EVALUATION OF THE TUBERCULOSIS SPECIMEN REFERAL SYSTEM

PERFORMANCE IN THE SOUTH WESTERN TB ZONE OF UGANDA

BY

BYABAJUNGU HENRY

2009/HD17/16778U

A RESEARCH DISSERTATION SUBMITTED TO THE COLLEGE OF VETERINARY

MEDICINE, ANIMAL RESOURCES AND BIOSECURITY IN PARTIAL FULFILMENT
FOR THE REQUIREMENTS FOR THE AWARD OF A MASTERS DEGREE IN
BIOMEDICAL LABORATORY SCIENCES AND MANAGEMENT OF MAKERERE
UNIVERSITY

NOVEMBER 2016
DECLARATION
I, Mr. Byabajungu Henry do declare that all the content of the work presented in this dissertation

is my original effort and has never been submitted to any institution of higher learning or

university.

…………………………………… ………………………………

Signiture Date

This work has been submitted with the verification and authorization of my supervisors:

1. .………………………………… …………….......................
Signature Date
Dr. Freddie Bwanga
M.B.Ch.B, M. Med, Ph.D.
Senior Lecturer, Department of Medical Microbiology
Makerere University College of Health Sciences

2. ………..………………… …………….......................
Signature Date
Dr. Moses Joloba
M.B.Ch.B, MS, Ph.D.
Dean, School of Biomedical Sciences,
Makerere University College of Health Sciences

i
 ABSTRACT
Background: Multidrug resistant tuberculosis (MDR-TB) stands at 12.5% in Uganda among the
retreatment TB cases. In an effort to accelerate the WHO-recommended MDR-TB diagnosis and
surveillance, the Uganda NTLP in 2008 initiated the Tuberculosis Specimen Referral System
(TSRS). Under the TSRS, sputum is collected from smear positive retreatment TB cases at the
peripheral health facilities and sent via the post office to the National TB Reference Laboratory
(NTRL) - the only public TB culture facility in Uganda. The aim of this study was to evaluate
the performance of the TSRS during the year 2010. Methods: This was a cross sectional study
carried out in the South West TB zone of Uganda. Onsite visits were made to the health facilities
participating in the TSRS to: i. review laboratory records on proportion of eligible specimens
referred, ii. interview health workers on reasons for failure to refer samples, and whether the
results were received and/or used for patient care. Results: Out of the 239 eligible smear positive
sputum from retreatment TB cases, 135 (57%) were referred to the NTRL. Of the135 samples,
106 (79%) result reports were issued by the NTRL and verified as dispatched to the health
facilities but the health facilities received only 71 (52%) of the dispatched reports. Of the 71
reports, 38 (54%) were verified as actually discussed with the patients for care, 23 (32%) were
never discussed with the patients and for the remaining 10 (14%) reports found on patient files,
the respondents were not certain of their status. The two major factors for failure to refer the
samples were insufficient health workers understanding of the TSRS attributed to high staff
turnover/transfers, and delayed transport refund reported by 59% of the respondents.
Conclusion: Almost half of the eligible sputum samples from the retreatment TB cases in the
South Western TB zone were never refered to the NTRL for culture and sensitivity testing. Out
of the 135 referred sputum samples, only 38 (28%) results were actually used for patient care,
raising questions on the actual utility of the TSRS under the current health care settings.
Insufficient understanding of the TSRS by health workers and delayed transport refund hindered
the sample referrals. Recommendations: The NTRL should conduct periodic health workers
training on the sample referrals. Countries contemplating initiation of similar TB specimen
referral systems should consider newer faster systems for refund of the transport costs and
improve on documentations.

TABLE OF CONTENTS

ii
DECLARATION...................................................................................................................................i
ABSTRACT........................................................................................................................................ii
TABLE OF CONTENTS......................................................................................................................iii
LIST OF TABLES..............................................................................................................................iiv
LIST OF FIGURES...............................................................................................................................v
LIST OF ABBREVIATIONS.................................................................................................................vi
1.0 CHAPTER ONE: INTRODUCTION.................................................................................................1
1.1 Background.......................................................................................................................1
1.2 Problem statement...........................................................................................................3
1.3 Research questions...........................................................................................................3
1.4 Objectives of the study.....................................................................................................4
1.5 Justification.......................................................................................................................4
2.0 CHAPTER TWO: LITERATURE REVIEW........................................................................................5
3.0 CHAPTER THREE: MATERIALS AND METHODS..........................................................................8
3.1 Study design......................................................................................................................8
3.2 Study site and setting........................................................................................................8
3.3 Study Population...............................................................................................................9
3.4 Sample size determination...............................................................................................9
3.5 Sampling technique...........................................................................................................9
3.6 Inclusion criteria................................................................................................................9
3.7 Exclusion criteria...............................................................................................................9
3.8 Methodological details......................................................................................................9
4.0 CHAPTER FOUR: RESULTS........................................................................................................13
5.0 CHAPTER FIVE: DISCUSSION....................................................................................................18
6.0 CHAPTER SIX: CONCLUSION.....................................................................................................23
7.0 CHAPTER SEVEN: RECOMMENDATIONS..................................................................................24
8.0 REFERFENCES...........................................................................................................................25
APPENDICES...................................................................................................................................28

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 LIST OF TABLES
Table 1: District performance in the TSRS in the South Western TB zone
Table2: Grouped proportion of samples refered to the NTRL
Table 3: Table showing proportions of sputum samples per district referred to the NTRL
Table 4: Grouped proportion of result reports received at the health facilities

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LIST OF FIGURES
Figure 1: Map of Uganda showing the location of the South Western TB zone ( in red)
Figure 2: Flow chart demonstrating the methodological details
Figure 3: Proportion of factors that hindered the TSRS

v
LIST OF ABBREVIATIONS
CB-DOTS: Community Based Directly Observed Therapy with Short course chemotherapy
CDC: Centres for Disease Control and Prevention
DALYs: Disability-adjusted life years
DST: Drug Susceptibility Testing
FIND: Foundations for Innovative and New Diagnostics
JCRC: Joint Clinical Research Centre
IRB: Institutional Review Board
LTFU: Loss To Follow Up
MDR TB: Multidrug resistant Tuberculosis
ml: Milliliters
NTLP: National Tuberculosis and Leprosy Programme
NTM: Non Tuberculosis Mycobacteria
NTRL: National Tuberculosis Reference Laboratory
PNFP: Private Not For Profit
TAT: Turn around time
TB: Tuberculosis
TSRS: Tuberculosis Specimen Referral System
HCIII: Health Centre level III
WHO: World Health Organisation
XDR-TB: Extensively Drug Resistant Tuberculosis

