COST-EFFECTIVENESS OF AN INTERVENTION TO IMPROVE DIAGNOSIS AND PREVENTION OF PAEDIATRIC TUBERCULOSIS IN UGANDA.pdf

1
S M Nazmuz Sakib (Orcid- https://orcid.org/0000-0001-9310-3014) (sakibpedia@gmail.com)
S M Nazmuz Sakib is an eLearning expert and done more than 500 MOOCs or Massive Open Online Courses and experienced as an instructor in
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and 97.06% grade marks on an average. He is also a certified Google IT Support Professional, Google Data Analytics Professional and IBM
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1Graduate of BSc in Business Studies, School of Business And Trade; Pilatusstrasse 6003, 6003 Luzern, Switzerland
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Student of BSc in Civil Engineering, Faculty of Science and Engineering, Sonargaon University; 147/I, Green Road, Panthapath, Dhaka
3Student of LLB(Hon’s), Faculty of Law, Dhaka International University; House # 4, Road # 1, Block - F, Dhaka 1213
4Student of BSc in Physiotherapy, Faculty of Medicine, University of Dhaka; Nilkhet Rd, Dhaka 1000
COST-EFFECTIVENESS OF AN INTERVENTION TO IMPROVE DIAGNOSIS AND
PREVENTION OF PAEDIATRIC TUBERCULOSIS IN UGANDA
Abstract
Background
'Decentralize Tuberculosis Services and Engage Communities to Transform lives of Children with
Tuberculosis' (DETECT Child TB Project) was a project set up to strengthen district and community
level health care delivery in two districts in Uganda to improve childhood TB case finding, treatment
and prevention and to develop a sustainable health systems delivery model for national and regional
scale-up.
Objective
To assess the cost-effectiveness of DEcentralize Tuberculosis Services and Engage Communities to
Transform Lives of Children with Tuberculosis (DETECT) intervention compared to the standard of
care for diagnosing, managing, and preventing pediatric tuberculosis in Uganda.
Methodology
A search was done on EMBASE and Medline databases for English articles published from 1st
January
2000 to 1st
August 2022. Systematic reviews, meta-analysis, evidence syntheses, editorials,
commentaries, preclinical studies, abstracts, theses and preprints were excluded.
Results
An initial search identified 513 studies. After the removal of duplicates, only 385 studies were left. The
abstracts and titles of the 101 studies were scanned to determine their significance for this systematic
review. After elimination, 18 articles remained; they were scrutinized based on predefined eligibility
criteria. Finally, 14 articles were identified that effectively passed the eligibility criteria.
Conclusion
The DEcentralize Tuberculosis Services and Engage Communities to Transform Lives of Children with
Tuberculosis (DETECT) intervention was found to be more cost-effective than the standard of care for
diagnosing, managing, and preventing pediatric tuberculosis in Uganda.

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COST-EFFECTIVENESS OF AN INTERVENTION TO IMPROVE DIAGNOSIS AND
PREVENTION OF PAEDIATRIC TUBERCULOSIS IN UGANDA: A SYSTEMATIC
LITERATURE REVIEW
Introduction
Clinical and Economic implications of Tuberculosis
Children below 15 years and infants between 0 and 4 years old are at significant risk for
developing tuberculosis (Drobac et al., 2012). In 2020, it was estimated that more than 1.1
million children had contracted tuberculosis (World Health Organization, 2021). According to a
previous study conducted by Hesselings et al. (2009), the risk is exceptionally high in patients
with HIV. The best way to manage the problem is through early diagnosis, treatment, and the
start of preventive therapy to reduce the mortality rate associated with tuberculosis in children
and infants (Marais BJ et al., 2004). People from specific communities have a higher probability
of tuberculosis infection than others; for instance, fishing areas have a high prevalence of the
condition (Karamagi et al., 2018). Children and infants, especially those below 15 years in
contact with people with tuberculosis, especially those that have tested positive for sputum
smear-positive disease, are at an extremely high risk of infection with mycobacterium
tuberculosis, considering the fact that the infection can spread quite quickly. Without early
diagnosis and treatment, the probability of mortality increases significantly (Shingadia et al.,
2003). There is a very high rate of mortality in children and infants in Uganda currently
(Kananura et al., 2016). The infection window is relatively small, especially for infants and
children with low immunity.
Screening and diagnostic strategies
Numerous researchers and medical experts have echoed that active screening of child
contacts and preventive therapy may be quite effective in the early diagnosis and treatment of
tuberculosis, reducing the risk of mortality or further spread, especially in highly populated areas
(Getahun et al., 2015). Active screening and household contact investigation are among the best
detection strategies that significantly increase the notification cases of tuberculosis. Contact
screening, as a form of active case-finding, results in identifying other TB cases of children and
other household members at a relatively earlier stage than passive case-finding, ideally before the
development of the disease to other stages. A previous study showed that approximately 55% of
tuberculosis cases are not diagnosed, especially in the younger age group (World Health
Organization, 2018). Currently, a significant percentage of countries in Urban Africa, including
Uganda, depend solely on passive case-finding of household contacts (Kranzer et al., 2010). In
the case of the passive case finding strategy, detection and diagnosis depend entirely on the self-
reporting patient to take the initiative and visit a healthcare center. The strategy completely
works on the assumption and expectation that an individual can identify symptoms of a disease

