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Outcomes of empiric treatment for pediatric tuberculosis, Kampala, Uganda, 2010–2015

Authors:
  • Mulago National Referral Hospital
  • National Tuberculosis and Leprosy Program, Uganda

Abstract and Figures

Background Childhood tuberculosis (TB) diagnoses often lack microbiologic confirmation and require empiric treatment. Barriers to empiric treatment include concern for poor outcomes and adverse effects. We thus determined the outcomes of empiric TB treatment from a retrospective cohort of children at a national referral hospital in Kampala, Uganda from 2010 to 2015. Methods Children were diagnosed clinically and followed through treatment. Demographics, clinical data, outcome and any adverse events were extracted from patient charts. A favorable outcome was defined as a child completing treatment with clinical improvement. We performed logistic regression to assess factors associated with loss to follow up and death. Results Of 516 children, median age was 36 months (IQR 15–73), 55% (95% CI 51–60%) were male, and HIV prevalence was 6% (95% CI 4–9%). The majority (n = 422, 82, 95% CI 78–85%) had a favorable outcome, with no adverse events that required treatment discontinuation. The most common unfavorable outcomes were loss to follow-up (57/94, 61%) and death (35/94, 37%; overall mortality 7%). In regression analysis, loss to follow up was associated with age 10–14 years (OR 2.38, 95% CI 1.15–4.93, p = 0.02), HIV positivity (OR 3.35, 95% CI 1.41–7.92, p = 0.01), hospitalization (OR 4.14, 95% CI 2.08–8.25, p < 0.001), and living outside of Kampala (OR 2.64, 95% CI 1.47–4.71, p = 0.001). Death was associated with hospitalization (OR 4.57, 95% CI 2.0–10.46, p < 0.001), severe malnutrition (OR 2.98, 95% CI 1.07–8.27, p = 0.04), baseline hepatomegaly (OR 4.11, 95% CI 2.09–8.09, p < 0.001), and living outside of Kampala (OR 2.41, 95% CI 1.17–4.96, p = 0.02). Conclusions Empiric treatment of child TB was effective and safe, but treatment success remained below the 90% target. Addressing co-morbidities and improving retention in care may reduce unfavorable outcomes.
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R E S E A R C H A R T I C L E Open Access
Outcomes of empiric treatment for
pediatric tuberculosis, Kampala, Uganda,
20102015
Eric Wobudeya
1*
, Devan Jaganath
2
, Moorine Penninah Sekadde
3
, Betty Nsangi
4
, Heather Haq
5
and
Adithya Cattamanchi
6,7,8
Abstract
Background: Childhood tuberculosis (TB) diagnoses often lack microbiologic confirmation and require empiric
treatment. Barriers to empiric treatment include concern for poor outcomes and adverse effects. We thus
determined the outcomes of empiric TB treatment from a retrospective cohort of children at a national referral
hospital in Kampala, Uganda from 2010 to 2015.
Methods: Children were diagnosed clinically and followed through treatment. Demographics, clinical data,
outcome and any adverse events were extracted from patient charts. A favorable outcome was defined as a child
completing treatment with clinical improvement. We performed logistic regression to assess factors associated with
loss to follow up and death.
Results: Of 516 children, median age was 36 months (IQR 1573), 55% (95% CI 5160%) were male, and HIV
prevalence was 6% (95% CI 49%). The majority (n= 422, 82, 95% CI 7885%) had a favorable outcome, with no
adverse events that required treatment discontinuation. The most common unfavorable outcomes were loss to
follow-up (57/94, 61%) and death (35/94, 37%; overall mortality 7%). In regression analysis, loss to follow up was
associated with age 1014 years (OR 2.38, 95% CI 1.154.93, p= 0.02), HIV positivity (OR 3.35, 95% CI 1.417.92,
p= 0.01), hospitalization (OR 4.14, 95% CI 2.088.25, p< 0.001), and living outside of Kampala (OR 2.64, 95% CI
1.474.71, p= 0.001). Death was associated with hospitalization (OR 4.57, 95% CI 2.010.46, p< 0.001), severe
malnutrition (OR 2.98, 95% CI 1.078.27, p= 0.04), baseline hepatomegaly (OR 4.11, 95% CI 2.098.09, p< 0.001),
and living outside of Kampala (OR 2.41, 95% CI 1.174.96, p= 0.02).
Conclusions: Empiric treatment of child TB was effective and safe, but treatment success remained below the 90%
target. Addressing co-morbidities and improving retention in care may reduce unfavorable outcomes.
Keywords: Child, Tuberculosis, Treatment, Outcomes
Background
Timely initiation of treatment is critical for effective
tuberculosis (TB) care and control in children. Of the
estimated 233,000 children that die from TB each year,
96% did not receive treatment [1,2]. For primary care
providers in TB endemic settings, challenges with
confirming a TB diagnosis in children and concern of
adverse effects with empiric treatment (i.e., without
microbiological confirmation) are key barriers to initiat-
ing anti-TB treatment [3,4]. Symptoms are non-specific,
chest x-ray findings variable, and diagnostic testing is
often unavailable or not feasible due to difficulty obtain-
ing sputum [3,5]. Even when diagnostic testing occurs,
sensitivity is decreased due to the paucibacillary nature
of pediatric TB [6]. This contributes to 55% of child TB
cases not being reported to national programs [2] from
high TB burden settings have consistently documented
that health care workers feel uncomfortable about
making a TB diagnosis in a child and that there are often
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribut ion 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
* Correspondence: ewobudeya@gmail.com
Eric Wobudeya and Devan Jaganath contributed equally to this work.
1
Directorate of Pediatrics & Child Health, Mulago National Referral Hospital,
P.O. Box 23491, Kampala, Uganda
Full list of author information is available at the end of the article
Wobudeya et al. BMC Public Health (2019) 19:446
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delays in care [79]. For example, a cross-sectional study
of six primary clinics in Kampala found that no children
who met clinical criteria for TB had been started on
anti-TB treatment [10]. While algorithms exist to iden-
tify children with TB based on clinical factors [1113], a
concern is that without microbiologic confirmation, mis-
diagnosis could result in poor outcomes or adverse
events from anti-TB treatment. A better understanding
of outcomes of children treated empirically for TB based
on a clinical diagnosis would provide more guidance to
providers about the effectiveness and safety. We thus an-
alyzed outcomes of children less than 15 years of age
with clinically diagnosed TB receiving empiric treatment
over a five-year period at a national referral hospital in
Kampala, Uganda, and factors associated with the
unfavorable outcomes of lost to follow up and death.
Methods
Study design and setting
This was a retrospective cohort study of children treated
for clinically diagnosed TB at Mulago National Referral
Hospital Pediatric TB Clinic. The clinic treats children
up to 14 years of age with drug-susceptible TB using
Fixed Dose Combination (FDC) treatment in accordance
with Uganda National TB and Leprosy Programme
(NTLP) guidelines [13]. Children are seen in clinic every
two weeks during the first month of treatment and
monthly thereafter for the standard six-month or
twelve-month treatment depending on the TB disease
type. At each visit, clinical notes are documented using
standardized forms and entered into a secure electronic
database. Adverse events are monitored based on clinical
symptoms and exam, without routine laboratory testing.
