be because they could stay in the hospital and be cared for than those in employment who may have left the hospital to go back to their workplaces. In addition to being unemployed, clinical factors were associated with being cured were namely, taking the treatment for the correct duration and adhering to treatment. On the contrary, failing to take the treatment correctly was associated with death. The findings of this study contrast with reports from Western Cape Province of South Africa, where it was reported that loss to follow-up and age, particularly older age was associated poor treatment outcomes (Moyo et al, 2015). Hence, healthcare providers and policy-makers should create an enabling environment so that patients who are in full employment can adhere to treatment. Hence, people that are employed who have been diagnosed with resistant tuberculosis should be given extended medical leave beyond the current 6 months applicable to all workers. This is because the findings from this study have shown that taking the initial regimen for 6 months and the MDR regimen for 18 months was associated with being cured. Moreover, the findings that most patients transferred had been having XDR-TB suggest the need for the establishment of more specialised facilities within the province of KwaZulu-Natal. This finding underscores the influence of health care system in outcomes of treatment (Loveday et al, 2014). With regards to mortality, the influence of co-morbidities, namely, HIV could be noted as more than 90% of patients who died were co-infected with this condition. It is possible also that HIV could be one of the factors that led to resistance in the first instance. This phenomenon has been explained considering the possibility that HIV may lead to malabsorption of TB drugs and acquired rifampicin resistance (Wells et al, 2007). The finding from this study concurs with reports by Satti and co-workers (2012) who reported that 70% of patients with MDR-TB were HIV-positive. Schnippel and co-investigators (2015) have reported from a large cohort study that, indeed, people with HIV, whether on treatment or not are at least more likely to die from resistant tuberculosis than those who are HIV-negative. Other co-morbidities were diabetes and obesity among others. Diabetes has been reported as a common co-morbidity associated with drug-resistant TB by other investigators (Hsu et al, 2013; Magee et al, 2013). In other settings, the presence of co-morbidities has been documented to be associated with negative outcomes. Baker and co- PULA: Botswana Journal of African Studies Vol. 28, No. 1, 2014 workers (2011) pointed out that diabetes is associated with an increased risk of treatment failure and death during tuberculosis treatment. With regard to adverse drug reactions (ADRs), this study has shown that although they were common; their impact was limited; none of them resulted in death but less than 10% led to hospitalisation and treatment interruption. These findings contrast with reports from other settings where ADRs have been associated with negative outcomes (Shin et al, 2007; Bezu et al, 2014; Scheelbeek et al, 2014; Huang et al, 2015). However, the distribution of ADRs in this study was similar to what has been reported by other investigators who noted that nausea, vomiting, diarrhea and other GIT symptoms were the most common ADRs (Shean et al, 2008; Shean et al, 2013; Zala et al, 2015). As limitations, this study was based on the review of records; hence inherent design limitations such as the incompleteness of data were noted. For instance, data on marital status
could not be found in several records. Secondly, as a cross-sectional study, causal links could
not be established due to the lack of temporal connection.

Conclusions
In conclusion, resistant tuberculosis affected mainly people of disadvantageous backgrounds
who were unemployed. The treatment success among patients with resistant tuberculosis was
29.9%. The outcomes of treatment were poor with low cure rate and a relatively high
mortality. Adherence to treatment for the correct duration of treatment was significantly
associated with the success of treatment.
Authors' contributions
NM and MIO conceptualized the study, MIO collected data; NM performed the analysis;
NP drafted the paper. All authors contributed intellectual inputs and approved the paper.
Acknowledgements
The institutional managers at the study site are hereby acknowledged for the immense support
during data collection.
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