Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar

BACKGROUND : The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases. METHODOLOGY : Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status. PRINCIPAL FINDINGS : A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections. CONCLUSIONS : These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar.The US Agency for International Development (USAID) (Grant No. AID-687-G-13-00003), and the US Centers for Disease Control and Prevention (Grant No. 5U51IP000812-02).http://www.plosntds.orgImmunolog

Can we make human plague history? A call to action

Plague is a communicable rodent-borne disease caused by Yersinia pestis, a Gram-negative bacillus member of the Enterobacteriaceae family. As a zoonosis, plague is primarily a wildlife disease that occasionally spills over to the human population, resulting in seasonal surges in human cases and localised outbreaks. The predominant clinical form among humans is bubonic plague, which, if untreated, has a lethality of 60%–90% but is readily treatable with antibiotics, reducing the death rate to around 5% if administered shortly after the infection. One to two per cent of all bubonic cases develop into secondary pneumonic plague, which in turn may be transmitted from person to person through respiratory droplets, producing primary pneumonic plague in close contacts. Without antibiotic treatment, pneumonic plague is nearly 100% fatal, but early antibiotic treatment substantially improves survival. Today, Y. pestis is present in at least 26 countries, with more than 30 different flea vectors and over 200 mammal host species. Although human plague cases continue to be reported from Asia and the Americas, most cases currently occur in remote, rural areas of sub-Saharan Africa, mostly in Democratic Republic of Congo and Madagascar (around300–500 per year). However, large-scale transmission may also occur. During the 14th century, the Black Death, caused by Y. pestis, is estimated to have killed 30%–40% of the European population. It is important to emphasise that human plague is mostly a poverty-related disease. Therefore, given that population density and the absolute number of people living in extreme poverty are both increasing in sub-Saharan Africa, there is no likelihood of plague being eliminated as a public health threat in the foreseeable future. However, the WHO does not consider plague to be either a neglected tropical disease or a ‘priority pathogen’ that poses a public health risk because of its epidemic potential. In September 2017, an unprecedented urban outbreak of pneumonic plague was declared in Madagascar, striking primarily its capital Antananarivo and the major seaport of Toamasina. This episode once again brought international attention to plague, reminding us of the capacity for human plague to spread in urban settings and cause substantial societal and economic disruption. This should raise alarm bells that a research agenda is needed

Human plague: An old scourge that needs new answers

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague’s resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a “One Health” approach

Correction to: Fine-scale Spatiotemporal Mapping of Asymptomatic and Clinical Plasmodium falciparum Infections: Epidemiological Evidence for Targeted Malaria Elimination Interventions

International audienc

Study on causes of fever in primary healthcare center uncovers pathogens of public health concern in Madagascar

<div><p>Background</p><p>The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases.</p><p>Methodology</p><p>Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status.</p><p>Principal findings</p><p>A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections.</p><p>Conclusions</p><p>These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar.</p></div

Proportions of diseases under surveillance within the FSSN according to their respective case definition.

<p>*p-value <0.05.</p

Number of inclusions per site and age group.

<p>Number of inclusions per site and age group.</p

Map of Madagascar showing the 21 sentinel sites selected for the study.

<p>[Source: This map was generated using a free source of public domain available at: <a href="http://www.maplibrary.org/library/stacks/Africa/Madagascar/index.htm" target="_blank">http://www.maplibrary.org/library/stacks/Africa/Madagascar/index.htm</a>].</p

Distribution of groups of infection and pathogens detected among febrile patients (N = 682).

<p>Distribution of groups of infection and pathogens detected among febrile patients (N = 682).</p