Management of any adverse events were completed
according to national guidelines [12]. The Mulago
Hospital Research and Ethics Committee approved the
study protocol and waived the requirement for informed
consent.
Study population
We included all children less than 15 years old treated
empirically for TB between January 2010 and December
2015. Clinical diagnosis was made per NTLP guidelines
[12,13]. We excluded children if they had multi-drug
resistant (MDR) TB, were transferred, or were missing
key variables (age and treatment outcome). As a com-
parison, outcomes on children with confirmed TB were
also collected.
Data collection and definitions
The data was not publically available hence we obtained
Mulago Hospital permission to use the data. We
extracted demographic and clinical data including HIV
status, type of TB, TB treatment outcome, and any
adverse events from the Pediatric TB Clinic electronic
database. We defined severe malnutrition as a weight-
for-age Z score less than 3. We defined a favorable
outcome if the child completed treatment and had
documented clinical improvement, and an unfavorable
outcome if the child died, failed treatment (no clinical
improvement or treatment discontinuation) or was lost
to follow-up prior to completion of treatment.
Statistical analysis
Descriptive statistics were assessed with proportions and
95% confidence intervals (CI) for categorical variables
and median and interquartile range (IQR) for continuous
variables. For bivariate analysis of characteristics associ-
ated with favorable versus unfavorable outcome, we
compared proportions using the chi-squared test. We
stratified unfavorable outcomes into loss to follow up
and death, and conducted logistic regression on char-
acteristics with p-value < 0.05 from the unfavorable
bivariate analysis. HIV status and severe malnutrition
(known to be associated with unfavorable outcome)
[14,15], and sex were also included. Odds Ratios
(OR) were presented with 95% Confidence Intervals
(CI); p-value < 0.05 was considered significant. We
performed analyses using STATA 15 (Stata Corp,
College Station, TX, USA).
Results
Cohort characteristics
Of 713 children treated for TB during the study period,
there were 64 with confirmed TB, 1 with MDR TB, 1
with missing age information, 23 who were transferred
out, and 108 with missing treatment outcome (Fig. 1),
for a total of 516 children empirically started on anti-TB
treatment.
Details of patient characteristics by outcome are
shown in Table 1. The median age was 36 months (IQR
1573), 55% (95% CI 5160%) were male, and about half
resided outside of Kampala district (46, 95% CI 41
50%). The majority (65, 95% CI 6169%) were below
five years old, and HIV prevalence was 6% (31/509,
95% CI 49%). The prevalence of severe malnutrition
was 22% (76/349, 95% CI 1826%). Over two-thirds
(69%, 354/515, 95% CI 6573%) of diagnoses were
pulmonary TB cases.
Outcomes of empiric treatment
Of the 516 children empirically started on anti-TB
treatment, 422 (82%) children had a favorable treatment
outcome. Of the 94 children with unfavorable outcomes,
61% (57/94) were lost to follow-up, 37% (35/94) died,
and 2% (2/94) failed treatment. The majority of deaths
were in children under five years (22/35, 63%); three
deaths occurred in children infected with HIV. The
Wobudeya et al. BMC Public Health (2019) 19:446 Page 2 of 6
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765 records
extracted
64 confirmed TB cases
1 MDR TB case
1 No age
23 Transferred out
108 No treatment outcomes
516 started on
empiric therapy
94 (18%)
unfavorable
outcome
422 (82%)
favorable
outcome
713 started on
TB therapy
Fig. 1 Participant Flowchart
Table 1 Demographic and clinical characteristics of children empirically treated for TB at Mulago Pediatric TB unit (N= 516)
*
Characteristic Favorable (N= 422) Unfavorable (N= 94) p-value
N (%, 95 CI) N (%, 95 CI)
Age group
< 5 years 280 (66, 6271) 57 (61,5070) 0.006
59 years 104 (25, 2129) 18 (19, 1228)
1014 years 38 (9, 712) 19 (20, 1330)
Male Sex 238 (56, 5261) 48 (51, 4161) 0.35
Reside outside of Kampala 174 (41, 3746) 62 (66, 5675) < 0.001
Pulmonary TB (n= 515) 291 (69, 6573) 53 (67, 5776) 0.69
HIV positive (n= 509) 19 (5, 37) 12 (14, 823) 0.001
Severe Malnutrition
(n= 349) 60 (20, 1625) 16 (32, 2046) 0.06
Hospitalized (n= 480) 33 (8, 611) 26 (34, 2445) < 0.001
Abnormal Chest X-ray (n= 367) 297 (93, 9096) 46 (94, 8298) 1.0
BCG vaccinated (n= 301) 239 (92, 8895) 35 (83, 6892) 0.06
Baseline Hepatomegaly (n= 383) 28 (8, 612) 13 (30, 1846) < 0.001
TST Positive (n= 246) 161 (75, 6980) 18 (58, 4074) 0.05
*N = 516 unles s missing data, with number available indicated in parentheses
p-value by Chi-squared or Fishers exact testing
Severe malnutrition defined as weight-for-age Z score less than 3
Wobudeya et al. BMC Public Health (2019) 19:446 Page 3 of 6
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proportion of children on empiric treatment with
favorable outcomes was similar to the children who had
confirmed TB (48 of 54 with outcomes, 89%, versus 82%
on empiric treatment, p= 0.17).
In total, there were eight drug reactions reported at
follow up visits, with complaints that included
paresthesia in the lower limbs, scaling in the plantar
foot, vomiting, pallor and myalgia. However, there were
no adverse events reported that required treatment
discontinuation.
Unfavorable outcomes were more likely among
children aged 1014 years, HIV positive, not residing in
Kampala, with baseline hepatomegaly, and
hospitalization (Table 1). When stratified by loss to
follow up and death (Table 2), loss to follow up was
associated with age 1014 years (OR 2.38, 95% CI 1.15
4.93, p= 0.02), HIV infection (OR 3.35, 95% CI 1.41
7.92, p= 0.01), hospitalization (OR 4.14, 95% CI 2.08
8.25, p< 0.001), and residing outside of Kampala (OR
2.64, 95% CI 1.474.71, p= 0.001). Death was associ-
ated with being hospitalized (OR 4.57, 95% CI 2.0
10.46, p< 0.001), severe malnutrition (OR 2.98, 95% CI
1.078.27, p= 0.04), hepatomegaly at baseline (OR 4.11,
95% CI 2.098.09, p < 0.001), and residing outside of
Kampala (OR 2.41, 95% CI 1.174.96, p=0.02).
Discussion
In this study, we describe empiric treatment outcomes
of children clinically diagnosed with TB at a referral cen-
ter in Kampala, Uganda from 2010 to 2015. The majority
of children (82%) had a favorable outcome with clinical
improvement. However, this is below the World Health
Organization (WHO) target of 90% treatment success
[16]. There were no adverse events that required discon-
tinuation of treatment. Loss to follow-up was the most
common unfavorable outcome and was associated with
older age (1014 years), HIV infection, hospitalization,
and living outside of Kampala. Death was the next cause
of unfavorable outcome, and was associated with
hospitalization, severe malnutrition, baseline hepatomeg-
aly, and living outside of Kampala. Thus, empiric
treatment was found to be safe and effective for most chil-
dren, but greater efforts are needed to improve outcomes.
