STROBE Statement—checklist of items that should be included in reports of observational studies
Characterization of Plasmodium vivax-Associated Admissions to Reference Hospitals in Brazil and India
André M. Siqueira1,2, Marcus V. G. Lacerda1,2*, Belisa M. L. Magalhães1,2,
Maria P. G. Mourão1,2, Gisely C. Melo1,2, Márcia A. A. Alexandre1,2, Maria G. C. Alecrim1,2, Dhanpat Kochar3, Sanjay Kochar3 , Pamendra
Sirohi3, Kailash Nayak3,
Hernando del Portillo4,5, Caterina Guinovart4,6, Pedro Alonso4,6, Quique Bassat4,6
Title and abstract
Item
No.
1
Recommendation
(a) Indicate the study’s design with a commonly used term in the title or the abstract
Page
No.
1
Relevant text from
manuscript
Characterization of Plasmodium
vivax-Associated Admissions to
Reference Hospitals in Brazil
and India
(b) Provide in the abstract an informative and balanced summary of what was done and what was
found
2
Methods
Patients admitted with P. vivax
mono-infection at reference
centers in Manaus (Amazon Brazil) and Bikaner (Rajhastan India), where P. vivax
predominates, were submitted to
standard thorough clinical and
laboratory evaluations in order
to characterize clinical
manifestations and identify
concurrent co-morbidities.
Results
In total, 778 patients (88.0%
above 12 years old) were
hospitalized at clinical
1
discretion with PCR-confirmed
P. vivax mono-infection (316 in
Manaus and 462 in Bikaner) of
which 197 (25.3%) presented at
least one severity criterion as
defined by the WHO (2010).
Hyperlactatemia, respiratory
distress, hypoglycemia and
disseminated intravascular
coagulation were more frequent
in Manaus. Noteworthy,
pregnancy status was associated
as a risk factor for severe
disease (OR= 2.03; 95%CI=1.23.4; p=0.007). The overall case
fatality rate was of 0.3/1000cases in Manaus and 6.1/1000cases in Bikaner, with all deaths
occurring amongst patients
fulfilling at least one severity
criterion. Within this subgroup,
case fatality rates increased
respectively to 7.5% in Manaus,
and 4.4% in Bikaner.
Introduction
Background/rationale
2
Explain the scientific background and rationale for the investigation being reported
3-5
In the absence of adequate
experimental models, or the
paucity of postmortem samples
to further elucidate the
pathophysiology of this
infection [5, 13, 24], systematic
2
multisite clinical studies become
a unique opportunity to better
understand this geographic
variability and characterize the
severe vivax malaria syndrome.
Objectives
3
State specific objectives, including any prespecified hypotheses
5
aiming to comprehensively
characterize and compare the
clinical complications of P.
vivax infection.
Methods
Study design
4
Present key elements of study design early in the paper
7-8
This was a hospital-based study
of patients admitted with vivax
malaria at the two study centers,
regional references mostly for
the adult population.
Setting
5
Describe the setting, locations, and relevant dates, including periods of recruitment, exposure,
5-6
follow-up, and data collection
The enrollment of cases was
performed in two different
reference tertiary hospitals
located in Brazil and India.
Participants
6
(a) Cross-sectional study—Give the eligibility criteria, and the sources and methods of selection
of participants
7
All initial microscopyconfirmed P. vivax infections
(or patients with negative thick
blood smears [TBS] but with
history of previous recent
diagnosis in use of
antimalarials) requiring
admission, at clinician’s
discretion (e.g., presence of
jaundice, thrombocytopenia,
bleeding, vomiting, diarrhea,
abdominal pain, non-lithiasic
3
cholecystitis, spleen rupture or
overall compromised clinical
status), regardless of age, were
eligible for enrollment provided
patients or their legal
representatives signed an
informed consent.
Variables
7
Clearly define all outcomes, exposures, predictors, potential confounders, and effect modifiers.
11
Give diagnostic criteria, if applicable
Unadjusted simple logistic
regression analyses were also
performed considering different
outcomes, especially the
fulfilment of WHO severe
criteria for P. falaciparum [20]
and death
Data sources/
8*
measurement
For each variable of interest, give sources of data and details of methods of assessment
9-11
(measurement). Describe comparability of assessment methods if there is more than one group
Patients were classified in
relation to their clinical
symptomatology and laboratory
results
Bias
9
Describe any efforts to address potential sources of bias
7
The same protocol for clinical
and laboratory investigations
was applied in both sites,
including standard operating
procedures (SOPs) and
questionnaires. The study
procedures were standardized
and supervised by coinvestigators from both sites and
supervised by study monitors
from ISGlobal (Q.B. and C.G)
to minimize potential
4
discrepancies in its application.