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and utilize their resources to seek treatment (Kranzer et al., 2010). Unfortunately, there are many
barriers to the realization of such expectations, including failure to identify the symptoms of
diagnosis early and the high cost of treatment, especially for low-income households.
Current practices in Uganda
Despite the fact that child contact screening and management has been found to be quite
effective for numerous reasons, it is rarely routinely implemented in tuberculosis-endemic
countries, including Uganda (Karamagi et al., 2018). In many cases, programs applied in high-
burden areas where notification cases are significant remain traditionally focused on active,
smear-positive detection of cases of tuberculosis cases at healthcare centers, while contact
screening is standard in low-burden areas (Hossain et al., 2022). The application of contact
screening for the detection of tuberculosis necessitates the integration of a more complex system
that has the capacity to reach beyond healthcare centers to access household contacts (Okello et
al., 2003). Among the most impactful strategies for active contact screening is community-based
health care; there is a significant economic case for the implementation of the strategy for
tuberculosis detection in Uganda (Okello et al., 2003). The application of community-based care
for tuberculosis, especially in rural areas in Uganda, will potentially increase access for families;
there has been evidence of superiority with respect to the effectiveness of community-based care
compared to hospital-based care (Okello et al., 2003). The most significant challenge for
childhood tuberculosis detection and diagnosis, especially in Uganda, is centralized care
(Zawedde-Muyanja et al., 2018). A study conducted by Zawedde-Muyanja et al. (2018) on the
decentralization of child tuberculosis services found that it increased the case finding and uptake
of preventive therapy in children in Uganda; this was predominantly due to the fact a more
significant percentage of children were diagnosed and treated (Zawedde-Muyanja et al., 2018).
The WHO presented a symptom-based screening strategy for child contact screening in
2006 that provided an exceptional opportunity for decentralization of tuberculosis diagnosis and
treatment services and contact screening; the strategy implemented was targeted for the primary
care level. Although some strategies are quite effective with respect to their sensitivity,
specificity, and the number of case notifications, the cost is a significant issue from the
perspectives of both the provider and the receiver of the new implementation. Numerous
interventions are associated with the diagnosis, treatment, and preventive strategies for
tuberculosis in children. For instance, even though Xpert MTB/RIF testing is the most common
option for testing for the presence of tuberculosis, there are much better options that may be
applied, especially in particular circumstances. Some previous studies have shown a trade-off
between the cost of implementing a strategy and its effectiveness. Unless a balance is found
where there is cost-effectiveness without losses, the maintenance of the conventional system is
necessary.
The current study will look into the cost-effectiveness of the DETECT project. The study
will highlight the conventionally applied strategies and their cost-effectiveness to assess the
possibility and merits of integration of other alternatives to either replace or combine with the
currently existing systems in Uganda.

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Topic Justification
The most significant issue for tuberculosis detection, diagnosis, and treatment is cost and cost-
effectiveness. There have been numerous studies published that assess the cost of the DETECT
model implemented in Uganda. However, a gap still exists with respect to the cost effectiveness
of the diagnostic and treatment strategies applied in the DETECT project in Uganda. There is
significant need to examine the cost-effectiveness of the model that may warrant its further
implementation.
Aims and Objectives
Although tuberculosis is a commonly occurring disease in Uganda, very few studies focus
exclusively on the cost-effectiveness of the intervention for diagnosing and treating patients with
the condition. Therefore, the objectives of the current systematic review were to:
1. Assess the cost-effectiveness of an intervention for the diagnosis of pediatric
tuberculosis.
2. Assess the cost-effectiveness of an intervention for the prevention of pediatric
tuberculosis.
3. To assess the cost-effectiveness of DEcentralize Tuberculosis Services and Engage
Communities to Transform Lives of Children with Tuberculosis (DETECT) intervention
as compared to the standard of care for diagnosing, managing, and preventing pediatric
tuberculosis in Uganda.
4. To develop a conceptual model (decision tree) for the pathways of care for the diagnosis,
management, and prevention of pediatric TB in Uganda.
5. To implement the decision tree model to estimate the cost per Disability-adjusted life
year and incremental cost-effectiveness ratio of implementing an intervention to improve
the diagnosis and prevention of pediatric tuberculosis in Uganda.
Literature Review
Overview
There are many challenges faced in the detection, screening and treatment of children with
tuberculosis in Uganda (Zawedde-Muyanja et al., 2018). The Decentralize Tuberculosis services
and Engage Communities to Transform Lives of Children with Tuberculosis was a project
developed to improve diagnosis and treatment for the condition. Uganda is a very high risk area
for tuberculosis recording very high number of infections especially among children. According
to Zawedde-Muyanja, Uganda alone represents at least 80% of the total tuberculosis burden
(Zawedde-Muyanja et al., 2018). The probability of successful diagnosis and treatment of
children in Uganda especially those below the age of 15 years is quite low. The risk of mortality
or unsuccessful treatment is particularly high for patients with HIV and tuberculosis. The
diagnosis and treatment strategies involved in the DETECT project included Xpert MTB/RIF
testing, passive case finding, household contact investigation, active household investigations, a