While the proportion with favorable outcome was
below the global target, it corresponds with child TB
outcomes in similar settings [16]. Retrospective studies
in Nigeria, South Africa and Ethiopia found child TB
(confirmed and clinically diagnosed) success rates of
77.4% [17], 78% [18], and 85.5% [19,20], respectively.
We also found a similar favorable proportion among the
confirmed child TB cases. Our data support that empiric
treatment of TB in children without microbiologic
confirmation does not lead to worse outcomes.
Loss to follow-up was the most common reason for an
unfavorable outcome. HIV co-infection has been associ-
ated with loss to follow up in youth [21,22], and may be
related to the additional pill burden, stigma and fear of
discrimination. Hospitalization and not living in
Kampala also were associated with loss to follow up;
improved efforts are needed to ensure follow up after a
child is discharged from the hospital, and to address
barriers to obtaining care if the child does not live near
the clinic. For example, Defeat TB is an initiative in
Uganda to improve TB treatment success through health
system strengthening to improve coordination of care
and decentralize TB diagnosis and management [23].
Children age 1014 years were more than twice as
likely to be lost to follow up as children under 5 years.
Compared to younger children, adolescents with TB face
unique challenges to their care, including greater peer
pressure, stigma, behavioral issues, substance abuse and
prevalence of co-morbidities including HIV [2]. A retro-
spective analysis in South Africa found that 15% of ado-
lescents with HIV aged 1519 years discontinued TB
Table 2 Factors associated with loss to follow up or death in children empirically treated at Mulago Pediatric TB unit, 20102015
Loss to Follow Up Death
OR (95% CI) p-value OR (95% CI) p-value
Age Group
< 5 yrs REF REF
59 yrs 0.88 (0.431.80) 0.73 0.87 (0.362.09) 0.76
1014 yrs 2.38 (1.154.93) 0.02 1.68 (0.654.36) 0.28
Male sex 0.75 (0.431.31) 0.31 0.84 (0.421.67) 0.62
HIV positive 3.35 (1.417.92) 0.01 1.60 (0.465.57) 0.46
Hospitalization 4.14 (2.088.25) < 0.001 4.57 (2.010.46) < 0.001
resides outside of Kampala 2.64 (1.474.71) 0.001 2.41 (1.174.96) 0.02
Severe Malnutrition 1.46 (0.653.3) 0.36 2.98 (1.078.27) 0.04
Baseline Hepatomegaly 1.36 (0.832.22) 0.22 4.11 (2.098.09) < 0.001
CI Confidence Interval, OR odds ratio, HIV Human Immunodeficiency Virus
Wobudeya et al. BMC Public Health (2019) 19:446 Page 4 of 6
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treatment [24]. A study in Botswana found that adolescents
were twice as likely to be lost to follow-up compared to
adult [21]. These results emphasize that adolescent-friendly
TB programs are needed to address their unique issues and
continue to engage adolescents in care.
Mortality was the second most common unfavorable
outcome. Our overall mortality was high at 7%, similar
to the study in Nigeria that found a child TB mortality
of 6% [17]. Consistent with past studies [1719], our
analyses found that factors related to more severe dis-
ease were associated with death, namely hospitalization,
severe malnutrition and hepatomegaly. Living outside of
Kampala district was also associated with death, and
may reflect socioeconomic factors or delays in diagnosis
and management.
Prior assessments of child TB outcomes have included
both confirmed and clinically diagnosed TB. Confirmed
cases may reflect children with higher bacterial load or
occur in settings where there is greater access to diag-
nostics. By focusing only on children empirically treated
for TB based on a clinical diagnosis, we sought to
provide outcome data that was more generalizable to the
majority of health care workers in low-resource settings.
There were also some potential limitations to our
study. As a retrospective cohort, we cannot comment on
the accuracy of the clinical diagnoses, although docu-
mented symptoms and signs were consistent with na-
tional guidelines. The study was conducted at a referral
hospital, and may lower generalizability to primary care
clinics. Mortality from alternative diagnoses were
possible, and the exact causes of death were unknown.
Adherence was not consistently documented. There was
no available data on contacts with multi-drug resistant
(MDR) TB to address empiric MDR treatment. The
sample had a low proportion with HIV infection and
limits the assessment of outcomes of empiric TB treat-
ment in HIV-TB co-infected children. In particular,
HIV-related mortality was low, and may be an underesti-
mate as we did not include children with confirmed TB,
who were transferred out or who had missing outcomes.
The low number of unfavorable outcomes did not pro-
vide the power for a multivariable stratified regression
analysis. Data was also not available on any follow-up la-
boratory testing to determine sub-clinical adverse events
such as elevated liver transaminases on treatment.
Conclusions
Our results highlight that initiation of empiric TB care
in children is overall safe and effective if health care
workers use appropriate clinical guidelines. However,
they also suggest that diagnosis and initiation of treat-
ment are only the beginning of the care cascade; health
facility strengthening and age-appropriate care is critical
to ensure favorable outcomes and retention in care.
Abbreviations
aOR: Adjusted odds ratio; BCG: Bacillus CalmetteGuérin; CI: Confidence
interval; FDC: Fixed Dose Combination; HIV: Human Immunodeficiency Virus;
IQR: Interquartile Range; MDR: Multi-drug resistant; OR: Odds ratio;
TB: Tuberculosis; TST: Tuberculin Skin Test; WHO: World Health Organization
Acknowledgements
We thank the families, staff, and administration at the Mulago National
Referral Hospital for their efforts in diagnosing and managing these
children with TB.
Funding
DJ is a Fellow in the Pediatric Scientist Development Program. This project
was supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (K12 HD000850) and the National
Heart, Lung, and Blood Institute (R01 HL139717). The funders had no role in
the design, collection, analysis, interpretation, or writing of the study.
Availability of data and materials
The datasets used and/or analyzed during the current study are available
from the corresponding author on reasonable request.
Authorscontributions
DJ, EW and AC conceptualized the study and analysis. EW, MPS, BN and HH
provided oversight and collection of the data. EW and DJ conducted the
analysis. DJ and EW drafted the manuscript, and all authors provided
revisions. All authors have read and approved the manuscript.
Ethics approval and consent to participate
The Mulago Hospital Research and Ethics Committee approved the study
protocol and waived the requirement for informed consent. We conduct
chart reviews and did not get into contact with human subjects.
Consent for publication
Not applicable.
Competing interests
EW is an associate editor of the BMC Public Health journal. All the authors
declare that they have no competing interests.
PublishersNote
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
Author details
1
Directorate of Pediatrics & Child Health, Mulago National Referral Hospital,
P.O. Box 23491, Kampala, Uganda.
2
Division of Pediatric Infectious Diseases,
University of California, 550 16th St. 4th floor, San Francisco, CA 94158, USA.
3
National TB and Leprosy Program (NTLP), Plot 6, Lourdel Road, Nakasero, P.
