Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 26, Number 2—February 2020

Early Detection of Public Health Emergencies of International Concern through Undiagnosed Disease Reports in ProMED-Mail

Article Metrics
citations of this article
EID Journal Metrics on Scopus
Camille Rolland, Clément LazarusComments to Author , Coralie Giese, Bastien Monate, Anne-Sophie Travert, and Jérôme Salomon
Author affiliations: Public Health Emergency Operations Center of the French Ministry of Health, Paris, France (C. Rolland, C. Lazarus, B. Monate, A.-S. Travert); Ministry of Health, Paris (C. Giese, J. Salomon)

Cite This Article


We conducted a retrospective analysis of all reports in ProMED-mail that were initially classified as undiagnosed diseases during 2007–2018. We identified 371 cases reported in ProMED-mail; 34% were later diagnosed. ProMED-mail could be used to supplement other undiagnosed disease surveillance systems worldwide.

To preserve human health security, a global surveillance system able to rapidly detect, verify, and assess burgeoning outbreaks is key. The World Health Organization (WHO) International Health Regulations (2005) (1) provides an international and legally binding framework for the early detection of, reporting of, and response to any public health threat (e.g., infectious disease outbreaks) that might be of international concern using an all-hazards approach (2).

Event-based surveillance through informal sources now represents a critical source for epidemic intelligence (3). Almost all major outbreaks during 1994–2017 investigated by the WHO were early reported and identified through informal sources (47). One of the most valued, internationally acknowledged sources for epidemic intelligence activities that is also available as an open source is ProMED-mail (4,8). By relying on local media, professional networks, and on-the-ground experts, ProMED-mail staff produce reports on occurrences of emerging infectious diseases and outbreaks in near real-time. Specialist moderators curate these reports and provide subject matter expert commentaries.

ProMED-mail captures many reports of undiagnosed diseases (i.e., reports of public health events for which the diagnosis has not yet been found or reported by field professionals and cannot be classified). Events in these reports take place all around the world, and reports are provided without enough information to formulate a comprehensive risk assessment.

Even though an undiagnosed disease report in ProMED-mail might be an early signal of a major future event (e.g., outbreak), such reports have not been described in the literature. In this study, we aimed to provide a descriptive analysis of reports of undiagnosed disease events related to human health published on ProMED-mail since 2007 to determine whether these reports should be considered in further risk assessments.

The Study

Figure 1

Thumbnail of Selection of ProMED-mail reports to analyze for undiagnosed disease events related to human health, January 1, 2007–December 30, 2017.

Figure 1. Selection of ProMED-mail reports to analyze for undiagnosed disease events related to human health, January 1, 2007–December 30, 2017.

We conducted a retrospective analysis of all reports of undiagnosed diseases in the ProMED-mail registry that were published during January 1, 2007–June 14, 2018 (Figure 1). ProMED-mail staff provided all the archives for undiagnosed diseases and unknown diseases relative to humans, animals, and plants. We also collected data directly from Disease Outbreak News on the WHO website ( for the period of the study; these data are also open access and disseminated as specified by Article 11 of the International Health Regulations (2005). From ProMED-mail reports, we collected data on case location (WHO zone), source of information, date of publication, number of cases, geographic distribution (i.e., regional, national, or international) of cases, affected population, and final diagnosis. We searched the WHO website for the existence of a related Disease Outbreak News report. We sought information on the confirmation (i.e., biologic confirmation) of the final diagnosis both in subsequent ProMED-mail reports and in Disease Outbreak News reports. When several notifications were linked to 1 undiagnosed disease event, we made the link between notifications using the date of occurrence and location data. We described quantitative variables using median and range and qualitative variables using percentages.

Figure 2

Thumbnail of Undiagnosed disease events in humans posted on ProMED-mail, by location (World Health Organization zone), January 1, 2007–December 30, 2017. AFRO, African Regional Office; EMRO, Eastern Mediterranean Regional Office; EURO, Europe Regional Office; PAHO, Pan American Health Organization; SEARO, South-East Asia Regional Office; WPRO, Western Pacific Regional Office.

Figure 2. Undiagnosed disease events in humans posted on ProMED-mail, by location (World Health Organization zone), January 1, 2007–December 30, 2017. AFRO, African Regional Office; EMRO, Eastern Mediterranean Regional Office; EURO, Europe Regional...

During January 1, 2007–June 14, 2018, a total of 775 ProMED-mail reports accounted for 371 individual undiagnosed disease events in humans (Figure 1). The median number of undiagnosed disease events per year was 34 (range 15–45) (Figure 2). The sources of these reports were mainly the national press (67%, 250/371); 25% (93/371) were from international media, and 8% (28/371) were from experts.

