Bubonic and Pneumonic Plague in Uganda
Abstract & Commentary
By Michele Barry, MD FACP and Brian G. Blackburn, MD
Dr. Barry is the Senior Associate Dean of Global Health at Stanford University School of Medicine.
Dr. Blackburn is a Clinical Assistant Professor in the Division of Infectious Diseases and Geographic Medicine at Stanford University School of Medicine.
The authors report no financial relationships relative to this field of study.
Synopsis: Plague is a life-threatening flea-borne disease caused by the bacterium Yersinia pestis. The most common form is bubonic plague, characterized by fever and regional lymphadenitis.
Source: Centers for Disease Control and Prevention. MMWR Morb Mort Wkly Rpt. July 24, 2009 / 58(28);778-81.
This report describes an outbreak of both bubonic and pneumonic plague in northwestern Uganda, where 127 clinically diagnosed plague cases were identified during a 5½ month span. Pneumonic plague (and associated person-to-person transmission) occurred outside the usual endemic area, and this investigation suggested that emergency response, laboratory diagnostic capabilities, access to care, and vector control continue to be challenges in this region.
The Uganda Ministry of Health and the U.S. Centers for Disease Control and Prevention (CDC) conducted a joint investigation in late 2006 in response to reports of an increase in the number of clinically diagnosed plague cases (see Figure 1) in the Arua and Nebbi districts of Uganda, which are in the northwestern corner of Uganda, abutting the Democratic Republic of the Congo and Sudan (see Figure 2).
For this study, cases were ascertained through a retrospective review of patient logs dating back to 4½ months prior to the initiation of the investigation in eight clinics and two hospitals that historically had accounted for 85% of reported plague cases in the region. In addition, active case-finding and collection of diagnostic samples (serum and bubo aspirates) were performed for cases diagnosed prospectively during the one-month investigation. Laboratory-confirmed plague was defined as isolation of Yersinia pestis or a four-fold change in serum antibody titers.
In rural Uganda, where laboratory capacity is limited, clinicians most commonly rely on clinical criteria for the diagnosis of plague, which the Ugandan Ministry of Health defined as the sudden onset of fever, chills, malaise, headache, or prostration accompanied by:
- painful regional lymphadenitis (bubonic plague); or
- cough with hemoptysis (pneumonic plague).
Overall, 127 clinical plague cases were identified, including a focal pneumonic outbreak. Among 102 patients with documented symptoms, 90 (88%) had bubonic plague and 12 (12%) had pneumonic plague. Twenty-eight (22%) of the 127 patients died, including 11 (92%) of the 12 patients with pneumonic plague.
The 127 plague cases came from nine different villages; more than half of the 11 pneumonic deaths came from one village in which four family members died when the index case, a 10 year-old boy, developed bubonic plague that subsequently progressed to pneumonic plague and he expired. The child's mother, grandmother, and aunt, all of whom cared for the boy, all died subsequently of pneumonic plague.
Bubo aspirates were obtained from 11 of 90 patients with bubonic manifestations. Yersinia pestis was not recovered from any of the aspirates, but eight of the 11 had received antecedent antibiotics, and convalescent sera from five patients with bubonic plague had titers that ranged from 1:16 to 1:256. Samples from patients with pneumonic plague were unavailable due to rapid mortality and the inability to obtain appropriate specimens.
While visiting villages, investigators recovered eight dead rats (Rattus rattus), four of which tested positive for Yersinia pestis by direct fluorescent antibody staining and two by culture. Fifty-nine percent of patients in this retrospective investigation reported seeing dead rats in their homes during the two weeks preceding their illness.
Commentary
African countries account for almost 90% of the 28,530 plague cases reported to the World Health Organization during the most recent reporting period (1994-2003).1
Plague, historically known as the "black death," is a life-threatening flea-borne disease caused by the bacterium Yersinia pestis. The principal forms of plague are bubonic, septicemic, and pneumonic. The most common clinical form is bubonic plague, which is characterized by high fever and regional lymphadenitis. Without treatment, infection can spread from lymph nodes to the bloodstream or lungs, resulting in the septicemic or pneumonic forms, with the potential for person-to-person transmission from the latter.