O. Box 7272, Kampala, Uganda.
4
USAID RHITES-EC, University Research Co.
LLC, Plot 40, Ntinda II Road, PO Box 28745, Kampala, Uganda.
5
Department
of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
6
Division of
Pulmonary and Critical Care Medicine, University of California, 1001 Potrero
Ave, SFGH 5, San Francisco, CA 94110, USA.
7
Center for Vulnerable
Populations, Department of Medicine, University of California, San Francisco,
USA.
8
Curry International Tuberculosis Center, University of California, San
Francisco, USA.
Received: 7 February 2019 Accepted: 15 April 2019
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... A variety of clinical, social, and economic factors have been identified as important factors associated with TB treatment outcomes in children in high-TB countries [12]. e most commonly reported factors associated with unsuccessful treatment outcomes for pediatric TB include adherence to anti-TB treatment, low body weight, HIV-positive status, male sex, clinical and/or bacteriological method of diagnosis, pulmonary positive case, unknown HIV status, type of health facility, pretreatment sputum smear, and household contact with cases of TB treatment failure [12][13][14][15][16][17][18][19][20][21][22][23]. ...
... e majority, 245 (40.2%) of the children were diagnosed with PTB+, and the minority, 177 (29%) had EPTB, which is a usual distribution. e authors from other limited resource countries have reported similar results [14,19]. Other authors, however, reported higher rates of EPTB and PTB-in Nigeria [13] and Ethiopia [20], which can be attributed to variations in clinical presentation and difficulties with case management. ...
... is proportion is considered to be high based on the national average and the WHO target of a 10% unsuccessful treatment rate [26,27]. Our findings are in contrast to studies conducted in Malaysia, Ethiopia, Nigeria, and Uganda, which reported 9.9% to 18.0% unsuccessful treatment outcomes [13,14,20,28]. However, a previous study conducted in the Democratic Republic of Congo found a high 86 (30.4%) proportion of unsuccessful treatment outcomes [24]. ...
Article
Full-text available
Background: In Cameroon, there are limited data on treatment outcomes of pediatric tuberculosis (TB). We sought to identify the factors associated with unsuccessful treatment outcomes and the risk factors for mortality among children receiving TB treatment in the Centre Region of Cameroon. Methods: This was a multicentre facility-based retrospective cohort study using routinely collected programmatic data. All children <15 years old treated for TB between 2018 and 2020 in 21 health facilities were included. We assessed risk factors for experiencing an unsuccessful treatment outcome and mortality through multivariable logistic regression analysis. Results: Of the 610 children with TB, 307 (50.3%) were females and the median age was 6 years (IQR = 2-12). One hundred and fifty-three (25.1%) of the children were TB/HIV co-infected patients. TB treatment success (cases categorized as cured and completed treatment) was observed in 488 (80.0%) of the patients. Unsuccessful treatment outcomes were experienced by 122 (20.0%) children. Of these, 73 (12.0%) died, 4 (0.6%) had treatment failure, 25 (4.1%) were lost to follow-up, and the outcomes of 20 (3.3%) children were not evaluated. In multivariable analysis, HIV-positive status (adjusted odds ratio [AOR] = 2.43; 95% CI, 1.55-3.80, p < 0.001) and clinical method of TB diagnosis (AOR = 2.46; 95% CI, 1.55-3.91, p < 0.001] were associated with unsuccessful treatment outcomes. HIV-positive status (AOR = 4.23; 95% CI, 2.44-7.33, p < 0.001) and clinical method of TB diagnosis (AOR = 2.22; 95% CI, 1.25-3.91, p=0.006) were the risk factors for mortality among children on TB treatment. Conclusion: The study found that HIV-TB co-infected children and those clinically diagnosed with TB were significantly more likely to have had unsuccessful TB treatment outcomes and mortality. Our findings underscore the need for healthcare workers to closely monitor and support HIV-TB co-infected children on TB treatment. TB/HIV collaborative activities should be strengthened by implementing TB preventive interventions among HIV-infected children.
... Over half of the articles (61.5%) used cohort study design [7,9,13,14,[25][26][27][28][29][30][31][32][33][34][35][36] whereas the rest 38.8% were retrospective cross-sectional studies [10,[37][38][39][40][41][42][43][44] (Table 1). A total of 306,351 study participants with a sample size ranging from 227 in Ethiopia [41] to 170,017 in South Africa [37]; for studies conducted in Ethiopia and South Africa respectively. ...
... The majority 163,126 (53.2%) of patients were male. Because of the two largest studies that included settings with a high prevalence of TB/HIV co-infection [25,31], the proportion of TB-HIV co-infection participants were extremely higher 165,551 (54.0%). The percentage of retreatment cases compared to newly diagnosed TB patients was found to be reasonable, with about 16,492 (5.4%) of the total participants included in the current study. ...
... The demographic and clinical factors expected to have a relationship with the TB treatment success rate were assessed. The association of HIV co-infection and retreatment status were assessed using 19 articles [7,9,13,14,[25][26][27]29,30,32,33,[38][39][40][41][42][43][44][45] reported tractable data on HIV co-infection and 11 articles [9,14,29,[32][33][34]36,[38][39][40][41] with data on retreatment used for analysis. Accordingly, the overall pooled and region-based subgroup estimates indicated that HIV co-infection and retreatment were significantly associated with an increased risk of unsuccessful treatment outcome; as compared to HIV negative and newly diagnosed TB patients with RR of 95% CI: (1.53 (1.36, 1.71)) and (1.48 (1.14, 1.94)), respectively (Figures 3 and 4). ...
Article
Full-text available
This review aimed to summarize and estimate the TB treatment success rate and factors associated with unsuccessful TB treatment outcomes in Africa. Potentially eligible primary studies were retrieved from PubMed and Google Scholar. The risk of bias and quality of studies was assessed using The Joanna Briggs Institute’s (JBI) appraisal criteria, while heterogeneity across studies was assessed using Cochran’s Q test and I2 statistic. Publication bias was checked using the funnel plot and egger’s test. The protocol was registered in PROSPERO, numbered CRD42019136986. A total of 26 eligible studies were considered. The overall pooled estimate of TB treatment success rate was found to be 79.0% (95% CI: 76–82%), ranging from 53% (95% CI: 47–58%) in Nigeria to 92% (95% CI: 90–93%) in Ethiopia. The majority of unsuccessful outcomes were attributed to 48% (95% CI: 40–57%) death and 47% (95% CI: 39–55%) of defaulter rate. HIV co-infection and retreatment were significantly associated with an increased risk of unsuccessful treatment outcomes compared to HIV negative and newly diagnosed TB patients with RR of 1.53 (95% CI: 1.36–1.71) and 1.48 (95% CI: 1.14–1.94), respectively. TB treatment success rate was 79% below the WHO defined threshold of 85% with significant variation across countries. Countries need to explore contextual underlining factors and more effort is required in providing TB preventive treatment, improve case screening and linkage for TB treatment among HIV high-risk groups and use confirmatory TB diagnostic modality. Countries in Africa need to strengthen counseling and follow-up, socio-economic support for patients at high risk of loss to follow-up and poor treatment success is also crucial for successful TB control programs.
