Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study

Abstract

In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.

Clinical and epidemiological features discriminating confirmed COVID-19 patients from SARS-CoV-2 negative patients at screening centres in Madagascar

“…Patients may have exaggerated when reporting symptoms like dyspnoea and other subjective signs or contact with confirmed cases because of panic and fear. The same situation has been observed in previous outbreak in Madagascar ( Salam et al, 2020 ). In addition, epidemiological link is difficult to identify when community transmission occurs.…”

Evaluating and optimizing the use of diagnostics during epidemics: Application to the 2017 plague outbreak in Madagascar

“…If a proportion of samples were of poor quality, estimates for the prevalence of infection would increase (Figure 2D). For example, in the extreme scenario where only 50% of samples were of good quality, estimates of the prevalence of infection would rise to 9% (6)(7)(8)(9)(10)(11)(12)(13) for PP and 45% (36-55) for BP. For this analysis we assumed sample quality to affect all tests equally.…”

“…Plague case fatality ratio (CFR) has been estimated between 10-40% (5-7). Diagnosis, particularly of PP, is challenging due to i) non-specific early symptoms (8,9), ii) the difficulty to collect high-quality sputum samples, especially from severely ill and young patients (10), iii) the scarcity of PP cases hampering evaluation of diagnostics; most assays have been evaluated on BP samples (11).…”

Deaths Associated with Pneumonic Plague, 1946–2017

“…Overall, the death rate for persons treated for primary pneumonic plague was high despite the sensitivity of Y. pestis to aminoglycosides, quinolones, and tetracyclines (2,3) and the relatively good penetration of some of these antimicrobial drugs into lungs (4,5). During the 2017 Madagascar pneumonic plague outbreak, the observed death rate for treated persons appeared to be substantially lower than that reported in the literature (6). Many articles that quoted a 50% death rate for treated primary pneumonic plague were cited in a 2000 study by Ratsitorahina et al (7), which described a small outbreak in Madagascar in 1997.…”