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combination of case findings alternatives, triage testing, and microscopic observation drug
susceptibility test, among others (Zawedde-Muyanja et al., 2018). The implementation of the
strategies of the DETECT strategies could help eliminate the challenges faced in the detection,
screening and treatment in Uganda.
Rationale
A systematic review of existing literature was done to examine the cost effectiveness of the
DETECT detection, screening and treatment of children with tuberculosis in Uganda. The
strategies have not been fully implemented, assessment of the cost-effectiveness will be
significant in assessing whether the intervention should be applied to replace the approaches
currently existing in Uganda.
Research question
The research question for the current analysis was structured according to the PICO (Patient,
Intervention, Comparison, and Outcome) model.
Population – Children between 0-14 years at risk of developing tuberculosis.
Intervention – Decentralize TB Services and Engage Communities to Transform Lives of
Children with TB using clinical assessment and bacteriological confirmation (Gene-Xpert and
smear microscopy) and/or chest X-ray for the diagnosis of childhood TB and treatment with
isoniazid preventive therapy (IPT).
Comparison – The standard of care (SOC) is Uganda's current pediatric TB diagnostic and
management procedure using clinical assessment and robust TB treatment and adherence
support.
Outcomes:
1. The number of children diagnosed with TB
2. The number of children who started treatment
Question: What is the cost-effectiveness of an intervention for the diagnosis and prevention for
children with tuberculosis?
Search Methods
Search Strategy
A complete database search, was done on numerous databases including EMBASE and Medline. Only
peer-reviewed articles were included. All the articles had to have been published through proper
channels. The participants in the included studies had to be below 15 years (this criterion was only

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applied in the case of clinical assessment and bacteriological confirmation but not in the case finding
strategies). Reference tracking was applied to complement and improve the search sensitivity. The
search terms were clustered using the PECO framework, (Population, Exposure, Comparator and
Outcome). The search keywords included:
Population: Children below 15 years,
Exposure: Tuberculosis, TB, Mycobacterium tuberculosis (M. tuberculosis)
Comparator: Conventional diagnosis and treatment strategies.
Limits: The study designs were limited to Randomized Controlled Trials, case series, prospective analysis,
retrospective analysis, controlled trials, comparative studies, and experimental studies. No grey
literature was included in the analysis. All articles were published between 2000 and 2022. All the
articles had to have been published through proper channels. Grey literature were not included. The
search terms and search strings are in table 1.
Number Search String MEDLINE EMBASE
#1 ('tuberculosis' OR
‘'TB,' OR
'epidemiology' OR '
Uganda’)
12 279 (journals
‘'TB,' OR
'epidemiology' AND '
Uganda’)
12 2573
‘'TB,' OR 'DETECT')
AND (' Uganda’)
3 2544
‘'TB,' OR 'DETECT'
OR ‘House Contact
Investigation’ OR’
Active case-finding‘)
AND (' Uganda’)
0 2706
Total 27 8102
Study Selection
The study selection process was carried out in four primary stages. The first stage was screening
where the titles of the studies were checked. During the second stage, the remaining studies were
checked for duplicity. After removal of duplicates, the next stage was checking of the abstracts
to assess their relevance for the research. The final stage was to check the eligibility criteria; the
remaining studies were included in the systematic literature review.

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Selection Criteria Inclusion Exclusion
Population Children below 15 years
(this criterion was only
applied in the case of
clinical assessment and
bacteriological confirmation
but not in the case finding
strategies)
Adults
Exposure Mycobacterium tuberculosis,
Any type of tuberculosis,
No cases of tuberculosis
Comparator Conventional diagnosis and
treatment strategies
Outcomes Cost-effectiveness
Study Types Randomized Controlled
Trials, case series,
prospective analysis,
retrospective analysis,
controlled trials,
comparative studies, and
experimental studies
Systematic reviews, meta-
analyses, evidence
syntheses, editorials,
commentaries, and
preclinical studies
Language Only English language Studies published in other
languages.
Other Only peer-reviewed articles,
Published between 2000 –
2022 focus exclusively on
Uganda, available online and
published through proper
channels.
Grey literature

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Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)
Flowchart
Records identified through
database searching
(n =8129)
Medline (n=27)
Embase (n=8102)
Screening
Included
Eligibility
Identification
Records after duplicates removed
(n =2435)
Records screened
(n = 101)
Excluded irrelevant
studies based on title
(n=2334)
(n = )
Full-text articles assessed
for eligibility
(n = 18 )
Full-text articles excluded based on
abstract, publication type (Systematic
reviews, meta-analyses, evidence
syntheses, editorials, commentaries,
and preclinical studies
(n = 83)
Studies included in
qualitative synthesis
(n = 14 )
Studies included in
quantitative synthesis
(n = 14)
Duplicates
removed
(n=5694)

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Figure 1: PRISMA DIAGRAM
Data Extraction.
The data and findings from the included studies that passed the eligibility criteria were extracted in table
2. Data extracted included the author, year of publication, country, mean age, number of participants,
type of intervention, outcome, and findings from the article.
Data Synthesis
A meta-analysis was not carried using the Review Manager software since the data collected mostly
associated with cost could not be analyzed using the application. EXCEL was used for analysis and
presentation of the findings.
Results
Literature Search
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist guidelines
2020 were applied. The initial search in the online databases using the earlier mentioned keywords
identified 8129 studies. After the removal of duplicates, only 2435 studies were left. The abstracts and
titles of the 101 studies were scanned to determine their significance for the systematic review. After
elimination, 18 articles remained; they were scrutinized based on the eligibility criteria. Finally, 14
articles were identified that effectively passed the predefined eligibility criteria. The PRISMA flowchart
diagram shows the process and results of the literature search.
Study Characteristics (Included Studies)
Data Extraction Findings
Author and
year
Intervention Country Number of
participants
Mean
Age
Outcome Information
Extracted
Okello et al.
(2003)
Community-based
care compared
with conventional
hospital-based
care.
Uganda 510 patients N/A The cost per patient
successfully treated
care.
The cost per patient
successfully treated
was $911 with the
hospital-based
strategy and $391
with community-
based care.
Mwangwa
et al. (2017)
Xpert Ultra stool
testing
Uganda 42 participants < 15
years
% of
bacteriologically
confirmed TB
cases likely higher
than SOC
% of
bacteriologically
confirmed TB
cases started on
treatment