... Over half of the articles (61.5%) used cohort study design [7,9,13,14,[25][26][27][28][29][30][31][32][33][34][35][36] whereas the rest 38.8% were retrospective cross-sectional studies [10,[37][38][39][40][41][42][43][44] (Table 1). A total of 306,351 study participants with a sample size ranging from 227 in Ethiopia [41] to 170,017 in South Africa [37]; for studies conducted in Ethiopia and South Africa respectively. ...
... The majority 163,126 (53.2%) of patients were male. Because of the two largest studies that included settings with a high prevalence of TB/HIV co-infection [25,31], the proportion of TB-HIV co-infection participants were extremely higher 165,551 (54.0%). The percentage of retreatment cases compared to newly diagnosed TB patients was found to be reasonable, with about 16,492 (5.4%) of the total participants included in the current study. ...
... The demographic and clinical factors expected to have a relationship with the TB treatment success rate were assessed. The association of HIV co-infection and retreatment status were assessed using 19 articles [7,9,13,14,[25][26][27]29,30,32,33,[38][39][40][41][42][43][44][45] reported tractable data on HIV co-infection and 11 articles [9,14,29,[32][33][34]36,[38][39][40][41] with data on retreatment used for analysis. Accordingly, the overall pooled and region-based subgroup estimates indicated that HIV co-infection and retreatment were significantly associated with an increased risk of unsuccessful treatment outcome; as compared to HIV negative and newly diagnosed TB patients with RR of 95% CI: (1.53 (1.36, 1.71)) and (1.48 (1.14, 1.94)) respectively (Figures 3 and 4). ...
Article
Full-text available
This review aimed to summarize and estimate the TB treatment success rate and factors associated with unsuccessful TB treatment outcomes in Africa. Potentially eligible primary studies were retrieved from PubMed and Google Scholar. The risk of bias and quality of studies was assessed using The Joanna Briggs Institute's (JBI) appraisal criteria, while heterogeneity across studies was assessed using Cochran's Q test and I2 statistic. Publication bias was checked using the funnel plot and egger's test. The protocol was registered in PROSPERO, numbered CRD42019136986. A total of 26 eligible studies were considered. The overall pooled estimate of TB treatment success rate was found to be 79.0% (95% CI: 76-82%), ranging from 53% (95% CI: 47-58%) in Nigeria to 92% (95% CI: 90-93%) in Ethiopia. The majority of unsuccessful outcomes were attributed to 48% (95% CI: 40-57%) death and 47% (95% CI: 39-55%) of defaulter rate. HIV co-infection and retreatment were significantly associated with an increased risk of unsuccessful treatment outcomes compared to HIV negative and newly diagnosed TB patients with RR of 1.53 (95% CI: 1.36-1.71) and 1.48 (95% CI: 1.14-1.94) respectively. TB treatment success rate was 79% below the WHO defined threshold of 85% with significant variation across countries. Countries need to explore contextual underlining factors and more effort is required in providing TB preventive treatment, improve case screening and linkage for TB treatment among HIV high-risk groups and use confirmatory TB diagnostic modality. Countries in Africa need to strengthen counseling and follow-up, socioeconomic support for patients at high risk of loss to follow-up and poor treatment success is also crucial for successful TB control programs.
... Adherence to treatment of TB infection, also known as TB preventive treatment (TPT), and to the treatment of TB disease remains a particular challenge for children and AYA. Studies have found that children have suboptimal adherence to treatment for TB infection and disease [5][6][7][8], and AYA with TB disease have higher rates of loss to follow-up compared to children and older adults [9][10][11], as well as higher TB-related mortality than children [12]. The social determinants of TB treatment adherence in adults have been well characterized [13][14][15], and several largescale interventions have been developed to address and evaluate these factors, including the use of digital adherence technologies (DATs) and conditional cash-transfer programs [16][17][18][19]. ...
... As AYA gain more autonomy and independence, individual patient factors become more important for treatment adherence in this age group. Few studies have investigated the reasons why AYA have lower adherence to TB treatment as compared to younger children or older adults [11,38,44,64]. The growing need for autonomy, reduced reliance on caregivers, greater dependence on peers and romantic/sexual partners, and increased focus on short-term gains over long-term health outcomes may all play a role, but these factors have not been evaluated in AYA with TB [1,60,65,66]. ...
Article
Global efforts to eliminate tuberculosis (TB) must address the unique barriers that children (ages 0 through 9 years) and adolescents/young adults (AYA; ages 10 through 24 years) face in adhering to treatment for TB infection and disease. We conducted a narrative review to summarize current knowledge on the social determinants of treatment adherence among these age groups to guide efforts and policy to address their unique needs. Our findings revealed that research on TB treatment adherence among children and AYA is still in its nascent stage. The current literature revealed structural/community-, health system-, household-, and individual-level factors that influence treatment adherence and varied with developmental stage. There is a need to develop multilevel interventions to address the unique challenges that children and AYA face in adhering to TB treatment.
... In Cambodia, childhood TB was high, representing 22.5% of the total 29,136 noti ed TB cases in 2020 (7), and almost all noti ed childhood TB cases in 2020 were clinically diagnosed (26). This situation may lead to empirical and inappropriate treatment and a low treatment success rate (27). Improving the quality of childhood TB diagnosis through investment in diagnostic tools such as GeneXpert® MTB/RIF and digital X-ray machines should be prioritized. ...
Preprint
Full-text available
Background Diagnosis and treatment of tuberculosis (TB) in children remain challenging, particularly in resource-limited settings. Healthcare providers and caregivers are critical in improving childhood TB screening and treatment. This study aimed to determine the barriers to childhood TB detection and management from the perspectives of healthcare providers and caregivers in Cambodia. Method We conducted this qualitative study between November and December 2020. Data collection included in-depth interviews with 16 healthcare providers purposively selected from four operational districts and 28 caregivers of children with TB and children in close contact with bacteriological confirmed pulmonary TB residing under the coverage of the selected health centers. Data were analyzed using thematic analyses. Results Mean ages of healthcare providers and caregivers were 40.2 years (standard deviation [SD] 11.9) and 47.9 years (SD 14.6), respectively. Male was predominant among healthcare providers (93.8%). Three-fourths of caregivers were female, and 28.6% were grandparents. Inadequate TB staff, limited knowledge on childhood TB, poor collaboration among healthcare providers in different units on TB screening and management, limited quality of TB diagnostic tools, and interruption of supplies of childhood TB medicines due to maldistribution from higher levels to health facilities were the key barriers to childhood TB case detection and management. Caregivers reported transportation costs to and from health facilities, out-of-pocket expenditure, time-consuming, and no clear explanation from healthcare providers as barriers to childhood TB care-seeking. Aging caregivers with poor physical conditions, lack of collaboration from caregivers, ignorance of healthcare provider's advice, and parent movement were also identified as barriers to childhood TB case detection and management. Conclusions The national TB program should further invest in staff development for TB, scale-up appropriate TB diagnostic tools and ensure its functionalities, such as rapid molecular diagnostic systems and X-ray machines, and strengthen childhood TB drug management at all levels. These may include drug forecasting, precise drug distribution and monitoring mechanism, and increasing community awareness about TB to increase community engagement.