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 1.0 CHAPTER ONE: INTRODUCTION

1.1 Background
The increase in the burden of multidrug-resistant tuberculosis (MDR-TB) and the emergence of
extensively drug resistant tuberculosis ( XDR-TB) present tremendous challenges to the global
efforts to combat tuberculosis (TB). These challenges are further complicated by the limited
capacity (laboratory infrastructure and human resource) to diagnose and manage MDR-TB in
resource-limited settings. To ensure early detection of MDR-TB and rapid initiation of measures
to control its transmission, the World Health Organization (WHO) recommends routine drug
susceptibility testing among retreatment TB cases to rule out MDR-TB (1). In Uganda, MDR-TB
among the retreatment TB cases stands at around 12.5% (2). Up to date, Uganda has only one
public facility - the National Tuberculosis Reference Laboratory (NTRL) located in Kampala
where mycobacteria tuberculosis culture and sensitivity testig can be carried out. By 2008, the
NTRL was serving only the population around Kampala and Wakiso Districts. In a drive to
accelerate MDR-TB detection country-wide in Uganda, the NTRL initiated a specimen transport
system where sputum was collected from smear positive retreatment TB cases at the peripheral
health facilities and sent to the NTRL for TB culture and drug susceptibility testing. This system,
named the Tuberculosis Specimen Referral System (TSRS) supported by various donors
including the CDC, Global Fund, and others was initiated in October 2008. In its design, Health
workers at the health facilities were trained on the TSRS, they identified the retreatment TB
cases, collected and packaged the sputum safely, took it to the nearest post office which would
transport the package to the NTRL. At the NTRL, sputum culture and drug sensitivity for MDR-
TB, as well as other tests were performed and results sent back to the health facility through the
post office.

The NTRL implemented the TSRS using a phased approach in each of the 8 TB zones (i.e.
Kampala, South Western, Western, Northern, North West, North East, Eastern and South East).
Implementation started off in the Kampala TB zone October 2008 followed by the South
Western TB zone in 2009 and then other zones eventually covering the whole country by end of
2010.

1
 The TSRS was implemented using the following strategies:
i. Participating health facilities: The NTRL in conjcuction with the zonal and district TB
supervisors selected 2-3 health facilities per district to participate in the TSRS. Selection was
based on TB workload at the health facilities; those with the highest numbers of retreatment
TB cases were selected first. This process was guided by the Uganda national TB surveillance
data provided by the National Tuberculosis and Leprosy Control programme (NTLP), Ministry
of Health, Uganda.
ii. Training: The NTRL prepared a training manual, and SOPs for use with the TSRS. At least
two health workers (both clinicians and loboratorians) from the selected health facilities, and at
least one Post Office personnel from the nearest post offices were trained by the NTRL in the
basics component of the TSRS that included: identification of the eligible retreatment TB
patients, filling of the various TSRS forms, safe packaging of sputum using the tripple
packaging system and the sample delivery paths via the Post Office to the NTRL in Kampala.
iii. Logistics: The NTRL also provided all the required sample packaging materials required for
the TSRS, these included: sample container tubes, safe packaging materials like-ziplock bags/
biohazard bags, cotton wool (absorbent material during sample transit), sample
shipment/transport box and the laboratory request form booklets.
iv. Payments: By design the NTRL was obliged to pay for the postal services, and also pay an
earlier agreed amount of money to compensate for the transport expenses incurred by the
health workers in movements to and from the Post Office to deliver the packages/pick the
results. This money was paid with the aid of mobile money transfers to the registered phone
numbers of specific health workers that were involved in the sample transportation exercise.

By the end of the year 2010, a total of 1357 samples had been referred to the NTRL with only
52 MDR-TB cases identified overall (3). However, since the introduction of the TSRS as a new
sample referral system in Uganda, it faced various challenges that required formal studies to
evaluate its performance. In this study, we evaluated the performance of the TSRS during the
year 2010 period.

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1.2 Problem statement
Wheras the NTRL initiated the TSRS in October 2008 to increase country-wide MDR-TB
surveillance in Uganda, no study has ever evaluated the performance of the system in terms of
proportion of eligible specimens referred, reasons for failure to refer samples, and wheather
results reach and get utilized for patient care at the participating health facilities. Studies that
evaluated sample referral systems else where reported various strength and challenges. A TB
specimen referral system introduced in Vietnam in 2010, noted a 27% increase in the number of
sputum samples sent to the reference laboratory as well as a 19% rise in the number of newly
diagnosed MDR-TB cases (4). However the limitation of this study was that the specimen
referral system was introduced to only 5 health facilities. In a 2011 study about the diagnosis of
tuberculosis in South Africa highlighted some of the factors that hindered the TB specimen
referral system that included: interrupted supplies of clinical/ logistical materials and human
resource concerns-insufficient training, high work load/ few health workers and poor morale (5).
This study was quite comprehensive in most aspects of TB care and control but did not quantify
the magnitude of the missing results for the samples that had been referred for culture and
sensitivity and it also never had any information whether the TB culture and sensitivity results
were ever discussed with the patients. A review of TSRS data from 2008-2011 showed that there
was a more than 10 fold increase in referral of sputum from presumptive MDR-TB cases and that
94% of the specimens reached the NTRL with in the specified turn around time (6). However,
this study did not show any information about the proportions of the eligible samples from the
presumptive MDR-TB cases identified in the peripheral health facilities that had been referred to
the NTRL. From the above review we have failed to find any data on the performance of the
TSRS in Uganda. Therefore, this study was carried out to find out out how the TSRS was
perfoming in terms of proportion of eligible specimens referred, reasons for failure to refer
samples, and utility of results for patient care at the participating health facilities of the South
Western TB Zone.

1.3 Research questions

i. A mong the eligible retreatment TB patients, how many get their sputum referred to the
NTRL through the TSRS?
ii. What factors hinder the referal of specimens to the NTRL?
iii. Among the dispatched results from the NTRL; how many are actually received at the
respective health facilities?

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1.4 Objectives of the study
i. Assess the proportion of sputum from smear positive retreatment TB cases in the South
Western TB zone that were referred through the TSRS to the NTRL.
ii. To find out the factors that hindered referral of eligible sputum to the NTRL.
iii. Assess the proportion of result reports from the NTRL received at the health facilities.
iv. Assess the proportion of result reports from the NTRL that reach the patients.

1.5 Justification
By finding, reviewing and addressing the challenges facing the TSRS in this report, the NTLP
stands an opportunity to be able to improve the systems for detection of MDR-TB in the country.
This has deepening inpacts on the control of drug resistant TB in Uganda.

