The analytical framework and key questions are represented in .
Key question 1. Among individuals with clinical suspicion of plague, does F1RDT accurately detect plague compared with isolation of Yersinia pestis by culture, PCR or paired serology?
| Participants | Adults and children suspected to have plague |
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| Intervention | F1RDT |
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| Comparison | Isolation of Y. pestis by culture, PCR or paired serology |
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| Outcomes | Test accuracy: sensitivity, specificity |
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We explored heterogeneity between study results by looking at findings for the following subgroups:
different forms of plague – bubonic, septicaemic and pneumonic;
type of reference standard – bacterial isolation by culture, PCR and enzyme-linked immunosorbent assay (ELISA);
context – plague-endemic areas, areas where an outbreak is in progress.
Therefore, the four main questions that derived from the first key question were the following.
Should an RDT be used to detect pneumonic plague in plague-endemic areas?
Should an RDT be used to diagnose pneumonic plague in patients in areas where an outbreak is in progress?
Should an RDT be used to detect bubonic plague in plague-endemic areas?
Should an RDT be used to diagnose bubonic plague in patients in areas where an outbreak is in progress?
Key question 2. Among individuals with plague, how effective and safe are the following antibiotics?
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| Participants | Adults and children with confirmed or suspected plague |
|---|
| Intervention | Any fluoroquinolone |
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| Comparison | Streptomycin Gentamicin Tetracyclines, doxycycline Chloramphenicol |
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| Outcomes |
- –
Death Cure (defined as resolution of fever and painful bubo swelling and, if initially present, recovery from pneumonia or any other symptoms of plague) - –
Complications after the initiation of antimicrobial therapy (including systemic inflammatory response syndrome, meningitis and secondary pneumonia)a - –
Defervescence time (number of days with fever) - –
Sputum negativity (for pneumonic plague) - –
Relapse (defined as the return of bubo tenderness, fever or other symptoms within 1 to 2 weeks after the end of therapy)a - –
Adverse effects
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- a
Mwengee
W, Butler
T, Mgema
S, Mhina
G, Almasi
Y, Bradley
C
et al. Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis. 2006;42:614–21. doi: 10.1086/500137. [PubMed: 16447105] [CrossRef]
We first gathered all the evidence from direct comparisons between any of the following antibiotics: any fluoroquinolone and streptomycin, gentamicin, doxycycline or chloramphenicol. As we anticipated that there were limited studies that directly compared one antibiotic with another, we then summarized the outcomes for each of the above antibiotics from single-arm studies and case reports.
These antibiotics were selected by the GDG members in consultation with the responsible technical officer.
Whenever possible, we aimed to examine the evidence of possible effect modifiers, including:
forms of plague – bubonic, septicaemic and pneumonic plague, and plague meningitis;
certainty of diagnosis – confirmed and probable or presumptive plague;
subgroup populations – adults, children.
Key question 3. What is the risk of plague transmission from exposure to the remains of people who died of plague?
We formulated a broad question because we anticipated that there was limited literature describing this topic. For this question, we aimed to answer, clarify and summarize the responses to a series of questions.
How contagious are the body fluids of people with bubonic, septicaemic or pneumonic plague?
How many studies described fluid or aerosol transmission among people?
How many cases of plague transmitted by human body fluid or other human remains have been documented? Was the possible route of transmission described?
How many cases of plague transmitted during the manipulation of contaminated material in a laboratory have been documented? Was the possible route of transmission described?
How many cases of plague transmitted by animal remains have been documented? Was the possible route of transmission described?
For how long can Y. pestis survive in a dead body and be infectious to a human?
We aimed to describe and summarize all reported cases of plague infection occurring during post-mortem exposure to human and animal remains. We collected data on the possible mode of transmission (inhalation, contact with blood or other body fluids and secretions, contact with infected tissues), duration of exposure and length of time since death.
