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Low paediatric tuberculosis case detection rate in Southern Mozambique

Authors:
Low paediatric tuberculosis case
detection rate in Southern Mozambique
To the Editor:
Two core indicators adopted for evaluating tuberculosis (TB) control programmes are treatment outcome
and case detection rate (CDR). While the former is easy to report, the CDR can only be estimated (calculated
as notifications of new and relapse cases divided by estimated incidence). According to the World Health
Organization (WHO), Mozambique has one of the lowest CDRs among the high TB burden countries
(HBCs), with 37% in 2013 [1]. In children, calculating CDR is even more challenging, given the difficulty in
diagnosing TB and the lack of accurate estimates for paediatric incidence [2]. Several paediatric TB incidence
estimates have been published recently [35], showing higher figures than those provided by WHO. The
large variation in estimates and the lack of population-based data from HBCs (particularly from
Sub-Saharan Africa) highlights the urgent need for new data to inform predictive models necessary to
implement the End TB Strategy and achieve elimination [6]. The objective of this study was to calculate
the paediatric CDR in Mozambique and to provide reference methodology and evidence for other countries.
The study was conducted in the Manhiça District, a high TB-HIV burden district in southern
Mozambique [7], where the Manhiça Health Research Centre runs a health and demographic surveillance
system (HDSS) [8]. It was a retrospective, population-based analysis, which estimated the TB CDR by
comparing the routine TB incidence rate in children aged <3 years reported in the district between 2006
and 2010 with the incidence rate in the study area computed during a prospective study (the ITACA study:
determination of the minimum incidence rate of tuberculosis in infants and children in the Manhiça
District, Mozambique; October 2011October 2012) [9]. The latter was considered as the most accurate
incidence rate estimate available. Prior to the ITACA study, no routine active case finding was performed
and bacteriological confirmation was mostly based on smear microscopy. During the ITACA period, all
presumptive TB cases were identified through an active and passive case detection system. Children with
TB-related symptoms and close contact with a sputum smear-positive TB patient were evaluated through
physical and radiological examination, HIV and tuberculin skin testing, as well as smear microscopy and
culture of both induced sputum and gastric aspirate samples [9, 10]. For the purpose of this analysis, TB
cases were defined as those who started anti-TB treatment. Relapse patients were included.
We calculated the TB incidence rate during the ITACA period as the number of cases in the HDSS area
divided by the mid-year population at risk. Pre-ITACA incidence rates were calculated yearly using the
number of TB cases in the whole district divided by the district mid-year population, using the
Mozambican National Statistics Institute (INE) latest official census data (2007) and taking into account
the estimated age-specific population growth for the whole period. Yearly confidence intervals were
calculated assuming a Poisson distribution. A pooled incidence rate was calculated for the pre-ITACA
period using a weighting scheme through a Poisson regression with random effects and jackknife 95% CI.
According to the 20002013 WHO data, there has been a slight increase in incidence during this
time-frame in Mozambique (figure 1) [1]. Using a log-linear regression and WHO data, we estimated an
overall 0.6% yearly increasing trend in TB incidence rate and applied this correction factor to the final
CDR to mitigate overestimation.
A total of 217 TB cases aged <3 years were diagnosed in the pre-ITACA period (20062010), with a pooled
incidence rate of 251 per 100 000 people (95% CI 227276 per 100 000). During ITACA, 57 TB cases aged
<3 years initiated anti-TB treatment in the HDSS area, equivalent to an incidence rate of 615 per 100 000
people (95% CI 466797 per 100000 people) (figure 1). The estimated CDR was 40.8% (95% CI 36.6
45.1%), and 41.8% (95% CI 37.246.4%) after correction. In the hypothetical case of a 5% increase in the
national incidence, sensitivity analysis showed that the CDR would increase to (49.1%; 95% CI 41.357.0%).
The HIV prevalence among the study population was 47% and 46% during the pre-ITACA and ITACA
periods, respectively. During the ITACA period, fewer patients aged <1 year initiated anti-TB treatment
(8.8% versus 35.9%), more TB cases were extrapulmonary (12.3% versus 7.4%) and the treatment success
rate was significantly better (82.5% versus 67.3%; p=0.025).
To our knowledge, this is the first study providing estimates of TB under-detection using population-based
data in the paediatric population in Africa and one of the few worldwide. We found a low CDR regardless
1
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LETTER
IN PRESS | CORRECTED PROOF
. Published on December 23, 2015 as doi: 10.1183/13993003.01454-2015ERJ Express
Copyright 2015 by the European Respiratory Society.
of age and sex, which underscores the urgent need to close the gap in case detection and reporting, in
order to better assess new control interventions [6, 11].
Our findings are in line with the low CDR for Mozambique reported by WHO [1]; however, the rate we
report is probably a maximum, given that the ITACA incidence rate is a conservative estimate (single-day
samples were obtained in contrast to the recommended 3-day consecutive sampling; contact tracing could
not be fully implemented mainly due to difficulties in patient identification; and some TB cases could have
been missed due to mortality prior to treatment initiation or transfers of severely ill patients to the tertiary
reference hospital) [9].
