The epidemiological characteristics of the disease, as well as the risk of transmission to humans, are conditioned by the nature of the main animal reservoir, which varies according to world regions and local socioeconomic conditions. Between January 1, 2010, and December 31, 2015, 3,248 human plague cases and 584 deaths were recorded worldwide. The increase in the number of cases since the 2000s makes plague a re-emerging disease. In Africa and South America it is a disease of poverty where transmission occurs through promiscuity with commensal rodents. In other endemic regions the disease is rather sporadic and related to work or leisure activities in the countryside. Madagascar remains the most affected in the world with 2,404 cases (mostly bubonic) from 2010-2015, including 476 deaths. On the American continent, plague cases are very regularly reported in Peru in four departments in the northwest territory. These are mainly sporadic cases of bubonic plague related to agricultural activity in rural areas. In the western United States, plague circulates among wild rodents once again in rural and semi-rural areas, degenerating into bubonic plague in some cases each year. Human contamination regularly occurs through domestic animals, cats or dogs. Central Asia is considered the birthplace of the plague and remains the largest natural outbreak. The population at risk is limited to herders and hunters in contact mainly with gerbils in the steppes and with marmots in mountainous areas. Transmission to humans is therefore very limited, and the bubonic form is quite sporadic in China, Mongolia, Kyrgyzstan, and the Russian Federation.
As described above, plague is an endemic disease in Madagascar. Each year it has a seasonal upsurge between September and April affecting mainly the central highlands at an altitude above 800 meters. In 2017, a large-scale epidemic hit the country. Between August 1, 2017 and November 22, 2017, a total of 2,348 plague cases (confirmed, probable, and suspected) were notified to the Madagascar Central Plague Laboratory, including 1,791 (76 percent) cases of pneumonic plague, 341 (15 percent) cases of bubonic plague, and 1 case of septicemic plague. The mortality rate stood at 8.6 percent (202 deaths). Several factors could explain the greater extent of this epidemic: for example, the large proportion of pulmonary forms facilitating human-to-human transmission, or the presence of plague cases outside the known outbreaks, particularly in the areas of Antananarivo and Toamasima. However, the real reasons influencing the continuing outbreaks are still poorly understood.
Plague affects people of all ages and genders and manifests itself in three typical forms, which can sometimes overlap:
- bubonic plague;
- pneumonic plague;
- septicemic plague.
Bubonic plague
Incubation lasts from 1 to 7 days. Onset of symptoms is sudden, usually with a high fever (39°C - 40°C), general malaise, chills, headache and severe pain in the area where the boil will develop, appearing after 24-48 hours. It is a severe bacterial, usually single, inflammatory adenitis (inflammation of a gland) that gradually increases in size. Gradually the boil softens and collects, from which time it can be incised. The natural course is ulceration, which releases pus in which many bacilli are present. Evolution can sometimes develop into local dissemination (secondary buboes) then general dissemination of the infection with potential secondary localizations. These may include meningeal or pulmonary damage (secondary pneumonic plague). Lethality is in the range of 50% in the absence of treatment. If the outcome is favorable, wound healing is slow and may last for several weeks.
Pulmonary plague
Pneumonic plague is a rare form, which may be primary (human-to-human airborne infection or inhalation of dust from contaminated soil) or secondary (dissemination by blood or lymphatics from a boil or septicemic plague). Due to increased human contact and airborne, it can pose a threat of rapid spread from an epidemic outbreak. Primary pneumonic plague has a short incubation period, which can last from a few hours to 3 days. This is a picture of sudden onset febrile pneumonia with cough, chest pain, sputum, and sometimes hemoptysis and dyspnea. The course of the disease progresses to a picture of acute respiratory distress with which other symptoms may also be associated, including diarrhea, agitation, prostration, or headache. Spontaneous development is usually fatal within 24-72 hours in more than 90% of cases. Secondary pneumonic plague has an incubation period of 5-7 days in a patient whose respiratory involvement is usually secondary. The course of secondary pulmonary forms is usually less severe than that of primary pneumonic plague.