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 2.0 CHAPTER TWO: LITERATURE REVIEW

Tuberculosis (TB) causes ill-health among millions of people each year and now ranks along the
human immunodeficiency virus (HIV) as the leading causes of death from an a single infectious
disease worldwide. In 2014, TB killed 1.5 million people (1.1 million HIV-negative and 0.4
million HIV-positive). The toll comprised 890 000 men, 480 000 women and 140 000 children.
HIV’s death toll in 2014 was estimated at 1.2 million, which included the 0.4 million TB deaths
among HIVpositive people. Worldwide, 9.6 million people are estimated to have fallen ill with
TB in 2014: 5.4 million men, 3.2 million women and 1.0 million children. Globally, 12% of the
9.6 million new TB cases in 2014 were HIV-positive (7).
The TB national burden in Uganda is high since Uganda is ranked 19 out of the 22 high TB
burden countries in the world with an estimated annual incidence of 350 new cases per 100,000
of the population. The country has an estimated annual risk of infection (ARI) of 3% -equivalent
to 150-165 new smear positive TB cases per 100,000 population per year or 300-330 total TB
cases per 100,000 per year. The TB mortality rate was 13/100,000 (in HIV negative patients),
and 25/100,000 in HIV positive patients (8). A number of Ugandan studies have revealed that
TB was the leading cause of death in HIV patients, many of whom died before TB was
confirmed by laboratory methods (9-11).

For decades, tuberculosis (TB) control programs have focused their efforts on patients with
newly diagnosed TB, who are responsible for most of the disease burden. However, compared
with patients with new TB cases, patients presenting with TB who have a history of treatment or
retreatment TB cases experience poorer treatment outcomes and have increased mortality and
higher rates of drug resistance (12). Importantly, multidrug-resistant (MDR) TB occurs 5–10-
fold more frequently among patients who previously received treatment for TB than among
patients with new TB (13).

In Uganda, a retreatment TB case is defined as a person previously treated with anti-TB drugs
for a month or more and is being treated again, in line with WHO definitions (14). The
retreatment category is further classified either as ‘relapse’, ‘treatment after failure’, ‘return after
Loss To Follow Up-LTFU’ or ‘others’. Relapses are patients who become bacteriologically
positive after having been treated for TB and declared cured or treatment completed. Treatment
after failure are patients who, while on first line anti-TB treatment are bacteriologically positive

5
at 5 months or later during the course of treatment. Return after LTFU patients are those who
return to treatment and are bacteriologically positive after having interrupted treatment for more
than 2 months. The case classification and pathogenesis of retreatment TB are still obscure (15).
In general terms, recurrence of TB may be a result of relapse in patients otherwise previously
treated successfully, or re-infection. A significant proportion of recurrent TB may be attributable
to relapse with the same Mycobacterium tuberculosis strain, particularly following recent
completion of treatment (16-17). Lambert et al. (2003) further suggests that re-infection per se
may have few implications for TB control except in settings with considerably high incidence,
while immunocompromised patients are reported to be at greater risk of re-infection TB. Poor
patient compliance, emergence of multi drug resistant mycobacteria, co-morbidity and chronic
alcoholism have been associated with TB re-treatment (18). Additionally, HIV seropositive
patients have generally been shown to have more frequent episodes of recurrence compared to
seronegative patients. A study in India showed that HIV infection increases the rate of TB
recurrence after successful completion of TB treatment in high HIV endemic areas, with
recurrence often being due to a reinfection (19). In another study to find the factors affecting
tuberculosis retreatment in Nanded-India (20) found out that: Illiteracy (p=0.001), alcoholic
addiction (p=0.003) and employment (p=0.009)were significantly associated with TB treatment
default. It was further demonstrated that in urban settings, adherence is linked to patient
knowledge about TB and provision of disease-specific education by the health care provider to
the patient (21).

The World Health Organization estimates current rates of multidrug resistant TB (resistance to at
least isoniazid and rifampicin) in new and previously treated cases globally at 3.6% and 20.2%
respectively, with the highest levels of MDR-TB coming from eastern Europe and central Asia
where in some countries MDR-TB was detected in more than 20% of new TB cases and 50% of
patients that had previously received TB treatment . Of the 480 000 cases of multidrug-resistant
TB (MDR-TB) estimated to have occurred in 2014, only about a quarter of these – 123 000 –
were detected and reported (7). The prevalence of MDR-TB in new TB cases has previously
been reported below less than 2% (22) and 12.7% among the re-treatment cases attending the
National Tuberculosis and Leprosy Program (NTLP) clinic in Kampala (23). In one peri-urban
population of Kampala the prevalence of MDR-TB was 4.4% in new cases (24). The most recent
Uganda National TB drug survey conducted by the NTLP between 2010- 2011 found prevalance
1.4% and 12.1% of MDR-TB among new and previously treated sputum smear positive TB

6
patients respectively (25). The treatment of MDR-TB was estimated to cost 30-40 times more
than treatment of drug sensitive TB in a recent study carried out in South Africa (26).

In the vast majority of cases, drug-resistant tuberculosis (DR-TB) develops during the treatment
of drug-sensitive TB: when patients fail to complete their full course of treatment; when
healthcare workers provide the wrong treatment, the wrong dose, or the wrong length of time for
taking the drugs; when the supply of drugs is interrupted; or when the drugs have expired or are
of poor quality (27). However there are circumstances through which primary resistance or initial
resistance can occur when there has been no treatment of the patient with the drug concerned. It
includes resistance in wild strains which have never come into contact with the drug (natural
resistance) and the resistance occurring as a result of exposure of the strain to the drug but in
another patient. Initial resistance is the resistance in patients who give a history of never having
received chemotherapy in the past. It includes primary resistance and resistance to previous
treatment concealed by the patient or of which the patient was unaware (28).

Management of patients who have been previously treated for TB has since long been a
contentious issue. In 1991, the WHO recommended the use of the “category II retreatment
regimen” for all patients with a prior history of TB treatment. In 2006, these guidelines were
fine-tuned and the WHO guidelines recommended DST prior to retreatment and treatment of
confirmed treatment failures and suspected MDR-TB cases with region-specific standardized
regimens (29).

The lack of laboratory infrastructure for culture and DST in many settings like Uganda with a
high burden of tuberculosis resulted in widespread empirical use of the retreatment regimen.
Retreatment outcomes, however, are often poor, especially in patients with treatment failure or
lost to follow up (30). DST mayhelp identify those patients with multidrug-resistant (MDR) TB
so that the appropriate antibiotics can be administered. In settings where DST results are not yet
routinely available, the empirical regimens should continue throughout the course of treatment.
Although relapses are usually due to susceptible bacilli, it is advisable to carry out DST to first-
line anti-TB drugs since the assumption that relapses and their presumed equivalent pattern of
drug susceptibility to that of the initial infection applies only when the patient has correctly
completed an adequate treatment regimen (31).

