Correspondence
The target of reversal of the spread of *Alberto L García-Basteiro,
tuberculosis by 2015 is far from being
achieved at country level. Reported
tuberculosis figures in Mozambique
are still following an upward trend,
which are hardly explained by an
improved case detection rate which,
according to WHO estimates, remains
worryingly stable at only 34%, the
lowest among the high-burden
countries. Thus, the true magnitude
of the disease burden is unknown
and current estimates are far from
precise. Childhood tuberculosis
continues to be relatively neglected
and, in Mozambique, a country in
which almost 50% of the population
is younger than 15 years, the lack of
childhood tuberculosis estimates
only perpetuates and magnifies
the problem. Moreover, the current
surveillance system only detects
16% of the estimated total number
of multidrug-resistant tuberculosis
cases3 posing a dramatic challenge
for the near future. As a country
with one of the highest tuberculosis/
HIV co-infection rates, ensuring
prompt diagnosis and treatment of
tuberculosis through newly available
technology (ie, Gene Xpert) and
ensuring high antiretroviral therapy
coverage, is not a minor undertaking
and is regarded as a top health priority
by the government.
For countries such as Mozambique,
the Global TB report identifies the
need for targeted efforts to improve
the tuberculosis surveillance system,
which should be integrated with
Published Online HIV surveillance efforts. Within this
November 14, 2013 framework, operational research
http://dx.doi.org/10.1016/
S0140-6736(13)62223-0
needs cannot be overlooked since
they will provide improved estimates
of disease burden and identify
programme failures and priority areas
for action and improvement. Political
commitment to sustain and increase
national and international donors’
budget allocations to tuberculosis
control and research is crucial in order
to relieve this longstanding scourge.
We declare that we have no conflicts of interest.
216
protocol (and not intention-to-treat
Elisa López-Varela, Ivan Manhiça,
Eusebio Macete, Pedro L Alonso
alberto.garcia-basteiro@manhica.net
Manhiça Health Research Center, Vila da Manhiça,
Maputo, Mozambique (ALG-B, EL-V, EM, PLA);
Barcelona Centre for International Health Research
CRESIB, Hospital Clínic-Universitat de Barcelona,
Barcelona, Spain (ALG-B, EL-V, PLA); and National
Tuberculosis Program, Ministry of Health, Maputo,
Mozambique (IM)
1 WHO. Global tuberculosis report 2013. Geneva:
World Health Organization, 2013. http://www.
who.int/tb/publications/global_report/en/
index.html (accessed Oct 23, 2013).
2 Zumla A, George A, Sharma V, Herbert N,
Baroness Masham of Ilton. WHO’s 2013 global
report on tuberculosis: successes, threats, and
opportunities. Lancet 2013; 382: 1765–67.
3 Falzon D, Jaramillo E, Wares F, Zignol M, Floyd K,
Raviglione MC. Universal access to care for
multidrug-resistant tuberculosis: an analysis of
surveillance data. Lancet Infect Dis 2013;
13: 690–97.
Calcium-based
phosphate binders and
chronic kidney disease
We have concerns regarding
Sophie Jamal and colleagues’ Article
(Oct 12, p 1268)1 on the effect of
calcium-based versus non-calcium-
based phosphate binders on mortality
in patients with chronic kidney disease.
First, Suki and colleagues’ large
randomised controlled trial with 2103
patients and 542 events was a well done
negative trial and should be considered
while interpreting the present results.2
The forest plot (figure 2)1 strongly
suggests a small-study effect;3 indeed a
subgroup analysis of small (<50 events;
RR 0·54, 95% CI 0·37–0·79) versus
large (>50 events; RR 0·93, 95% CI
0·82–1·04) trials shows a significant
difference in effect size. This also
resolves the heterogeneity with I2 values
of 0. Second, we found that the Duval‘s
trim and fill analysis4 for publication
bias using the correct options does
add three studies with an adjusted
value of the RR being 0·82 (95% CI
0·64–1·04). Lastly, the trial by Di Iorio
and colleagues had a correction,5 it
was not registered, it was reported per
analysis) and patients were censored at
dialysis inception (thus mortality after
dialysis initiation was not reported)
despite all cause mortality being the
primary outcome. Neither the patients
nor the investigators were blinded, and
the categorisation of this trial5 as low
risk of bias is questionable. Exclusion of
this trial on sensitivity analysis leads to a
revised RR of 0·82 (95% CI 0·66–1·04).