The CDR higher than the 35% estimated by D
ODD et al. [5] for children aged <15 years in all HBCs (based
on mathematical modelling of 2010 data) could be due to several reasons.
Given that Mozambique has one of the lowest CDRs among all HBCs and that under-estimation is more
frequent in children aged <5 years, the difference observed between our CDR and the one reported by
D
ODD et al. [5] could support the hypothesis that the true CDR in Manhiça is probably lower than 40.8%.
Besides, TB incidence and CDR vary greatly across countries and regions (depending on the local
epidemiology of TB/HIV and healthcare system characteristics, among others) and Manhiça could show an
improved CDR compared with other settings.
Although under-ascertainment, under-reporting and under-diagnosis can all contribute to TB
under-estima tion [12], the la tter is the most probable in Mozambique, where broad paediatric TB case
definitions, lack of clear clinical algorithms, low referral rates and difficulties in obtaining samples all contribute
to under-diagnosis. Under-reporting is not common, as the private sector has a small role in TB diagnosis and
management. Under-ascertainment alone, although common in Manhiça, cannot explain the low CDR, given
the small impact of the active case-finding component of this study.
This study has several limitations. First, the use of a historical control for the calculation of CDR may be
imperfect as the incidence rate and CDR vary over time. Although we expected that the 0.6% yearly
correction could compensate, we acknowledge that the extent of increase in incidence reported for adults
may not be the same for children aged <3 years. Furthermore, we compared incidence rates calculated with
different denominators (the intervention HDSS population, based on real annual census data for a smaller
urban-shaped area versus the whole district population, based on projections from the INE 2007 census
and considering age-specific annual population growth). We did, however, verify that the CDR did not
vary substantially when we calculated the ITACA incidence based on INE district data (and using as
denominator the percentage of the INE population belonging to HDSS).
This study provides a novel population-based CDR for paediatric TB in a HBC. Although this estimate is
probably a maximum, differences in local detection rates can explain a higher CDR than those reported by
others [1, 5]. Given the multiple downstream ramifications of inaccurate estimates [13] and the high
800
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20
10
0
500
400
300
600
700
200
100
0
Incidence rate per 100 000 persons
Case detection rate %
Year
2006 2007 2008
2009 2010 2011 2012
Case detection rate for all ages (WHO estimates)
Incidence rate for all ages (WHO estimates)
Manhiça District incidence rate for age <3 years (pre-ITACA)
Manhiça District incidence rate for age <3 years (ITACA)
FIGURE 1 Yearly tuberculosis incidence rate in the population aged <3 years in the Ma nhiça Dis trict. World Heal th
Organization (WHO) estimates for all-age incidence rate and case detection rate for Mozambique are shown for
the pre-ITACA period. ITACA: study for determination of the minimum incidence rate of tuberculosis in infants and
children in the Manhiça District, Moza mbique; October 2011October 2012.
2
mortality of undiagnosed TB in younger children [14], this finding calls for urgent public health
interventions to ensure that all TB cases are promptly identified and treated.
@ERSpublications
In this study, the case detection rate of TB in children <3 years in Manhiça, Mozambique was
estimated to be 40.8% http://ow.ly/UQg0g
Elisa López-Varela
1,2
, Orvalho Joaquim Augusto
1
, Luis Guerra
1
, Durval Respeito
1
, Charfudin Sacoor
1
,
Jahit Sacarlal
1
, Giovanni Battista Migliori
3
, Giovanni Sotgiu
4
, Pedro L. Alonso
1,2
and Alberto L. García-Basteiro
1,2,5
1
Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
2
Instituto de Salud Global de Barcelona
(ISGLOBAL), Barcelona, Spain.
3
WHO Collaborating Centre for TB and Lung Diseases, Fondazione S. Maugeri, Care
and Research Institute, Tradate, Italy.
4
Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences,
University of Sassari Research, Medical Education and Professional Development Unit, AOU Sassari, Sassari, Italy.
5
Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
Correspondence: Elisa López-Varela, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.
E-mail: elisa.lopez@manhica.net
Received: Sept 01 2015 | Accepted after revision: Nov 09 2015
Conflict of interest: None declared.
Acknowledgements: The authors thank the participants and their families. The authors are grateful to the National TB
Program (Maputo, Mozambique), Denise Naniche (ISGLOBAL, Barcelona, Spain), Alberto Bila Junior (CISM, Manhiça,
Mozambique), health staff at the Manhiça District Hospital (Manhiça, Mozambique) and peripheral health centers for
their contribution.
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Eur Respir J 2015; In press | DOI: 10.1183/13993003.01454-2015 | Copyright ©ERS 2015
3
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Introduction Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhiça, southern Mozambique, an area with a high prevalence of TB and HIV. Methods Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied. Results A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children. Conclusion Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms.
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Extract Tuberculosis (TB) remains an important public health concern, and a leading cause of disease and death worldwide. Mozambique is one of the few high TB burden countries where TB figures have not improved in recent years, with an estimated TB incidence in 2013 of 552 cases per 100 000 population [1]. With 58% of all notified TB cases being HIV-positive, Mozambique also has one of the highest TB/HIV co-infection rates. Published data on the burden of TB or HIV disease in the country are scarce, and improving epidemiological surveillance has been identified as an urgent step to improve TB control [2].
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