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 3.0 CHAPTER THREE: MATERIALS AND METHODS
3.1 Study design
This was a cross sectional retrospective study

3.2 Study site and setting

The study was carried out in the South Western TB zone of Uganda composed of 16 districts:
Masaka, Sembabule, Rakai, Lyantonde, Kiruhura, Mbarara, Bushenyi, Kabale, Isingiro, Kisoro,
Kasese, Kanungu, Kalangala, Rukungiri, Ibanda and Ntungamo. This zone was selected primarly
for two reasons: it is the largest TB zone in the country and it is also the second highest burdened
TB zone in Uganda after Kampala. The South Western TB zone is highlighted in red in figure 1.

Figure 1: Map of Uganda showing the location of the South Western TB zone ( in red)

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 3.3 Study Population
The study population was the 39 health facilities participating in the TSRS in South Western TB
zone of Uganda. The unit of analysis was each smear positive retreatment TB case documented
in the health facility TB register.
3.4 Sample size determination
In this study the sample size determination was open to all the identified smear positive
retreatment TB cases registed at the TSRS health facilities.
3.5 Sampling technique
Consective sampling technique was the sampling technique of choice due to the fact that this
study involved already pre-defined participants, i.e.all the TSRS participating health facilities
were already known and all had to be included in the study.
3.6 Inclusion criteria
All the 39 health facilities involved in the TSRS in the South Western TB zone of Uganda. All
smear positive retreatment TB cases registered at the health facility were included in the
analysis. Only health workers that were attached to the TB ward or laboratory that directly dealt
with TB patients on a daily basis were eligible for participating in this study.
3.7 Exclusion criteria
All the other health facilities in the South Western TB zone that were not designated and trained
as TSRS sites. Also all other health care workers at the TSRS sites that were not directly
mandated to handle TB patients like the staff in the theater or hospital admistrative staff.
3.8 Methodological details
The data collection was carried out between March to June 2011and involved a cascade of 8
events:
i. Seeking Ethical clearance to conduct the study from the School of Biomedical Sciences,
Makerere University’s institutional review board (IRB).
ii. Introduction and seeking admistrative permission to carry out the data collection at each of
the visited TSRS health facilties.
iii. Seeking conscent from the health workers before admistration of the questionnaires or data
collection.
iv. Review and collection of the data from the three data collection tools at the health facility
(TB laboratory registers, TB unit registers and the TSRS laboratory request booklet).
v. Administration of the questionnaires

9
 vi. Reveiew of the activities at NTRL to assess the dispatched results.
vii. Data entry and cleaning
viii. Data analysisties.
The flow chat below samarises the methodological details:
IRB clearance

Admistrative clearance at the

health facility

Conscent from health workers

Review of lab TB registers

Questionaire administration

Review of NTRL activities

Data cleaning and entry

Data analysis

Figure 2: Flow chart demonstrating the methodological details

3.8.1 Ethical Clearance

Ethical clearance had to be sought from the School of Biomedical Sciences, College of
Medicine, Makerere University before this study could be approved for commencement.
3.8.2 Administrative clearance at the health facility
On arrival to the health facilities, a visit was made to the facility incharge for introductions and
explaining to them the purpose of this study. During this interaction the incharges were notified

10
about the scope of the exercise, i.e. it would involve the of specificTB data at the health facility
as well as the interaction with their staff with the aid of a questionnaire. At this point the health
workers were notified that the purpose of this exercise was not to identify the best or poorly
performing health workers or health facilities but it was intended to assess the current status of
the TSRS as well as find ways to improve the system.
3.8.3 Seeking health workers conscent
A verbal conscent had to be sought from each of the health workers before any data had to be
collected from either the laboratory or unit TB registers. The conscent also covered the scope of
the questionnaires that were later administered to find the predominant factors that affected the
performance of the TSRS.
3.8.4 Review of TB lab registers
There were 3 primary data collection tools at the health facilities: i. TB unit register-this was the
register used to identify all the retreatment TB cases that were documented at a specific health
facility. This register was very usefull in summing up all the registered TB retreatment cases for
the period of the study, ii. TB laboratory register-this register was used to find out the
microscopy results for all the documented retreatment TB cases registed in the TB unit register
and iii. TSRS laboratory request form booklet-this booklet was used to find out the proportion of
the smear positive retreatment TB cases documented in the unit TB register that had sputum
samples collected from them and referred to the NTRL for TB culture and sensitivity.
Information about the proportion of result reports verified as received at the health facilities in
respect to the sputum samples sent to the NTRL was also collected.
3.8.5 Administration of questionnaires
Questionaires were administered to atleast one clinician and one laboratory personnel at each of
the TSRS health facilities. These questionnaires were tailored to aid in the identification of the
predominant factors that affected the performance of the TSRS in each of the health facilities.
The questionnaires were also usefull in giving information whether the results were returned on
time from the NTRL and also whether these results were easily interpretable and discussed with
the respective patients. A sample of the questionnaire can be found in the appendix.
3.8.6 Review of NTRL activities
At the NTRL, three activities were done: i. varification for the receipt of all samples documented
at the health facilities as having been referred to the NTRL, ii. assess the the availability or
status of the results for all the samples that had been received and iii. confirm the dispatch of all
the results for the samples that had been received from the South Western TB zone. These three

11
activities were executed by use of the NTRL electronic database as well as by the use of the hard
copy result report file folders and result report dispatch log book. Asearch was made in the
electronic data base for all the samples that were documented as sent to the NTRL from the
health facilities to verify whether they were ever received and also confirm the status of their
results. Once this was done then the results report files were reviewed to assess whether these
results were ever printed out and a copy left behind after dispatching the original results to the
requesting health facilities. Confirmation of the dispatch of the results was through the review of
the result report dispatch log book to assess whether all these results had been documented.
3.8.7 Data cleaning and entry
Data was reviewed prior to entry to ensure completeness are deletion of duplicated records. The
data was then entered into an excel spread sheet that acted as the master source document for the
data analysis step.
3.8.8 Data analysis
Data was analysed using PASW statistics software version 17. During the analysis various
frequency runs/tables and cross tabulations were made for various parameters that included:
grouped proportions of referred retreatment TB cases, perceived irrelevance of results by the
health workers, personnel knowledge about the TSRS, personnel training in the TSRS, TSRS
supplies, transport refund returned on time, result reports returned on time e.t.c.

