Richard 2015.

Study characteristics
Patient Sampling	Retrospective study. Study authors included all cases with suspicion of plague during outbreaks. Consequently, there was no consecutive or random sampling. Furthermore, RDT was only performed in 2 participants, as biological samples could not be retrieved for the first cases when plague was not suspected yet, and other cases were suspected on recovery, with no biological samples taken in acute phase.
Patient characteristics and setting	Country: Madagascar. Plague endemicity: endemic in Madagascar, although the remote region where the outbreak occurred was supposedly free of Y pestis. Clinical setting: 7 villages along a field path in the communes of Ambarakaraka and Anaborano, Ambilobe District, in the north of Madagascar. Study dates: outbreak in January 2011. Inclusion criteria: all participants with suspected plague during this outbreak. Exclusion criteria: none mentioned. Target condition: any form of plague, but outbreak of pneumonic plague. Sample size: 20 cases in the outbreak, but RDT was only performed on 2 participants. Samples collected: sputum. Age: not reported. Sex: not reported. Signs and symptoms presented: sudden onset of fever, cough, haemoptysis, and chest pain. Antibiotic treatment prior to enrolment: both participants received antibiotics, but unclear whether before or after biological sample collection. We judged there were unclear concerns regarding applicability, as the test was performed on only 2 people, with limited information.
Index tests	Type: the authors referenced Chanteau 2003a for the RDT used, produced at the IPM. Brand name: RDT developed by the Naval Medical Research Institute (Bethesda, MD, USA), as described in Chanteau 2003a. Threshold for positive result: not stated in the paper, but Ag threshold of 0.5 ng/mL as specified in the referenced study Chanteau 2003a, and used as a positive/negative test. Place where the test was performed: unclear, probably bedside of the participant. Transport and storage conditions of the RDT: not reported. Transport and storage conditions of the samples to be tested: not reported. Need for sample preparation: not reported. Who performed the test: not reported. Blinding of operator to the results of the reference standard: not reported. It is likely that RDT was performed at the bedside of the participants, and, therefore, interpreted before sending sample for reference standard. Special training provided to personnel performing the test: not reported.
Target condition and reference standard(s)	Definitions of cases of plague: Confirmed: 4‐fold increase in titre of antibodies against F1 Ag in paired serum samples or a positive culture. Presumptive: positive serological result for antibodies anti F1 Ag. Suspected: specific clinical symptoms. Reference standard(s) used in this review: Culture + inoculation in mice. Serological analysis with a 4‐fold increase in titre in the second serum sample. Molecular analysis: PCR (specific for the Y. pestis plasminogen activator and capsule Ag fraction 1 genes). Place where the reference standard(s) was (were) performed: WHO Collaborating Center for Plague at the IPM in Antananarivo. Who performed the reference standard(s): not reported. Blinding of operator to RDT result: not reported. However, there is low risk of introducing bias in the interpretation of the reference standard (objective finding) by knowing the RDT result.
Flow and timing	Time between collection of sample for RDT and reference standard(s): not reported. Administration of antibiotics between sample collection for index test and reference standard: not reported. Time of sample transportation: distance > 900 km, time of transportation not reported. The judgements we make below are considering only the 2 participants for whom RDT was performed.
Comparative
Notes	Source of funding: supported by the IPM, the President's Malaria Initiative/US Agency for International Development, and the US Department of Homeland Security (project no. DHS‐09‐ST‐108‐001/MGN3EL7‐01).
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient Selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	Yes
Did the study avoid inappropriate exclusions?	Unclear
Did the study considered prior administration of antibiotics?	No
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			Unclear
DOMAIN 2: Index Test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Unclear
If a threshold was used, was it pre‐specified?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Unclear risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Unclear
DOMAIN 3: Reference Standard
Is the reference standards likely to correctly classify the target condition?	Yes
Were the reference standard results interpreted without knowledge of the results of the index tests?	Unclear
Could the reference standard, its conduct, or its interpretation have introduced bias?		Low risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Low concern
DOMAIN 4: Flow and Timing
Was there an appropriate interval between index test and reference standard?	Unclear
Did all patients receive the same reference standard?	Yes
Were all patients included in the analysis?	Yes
Did all patients receive a reference standard?	Yes
Could the patient flow have introduced bias?		Unclear risk