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Nansumba
et al.
(2016)
Xpert Ultra stool
testing
Uganda 137
participants
with
presumptive
TB
3 -14
years
% of presumptive
TB cases for TB
diagnosis
% of presumptive
TB cases with
confirmed
% of
bacteriologically
confirmed TB
cases started on
treatment
Orikiriza et
al. (2018)
Xpert Ultra stool
testing
Uganda 392 14 years % of presumptive
TB cases with
confirmed TB
% started on TB
treatment
Reither et al.
(2015)
Xpert Ultra stool
testing
Uganda
and
Tanzania
451 <15
years
% of presumptive
TB cases with
confirmed, highly
probable and
probable TB
Sekadde et
al. (2013)
Xpert Ultra stool
testing
Uganda 235 <12
years
% of presumptive
TB cases
submitting induced
sputum
% of presumptive
TB cases with
confirmed TB
Ssengooba
et al. (2020)
Xpert Ultra stool
testing
Uganda 353 <15
years
% of samples
MTB-positive, by
type of sample
only diagnosed TB
patients included
Walusimbi
et al. (2016)
microscopic
observation drug
susceptibility test
versus Xpert
MTB/Rif test for
diagnosis of
pulmonary
tuberculosis
Uganda N/A N/A The unit cost of
MODS versus US$
The unit cost of
MODS was US$
6.53 versus US$
12.41 of Xpert
Sekandi et
al. (2015)
Community Active
Case Finding and
Household Contact
Investigation
Urban
Africa
N/A N/A Cost effectiveness
of passive case
finding (PCF),
active case finding
(ACF), Household
Contact
Investigations
(HCI)
PCF+HCI strategy
was cost-effective
at US$443.62/ TB
case detected.
PCF+ACF was not
cost-effective at
US$1492.95/ TB
case detected.
Hsiang et al.
(2016)
MTB/RIF Ugandan
peripheral
settings
N/A N/A cost of
implementing
Xpert MTB/RIF in
Ugandan peripheral
settings
mean unit cost of
an Xpert test was
US$21 based on a
mean monthly
volume of 54 tests
per site though unit
cost varied widely
(US$16–58)
(Muyanja et
al., 2018)
Decentralization of
tuberculosis
diagnosis and
treatment services.
Uganda 910 <15
years
Effectiveness of
decentralization of
tuberculosis
diagnosis and
treatment services.
The % of children
that completed
treatment
Number of children
screened.
Number of children

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% of children that
started preventive
therapy
% of children that
completed therapy.
Karamagi et
al. (2018)
Quality
improvement with
facility-led active
case finding (QI-
ACF)
Uganda 48 facilities N/A Effectiveness of
active case finding
TB case
notification.
TB patient contacts
with the majority
of TB positive
cases.
Communities with
the highest TB
cases
Murray et
al. (2016)
Triage Testing for
Tuberculosis
Uganda N/A N/A Effectiveness of
triage testing
compared against
passive case
detection with
Xpert MTB/RIF
Systematic
screening cost
US$610 per per
year of life gained
(YLG) (95%
uncertainty range
US$200–US$1859)
with chest X-ray
(CXR) (US$5/ test,
specificity 0.67), or
US$588 (US$221–
US$1746) with C
reactive protein
(CRP) (US$3 per
test, specificity
0.59)
Jaganath et
al. (2013)
Contact screening Uganda 761 child
contacts
Child
contacts
aged <15
years
Yield of contact
tracing on
childhood
tuberculosis and
indicators for
disease progression
in Uganda.
Contact tracing for
children in high-
burden settings
helps to identify a
large % of culture-
confirmed positive
tuberculosis cases
Table 1: Data Extraction Findings
Findings and Analysis
All the costs have been calculated based on the current inflation rate
Sekandi et al. (2015)
Passive Case Finding Cost
(Inflation rate = 2.71% from 2013 to 2022)
Cost Category Mean Cost Range (+/- 50%) Data Source
Program Cost $9.81 $4.905 – 14.715 Uganda TB program
records 2008–09
Direct Medical Cost $59.95 $29.975 – 89.925 Uganda TB program
records 2008–09

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Total Patient
&Caregiver Costs
$36.73 $18.365 - $55.095 TB patient cost
survey
Total per patient Cost $106.49 $53.245 - $159.735 N/A
Table 2: Passive Case Finding Cost
Table 3 above shows the mean cost, range and data source for the passive case finding strategy. As
shown, the highest cost of passive case finding stemmed from the direct medical cost.
Total Costs and Incremental Cost-effectiveness Ratios Referencing Passive Case Finding
Total Cost ($) $48,226
Total Effectiveness (rounded to the nearest
whole number per 1000 person screened)
253
Total cost/total effectiveness (ACER)
(rounded off to 5 significant figures)
$190.61
Table 3: Total Costs and Incremental Cost-effectiveness Ratios Referencing Passive Case Finding
Table 3 above shows the mean cost, range and data source for the total costs and incremental cost-
effectiveness ratios referencing passive case finding strategy. As shown, total cost is quite high in
Uganda but the total effectiveness was significant.
Cost of Active Case Finding
Program Cost $34.19 $17.095 – $51.285 Primary study
research budgets
Direct Medical Cost $60.26 $30.13 – $90.39 Primary study
research budgets
Total Patient
&Caregiver Costs
$6.05 $3.025 - $9.075 Primary study
research budgets
Table 4: Cost of Active Case Finding
Table 5 above shows the mean cost, range and data source for the passive case finding strategy. As
shown, similar to the case of the passive case finding strategy, the highest cost of the active case finding