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 4.0 CHAPTER FOUR: RESULTS
The South Western TB zone has 39 health facilities participating in the TSRS. Of these, 30
(77%) were visited, but data was collected from 27 health facilities because the other 3 health
facilities (Lyantonde Muslem HCIII & Mpumudde HCIII in Lyantonde district and Makenke
UPDF HCIII in Mbarara district ) were not eligible for analysis since they did not identify any
retreatment TB case.
Proportion of retreatment cases whose sputum samples were refered to the NTRL
A total of 239 retreatment TB cases were identified in the South Western TB zone from January
2010 to December 2010. Of these, 135 (57%) retreatment TB cases had their sputum referred to
the NTRL under the TSRS. Among the districts in the South Western TB Zone, the proportion
of refered sputum samples from Ibanda, Ntungamo, Kiruhura and Lyandonde was 83%, 76%,
17% and 10%, respectively. Table 1 highlights the district performace in TSRS for the entire
South Western TB zone.

Table 1 : District participation in TSRS in the South Western TB zone

No. District Number of identified Number (%) of samples Number (%) not sent to NTRL
retreatment cases sent to NTRL
1. Ibanda 23 19 (83%) 04 (17%)
2. Ntungamo 21 16(76%) 05 (24%)
3. Kasese 20 15(75%) 05 (25%)
4. Masaka 29 21 (72%) 08 (28%)
5. Mbarara 29 21 (72%) 8 (28%)
6. Sembabule 19 10 (53%) 09 (47%)
7. Bushenyi 20 07 (35%) 13 (65%)
8. Rakai 23 08 (35%) 15 (65%)
9. Isingiro 14 04 (29%) 10 (71%)
10. Rukungiri 19 05 (26%) 14 (74%)
11. Kiruhura 12 02 (17%) 10 (83%)
12. Lyantonde 10 01 (10%) 09 (90%)
  TOTAL 227 129(56.8%) 98 (43.2%)

Looking at Health facilities, 8 (30%) referred 76 - 100% of the sputum samples from the
identified retreatment TB cases, while 19 (70%) of the health facilities referred upto 70% of the
samples. Details for the cumulative grouped percentage referral of samples from the 27 health
facilities to NTRL is shown in table 2 below.

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 Table2: Grouped proportion of samples refered to the NTRL

Proportion of retreatment TB cases whose No. of Health

sputum was referred to NTRL Facilities Percent Cumulative Percent
< 25% 5 18.5 18.5
25-50% 10 37.0 55.5
51-75% 4 14.8 70.3
76-100% 8 29.6 100.0
Total 27 100.0  100

Looking at individual health facilities, Villa Maria hospital in Masaka district and Ruhoko HCIV
in Ibanda district refered 100% samples from all their identified retreatment TB cases while
Kitovu hospital in Masaka, Kakuuto HCIV in Rakai and Nakivale HCIII in Isingiro districts did
not refer any sample from their identified retreatment TB cases. Table 3 details the proportions
of sputum samples refered from all health facilities participating in the TSRS in the South
Western TB zone.

Table 3: Table showing proportions of sputum samples per district referred to the NTRL

14
 No. District  Health Facility Number of Number (%) Number/ (%) not
retreatment whose sputum was sent to NTRL
cases sent to NTRL

1. Ibanda Ruhoko HCIV 4 04 (100%) 00 (0%)

Ishongororo HCIV 12 10 (83%) 02 (17%)
Ibanda Hospital 7 05 (71%) 02 (29%)
4. Ntungamo Kitwe HC IV 8 07(86%) 01 (14%)
Itojo Hospital 13 09(69%) 04 (31%)
6. Kasese Kilembe Hospital 9 07 (78%) 02 (22%)
Kagando Hospital 11 08(73%) 03 (27%)
8. Masaka Villa Maria Hospital 11 11 (100%) 00 (0%)
Masaka Hospital 15 10 (67%) 05 (33%)
Kitovu Hospital 3 00 (0%) 03 (100%)
11. Mbarara Mbarara Hospital 21 17(81%) 04 (19%)
Bwizibwera HCIV 8 04(50%) 04 (50%)
13. Sembabule Matete HC III 7 06(86%) 01 (14%)
Sembabule HC IV 4 02(50%) 02 (50%)
Bamu Hospital 8 02 (25%) 06 (75%)
16. Bushenyi Ishaka Adventist Hosp 9 04 (44%) 05 (56%)
Kitagata Hospital 11 03 (27%) 08 (73%)
18. Rakai Kalisizo Hosptal 12 05 (42%) 07 (58%)
Rakai Hospital 9 03 (33%) 06 (67%)
Kakuuto HCIV 2 00 (0%) 02 (100%)
21. Isingiro Kabuyanda HCIV 9 04 (44%) 05 (56%)
Nakivale HCIII 5 00 (0%) 05 (100%)
23. Rukungiri Nyakibale Hospital 9 02 (23%) 07 (77%)
Kisiizi Hospital 10 03 (30%) 07 (70%)
25. Kiruhura Kazo HCIV 4 01 (25%) 03 (75%)
Rushere Hospital 8 01 (13%) 08 (87%)
27. Lyantonde Lyantonde Hospital 10 01 (10%) 09 (90%)
  TOTAL   227 129(56.8%) 98 (43.2%)

Factors that hindered TB specimen referral to NTRL

A total of 51 health workers were interviewed-these included laboratory personnel: 27 (53%)
and clinicians: 24 (47%). Perceived none relevance of the results by the health workers and the
delayed receipt of the transport refund from the NTRL were the two most significant factors
noted to have hindered the effectiveness of the TSRS with each accounting to 59% of the
respondents views. Absence of one or more of the TSRS supplies was noted by the respondents
to negatively affect the TSRS in varying proportions, i.e. 7.8% and 45% of the respondents noted
stock outs for transportation safety box and ziplock/biohazard bags, respectively. Figure 1, below
expounds the proportion of the other factors that hindered the TSRS in South Western TB zone.
15
 58.8 58.8

45.0

39.2
35.3
33.3 33.4

27.4

21.5

11.7
7.8

Figure 3: Proportion of factors that hindered the TSRS

Proportions of result reports returned to the health facilities

Of the 135 retreatment TB cases whose samples were received at the NTRL, 106 (79%) results
reports were verified as dispatched back to the health facilities while 29 (21%) of the result
reports from the NTRL could not be verified as dispatched back. However, after visiting the
health facilities during this study, it was found that 71 (67%) of the 106 dispatched reports
actually reached the facilities, while 35 (33%) of the result reports dispartched by the NTRL
could not be traced at the health facilities. Taking referred samples (135) in the denominater and
received reports (71), in the numerater, only 52% of the expected results were verified as
received back at the health facilities. Sixteen (59.2%) of the health facilities received more than
50% of all the result reports while 7 (25.9%) of the health facilities received less than 25% of the
results reports dispartched from the NTRL, as detailed in table 4 below.

