Madagascar is one of the most active plague regions in the world and was the origin of a natural multi-drug resistant strain of
Y. pestis [
6]. Incidence has declined in the last 2 years but there has been an increase in the overall case-fatality rate (23% in 2015) associated with the high frequency of pneumonic form (23.3%) [
3]. Within 24–36 h after the onset of symptoms, pneumonic plague progresses to an irreversible and lethal syndrome that cannot be effectively treated [
14]. Indeed, most pneumonic plague patients succumb in less than 3 days without prompt and adequate treatment. For the present case, which is most likely a primary pneumonic infection, the early doses of trimethoprime-sulfamethoxazole self-administered might have induced a latent phase in pneumonic plague infection, a delayed infection course which allowed the patient to survive despite a delay of plague treatment. It was demonstrated that the most common indications for self-medication were pain, fever and cough [
9]. In addition, antibiotic medication rapidly clears the sputum of plague bacilli, so that a patient is generally not infective within hours after initiation of effective antibiotic treatment [
15]. In this report, clinical presentation and epidemiological evidence (residence in a plague endemic area) are consistent with a pneumonic plague infection. Additionally, laboratory results met the criterion of the WHO standard case definition for a “Confirmed plague case” [
5]. It is noteworthy that F1 antigen is specific to
Y. pestis [
16]
, temperature-stable and is excreted in large amount in samples from plague infected people [
10]. The failure of
Y. pestis isolation by bacterial culture is not uncommon if antibiotic treatment was administered before sampling [
17,
18]. Positive results of F1 antigen RDT on all sputum samples showed that
Y. pestis F1 antigen could persist and be detected several days after the beginning of treatment, when the plague bacillus is no longer viable [
10,
17,
19]; for this case, F1 antigen persisted for 10 days after the beginning of treatment and 20 days after disease onset. Due to the failure of the culture, sensitivity of
Y. pestis to streptomycin was not tested; however a resistance is doubtful because the patient would have likely succumbed to pneumonic plague infection if the complete streptomycin treatment was not effective. The isolation of MDR-
S. maltophilia from his sputum collected at MDH suggested that the patient had a mixed infection with
Y. pestis and
S. maltophilia. This nosocomial infection has probably been acquired during his stay at this hospital and may have been favored by patient immunocompromised condition. Without other medical information, his immune response maybe attenuated by the course of his disease or by malnutrition with a notable weight loss. However, it has been shown that pulmonary infection by
Y. pestis may establish a permissive environment for proliferation of usually nonpathogenic bacteria [
2]. In middle or low resources areas, which is the case of most plague endemic countries, control and prevention of infections in health facilities is not optimal. Co-infection with an opportunistic pathogen agent is a risk which must not be disregarded. Indeed,
S. maltophilia is an important emergent opportunistic pathogen, causing lung colonization or pulmonary infections among immunosuppressed patients. According to available clinical information, distinction between
S. maltophilia colonization and infection can be confusing [
20]. His chest X-ray, 10 days after MDH admission, showed right nodular opacity (Fig.
2b) and might be evocative of
S. maltophilia colonization or infection of a severely impaired host [
21,
22].
S. maltophilia infection/colonization management is often problematic due to its inherent resistance to multiple broad-spectrum antibiotic agents [
21]. Thus, for the presenting case, the initial streptomycin treatment was effective for
Y. pestis infection but not for
S. maltophilia. The use of ciprofloxacin in secondary bi-therapy allowed the recovery of the patient and this antibiotic is also recommended as an alternative treatment for
S. maltophilia infection [
23]. Indeed, recent study also supported the broader use of oral ciprofloxacin for treatment of human plague including pneumonic form. Its bactericidal activity is comparable to that of streptomycin, and its mode of administration is less restrictive; more acceptable for exposed population [
24]. In addition, a wide range of antibiotics was already in vitro tested for their susceptibility to geographically diverse strains of
Y. pestis which provide alternatives for plague treatment [
25]. Another study had also investigated the susceptibility patterns of
Y. pestis strains from diverse sources to 12 antimicrobial agents and showed that a large panel of
Y. pestis remained susceptible not only to drugs traditionally used to treat plague (streptomycin, doxycycline and chloramphenicol), but also to newer agents (broad-spectrum cephalosporins and quinolones). The most active compounds against
Y. pestis included ceftriaxone and trimethoprim-sulfamethoxazole, quinolones [
26].
To date, coinfection involving pneumonic plague and other pulmonary infections has been rarely described. Indeed, Quan et al. reported the recovery of
Y. pestis and other respiratory pathogens from mammals and ectoparasites but not in human during plague investigations [
28]. However in 2004, two cases of confirmed infection for plague and leptospirosis have been observed in the Democratic Republic of Congo, both of which can cause severe pulmonary manifestations [
29]. To our knowledge, this study is the first describing a co-infection with
Y. pestis and
S. maltophilia in Madagascar and emphasizes on the complicated management of such pneumonic infections.