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strategy stemmed from the direct medical cost. The total per patient cost was lower than the passive
case finding strategy.
Cost of Household Contact Investigations
research budgets
research budgets
Total Patient
&Caregiver Costs
$6.05 $3.025 - $9.075 Estimated from
primary study
Table 5: Cost of Household Contact Investigations
Table 6 above shows the mean cost, range and data source for the household contact investigation
strategy. As shown, similar to the case of the passive case finding and the active case finding strategies,
the highest cost for the household contact investigations strategy stemmed from the direct medical
costs ($58.97). The total per patient cost was lower compared to the passive case finding and the active
case finding strategies.
Cost of a Combination of Passive Case Finding and Passive Case Finding
research budgets
research budgets
Total Patient
&Caregiver Costs
$42.78 $21.39 - $64.78 Estimated from
primary study
Total per patient Cost NM NM N/A
Table 6: Cost of a Combination of Passive Case Finding and Passive Case Finding
Table 7 above shows the mean cost, range and data source for the household contact
investigation strategy. Similar to the previous cases, the highest cost stemmed from the direct
medical cost ($119.03). There was no information on the total per patient cost.

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Total Costs and Incremental Cost-effectiveness of A Combination of Passive and Active
Case Finding Ratios Referencing Passive Case Finding
Total Cost ($) $52, 347.52
Incremental Cost $4120.65
255
Incremental effectiveness compared to passive
case finding alone
2
$205.28
Cost per additional case detected $1898.74
Table 7: Total Costs and Incremental Cost-effectiveness of A Combination of Passive and Active Case Finding Ratios Referencing
Passive Case Finding
Table 8 above shows Total Costs and Incremental Cost-effectiveness of a combination of passive and
active case finding ratios referencing passive case finding. The total cost was quite high ($52, 347.52)
compared to the active case finding, passive case finding and household contact investigation strategies.
The total cost per additional case detected was also found to be quite high ($1898.74).
Cost of a Combination of Passive Case Finding and Household Contact Investigation
research budgets
research budgets
Total Patient
&Caregiver Costs
$42.78 $21.39 - $64.78 Estimated from
primary study
Total per patient Cost NM NM N/A
Table 8: Cost of a Combination of Passive Case Finding and Household Contact Investigation

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Table 9 above shows the cost of a combination of passive case finding and household contact
investigation. Similar to the previous cases, the highest cost stemmed from the direct medical cost
($119.03). There was no information on the total per patient cost.
Total Costs and Incremental Cost-effectiveness of a Combination of Passive and Household
Contact Investigation Ratios Referencing Passive Case Finding
Total Cost ($) $74,400.62
Incremental Cost $26.173.76
300
Incremental effectiveness compared to
passive case finding alone
47
$248.00
Cost per additional case detected $564.2
Table 9: Total Costs and Incremental Cost-effectiveness of a Combination of Passive and Household Contact Investigation Ratios
Referencing Passive Case Finding
Table 8 above shows total costs and incremental cost-effectiveness of a combination of passive
and household contact investigation ratios referencing passive case finding. The total cost was
higher ($ 74, 400.62) compared to the combination of passive and active case finding strategies
($52, 347.52). The incremental effectiveness compared to passive case finding alone and the
total cost per additional case detected was also found to be high.
Analysis

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Figure 2: Costs of Case Finding Strategies
The chart above shows the individual costs for individual case-finding strategies for tuberculosis
detection. As shown in the chart, the highest total per-patient costs are incurred in the case of
passive case finding. Direct medical costs are highest in the active case-finding strategy. The
total patient and caregiver costs are lowest in active case finding, followed by household contact
investigation. The program costs are significantly lower in the case of the passive cost-finding
strategy; this explains the reason behind the prevalent implementation of the strategy in Uganda
among other countries, especially in Africa.
Analysis of Total Costs and Incremental Cost-effectiveness of a Combination of Case
Finding Strategy Ratios Referencing Passive Case Finding
Figure 3: Passive Case Finding Combined with Other Strategies
$0.00 $20.00 $40.00 $60.00 $80.00 $100.00 $120.00
Passive Case Finding
Active Case Finding
Household Contact Investigation
Costs of Case Finding Strategies
Total per patient Cost Total Patient &Caregiver Costs
Direct Medical Cost Program Cost
Total Effectiveness
Incremental effectiveness compared to passive case finding alone
Cost per additional case detected
253.00 $190.61
255.00 2.00 $205.28
$1,898.74
300.00 47.00 $248.00 $564.20
PASSIVE CASE FINDING COMBINED WITH OTHER
STRATEGIES
Passive Case Finding $48,226.00
Passive and Active Case Finding Combination $52, 347.52 $4,120.65
Passive Case Finding and Household Contact Investigation Combination $74,400.62 $26.173.76