Table 4: Grouped proportion of result reports received at the health facilities

Proportion of Results Reports received at No. of health Percent Cumulative Percent

16
 health facilities facilities
< 25% 7 25.9 25.9
25-50% 4 14.8 40.7
51-75% 9 33.4 74.1
76-100% 7 25.9 100.0
Total 27 100  

A review of the perception on result reports turn around time from the 51 respondents revealed
the following results; result reports received on time - 22 (43%), result reports returned late - 20
(39%) and not certain when the result reports were returned - 9 (18%). On interpretation of the
result reports, 45 (88%) of the respondents noted that the reports were easily interpretable while
6 (12%) of the respondents were not sure about the interpretablility of the results.

Proportion of results dispartched and received by the patients

All the studied health facilities did not have a concrete system for documentation of results
issued to the patients, so it was difficult to collect data on this parameter. However, 54% of the
respondents reported that the result reports were dispatched back to the patients while 32% of the
respondents reported that the result reports were not issued back to the patients and 14% of the
respondents claimed that they were not certain whether the result reports were issued back to the
patients. Of the 51 respondents, 33 (64%) of them reported that they were not sure whether the
patients were ever phone-called to pick their results, while 18 (36%) were certain that the
patients were never called on phone to pick their results.

17
 5.0 CHAPTER FIVE: DISCUSSION
The increase in multidrug-resistant tuberculosis (MDR TB) and the emergence of extensively
drug resistant tuberculosis present tremendous challenges to the global efforts to combat
tuberculosis. These challenges are further complicated by the limited capacity (infrastructure and
human resource) to diagnose and manage MDR-TB in third world countries. Uganda has only
one public facility-the National Tuberculosis Reference Laboratory, NTRL located in Kampala
where specimens from MDR-TB suspects can be refered for diagnosis. In October 2008, the
National Tuberculosis and Leprosy control Programe initiated what was dubbed the Tuberculosis
Specimen Referal System, TSRS. Under this system, trained health workers at selected
peripheral health facilities identify smear positive retreatment TB cases from whom they collect
sputum, safely package it using the triple packaging guidelines and deliver the packages to the
nearest Post office for transportation to the NTRL in Kampala. At the NTRL laboratory, MTB
culture and sensitivity testing is performed and once results are ready, they are dispartched back
through post office to the respective health facilities for patient care and management. Since its
initiation in October 2008, the TSRS has never been evaluated to assess whether it meets its
intended objectives and outputs. This study evaluated various aspects of the TSRS including:
proportion of smear microscopy positive retreatment TB cases whose sputum samples were
refered to the NTRL, factors that hindered the referral of specimens, proportion of results
returned to the health facilities, and results that actually reached the patient. The study was
focused on the year 2010 performance.

This study found that only slightly more than half of the samples from the eligible retreatment
TB cases in the South Western TB zone were referred to the NTRL, with almost half (43%) of
the sputum samples missing out. A review of the data by district performance showed that
Ibanda and Ntungamo districts had the highest and second highest number of samples refered,
with only less than 25% of the eligible samples missing out. The good performance of both
Ibanda and Ntungamo could be attributed to having a high number of health workers that had
been trained in the TSRS. Masaka and Mbarara districts both ranked third in TSRS participation
because each of these districts had a regional referral hospital whose TB personnel were well
trained and aware about the purpose of the TSRS. Further more these regional referral hospitals
also had a high work load of retreatment TB patients since they received a number of

18
complicated TB cases refered from other health facilities in the region. Performace from other
districts varied but Kiruhura and Lyantonde referred the least number of samples with 80 – 90%
of the eligible samples missing out. Various factors could explain the poor performance of the
latter two districts and top on the list was abscence of trained health workers; Kiruhura and
Lyantonde had only a quarter of their health workers trained in the TSRS. This discrepancy in
knowledge gap on matters to do with the TSRS was due to the different rates of staff turn overs
and transfers in these poorly performing districts.

Looking at performance by health facilities, only 44% of the health facilities were able to refer
more than half the eligible sputum samples of their identied retreatment TB cases. The reasons
for this lukewarm performance are quite diverse as detailed later on in this section under the
factors that hindered the effectiveness of the TSRS. It was observed that both public and Private-
Not-For-Profit (PNFP) health facilities had similar patterns of participation in TSRS, e.g Ruhoko
public HCIV in Ibanda district and Villa Maria PNFP Hospital in Masaka district both refered
100% of the identified samples from the retreatment TB cases, while Kakuuto HCIV in Rakai,
Nakivale HCIII in Isingiro (public facilities) and Kitovu Hospital Masaka (PNFP facility) did not
refer any sample from their eligible retreatment TB cases. This pattern of behavior between the
public and PNFP health facilities in TSRS activities shows that there is still more effort required
in mentorship and refresher trainings in TB management for both categories of health care
providers. This occurance could also be explained by the high rate of staff turnover or transfers
from the health facilities with poor or insufficient training of the new staff.

When we delved further into the reasons for failure to refer samples, the top two factors were
perceived irrelevance of the results to patient care and delay in receipt of transport refund from
the NTRL. These two factors were reported by close to 60% of the respondents. It is likely that
lack of initial training on the TSRS operations and importance of detecting MDR-TB was the
major underlying reason for the health workers’ poor perception about the results. Dealyed
refund of the used transportation costs (health facility to post office and back) meant that the
health workers did not have any more money to invest into this activity if their previously
incurred costs had not been refunded on time. The NTRL however was accused of delaying the
refunds or even at times issuing the refunds to the none responsible personnel, thus demotivating
the peripheral health workers’ interest in the TSRS. Shortage or absence of some of the TSRS

19
supplies/logistics e.g. sample containers, cotton wool, ziplock/bioharzard bags, safety boxes,
stationery, e.t.c. further compounded the challenges of sending sputum samples to the NTRL
since the health workers did not have the tools to use to package the specimens. The lack of a
proper logistic management system in the participating health facilities could partly explain the
occurance of the supply stockouts. Respondednts, also reported that some supplies like
ziplock/biohazard bags ran out because they were being used for packaging and referral of other
types of samples e.g. blood samples for other tests done in other reference laboratories. Cotton
wool was also being shared with other departments of the health facility and yet it was initially
intended for the safe packaging of TB specimens. We realized that an integrated model of
logistics management might be better at managing these supplies than the project based logistic
managaent at these facilities. That is, specific supplies for specific diagnostic tests should be
discouraged and encourage sharing all the relevant supplies for various diagnostic procedures.
Indeed, in Uganda, from 2012, an integrated system for sample referral for HIV early infant
diagnosis, HIV viral load, sputum samples for culture and sensitivity and other samples with
similar referral needs was introduced in an attempt to solve the project based systems. In this
integrated model, regional laboratory hubs were introduced and samples from specific health
facilities are collected and transferred to the hub laboratory for advanced diagnostics and in the
event that the diagnostic assay is not available at the hub laboratory then the specimens will be
taken to the post office for onward transmission to the referral laboratories.