On the basis of these issues, the
conclusion of the superiority of calcium-
based phosphate binders in reducing
mortality is not robust.
We declare that we have no conflicts of interest.
*Swapnil Hiremath, Ayub Akbari
shiremath@toh.on.ca
University of Ottawa, Ottawa, ON K1H 7W9, Canada
1 Jamal SA, Vandermeer B, Raggi P, et al. Effect
of calcium-based versus non-calcium-based
phosphate binders on mortality in patients
with chronic kidney disease: an updated
systematic review and meta-analysis. Lancet
2
2013; 382: 1268–77.
Suki WN. Effects of sevelamer and calcium-
based phosphate binders on mortality in
hemodialysis patients: results of a randomized
clinical trial. J Ren Nutr 2008; 18: 91–98.
3 Nuesch E, Trelle S, Reichenbach S, et al. Small
study effects in meta-analyses of osteo-
arthritis trials: meta-epidemiological study.
BMJ 2010; 341: c3515.
4 Duval S, Tweedie R. Trim and fill: a simple
funnel-plot-based method of testing and
adjusting for publication bias in meta-analysis.
Biometrics 2000; 56: 455-63.
5 Di Iorio D. Correction. http://cjasn.asnjournals.
org/content/7/8/1370 (accessed July 31, 2013).
Polio and the risk for the
European Union
Martin Eichner and Stefan Brockmann
warn that “Vaccinating only Syrian
refugees—as has been recommended
by the ECDC—must be judged as
insufficient; more comprehensive
measures should be taken into
consideration.”1
In response to the recent develop-
ments regarding wild-type polio
virus (WPV) circulation in Israel and
a cluster of poliomyelitis cases in
Syria, the European Centre for Disease
Prevention and Control (ECDC) has
published two risk assessments for
www.thelancet.com Vol 383 January 18, 2014

the European Union (EU).2,3 In those
assessments, we stated that European
countries are currently at high risk of
WPV introduction and that there are
areas of low vaccination coverage at
increased risk for an establishment of
local transmission of WPV.
Importantly, in addition to
vaccinating Syrian refugees, ECDC
has invited European Member States
to assess their national vaccination
coverage against polio (we estimate
that 12 million residents in the
European Union younger than 30 years
are unvaccinated), detect areas at risk,
and to engage in complementary
action, especially among vulnerable
groups living in poor sanitary
conditions, recommend to travellers
to areas with WPV circulation to ensure
they have an updated polio vaccination
status, enhance their surveillance
system based on the requirements
established by the Regional
Certification Commission for Polio
Eradication,4 strengthen their existing
environmental and enterovirus
surveillance to complement acute
flaccid paralysis surveillance (with
the present suboptimum quality
of EU polio surveillance systems it
is probable that WPV circulation is
not promptly detected), assess their
laboratory capacity, and to update their
preparedness plans for polio outbreaks.
We declare that we have no conflicts of interest.
*Lucia Pastore Celentano,
Pier Luigi Lopalco, Emma Huitric,
Denis Coulombier, Johan Giesecke
lucia.pastore.celentano@ecdc.europa.eu
European Centre for Disease Prevention and
Control, Stockholm SE-171 83, Sweden
1 Eichner MB, Brockmann SO. Polio emergence
in Syria and Israel endangers Europe. Lancet
2013; published online Nov 8. http://dx.doi.
org/10.1016/S0140-6736(13)62220-5.
2 ECDC. Wild-type poliovirus 1 transmission in
Israel – what is the risk to the EU/EEA?
Stockholm: ECDC, 2013. http://ecdc.europa.
eu/en/publications/Publications/polio-risk-
assessment-transmission-in-Israel.pdf
(accessed Nov 11, 2013).
3 ECDC. Rapid risk assessment: Suspected
outbreak of poliomyelitis in Syria: Risk of
importation and spread of poliovirus in the EU.