This investigation highlights the challenges associated with identifying and controlling plague in rural Africa due to limited laboratory capacity, limited manpower, and logistical barriers such as impassible roads and poor access to health care and laboratory testing. Another important barrier is the impact of local beliefs, which in some cases resulted in persons attributing their illness to the supernatural. All of these issues delayed prompt diagnosis and treatment in affected patients and likely contributed to the adverse outcomes observed.
Although most plague cases occur in small clusters, the development of pneumonic plague and subsequent person-to-person spread is of concern. In this investigation, the occurrence of pneumonic plague in one family led to the deaths of three persons who cared for an ill child. In addition, approximately six weeks after the investigation concluded, an outbreak of pneumonic plague with seven deaths was reported from a neighboring region in Uganda where plague is not endemic; the index patient was an adolescent girl who had visited the plague-infected district of Nebbi. Early treatment of bubonic plague likely would have prevented many of these secondary deaths by preventing progression to the pneumonic form of the disease. This again demonstrates the difficulties with poor access to care in this part of Uganda.
In Uganda, 200-400 clinically diagnosed plague cases are reported annually, with an estimated case-fatality rate of 30%.2 The low rate of seropositivity observed in this study is disappointing and may reflect the retrospective nature of the study and the likelihood that the sickest patients died before appropriate specimens were collected, and poor selection of cases given the use of only clinical criteria. Lymphadenitis has many other etiologies; both hemoptysis and cough also generate a long list of differential diagnoses in Uganda aside from plague. This report highlights the urgent need for better point-of-care diagnostics for this area. Not only are some plague cases likely being under-diagnosed and mistreated as other potential infectious illnesses, but some patients with non-plague illnesses may be inappropriately being treated for plague, resulting in progression of other diseases. Clearly, with dead rats (R. rattus) testing positive for Yersinia pestis and trappings of live rats revealing an average of two fleas per rat, these districts are endemic settings with the grave potential for the spread of plague.
A Short History of Plague. Three pandemics of "black death" have been recorded since 542 AD. The disease is estimated to have killed 30-60% of Europe's population between 1348 and 1350. The last global surge of plague arose in the latter half of the 19th century in Yunnan Province, China and moved into Hong Kong, resulting in 26 million cases. The last rat-borne epidemic in the United States occurred in Los Angeles in 1924-25. Since then, all human plague cases in the United States have been sporadic, with fewer than 20 cases per year.2 Currently, most major endemic global foci are located in rural Africa and Asia.
Clinical Presentation. Bubonic plague usually develops 2-6 days after a person has been bitten by a plague-infected flea. Initial symptoms are fever and headache, followed by painful swollen regional lymph nodes. Progression can lead to septicemia and pneumonia; the latter is highly contagious through respiratory droplets; persons subsequently exposed in this manner can develop primary pneumonic plague. Case-fatality rates for pneumonic plague are extremely high. Rare cases of meningitis and pharyngeal plague also have been reported.
Diagnosis. In the absence of microbiological isolation of Yersinia pestis from body fluids, plague cases can be confirmed by demonstrating a four-fold or greater change in serum antibody titers to Yersinia pestis F1 antigen by passive hemagglutination testing or a single serum titer of 1:128 or greater. Most patients seroconvert by 1 to 2 weeks, although early administration of antibiotics can abort seroconversion. A fluorescent antibody or a Wayson's stain demonstrates the typical bipolar "closed safety pin" small gram negative coccobacilli. Rapid diagnostics and polymerase chain reaction-based tests are being developed for point-of-care diagnosis.
Prevention. Reducing exposure is the best prevention. In known endemic areas, avoidance of dead rodent carcasses, use of insect repellents, and both flea and rodent control should be emphasized. Persons who are exposed via unprotected face-to-face contact within two meters of a confirmed or suspected case of pneumonic plague should be treated with 5-7 days of doxycycline or ciprofloxacin. A killed whole cell vaccine has been developed and used by the U.S. military. Newer vaccines are under development due to concern for plague as a bioterrorism agent. The current available vaccine does not protect against pneumonic plague.
References
- Dennis D, Mead P. Plague. In: Guerrant R, Walker D, Weller P. (eds.). Tropical Infectious Diseases, second Edition 2006; 471-481.
- http://www.cdc.gov/mmwr. Accessed August 28, 2009.
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