A third of the respondents also noted that even after the referral of the samples to the NTRL, the
results took long to be returned yet these persons were also ignorant about the toll-free phone
number at the NTRL that could be used to contact the laboratory to inquire about the fate of their
results or even communicate about the scarcity or fore seen shortage of the TSRS basic supplies.
This still implied that the TSRS training was still inadequate or there were newly recruited
personnel not yet oriented/ mentored in the TSRS operations. This ignorance about the details
about the TSRS was further demostated by some of the respondents who were not aware about
the expected turn around time for TB culture and sensitivity results.

There were some loop holes observed in the documentation of the dispatched results reports from
the NTRL and receipt of the result reports at the health facilities. For instance almost a quarter of
the result reports could not be verified at NTRL as dispatched, while a third of the dispatched
reports from NTRL could not be verified as received at the health facilities. This discrepancy
was due to the fact that not all results dispatched from the NTRL were registed in the result

20
dispatch register at the time. Similary, not all result reports received at the health facility were
registered in the health unit TB register. A more in depth analysis of this issue revealed
interesting findings: by compairing all the 135 samples refered to the NTRL, only around half of
the result reports were verified as received at the health facilities, and it was not clear where the
other reports ended up. None of the health facility did record the date of receipt of the result
reports since this was not a compulsory procedure once the results had been received hence the
parameter of assessing the turn around time was subjective to the memory and opinion of each
respondent. Still based on memory, slightly more than a third of the respondents perceived the
reports to have been received late, which made it hard for them to conclusively determine
whether the appropriate treatment had been prescribed to their patients. However, what was good
was that for the received reports, majority of the respondents noted that the result reports were
easy to interpret making it possible for them to determine the correct course of management for
their patients. One obstacle was that even for the received reports, the requirment to contact
patients/attendandts on phone to come back to the health facility was a hindrance to the intention
of utilizing the results for patient care. The respondents expressed concern that they did not have
the airtime and other resources/systems to call the patients to return and pick their results. In fact
only around half of the respondents reported that the result reports were dispatched back to the
patients, the rest lay redandunt at the health facility. These issues highlight the need for proper
planning and financing of the different aspects of the TSRS especially for countires that intend to
initiate a similar sample referral model. The key areas to take note of are planning working
systems for continued training, tansport refund to the health workers, logistics management,
documentation at all levels, system that ensure that the results reach the intended patients and
review of those results by the health worker in presence of the patient.

In this line, the NTRL in 2012 introduced a system of electronic dispatch of results to all
facilities with capacity to access internet and printing resources. With this system the results are
emailed by the NTRL to the health facilities, which thus receive their results in a short period of
time afer the appropriate assays have been performed and possibly, quicker treatment decisions
are made. This highlights the potential impact of communication technologies in improvement of
health systems, but the analysis of the impact will require another study. Futher more the NTRL
has currently adopted the WHO recommendation for use of the genexpert technology for the
rapid diagnosis of MTB TB and drug resistance. In Uganda, there has been a dedicated effort to

21
roll out the gene expert machines to most regional centers/hospitals across the country in an
attempt to detect and manage rifampicin resistant MTB early. Only sputum samples with
rifampicin-resistant MTB are currently being referred to the NTRl for full profile drug
susceptibility testing. The decentralization of the gene expert technology to more than 112 health
facilities in the country has increased coverage of the MDR-TB surveillance, reduced results turn
around time, costs of sample shipment and workload to the NTRL.

22
 6.0 CHAPTER SIX: CONCLUSION
While the TSRS helped to detect MDR-TB from peripheral areas of Uganda, this study found
that almost half of the eligible sputum samples from the targeted retreatment TB cases in the
South Western TB zone were never refered to the NTRL for culture and sensitivity testing. The
three major factors underlying failure to refer the samples were insufficient understanding of the
TSRS due to inadequate health workers training, delayed refund of transport costs incurred by
the health workers as they took the packages to the post office and poor logistics management.
Additionaly, our study has found that there was no system for documentation of the result
movement from the NTRL to the health facility and finally to the patient, making it impossible to
assess the ultimate utilisation of the culture and sensitivity results generated under the TSRS.

23
 7.0 CHAPTER SEVEN: RECOMMENDATIONS

i. The NTRL should work with other TB control stake holders to ensure that all
health workers are regularly trained and oriented about the importance of the
TSRS.
ii. The NTRL should ensure that all health facilities now use the hub network system
for sample collection since this approach does not involve any cost to the health
worker and is more sustainable as well as has a larger coverage network of health
facilities in the districts.
iii. The NTRL should actively engage in strategies to reduce or avoid stock outs for
the TSRS supplies. Such strategies may include engagement of the National
Medical Stores in the procurement and delivery of the TSRS supplies directly to
the health facilities.
iv. All countries or partners that contemplate the initiation or use of a specimen
referral system should ensure that appropriate documentation systems are
instituted from the point of identification of the patients, sample collection and
referral, result dispartch and final issuance of the results to the patients.

