A Clinical Trial to Evaluate the Safety and Efficacy of Ciprofloxacin in the Treatment of Plague in Humans

Inclusion Criteria

• Suspect cases of plague will be eligible and will be asked to give consent for study enrollment using the following criteria:
• any person, including women and persons who are minorities, who;
• must be aged 8 years or older, and;
• must have had potential exposure to rodents and/or fleas or contact with a confirmed plague case, and;
• must have a fever of at least 38ºC that developed rapidly, and have at least one of the following:
• One or more buboes, defined as a tender lymph node swelling > 1cm in diameter, or;
• Clinical suspicion of pneumonic plague (e.g. prostration, cough, increased respiratory rate, hemoptysis and/or purulent sputum), or
• Clinical suspicion of cutaneous plague (lesion)
• Clinical suspicion of plague and epidemiologic link with other cases

Exclusion Criteria

• Patients with suspected plague illness will be considered ineligible for the study and will be excluded from study enrollment using the following criteria:
• Any women who is pregnant, or;
• Any woman who is breast-feeding, or;
• Any person aged 16 at time of enrollment (see below)
• known allergy to ciprofloxacin or doxycycline
• taken tetracyclines, quinolones, gentamicin, streptomycin, trimethoprim-sulfamethoxazole, or chloramphenicol in the 24 hours preceding study enrollment

Patients who are pregnant, breast-feeding, or aged < 8 years will be excluded because doxycycline has a relative contraindication for use in these populations due to drug deposition in calcifying areas of bones and teeth, enamel hypoplasia, and decreased linear skeletal growth rate. [22, 23] Please see section 10.2 for additional background describing the reasoning to exclude patients from these populations. Please see section 3.5 for the specifics regarding the timing of urine pregnancy testing.

The illness severity score is a composite measure adapted from the APACHE-II and Glasgow Coma scores that estimates the severity of a patient's illness at enrollment. Because most clinic locations are remote with little or no laboratory capacity, the illness severity score utilizes only non-biochemical parameters.

Patients will not be tested for Human Immunodeficiency Virus (HIV), and known or suspected HIV-positive patients will not be excluded.

Because this study will be conducted in a remote region of Uganda where no prisons are located, the enrollment of prisoners is not applicable to our study. If for some unforeseen reason a prisoner presents to a study clinic location for treatment of suspected plague, the prisoner will be excluded from the trial.

All study resources will be available and treatment following the UMOH national plague treatment guidelines will be offered to patients with suspected plague at the UMOH collaborating clinics who are not eligible for enrollment or who declined to consent.