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As shown in figure 3 above, the passive case finding strategy of case detection is the least effective
option and has the least ACER (Average Cost-Effectiveness Ratio); therefore, compared to the other
categories, it is the worst alternative. The most cost-effective prospect among the three is the
combination of passive and active case-finding strategies; the amalgamation of the two has the highest
incremental effectiveness compared to passive case-finding solely. The combination has the least cost
per additional case detected compared to the combination of passive case finding and household
contact investigation. Implementing the two strategies (passive case finding and active case finding) is
more expensive compared to single options, but the former is more effective in terms of cost and
otherwise.
Quality improvement with facility-led active case finding (QI-ACF)
Karamagi et al. (2018)
Tuberculosis case notification per 100,000
people
171 to 223 cases
Tuberculosis patient contacts 40 (6.1%)
The positivity rate for specific areas Fishing communities – (6.8%)
Prisons – (34, 2.3)
Table 10: Quality improvement with facility-led active case finding (QI-ACF)
Table 11 above shows the effectiveness of facility-led case-finding strategies for tuberculosis
detection. The number of tuberculosis case notifications increased significantly, similar to the
specific number of tuberculosis patient contacts. It was easy to identify areas where tuberculosis
is prevalent; this helps in the management of resources to target particular areas of higher
prevalence.
Effectiveness of Triage Testing Compared Against Passive Case Detection with Xpert
MTB/RIF
Murray et al. (2016)
All the costs have been calculated based on the current inflation rate
Strategy Average
Cost
Incremental
Cost
Average
Years of
Life Lived
Incremental
days of life
Incremental
Cost-
effectiveness
ratio
Standard of
Care
$23.19 17.417
CRP $30.9 $7.71 17.427 3.7 $747.82
CXR $31.18 $8.00 17.427 3.7 $775.8
Table 11: Effectiveness of Triage Testing Compared Against Passive Case Detection with Xpert MTB/RIF
In table 12, shown above, the standard of care is the conventional passive case detection with
Xpert MTB/RIF testing applied in Uganda. According to the analysis, the average costs of C
reactive protein (CRP) and chest X-ray (CXR) are higher though by a small margin of $7.71 and
$8, respectively. The incremental days of life after implementation of the triage tests are

18
insignificant (approximately four days). The incremental cost-effectiveness ratio shows that
triage testing is more cost-effective compared to the Xpert MTB/RIF testing in Uganda.
Community-based Care versus Conventional Hospital-Based Approach
Okello et al. (2003)
Category Cost for community-
based Care
Conventional Hospital based
approach
Cost/patient treated for new
smear-positive patients
$289 $510
Program Supervision $27 N/A
Training $18
Cost per patient successfully
treated
$391 $911
Table 12: Community-based Care versus Conventional Hospital-Based Approach
Okello et al. (2003) found that the effectiveness of community-based approach was 74% higher
compared to 56% for community-based care. The average length of stay for the hospital-based
approach was 60 days, while that of the community-based approach was 19 days. As shown in
table13, some additional costs are incurred in community-based care; however, the cost per
patient treated for new smear-positive patients is significantly lower. There may be a trade-off
between cost and effectiveness in cost-effectiveness analysis.
Discussion
Sensitivity and Specificity
Compared to the passive case finding strategy, the household contact investigation and the active
case finding strategy are more effective. Combining the aforementioned strategies is also more
effective in case detection, screening and treatment of children with tuberculosis. The table
below shows the sensitivity and specificity of the tests.
Lee et al. (2011) and Sekandi et al. (2015)
Test Sensitivity Specificity
Xpert Test 1 (0.883–1.00) 0.776 ( 0.61–1.0)
Smear Microscopy 0.609 (0.30- 0.80) 0.883 ( 0.80–0.97)
Chest X-ray 0.92 (0.70–0.95) 0.63 (0.52–0.99)
Skin test 0.94 (95% CI, 0.87- 0.98%) 0.88 (95% CI, 0.74-0.96%)
The sensitivity and specificity analysis above shows that the tests are very effective and had very
high sensitivity and specificity. Skin test is the most common test for tuberculosis with the
highest specificity.

19
Passive Case Finding Intervention
Passive Case Finding is the conventional strategy for detecting tuberculosis; in such a
case, the patient with the symptoms takes the initiative to visit the healthcare center for
diagnosis. In most situations, the patients initially report cough symptoms that have persisted for
two weeks or more. During diagnosis, the patients with a persistent cough go for physical
examination, and a spot of sputum sample is collected for both a culture test and an acid-fast
bacilli (AFB) smear microscopy test. The cost for the diagnosis is very low considering the fact
that it is a free service in healthcare centers in Uganda. The patients do not have to wait too long
for their diagnosis depending on the patient load in the healthcare center; the waiting period may
range from a few hours to approximately two days (Mauch et al., 2013). If one or both tests are
positive, the diagnosis of tuberculosis is confirmed.
Alternative Case Finding Strategies
According to figure 3, the household contact and active case finding strategies combined
with the passive case finding strategies are the most cost-effective. A study conducted by
Zawedde-Muyanja et al. (2018) on the decentralization of child tuberculosis services found that
it increased the case finding and uptake of preventive therapy in children in Uganda; this was
primarily due to the fact a more significant percentage of children were diagnosed and treated
(Zawedde-Muyanja et al., 2018). According to the case report, within less than two years, the
percentage of child tuberculosis among all the included cases increased significantly from 8.8%
to 15% (Zawedde-Muyanja et al., 2018). Among the children < 15 years that were available,
2.4% tested positive for tuberculosis after their sputum was tested (Zawedde-Muyanja et al.,
2018). 82% of the diagnosed children completed the treatment successfully (Zawedde-Muyanja
et al., 2018). 74% of the children who tested positive for tuberculosis began therapy, and 85%
completed it (Zawedde-Muyanja et al., 2018). The findings from the case report highlight the
significance and effectiveness of decentralization of child tuberculosis services through the
integration of household contact investigation or active case finding. Although it may be more
expensive, decentralizing the healthcare services, as shown by the current analysis, is more cost-
effective considering the number of children diagnosed and treated successfully.
Contact tracing is an additional intervention that could promote the early detection of
tuberculosis in children. According to a previous study conducted by Jaganath et al. (2013),
contact tracing for children, specifically in settings considered to be a high burden, can help in
the identification of a significant percentage of culture-confirmed positive cases of tuberculosis
before dissemination of the infection to other potential contacts (Jaganath et al., 2013). It also
suggests aspects of disease progression to identify those who may benefit from targeted
screening. Pediatric cases of tuberculosis management are conventionally difficult to manage
owing to the prevalent cases or under-diagnosis or presumptive situations; these are significant
barriers to proper health for young children, especially in low-income areas (Zawedde-Muyanja
et al., 2018. The problem is more pronounced at the tertiary care level, especially for children
below the age of 5 years that cannot sufficiently verbally convey their symptoms (Zawedde-
Muyanja et al., 2018). Although pulmonary tuberculosis is the most common, especially among
children, it is the most challenging to diagnose compared to extra-pulmonary tuberculosis; in

