This clinical trial will compare the effectiveness of streptomycin, which historically is the standard drug for treatment of plague, with gentamicin. The hypothesis is that gentamicin is not inferior to streptomycin but that it will have less severe side effects. The study is being done in Madagascar because that country reports the most plague cases in the world. Patients coming into a participating clinic with suspected plague (bubonic, pneumonic, or septicemic) will be randomized into one of two treatment arms after giving informed consent. Patients will be monitored for side effects and for improvement of symptoms.
In addition, rapid diagnostic test strips have been developed but not fully evaluated for use on humans. The investigators will evaluinformed consent. Patients will be monitored for side effects and for improvement of symptoms.
In addition, rapid diagnostic test strips haveate these new tests on specimens from the same patients, comparing their performance with that of classical diagnostic methods such as culture and serology.
This protocol will guide clinical trials of treatment of naturally occurring human plague cases in African countries with a high incidence of human plague. The safety and efficacy of gentamicin will be compared to the standard drug regimen that is already used in Madagascar (streptomycin/co-trimoxazole) for treatment of plague. Data from this trial will be valuable to optimize clinical management of plague in many countries, including Madagascar and the United States.
In collaboration with the governments and health officials of Madagascar, the investigators will implement a randomized, controlled, non-blinded drug trial to compare the effectiveness and side effect profile of gentamicin to the national standard plague treatment.
Cases of plague will be identified through clinic-based surveillance in areas with a high incidence and/or in areas that have experienced outbreaks in recent years. After giving informed consent, patients will be randomly assigned to one of two treatment arms, each arm receiving a different antimicrobial. One patient group will be treated with gentamieas that have experienced outbreaks in recent years. After giving informed consent, patients will be randomly assigned to one of two treatment cin; the other group ("control group") will receive streptomycin alone or with co-trimoxazole.
This protocol will follow the national guideline of the Madagascar Ministry of Health, which means that patients with bubonic plague in the streptomycin treatment arm will receive streptomycin followed by trimethoprim-sulfamethoxazole. The only adaptation is that enrolled patients with renal insufficiency will receive adjusted dosing of streptomycin, whereas the national standard treatment does not call for dose adjustment in renal failure.
The investigators will also evaluate several newly available, rapid "dipstick" tests for the diagnosis of plague using serum, bubo aspirate, sputum, and urine specimens that will have already been collected from the patients enrolled in the drug trial. These rapid tests have been developed by several American companies and the Institut Pasteur in Madagascar, and have not been fully evaluated for use with human specimens. These results will be compared to standard diagnostic techniques. Such rapid diagnostic tests will be useful for plague diagnosis in developing nations and during bioterrorism events.
Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Interv rapid diagnostic tests will be useful for plague diagnosis in developing nations and during bioterrorism events.
Aention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Plague
gentamicin, streptomycin
Ministry of Health
Antananarivo
Madagascar
Completed
Centers for Disease Control and Prevention
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Sisomicin
Antibiotic produced by Micromonospora inyoensis. It is closely related to gentamicin C1A, one of the components of the gentamicin complex (GENTAMICINS).
Plague Vaccine
A suspension of killed Yersinia pestis used for immunizing people in enzootic plague areas.
Plague
An acute infectious disease caused by YERSINIA PESTIS that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in syl in enzootic plague areas.
Plague
An acute infectious disease caused by YERSINIA PESTIS that affects hvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form.
Netilmicin
Semisynthetic 1-N-ethyl derivative of SISOMYCIN, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity.
Streptomyces Griseus
An actinomycete from which the antibiotics STREPTOMYCIN, grisein, and CANDICIDIN are obtained.