The countries most affected by undiagnosed diseases were India (68/371), Sudan (20/371), Bangladesh (16/371), Nepal (15/371), China (14/371), the Democratic Republic of the Congo (13/371), Uganda (13/371), the United States (13/371), Vietnam (11/371), and Nigeria (9/371) (Appendix Figure). Overall, 44% of undiagnosed disease events were in rural areas and 56% were in urban areas; 8% (31/371) took place within a capital city. For 54% (200/371) of undiagnosed disease events, no specific population (e.g., children <18 years of age, persons >65 years of age, health professionals) was identified. For 2.4% (9/371) of undiagnosed disease events, healthcare professionals were affected.

We found a Disease Outbreak News report for 6.5% (24/371) of the undiagnosed disease events described in ProMED-mail. The median delay between the first ProMED-mail notification and the Disease Outbreak News publication was 18.5 (range –1 to 254) days (Table).

A final diagnosis was found for 34% (127/371) of undiagnosed disease events (Appendix Table). Among the 127 events for which a final diagnosis could be determined, the most frequent diseases were chikungunya (6/127), leptospirosis (6/127), Nipah virus infection (6/127), Ebola (5/127), meningitis (5/127), yellow fever (5/127), anthrax (4/127), Crimean-Congo hemorrhagic fever (4/127), and nodding disease (4/127).

Undiagnosed diseases might be reported in various medical situations. They often occur in cases of delayed diagnosis of common diseases when access to appropriate medical care or services (e.g., epidemiologic investigations, laboratory testing) is limited. As such, most undiagnosed disease events occurred within low-resource countries. Undiagnosed disease reports less frequently account for unusual or unexpected diseases, such as imported or emerging diseases.

Reporting of undiagnosed diseases through ProMED-mail can be limited by climatic or geopolitical events in the region, which was probably reflected by the yearly and geographic variation in the reporting of undiagnosed disease events we observed. Although informal sources of public health information are valuable, the editorial content of the news sources the reports are based on can strongly limit their usefulness. Hence, our data analysis was limited by missing data.


The impact of ProMED-mail on the public health emergency preparedness response is reflected by the percentage of undiagnosed disease events published through this informal reporting system (6.5%) that were also shared internationally through WHO’s Disease Outbreak News website. Regions and countries could benefit from complementing their undiagnosed disease surveillance systems with ProMED-mail (9). Using this approach would help further establish undiagnosed disease event-based monitoring as an invaluable public health tool. ProMED-mail provides critical content and an alternative to standard indicator-based outbreak reporting for undiagnosed diseases (4).

Dr. Rolland is a public health resident who works in the Public Health Emergency Operations Center of the French Ministry of Health in Paris, France. She participates in the operational management of public health alerts in France as well as internationally. Her research interests are infectious diseases (including sexually transmitted infections), emerging diseases, and international health surveillance.



We thank the ProMED-mail staff, who made this research possible, and Elsa Dorne for her assistance in reviewing the language of the manuscript.



  1. World Health Organization. International Health Regulations (2005) third edition. 2016 [cited 2019 Jul 22].
  2. Hartley  D, Nelson  N, Walters  R, Arthur  R, Yangarber  R, Madoff  L, et al. Landscape of international event-based biosurveillance. Emerg Health Threats J. 2010;3:e3. DOIPubMedGoogle Scholar
  3. World Health Organization Western Pacific Region. A guide to establishing event-based surveillance. 2008 [cited 2019 Jul 22].
  4. Keller  M, Blench  M, Tolentino  H, Freifeld  CC, Mandl  KD, Mawudeku  A, et al. Use of unstructured event-based reports for global infectious disease surveillance. Emerg Infect Dis. 2009;15:68995. DOIPubMedGoogle Scholar
  5. Grein  TW, Kamara  KB, Rodier  G, Plant  AJ, Bovier  P, Ryan  MJ, et al. Rumors of disease in the global village: outbreak verification. Emerg Infect Dis. 2000;6:97102. DOIPubMedGoogle Scholar
  6. Heymann  DL, Rodier  GR; WHO Operational Support Team to the Global Outbreak Alert and Response Network. Hot spots in a wired world: WHO surveillance of emerging and re-emerging infectious diseases. Lancet Infect Dis. 2001;1:34553. DOIPubMedGoogle Scholar
  7. Carrion  M, Madoff  LC. ProMED-mail: 22 years of digital surveillance of emerging infectious diseases. Int Health. 2017;9:17783. DOIPubMedGoogle Scholar
  8. Krishnan  S. Undiagnosed deaths—India (Uttar Pradesh) (02). ProMed. 2006 Aug 14 [cited 2019 Jul 22]., archive no. 20060814.2279.
  9. Woodall  JP. Global surveillance of emerging diseases: the ProMED-mail perspective. Cad Saude Publica. 2001;17(Suppl):14754. DOIPubMedGoogle Scholar




Cite This Article

DOI: 10.3201/eid2602.191043

Original Publication Date: January 07, 2020

Table of Contents – Volume 26, Number 2—February 2020

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Clément Lazarus, Public Health Emergency Operations Center, 14 Avenue Duquesne, Paris 75007, France

Send To

10000 character(s) remaining.


Page created: January 20, 2020
Page updated: January 20, 2020
Page reviewed: January 20, 2020
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.