... In Cambodia, childhood TB was high, representing 22.5% of the total 29,136 noti ed TB cases in 2020 (7), and almost all noti ed childhood TB cases in 2020 were clinically diagnosed (26). This situation may lead to empirical and inappropriate treatment and a low treatment success rate (27). Improving the quality of childhood TB diagnosis through investment in diagnostic tools such as GeneXpert® MTB/RIF and digital X-ray machines should be prioritized. ...
Preprint
Full-text available
Childhood tuberculosis (TB) case detection remains low in many high-burden countries, including Cambodia. This study aimed to determine the barriers to childhood TB detection and management from the perspectives of healthcare providers and caregivers in Cambodia. We conducted in-depth interviews with 16 healthcare providers from four operational districts and 28 caregivers of children with TB and children in close contact with bacteriological confirmed pulmonary TB residing under the selected districts. Data were analysed using thematic analyses. Identified key barriers to childhood TB case detection and management included inadequate TB staff, limited knowledge on childhood TB, poor collaboration among healthcare providers, limited quality of TB diagnostic tools, and interruption of supplies of childhood TB medicines, lack of collaboration from caregivers, ignorance of healthcare provider's advice, parent movement, transportation costs, out-of-pocket expenditure, time-consuming, no clear explanation from healthcare providers, and aging of caregivers. The national TB program should further invest in staff development for TB, scale-up appropriate TB diagnostic tools and ensuring its functionalities such as rapid molecular diagnostic systems and X-ray machines, strengthen childhood TB drug management at all levels such as drug forecasting, a clear mechanism for drug distribution, and drug monitoring, and increasing community awareness about TB in order to increase community engagement.
... In Cambodia, childhood TB was high, representing 22.5% of the total 29,136 noti ed TB cases in 2020 (7), and almost all noti ed childhood TB cases in 2020 were clinically diagnosed (26). This situation may lead to empirical and inappropriate treatment and a low treatment success rate (27). Improving the quality of childhood TB diagnosis through investment in diagnostic tools such as GeneXpert® MTB/RIF and digital X-ray machines should be prioritized. ...
Preprint
Full-text available
Background: Childhood tuberculosis (TB) case detection remains low in many high-burden countries, including Cambodia. Healthcare providers and caregivers play a critical role in improving childhood TB screening and treatment. This study aimed to determine the barriers to childhood TB detection and management from the perspectives of healthcare providers and caregivers in Cambodia. Method: We conducted this qualitative study between November and December 2020. In-depth interviews were done with 16 healthcare providers purposively selected from four operational districts and 28 caregivers of children with TB and children in close contact with bacteriological confirmed pulmonary TB residing under the coverage of the selected health centers. Data were analyzed using thematic analyses. Results: Mean ages of healthcare providers and caregivers were 40.19 years (standard deviation [SD] 11.89) and 47.93 years (SD 14.63), respectively. Male was predominant among healthcare providers (93.75%), whereas three-fourths of caregivers were female, and 28.57% of caregivers were grandparents. Inadequate TB staff, limited knowledge on childhood TB, poor collaboration among healthcare providers in different units on TB screening and management, limited quality of TB diagnostic tools, and interruption of supplies of childhood TB medicines due to maldistribution from higher levels to health facilities were the key barriers to childhood TB case detection and management. Caregivers reported transportation costs to and from health facilities, out-of-pocket expenditure, time-consuming, and no clear explanation from healthcare providers as barriers to childhood TB care-seeking. Aging of caregivers with poor physical conditions, lack of collaboration from caregivers, ignorance of healthcare provider's advice, and parent movement were also identified as barriers to childhood TB case detection and management. Conclusions: The national TB program should further invest in staff development, such as developing a national strategy for human resources for TB and increasing staff motivation, including performance-linked incentives provision. Appropriate TB diagnostic tools (e.g., rapid molecular diagnostic systems and scale-up of functional X-ray machines) should also be rolled out. To avoid drug supply interruptions, childhood TB drug management at all levels should be strengthened, such as drug forecasting, a clear mechanism for drug distribution, and drug monitoring. Increasing community awareness about TB should also be prioritized to increase community participation.
... Several factors are associated with non-adherence and loss to follow-up among TB patients including children in developing countries leading to DTT among children and include among others, long treatment durations, high pill burden, medicationrelated side-effects, and symptom resolution [9]. DTT thus remains a major obstacle to efficient TB control in developing countries like Uganda and has the potential to worsen the emergence of multi-drug resistant TB and death [10,11]. ...
Article
Full-text available
Introduction Discontinuation of tuberculosis treatment (DTT) among children in sub-Saharan Africa is a major obstacle to effective tuberculosis (TB) control and has the potential to worsen the emergence of multi-drug resistant TB and death. DTT in children is understudied in Uganda. We examined the level and factors associated with DTT among children at four large health facilities in Kampala Capital City Authority and documented the reasons for DTT from treatment supporters and healthcare provider perspectives. Methods We conducted a retrospective analysis of records for children < 15 years diagnosed and treated for TB between January 2018 and December 2019. We held focus group discussions with treatment supporters and key informant interviews with healthcare providers. We defined DTT as the stoppage of TB treatment for 30 or more consecutive days. We used a stepwise generalized linear model to assess factors independently associated with DTT and content analysis for the qualitative data reported using sub-themes. Results Of 312 participants enrolled, 35 (11.2%) had discontinued TB treatment. The reasons for DTT included lack of privacy at healthcare facilities for children with TB and their treatment supporters, the disappearance of TB symptoms following treatment initiation, poor implementation of the community-based directly observed therapy short-course (CB-DOTS) strategy, insufficient funding to the TB program, and frequent stock-outs of TB drugs. DTT was more likely during the continuation phase of TB treatment compared to the intensive phase (Adjusted odds ratio (aOR), 5.22; 95% Confidence Interval (CI), 1.76–17.52) and when the treatment supporter was employed compared to when the treatment supporter was unemployed (aOR, 3.60; 95% CI, 1.34–11.38). Conclusion Many children with TB discontinue TB treatment and this might exacerbate TB morbidity and mortality. To mitigate DTT, healthcare providers should ensure children with TB and their treatment supporters are accorded privacy during service provision and provide more information about TB symptom resolution and treatment duration versus the need to complete treatment. The district and national TB control programs should address gaps in funding to TB care, the supply of TB drugs, and the implementation of the CB-DOTS strategy.