20
many cases, it may be mistaken for pneumonia owing to radiological or clinical overlap.
According to the study by Zawedde-Muyanja et al. (2018), decentralization of tuberculosis
diagnosis and treatment services increases the probability of early diagnosis and treatment; this
significantly reduces the mortality rate of children of tuberculosis or a combination with HIV.
Quality improvement is among the most significant merits of implementing active case-
finding strategies. The same findings were echoed in the study by Karamagi et al. (2018),
showing the effectiveness of active case findings. Unlike the case of passive case finding,
decentralization helps in the identification of areas where there is a high prevalence of
tuberculosis. The study conducted by Karamagi et al. (2018) found that there were higher cases
of tuberculosis-positive contacts in fishing areas. It is vital for targeting to be implemented at all
points of tuberculosis intervention to advance yield: targeting areas with the least number of case
notifications and high mortality rates as a function of the illness, as well as HIV patients, those
from fishing communities and index patient contacts (Karamagi et al., 2018).
Xpert Testing
Xpert testing is the most common method for diagnosing patients with tuberculosis.
According to the study by Hsiang et al. (2016), the average unit per every Xpert diagnostic test is
approximately $25.92 ranging between $19.75 and $71.60. According to the diagnosis, the cost
for diagnosis was found to be approximately 2.4 times more in clinics utilizing Xpert testing than
those not applying the procedure (Hsiang et al., 2016). The Xpert averaged costs in Uganda were
also calculated and found to be $146.9 in the high volume areas for every new case detected and
may be as high as $1092.49 in low volume communities (Hsiang et al., 2016). Therefore,
generally, Xpert testing is less cost-effective compared to some alternatives that have been
discussed in other studies (Hsiang et al., 2016). Even though the test can accurately and
sufficiently detect tuberculosis cases, it may increase the cost by more than twice for arguably
small gains resulting in a reduction in cost-effectiveness with continuous lower test volumes
(Hsiang et al., 2016).
Cost-effectiveness of Triage Testing
Triage testing is an arguably common method for diagnosing patients that have shown
symptoms of tuberculosis or those with high-risk factors for the medical condition. According to
the study conducted by Murray et al. (2016), the cost-effectiveness of triage testing in
comparison to the Xpert MTB/RIF testing in Uganda was dependent on the specificity of the
diagnosis intervention and people's willingness to pay in the particular areas (Murray et al.,
2016). The study showed that if people's willingness to pay was $864.83 per year of life gained
and the specificity was 0.67, then there was a high probability that triage testing would be
preferred compared to Xpert MTB/RIF testing in Uganda (Murray et al., 2016). If the triage cost
could be decreased by at least $1.27 and the probability of death every month from tuberculosis
increased by 0.03%, then triage testing would be preferred by almost 100% (Murray et al., 2016).
On the other hand, if the percentage of those screened for tuberculosis was less than 2% then
triage was found not to be cost effective because the threshold of the willingness to pay was
relatively low (Murray et al., 2016). The only option in such a case would be to lower the cost to