24
 8.0 REFERFENCES
1.WHO. Global Tuberculosis Report 2011. Geneva.
http://apps.who.int/iris/bitstream/10665/137094/1/9789241564809_eng.pdf. 2012.
2. Lukoye D, Cobelens FG, Ezati N, Kirimunda S, Adatu FE, Lule JK, et al. Rates of anti-
tuberculosis drug resistance in Kampala-Uganda are low and not associated with HIV
infection. PLoS One. 2011 Jan 10;6(1):e16130.
3. WHO. Global tuberculosis control. 2011.
4. Nguyen. VIETNAM: BETTER TB SPECIMEN REFERRAL SYSTEM IMPROVES MDR-
TB DIAGNOSTIC ACCURACY AND SAFETY. 2013 AUGUST 15, 2013.
5. Wilson D, Howell V, Toppozini C, Dong K, Clark M, Hurtado R. Against all odds: diagnosing
tuberculosis in South Africa. J Infect Dis. 2011 Nov 15;204 Suppl 4:S1102-9.
6. Joloba M, Mwangi C, Alexander H, Nadunga D, Bwanga F, Modi N, et al. Strengthening the
Tuberculosis Specimen Referral Network in Uganda: The Role of Public-Private
Partnerships. J Infect Dis. 2016 Apr 15;213 Suppl 2:S41-6.
7. WHO. Global tuberculosis report 2015. 2015.
8. WHO. Global tuberculosis report 2013
9. Amuron B, Levin J, Birunghi J, Namara G, Coutinho A, Grosskurth H, et al. Mortality in an
antiretroviral therapy programme in Jinja, south-east Uganda: a prospective cohort study.
AIDS Res Ther. 2011 Oct 22;8:39.
10. Kyeyune R, den Boon S, Cattamanchi A, Davis JL, Worodria W, Yoo SD, et al. Causes of
early mortality in HIV-infected TB suspects in an East African referral hospital. J Acquir
Immune Defic Syndr. 2010 Dec;55(4):446-50.
11. Moore DM, Yiannoutsos CT, Musick BS, Tappero J, Degerman R, Campbell J, et al.
Determinants of early and late mortality among HIV-infected individuals receiving home-
based antiretroviral therapy in rural Uganda. J Acquir Immune Defic Syndr. 2011 Nov
1;58(3):289-96.
12. Espinal MA, Kim SJ, Suarez PG, Kam KM, Khomenko AG, Migliori GB, et al. Standard
short-course chemotherapy for drug-resistant tuberculosis: treatment outcomes in 6
countries. JAMA. 2000 May 17;283(19):2537-45.
13. Zignol M, Hosseini MS, Wright A, Weezenbeek CL, Nunn P, Watt CJ, et al. Global
incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006 Aug 15;194(4):479-85.
14. NTLP. NTLP Manual 2nd Edition 2010. 2010.

25
15. Lambert ML, Hasker E, Van Deun A, Roberfroid D, Boelaert M, Van der Stuyft P.
Recurrence in tuberculosis: relapse or reinfection? Lancet Infect Dis. 2003 May;3(5):282-
7.
16. Bandera A, Gori A, Catozzi L, Degli Esposti A, Marchetti G, Molteni C, et al. Molecular
epidemiology study of exogenous reinfection in an area with a low incidence of
tuberculosis. J Clin Microbiol. 2001 Jun;39(6):2213-8.
17. Sonnenberg P, Murray J, Glynn JR, Shearer S, Kambashi B, Godfrey-Faussett P. HIV-1 and
recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South
African mineworkers. Lancet. 2001 Nov 17;358(9294):1687-93.
18. Fitzpatrick LK, Okwera A, Mugerwa R, Ridzon R, Ehiner J, Onorato I. An investigation of
suspected exogenous reinfection in tuberculosis patients in Kampala, Uganda. Int J Tuberc
Lung Dis. 2002 Jun;6(6):550-2.
19. Narayanan S, Swaminathan S, Supply P, Shanmugam S, Narendran G, Hari L, et al. Impact
of HIV infection on the recurrence of tuberculosis in South India. J Infect Dis. 2010
Mar;201(5):691-703.
20. Bhagat VM, Gattani PL. Factors affecting tuberculosis retreatment defaults in Nanded, India.
Southeast Asian J Trop Med Public Health. 2010 Sep;41(5):1153-7.
21. Mulenga C, Chonde A, Bwalya IC, Kapata N, Kakungu-Simpungwe M, Docx S, et al. Low
Occurrence of Tuberculosis Drug Resistance among Pulmonary Tuberculosis Patients
from an Urban Setting, with a Long-Running DOTS Program in Zambia. Tuberc Res
Treat. 2010;2010:938178.
22. Joloba ML, Whalen CC, Cave DM, Eisenach KD, Johnson JL, Okwera A, et al.
Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of
Mycobacterium tuberculosis from Kampala, Uganda. East Afr Med J. 2000
Feb;77(2):111-5.
23. Temple B, Ayakaka I, Ogwang S, Nabanjja H, Kayes S, Nakubulwa S, et al. Rate and
amplification of drug resistance among previously-treated patients with tuberculosis in
Kampala, Uganda. Clin Infect Dis. 2008 Nov 1;47(9):1126-34.
24. Asiimwe BB, Ghebremichael S, Kallenius G, Koivula T, Joloba ML. Mycobacterium
tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis
patients in peri-urban Kampala, Uganda. BMC Infect Dis. 2008 Jul 28;8:101.

26
25. Lukoye D, Adatu F, Musisi K, Kasule GW, Were W, Odeke R, et al. Anti-tuberculosis drug
resistance among new and previously treated sputum smear-positive tuberculosis patients
in Uganda: results of the first national survey. PLoS One. 2013;8(8):e70763.
26. Pooran A, Pieterson E, Davids M, Theron G, Dheda K. What is the cost of diagnosis and
management of drug resistant tuberculosis in South Africa? PLoS One. 2013;8(1):e54587.
27. MSF. MSF Report-‘From the ground up: Building a drug resistant-TB program in
Uganda’2012. 2012.
28. Sharma SK, Mohan A. Multidrug-resistant tuberculosis. Indian J Med Res. 2004
Oct;120(4):354-76.
29. Muller B, Borrell S, Rose G, Gagneux S. The heterogeneous evolution of multidrug-resistant
Mycobacterium tuberculosis. Trends Genet. 2013 Mar;29(3):160-9.
30. Ottmani SE, Zignol M, Bencheikh N, Laasri L, Chaouki N, Mahjour J. Results of cohort
analysis by category of tuberculosis retreatment cases in Morocco from 1996 to 2003. Int J
Tuberc Lung Dis. 2006 Dec;10(12):1367-72.
31. Caminero JA. Management of multidrug-resistant tuberculosis and patients in retreatment.
Eur Respir J. 2005 May;25(5):928-36.

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 APPENDICES
APPENDIX 1: Questionare used to assess the hinderences to the TSRS

   Particulars Yes/No
1 Are the clinicians aware of the TSRS?
2 Are the laboratory personnel aware of the TSRS?
3 Did any of the clinicians receive the TSRS training by NTRL?
4 Did any of the laboratory personnel receive the TSRS training by NTRL?
5 Are all the materials required to ship specimens available?
           Shipment boxes
           Cotton wool
           Zip lock bags
           50ml Falcon tubes
           Request form booklet
6 Are the personnel aware of the toll free helpline number?
Is the transport refund issued on time (atleast 1 month after dispatch of
7 specimen to NTRL) to the personnel concerned:
           Is the money refunded on time?
         Is the money not returned at all?
Are the results delivered to health facilty on time? (At least 2 months after
8 sending the sample to NTRL).
9 Are the results received interpretable?
10 Do patients receive back their results? If no, is it because:
         Patients don’t bother to come back for the results?
         Patients completely forget about their results?
         No contacts to reach the patients for their results?
         Others, specify:
 

28