Article
Full-text available
Background Tuberculosis (TB) is a leading cause of morbidity and mortality in children but epidemiological data are scarce, particularly for hard-to-reach populations. We aimed to identify the risk factors for unsuccessful outcome and TB mortality in migrant children at a supportive residential TB programme on the Thailand–Myanmar border. Methods We conducted retrospective analysis of routine programmatic data for children (aged ≤ 15 years old) with TB diagnosed either clinically or bacteriologically between 2013 and 2018. Treatment outcomes were described and risk factors for unsuccessful outcome and death were identified using multivariable logistic regression. Results Childhood TB accounted for a high proportion of all TB diagnoses at this TB programme (398/2304; 17.3%). Bacteriological testing was done on a quarter (24.9%) of the cohort and most children were diagnosed on clinical grounds (94.0%). Among those enrolled on treatment (n = 367), 90.5% completed treatment successfully. Unsuccessful treatment outcomes occurred in 42/398 (10.6%) children, comprising 26 (6.5%) lost to follow-up, one (0.3%) treatment failure and 15 (3.8%) deaths. In multivariable analysis, extra-pulmonary TB [adjusted OR (aOR) 3.56 (95% CI 1.12–10.98)], bacteriologically confirmed TB [aOR 6.07 (1.68–21.92)] and unknown HIV status [aOR 42.29 (10.00–178.78)] were independent risk factors for unsuccessful outcome. HIV-positive status [aOR 5.95 (1.67–21.22)] and bacteriological confirmation [aOR 9.31 (1.97–44.03)] were risk factors for death in the secondary analysis. Conclusions Children bear a substantial burden of TB disease within this migrant population. Treatment success rate exceeded the WHO End TB target of 90%, suggesting that similar vulnerable populations could benefit from the enhanced social support offered by this TB programme, but better child-friendly diagnostics are needed to improve the quality of diagnoses.
Article
Introduction: With growing attention globally to the childhood tuberculosis epidemic after decades of neglect, and with the burden of severe acute malnutrition (SAM) remaining unacceptably high worldwide, the collision of these two diseases is an important focus for improving child health. Areas covered: This review describes the clinical and public health implications of the interplay between tuberculosis and SAM, particularly for children under the age of five, and identifies priority areas for improved programmatic implementation and future research. We reviewed the literature on PubMed and other evidence known to the authors published until August 2021 relevant to this topic. Expert opinion: To achieve the World Health Organization's goal of eliminating deaths from childhood tuberculosis and to improve the abysmal outcomes for children with SAM, further research is needed to 1) better understand the epidemiologic connections between child tuberculosis and SAM, 2) improve case finding of tuberculosis in children with SAM, 3) assess unique treatment considerations for tuberculosis when children also have SAM, and 4) ensure tuberculosis and SAM are strongly addressed in decentralized, integrated models of providing primary healthcare to children.
Article
Full-text available
TB remains a leading cause of mortality and morbidity in sub-Saharan Africa, due to the HIV epidemic. As TB treatment is lengthy, the completion of the full course of treatment may be especially challenging for young people. We therefore aimed to identify the extent of and reasons underlying loss to follow-up from TB treatment among young people in Cape Town. Accordingly, we reviewed the outcomes of young people treated for TB in Cape Town during 2009–2013, across three age groups: younger adolescents (10–14 years); older adolescents; (15–19 years) and young adults (20–24 years). We employed logistic regression analysis to identify risk factors for loss from TB care. 23,737 patients aged 10–24 were treated for drug sensitive TB over the study period. Of these, the HIV co-infection prevalence was 18.5% for younger adolescents, 12.9% for older adolescents and 33.1% for young adults. From age 16, HIV prevalence increased disproportionately among young women: by age 22, over 50% of women were TB/HIV co-infected compared to 14% of men. TB treatment success (cure plus completion) was 84.4%, while 1.7% of patients died, 9.5% were lost-to follow-up and 0.4% failed treatment. Being an older adolescent (aOR 1.75 [95% CI: 1.38–2.21]) or young adult (aOR: 1.96 [95% CI: 1.57–2.45]) increased the risk of loss-to-follow up, relative to being a younger adolescent. Further risk factors for loss from TB care were male gender (aOR: 1.33 [95% CI:1.20–1.46]), being a TB/HIV co-infected young person (aOR 1.74 [95% CI: 1.57–1.93]) and having had prior treatment for TB (aOR 3.17 [95% CI 2.87–3.51]). We identified risk factors for loss to follow-up and highlighted the need to focus on HIV prevention and retention in TB care among young people. TB care tailored to the needs of young people could improve patient retention, similar to improved outcomes reported by youth friendly HIV clinics.
Article
Full-text available
Objective: To assess the quality of routine childhood tuberculosis (TB) evaluation in Kampala, Uganda. Setting and design: This was a cross-sectional study of children aged <15 years attending six government-run clinics from November 2015 to December 2016. Clinicians completed a standardized patient record form for all child visits. We assessed the following performance indicators of TB evaluation developed based on the Desk Guide of the International Union Against Tuberculosis and Lung Disease, an evidence-based decision aid on childhood TB diagnosis and management for clinicians: proportion screened for TB symptoms or contact history, proportion referred for laboratory evaluation if screen-positive, and proportion treated for TB if test-positive or meeting clinical criteria. Results: Of 24 566 consecutive children enrolled, 11 614 (47%) were fully screened for TB symptoms. Of 1747 (15%) children who screened positive, 360 (21%) had sputum examined, including 159 (44%) using smear microscopy, 244 (67%) using Xpert® MTB/RIF, and 52 (14%) using both techniques. Treatment was initiated in 18/20 (80%) children who tested positive. An additional 65 screen-positive children met the clinical criteria for TB; none were initiated on treatment. Conclusions: Large gaps exist along the pathway to diagnosis and treatment of childhood TB. There is an urgent need for enhanced implementation of evidence-based approaches to TB diagnosis to improve outcomes in childhood TB.
Article
Full-text available
Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Considering the World Health Organization recommendation to implement child contact management (CCM) for TB, we conducted a mixed-methods systematic review to summarize CCM implementation, challenges, predictors, and recommendations. We searched the electronic databases of PubMed/MEDLINE, Scopus, and Web of Science for studies published between 1996-2017 that reported CCM data from high TB-burden countries. Protocol details for this systematic review were registered on PROSPERO: International prospective register of systematic reviews (#CRD42016038105). We formulated a search strategy to identify all available studies, published in English that specifically targeted a) population: child contacts (
Article
Full-text available
Background: Tuberculosis in children is increasingly recognised as an important component of the global tuberculosis burden, with an estimated 1 million cases in 2015. Although younger children are vulnerable to severe forms of tuberculosis disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosis has never been included in official estimates of under-5 child mortality. We aimed to produce a global mortality burden estimate in children using a complementary approach not dependent on vital registration data. Methods: In this mathematical modelling study, we estimated deaths in children younger than 5 years and those aged 5-14 years for 217 countries and territories using a case-fatality-based approach. We used paediatric tuberculosis notification data and HIV and antiretroviral treatment estimates to disaggregate the WHO paediatric tuberculosis incidence estimates by age, HIV, and treatment status. We then applied systematic review evidence on corresponding case-fatality ratios. Findings: We estimated that 239 000 (95% uncertainty interval [UI] 194 000-298 000) children younger than 15 years died from tuberculosis worldwide in 2015; 80% (191 000, 95% UI 132 000-257 000) of these deaths were in children younger than 5 years. More than 70% (182 000, 140 000-239 000) of deaths occurred in the WHO southeast Asia and Africa regions. We estimated that 39 000 (17%, 23 000-73 000) paediatric tuberculosis deaths worldwide were in children with HIV infections, with 31 000 (36%, 19 000-59 000) in the WHO Africa region. More than 96% (230 000, 185 000-289 000) of all tuberculosis deaths occurred in children not receiving tuberculosis treatment. Interpretation: Tuberculosis is a top ten cause of death in children worldwide and a key omission from previous analyses of under-5 mortality. Almost all these deaths occur in children not on tuberculosis treatment, implying substantial scope to reduce this burden. Funding: UNITAID, National Institutes of Health, and National Institute for Health Research.