Septicemic plague
This clinical form is discussed. It accounts for about 10-25% of cases and is defined by isolation of the bacillus from blood cultures in the absence of any bubo found. It is associated with a severe (arterial hypotension, septic shock) and sudden clinical picture, with severe worsening of general condition, hemorrhagic, cardiovascular, neurologic, and renal complications. It corresponds to the forms historically described as rapidly evolving. The lethality of this form is greater than 90%.
However, for some authors, it would only be a bubonic plague with hidden buboes, the blood passage of the bacillus being frequent.
The sudden onset with fever and buboes, the rapid and intense inflammatory reaction in the bubo, the usual absence of visible lesions on the overlying skin and ascending lymphangitis, and the fulminant course, which can lead to death in 2 to 3 days, make the picture of plague characteristic, which must, however, be differentiated from other infections causing acute lymphadenitis.
The key to successful treatment of plague is early recognition and timely administration of effective antibiotics. A delay of even 24 hours in administering effective antibiotics and antishock therapies is usually fatal for patients. If left untreated, it has a mortality rate of 50-90% of cases for bubonic forms and almost total for other clinical forms. Early diagnosis and appropriate antibiotic therapy reduce this mortality to 5-15%. Y. pestis is sensitive in vitro to many antibiotics including aminoglycosides. Of these, streptomycin has been historically used and proven effective since the 1940s. Currently, the good efficacy of fluoroquinolones in vitro and in animal models, as well as the practical methods of their use, have allowed this class of drugs to be offered as first-line treatment in French, American and other recommendations. Most isolates of Y. pestis worldwide are susceptible to streptomycin; however, a multidrug-resistant (MDR) strain was isolated from Madagascar Fortunately, it has never again emerged naturally in this region or elsewhere in the world. Streptomycin and gentamicin are recommended for adult patients, including immunocompromised patients and pregnant women. In a large-scale plague outbreak or in the context of a bioterrorism attack, oral doxycycline and ciprofloxacin are recommended on adult patients than children. Alternatively, chloramphenicol could also be chosen to treat adult patients; however, for children, the combination of chloramphenicol and ciprofloxacin should be used.
The main goal of plague control is to reduce the likelihood of people being bitten by infected fleas, coming into direct contact with infected tissues and/or exudates, or being exposed to contact with humans or animals with the disease. Plague remains strongly linked to poverty with rural areas being the most affected. Surveillance and control of the animal reservoir is important in regions where plague is endemic. Some of the following specific measures may be proposed.
Measures targeting animals are:
- collect and analyze fleas from wild rodents;
- combating fleas by applying insecticides in the outbreak area;
- suppression of rats by poisoning may be necessary; and
- increase basic sanitation measures.
However, rat control should always be preceded by flea control measures, as it is possible to suppress the normal food supply of fleas by poisoning their hosts. A key element remains raising awareness among the general population in urban enzootic areas (habitual presence of the disease in rodents) about:
- how humans and pets are exposed;
- protection of buildings against mice by preventing rodents from accessing food and shelter through proper storage and disposal of food, waste and garbage;
- the use of insecticides and repellents to prevent flea bites;
- the risk involved in camping near burrows or handling rodents;
- reporting dead or diseased animals to health authorities.
For suspected bubonic form cases, measures to avoid contact should be used while for suspected pulmonary cases, additional precautions should be added (wear a surgical mask when entering the patient's room). Patients with bubonic plague without secondary pneumonic and septicemic plague have a very low risk of spreading plague to close contacts. Vaccine prevention was abandoned because early serums (live attenuated) caused many side effects, sometimes serious. Other forms of vaccine (inactivated whole) were later developed that were not effective enough in pulmonary forms and provided only short-lived immunity. Recent concerns about the use of the plague agent for bioterrorism have revived research on the subject. Two virulence factors of Y. pestis, capsular antigen F1 and LcrV (low-calcium response antigen), are currently the most promising avenues for developing new forms of the vaccine. Indeed, a subunit vaccine combining F1 and LcrV has shown promising results in animal models, although its efficacy in humans has yet to be evaluated. This vaccine could be available in a few years for populations in endemic areas. However, because the immune response to the latter depends mainly on humoral immunity, a booster dose may be necessary.