Stockholm: ECDC, 2013. http://ecdc.europa.
eu/en/publications/Publications/RRA%20
poliomyelitis%20Syria%2021%2010%202013.
pdf (accessed Nov 11, 2013).
www.thelancet.com Vol 383 January 18, 2014
4 WHO. Report of the 27th meeting of the
European Regional Certification Commission
for poliomyelitis eradication: Copenhagen,
Denmark 30–31 May, 2013. http://www.euro.
who.int/__data/assets/pdf_file/0016/200752/
Report-of-the-27th-Meeting-of-the-
European-Regional-Certification-Commission-
for-Poliomyelitis-Eradication.pdf (accessed
Nov 11, 2013).
Immunisation against
meningococcus B:
the case of Spain
Federico Martinón-Torres commented
recently (Nov 9, p 1552)1 on the
proposal drawn up by the Committee
on Immunisation Programmes and
Registries on the use of the new vaccine
against meningococcal B disease
(4CMenB vaccine) in Spain.2 As the
main contributors to this report,2 we
would like to express some concerns.
First, from a public health perspective,
the 4CMenB vaccine is surrounded by
several uncertainties regarding safety,
clinical effectiveness, and laboratory
surveillance and monitoring, which,
together with the decreasing trend in
the incidence of invasive meningococcal
B disease in Spain, warrant a cautious
decision regarding the use of this
vaccine in a routine programme at
present and reserving it for specific
high-risk situations (such as outbreaks)
and for immunosuppressed patients.
Second, an economic analysis was
not done taking into consideration
that the main variables (such
as vaccine price, effectiveness,
vaccination schedule, effect of fever
rates after immunisation on parental
acceptability, effect on acquisition of
carriage, and duration of protection,
are currently unknown. The data and
the analyses included in the report2
took more than a year to complete
and were not done in a hasty way as
Martinón-Torres suggests. In addition,
the framework for assessment of new
vaccines in Spain3 advises taking the
economic analysis into consideration
(step 3 in the mentioned framework)
after criteria such as burden of disease,
Correspondence
efficacy, and safety of vaccine (in
step 1), effect of the introduction
of the vaccine in the immunisation
programme and ethical aspects (in
step 2)—have been assessed.3
Third, although the vaccines against
meningococcal diseases serogroup
B and serogroup C are completely
different, Martinón-Torres compares
the epidemiological situation of both
diseases at the time of authorisation
of each vaccine and considers these
similar. However, the evaluation
done in September, 2000, showed
an incidence rate for disease by
serogroup C during the 1999–
Hero Images/Corbis
2000 season of 1·01 per 100 000
(404 cases), whereas the incidence
rate for disease by serogroup B in the
2011–12 season was about half of that:
0·52 per 100 000 (240 cases).2,4
In conclusion, we would like to
emphasise that public health decisions
regarding the inclusion of a vaccine
into the National Immunisation
Programme should be made not on
emotional and rapid considerations,
but only after an in-depth assessment
of all epidemiological data and
available information concerning the
vaccine in the first place; other criteria
should be considered afterwards.
We declare we have no conflict of interest.
*Aurora Limia Sánchez,
José A Navarro-Alonso,
Francisco Salmerón García
alimia@msssi.es
Coordination of Immunisation Programme,
Ministry of Health, Madrid, Spain (ALS); Regional
Department of Health, Murcia, Spain (JAN-A); and
Spanish Medicines Agency, Ministry of Health,
Madrid, Spain (FSG)
1 Martinón-Torres F. immunisation against
meningococcus B: the case of Spain. Lancet
2013; 382: 1552–53.
2 Limia A, Navarro-Alonso JA, Vázquez J, Cano R,
Salmerón F. Vaccine against invasive
meningococcal disease by serogroup B and its
use in Public Health, June 2013 (in Spanish).
http://www.msssi.gob.es/profesionales/
saludPublica/prevPromocion/vacunaciones/
docs/MenB.pdf (accessed Nov 19, 2013).
3 Committee on Immunisation Programmes
and Registries. Criteria for the assessment of
changes in the immunisation programme in
Spain (in Spanish). http://www.msssi.gob.es/
ciudadanos/proteccionSalud/vacunaciones/
docs/Criterios_ProgramaVacunas.pdf
(accessed Dec 12, 2013).
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