Article
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Background: Tuberculosis (TB) is the deadliest infectious disease globally, with 10.4 million people infected and more than 1.8 million deaths in 2015. TB is a preventable, treatable, and curable disease, yet there are numerous barriers to initiating treatment. These barriers to treatment are exacerbated in low-resource settings and may be compounded by factors related to childhood. Objective: Timely initiation of tuberculosis (TB) treatment is critical to reducing disease transmission and improving patient outcomes. The aim of this paper is to describe patient- and system-level barriers to TB treatment initiation specifically for children and youth in sub-Saharan Africa through systematic review of the literature. Design: This review was conducted in October 2015 in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six databases were searched to identify studies where primary or secondary objectives were related to barriers to TB treatment initiation and which included children or youth 0–24 years of age. Results: A total of 1490 manuscripts met screening criteria; 152 met criteria for full-text review and 47 for analysis. Patient-level barriers included limited knowledge, attitudes and beliefs regarding TB, and economic burdens. System-level barriers included centralization of services, health system delays, and geographical access to healthcare. Of the 47 studies included, 7 evaluated cost, 19 health-seeking behaviors, and 29 health system infrastructure. Only 4 studies primarily assessed pediatric cohorts yet all 47 studies were inclusive of children. Conclusions: Recognizing and removing barriers to treatment initiation for pediatric TB in sub-Saharan Africa are critical. Both patient- and system-level barriers must be better researched in order to improve patient outcomes.
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Children suffer a huge burden of disease in tuberculosis (TB) endemic countries. This disease burden was largely invisible when TB control programs focussed exclusively on adults with sputum smear-positive disease. High level advocacy and better data have improved visibility, but the establishment of functional paediatric TB programs remains challenging. The key issues that limit children's access to TB preventive therapy and treatment in endemic areas are briefly discussed. Barriers to preventive therapy include: 1) the perceived inability to rule out active disease, 2) fear of creating drug resistance, 3) non-implementation of existing guidelines in the absence of adequate monitoring and 4) poor adherence with long preventive therapy courses. Barriers to TB treatment include: 1) perceived diagnostic difficulties, 2) non-availability of chest radiography, 3) young children presenting to unprepared maternal and child health (MCH) services and 4) the absence of child friendly formulations. With drug resistant disease there is currently no guidance on the use of preventive therapy and treatment is usually restricted to cases with bacteriologically confirmed disease, which excludes most young children from care, even if their likely source case has documented drug resistant TB.
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Setting: The Khayelitsha subdistrict has the highest burden of reported tuberculosis (TB) cases in Cape Town, Western Cape Province, South Africa. Objectives: To characterise the TB burden, spectrum and treatment outcomes among children managed at a district-level hospital, the Khayelitsha District Hospital. Design: Retrospective medical record review of all children (age <13 years) diagnosed with TB in January-July 2014. A lay health care worker completed daily surveillance and supported linkage to TB care. Symptoms and investigations at presentation, TB disease spectrum, referral pathways and outcomes were reported. Results: Most children were aged 2 years (84/99, 85%), 18/96 (19%) were infected with the human immunodeficiency virus, 31/91 (34%) were malnourished and 80/99 (81%) had pulmonary TB only. The majority of the children (63/80, 79%) presented with cough of acute onset (<2 weeks). Only 5/36 (14%) eligible child contacts had documentation of receiving isoniazid preventive therapy. Twelve (13%) children had bacteriologically confirmed pulmonary TB. Overall, 93/97 (96%) children successfully continued TB care after hospital discharge. Favourable TB treatment outcomes were recorded in only 77 (78%) children. Conclusions: Children with TB managed at this district-level hospital were young, and frequently had acute symptoms and substantial comorbidities. Missed opportunities for TB prevention were identified. Linkage to care support resulted in excellent continuation of TB care; however, treatment outcomes could be further improved.
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Background: Quantifying health care workers' (HCWs') knowledge about tuberculosis (TB) informs educational interventions. We assessed HCWs' knowledge about childhood TB in Botswana. Methods: Semi-structured interviews were conducted with HCWs at 46 sites around Botswana using a piloted instrument. Transcripts were double-coded using a coding schema. Discrepancies were resolved by consensus and a systematic thematic analysis was performed. Results: The sites (42 clinics and 4 hospitals) were urban (n = 9, 20%), semi-urban (n = 10, 22%) and rural (n = 27, 58%). HCWs included nurses (n = 42, 89%) and nurse assistants (n = 4, 11%). Sixteen (56%) HCWs were the TB focal persons for their site. Themes did not vary by type of site, HCW or TB focal person. Although the level of knowledge about secondary prevention using isoniazid prophylaxis therapy was fair, implementation was poor and contact tracing was not being performed. Barriers to TB diagnosis included poor knowledge about TB in the community, minimal diagnostics at site of care and not receiving test results. However, most HCWs reported that treatment initiation and the calculation of appropriate dosages were easy once the diagnosis had been made. Conclusions: In Botswana, HCWs' levels of knowledge about childhood TB varied greatly. The areas of TB diagnosis, screening and prophylaxis in children need additional attention in TB training courses; however, increased knowledge alone would not overcome all the barriers identified by the HCWs.
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SETTING: Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana. OBJECTIVE: To describe clinical characteristics and outcomes among adolescents with TB and compare loss to follow-up (LTFU) rates with that among youth and adult cases. DESIGN: Retrospective cohort study of TB cases registered from 2012 to 2014. Clinical characteristics and treatment outcomes were compared among adolescents (age 10–19 years), youth (20–24 years) and a systematic sample of adults (25 years). RESULTS: We analyzed 120 adolescent, 210 youth, and 548 adult cases. Adolescents had twice the risk of LTFU over adults (RR 2.0, 95%CI 1.1–3.7, P = 0.03), and higher LTFU than youth; this was not significant (RR 1.4, 95%CI 0.7–2.9, P = 0.32). Of those with human immunodeficiency virus (HIV) infection, 8/35 (22.9%) adolescents were LTFU, compared with 3/51 (5.9%) youth, and 25/407 (6.1%) adults (P = 0.001). In a multivariable model, adolescence (OR 3.0, 95%CI 1.3–6.5, P < 0.01), HIV positivity (OR 2.2, 95%CI 1.1–4.5, P = 0.02), and extra-pulmonary TB (OR 2.2, 95%CI 1.2–4.0, P = 0.01) were each associated with LTFU. CONCLUSION: Adolescents treated for TB had greater LTFU than youth and adults, particularly in the setting of TB-HIV coinfection. Further work should clarify the generalizability of these findings and investigate poor outcomes among adolescents with TB.