Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission

Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research

Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX) patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations—including complications and sequelae—as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data—and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth—suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications), ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies

Sounding the alarm: Defining thresholds to trigger a public health response to monkeypox.

Endemic to the Democratic Republic of the Congo (DRC), monkeypox is a zoonotic disease that causes smallpox-like illness in humans. Observed fluctuations in reported cases over time raises questions about when it is appropriate to mount a public health response, and what specific actions should be taken. We evaluated three different thresholds to differentiate between baseline and heightened disease incidence, and propose a novel, tiered algorithm for public health action. Monkeypox surveillance data from Tshuapa Province, 2011-2013, were used to calculate three different statistical thresholds: Cullen, c-sum, and a World Health Organization (WHO) method based on monthly incidence. When the observed cases exceeded the threshold for a given month, that month was considered to be 'aberrant'. For each approach, the number of aberrant months detected was summed by year-each method produced vastly different results. The Cullen approach generated a number of aberrant signals over the period of consideration (9/36 months). The c-sum method was the most sensitive (30/36 months), followed by the WHO method (12/24 months). We conclude that triggering public health action based on signals detected by a single method may be inefficient and overly simplistic for monkeypox. We propose instead a response algorithm that integrates an objective threshold (WHO method) with contextual information about epidemiological and spatiotemporal links between suspected cases to determine whether a response should be operating under i) routine surveillance ii) alert status, or iii) outbreak status. This framework could be modified and adopted by national and zone level health workers in monkeypox-endemic countries. Lastly, we discuss considerations for selecting thresholds for monkeypox outbreaks across gradients of endemicity and public health resources

Characteristics of suspect monkeypox (MPX) cases identified between December 2009 and February 2014 (n = 752).

<p>Characteristics of suspect monkeypox (MPX) cases identified between December 2009 and February 2014 (n = 752).</p

The number of suspect monkeypox (MPX) cases that were captured by Case Definitions A and B by their MPX laboratory case classification.

<p>The number of suspect monkeypox (MPX) cases that were captured by Case Definitions A and B by their MPX laboratory case classification.</p

Association between clinical characteristics and laboratory-confirmed monkeypox (MPX) or varicella (VZV) case classification.

<p>Association between clinical characteristics and laboratory-confirmed monkeypox (MPX) or varicella (VZV) case classification.</p

Summary of the diagnostic parameters for both case definitions.

<p>Summary of the diagnostic parameters for both case definitions.</p

Accuracy of the minimum number of signs/symptoms in predicting laboratory-confirmed monkeypox cases.

<p>Accuracy of the minimum number of signs/symptoms in predicting laboratory-confirmed monkeypox cases.</p

Flow chart of the cases selected for each analysis.

<p>Flow chart of the cases selected for each analysis.</p

Diagnostic measures^a of significant^b clinical signs/symptoms.

<p>Diagnostic measures<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005857#t003fn001" target="_blank">^a</a> of significant<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005857#t003fn002" target="_blank">^b</a> clinical signs/symptoms.</p