21
triage testing (Murray et al., 2016). Overall, for a triage test with significant sensitivity (98%) to
be cost-effective compared to Xpert MTB/RIF testing, the mortality risk must be at least 1%
every month, and the specificity can range between 59% and 67% minimum for a cost of $3.82.
A study conducted by Orikiza et al. (2018) and Ssengooba et al. (2020) found the specificity for
Xpert testing to be>90% in sputum, which is relatively high and fits the profile for sufficient
cost-effectiveness (Orikiza et al., 2018). A similar conducted by Reither et al. (2015) also
reported that the Gene Xpert test has excellent specificity reaching 100% in some cases (Reither
et al., 2015).
Uganda does not fit the aforementioned profile required to attain the cost-effectiveness of
triage testing. This translates that it is more cost-effective to implement Xpert MTB/RIF testing
in comparison to triage testing in most areas in Uganda (Murray et al., 2016). The cost of triage
testing in Uganda ($3.82 - $6.36) is currently arguably relatively high (Murray et al., 2016).
Generally, triage testing is more cost-effective, though only in particular cases. The trade-off
highlighted in the study conducted by Murray et al. (2016) is also significant in the effectiveness
of triage testing in Uganda. To attain the cost-effectiveness of triage testing compared to Xpert
MTB/RIF testing, we can propose the implementation of 0.9 sensitivity, 0.75 specificities and
$6.36 cost (Murray et al., 2016). The proposed structure would aim to reduce the cost of
diagnosis relative to Xpert testing. In the study conducted by Murray et al. (2016), a different
strategy for diagnosis was proposed where the patients could undergo cough screening followed
by triage testing; this would potentially increase the probability of a higher number of diagnosed
patients relative to the Xpert testing application (Murray et al., 2016). Generally, it is more
advisable to apply triage testing in high-risk populations including fishing communities and areas
with a high prevalence for HIV.
Cost Effective Analysis of Microscopic Observation Drug Susceptibility Test versus Xpert
MTB/Rif Test for Diagnosis of Pulmonary Tuberculosis
A study by Walusimbi et al. (2016) compared the cost-effectiveness of the Microscopic
Observation Drug Susceptibility (MODS) test with the Xpert MTB/Rif test. According to the
findings from the study, the MODS test for diagnosis of pulmonary tuberculosis was found to be
more effective than the Xpert test among patients with HIV (Walusimbi et al., 2016). The unit
cost for Xpert was found to be $15.78, while that for MODS was $8.3. The consumables
accounted for 84 % ($13.19 of $15.78) of unit cost in the case of Xpert testing and 59 % ($4.88
of 8.3) of the unit cost in the case of MODS (Walusimbi et al., 2016). Similar findings were
reported in the study conducted by Hsiang et al. (2016), where a significant percentage of the
mean cost (93%) stemmed from expenses on the equipment and reagents. The ratio of cost-
effectiveness was also found to be $90.3 for Xpert testing and $43.24 for every tuberculosis
patient diagnosed (Walusimbi et al., 2016).
According to the analysis, MODS is more cost-effective compared to Xpert testing by all
accounts (Walusimbi et al., 2016). Unfortunately, most non-economic factors favor the use of
Xpert testing compared to MODS (Walusimbi et al., 2016). To make Xpert more competitive, it
is vital that Xpert cartridge costs must be reduced significantly (by more than 50%). A study
conducted by Mwangwa et al. (2017) found that considering the number of smear-positive cases

22
in Uganda (45%), medical personnel rely too much on smear microscopy and not sufficiently on
other forms of clinical diagnosis for tuberculosis in children. Many variables determine the
effectiveness of the Xpert test, including the nature of the sputum induction; the success rate of
intervention impacts its general cost-effectiveness (Nansumbe et al., 2016). Sekadde et al. (2013)
found that the Xpert MTB/RIF test identified double the number of those detected by smear
microscopy. The topic of the cost-effectiveness of different interventions should assess further,
focusing in a broader population.
A Decision Tree Diagram Showing the Sequence of Events for Diagnosis and Treatment of
Patients with Tuberculosis
Tesfaye et al. (2019)
Conclusion
Numerous interventions were taken into account in the current systematic review,
including passive case finding, household contact investigation, contact screening and active
case finding for diagnosis. Other aspects of diagnosis include the conventional use of the Xpert
MTB/RIF test, among other alternatives such as MODS and triage testing. Despite the fact that
there are numerous options to test for diagnosis, information on cost-effectiveness was not
available. According to the findings from the systematic review and analysis of results, though it

23
is more expensive, decentralization of the healthcare services is more cost-effective, considering
the number of case notifications, diagnoses and children that begin treatment. Xpert testing is
less cost-effective than other alternatives; it may increase the cost significantly for arguably
trivial causing a reduction in cost effectiveness and test volumes. The cost-effectiveness of a
triage test compared to Xpert testing was found to be dependent on particular aspects (people's
willingness to pay was $864.83 per year of life gained, and the specificity was 0.67). MODS test
was also found to be more cost-effective compared to Xpert tests. The non-economic factors
associated with the diagnosis of tuberculosis support the use of Xpert tests despite the fact that
there are much better alternatives.
Limitations
Considering the fact that the research topic focused solely on the pediatric treatment of
tuberculosis, this was a very significant limitation since there were very few studies discussing
the cost-effectiveness of diagnosis, treatment and prevention strategies in children below 14
years. Therefore, the inclusion criteria were modified to accommodate studies that included
participants beyond the aforementioned age group; however, this modification was only applied
in the case of decentralization of case detection strategies. There were very few studies that
focused exclusively on pediatric tuberculosis treatment, especially in relation to the cost-
effectiveness of the DETECT model. There was potential for more analysis and findings, but this
was limited by the eligibility criteria. The conclusions of the current systematic review will form
a foundation for future research into the cost-effectiveness of interventions for the improvement
of diagnosis and prevention of pediatric tuberculosis.
Assumptions
The screening procedures were carried out effectively at a healthcare facility.
Some assumptions were made in the analysis of cost.
Some patients did not return for a re-evaluation following an initial negative result/no Tb
diagnosis.
Author Contributions
The author contributed significantly to the design and analysis of the systematic review.
Additionally, he participated meaningfully in the process of study selection, screening, and
scrutiny, extraction of data and information, quality assessment of the randomized controlled
trials, and data synthesis. The author took part in the entire process of reviewing and approving
the final manuscript.

24
Conflicts of Interest
No conflicts of interest were declared.
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