Study size
10
Explain how the study size was arrived at
N/A
Continued on next page
5
Quantitative
11
variables
Statistical
Explain how quantitative variables were handled in the analyses. If applicable, describe which
11
groupings were chosen and why
12
methods
(a) Describe all statistical methods, including those used to control for confounding
11
(b) Describe any methods used to examine subgroups and interactions
N/A
(c) Explain how missing data were addressed
N/A
(d) Cohort study—If applicable, explain how loss to follow-up was addressed
N/A
Case-control study—If applicable, explain how matching of cases and controls was addressed
Cross-sectional study—If applicable, describe analytical methods taking account of sampling
strategy
Results
Participants
13*
(e) Describe any sensitivity analyses
N/A
(a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined
Figure 2
for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed
Descriptive data
14*
(b) Give reasons for non-participation at each stage
Figure 2
(c) Consider use of a flow diagram
Figure 2
(a) Give characteristics of study participants (eg demographic, clinical, social) and information on
Table 1
exposures and potential confounders
(b) Indicate number of participants with missing data for each variable of interest
Table 1 & 4
(c) Cohort study—Summarise follow-up time (eg, average and total amount)
Outcome data
15*
Cohort study—Report numbers of outcome events or summary measures over time
Case-control study—Report numbers in each exposure category, or summary measures of exposure
Table 4
Cross-sectional study—Report numbers of outcome events or summary measures
Main results
16
(a) Give unadjusted estimates and, if applicable, confounder-adjusted estimates and their precision
Table 4
(eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were
included
(b) Report category boundaries when continuous variables were categorized
Table 4
(c) If relevant, consider translating estimates of relative risk into absolute risk for a meaningful time
Table 4
period
6
Unadjusted linear
regression was undertaken
to explore the association
between number of severe
criteria and risk factors
Continued on next page
7
Other analyses
17
Report other analyses done—eg analyses of subgroups and interactions, and sensitivity analyses
N/A
18
Summarise key results with reference to study objectives
19
Discussion
Key results
the associated CFR amongst admitted
patients to the study in the Brazilian
Amazon (0.9%) and Indian Rajasthan
(1.5%) is not negligible,
Limitations
19
Discuss limitations of the study, taking into account sources of potential bias or imprecision. Discuss
19
both direction and magnitude of any potential bias
by not performing a systematic
investigation in all admitted cases from
both sites, there was an important
limitation on estimating the prevalence
of their occurrence and association with
severe syndromes,
Interpretation
20
Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of
19
analyses, results from similar studies, and other relevant evidence
Our data provide yet again a robust
confirmation of the potential of this
species to cause significant morbidity
and even mortality, a fact now widely
recognized by the scientific community
and by WHO in its recently published
severe malaria monograph
Generalisability
21
Discuss the generalisability (external validity) of the study results
19
Indeed, the associated CFR amongst
admitted patients to the study in the
Brazilian Amazon (0.9%) and Indian
Rajasthan (1.5%) is not negligible, and
comparable to CFRs previously
described in Papua New Guinea [38]
and Indonesia [18], and not too
dissimilar to those for P. falciparum in
Africa [2], although these findings must
be taken cautiously as the low incidence
of P. falciparum in the study areas and
the hospital-based design can limit
8
comparisons and estimates of
community CFRs
Other information
Funding
22
Give the source of funding and the role of the funders for the present study and, if applicable, for the
original study on which the present article is based
27
This work was mainly supported by
Fundació Cellex, and also by PRONEX
Malaria Network, funded by the
Brazilian Ministry of Science and
Technology (MCT), National Council
for Scientific and Technological
Development
(CNPq),
Brazilian
Ministry of Health (DECIT/SCTIE/MS)
and the Research Support Foundation of
Amazonas
(FAPEAM)
(grant
555.666/2009-3). MVGL is a level 1
CNPq fellow and HAP is also funded
by the Science without Borders (CsF),
from CNPq. QB has a fellowship from
the program Miguel Servet of the ISCIII
(grant number: CP11/00269). The
funders had no role in study design,
data collection and analysis, decision to
publish, or preparation of the
manuscript.
*Give information separately for cases and controls in case-control studies and, if applicable, for exposed and unexposed groups in cohort and cross-sectional studies.
Note: An Explanation and Elaboration article discusses each checklist item and gives methodological background and published examples of transparent reporting. The STROBE
checklist is best used in conjunction with this article (freely available on the Web sites of PLoS Medicine at http://www.plosmedicine.org/, Annals of Internal Medicine at
http://www.annals.org/, and Epidemiology at http://www.epidem.com/). Information on the STROBE Initiative is available at www.strobe-statement.org.
9