Adam MacNeil

A New Phlebovirus Associated with Severe Febrile Illness in Missouri

Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Kochs postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.

Hantavirus pulmonary syndrome.

Hantavirus pulmonary syndrome (HPS) is a severe disease characterized by a rapid onset of pulmonary edema followed by respiratory failure and cardiogenic shock. The HPS associated viruses are members of the genus Hantavirus, family Bunyaviridae. Hantaviruses have a worldwide distribution and are broadly split into the New World hantaviruses, which includes those causing HPS, and the Old World hantaviruses [including the prototype Hantaan virus (HTNV)], which are associated with a different disease, hemorrhagic fever with renal syndrome (HFRS). Sin Nombre virus (SNV) and Andes virus (ANDV) are the most common causes of HPS in North and South America, respectively. Case fatality of HPS is approximately 40%. Pathogenic New World hantaviruses infect the lung microvascular endothelium without causing any virus induced cytopathic effect. However, virus infection results in microvascular leakage, which is the hallmark of HPS. This article briefly reviews the knowledge on HPS-associated hantaviruses accumulated since their discovery, less than 20 years ago.

Proportion of Deaths and Clinical Features in Bundibugyo Ebola Virus Infection, Uganda

The first known Ebola hemorrhagic fever (EHF) outbreak caused by Bundibugyo Ebola virus occurred in Bundibugyo District, Uganda, in 2007. Fifty-six cases of EHF were laboratory confirmed. Although signs and symptoms were largely nonspecific and similar to those of EHF outbreaks caused by Zaire and Sudan Ebola viruses, proportion of deaths among those infected was lower (≈40%).

Hantavirus pulmonary syndrome, United States, 1993-2009.

Hantavirus pulmonary syndrome (HPS) is a severe respiratory illness identified in 1993. Since its identification, the Centers for Disease Control and Prevention has obtained standardized information about and maintained a registry of all laboratory-confirmed HPS cases in the United States. During 1993-2009, a total of 510 HPS cases were identified. Case counts have varied from 11 to 48 per year (case-fatality rate 35%). However, there were no trends suggesting increasing or decreasing case counts or fatality rates. Although cases were reported in 30 states, most cases occurred in the western half of the country; annual case counts varied most in the southwestern United States. Increased hematocrits, leukocyte counts, and creatinine levels were more common in HPS case-patients who died. HPS is a severe disease with a high case-fatality rate, and cases continue to occur. The greatest potential for high annual HPS incidence exists in the southwestern United States.

Ebola and Marburg hemorrhagic fevers: neglected tropical diseases?

Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease.

Filovirus Outbreak Detection and Surveillance: Lessons From Bundibugyo

The first outbreak of Ebola hemorrhagic fever (EHF) due to Bundibugyo ebolavirus occurred in Uganda from August to December 2007. During outbreak response and assessment, we identified 131 EHF cases (44 suspect, 31 probable, and 56 confirmed). Consistent with previous large filovirus outbreaks, a long temporal lag (approximately 3 months) occurred between initial EHF cases and the subsequent identification of Ebola virus and outbreak response, which allowed for prolonged person-to-person transmission of the virus. Although effective control measures for filovirus outbreaks, such as patient isolation and contact tracing, are well established, our observations from the Bundibugyo EHF outbreak demonstrate the need for improved filovirus surveillance, reporting, and diagnostics, in endemic locations in Africa.

Reemerging Sudan Ebola Virus Disease in Uganda, 2011

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities.

Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus

Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV.

Using next generation sequencing to identify yellow fever virus in Uganda

In October and November 2010, hospitals in northern Uganda reported patients with suspected hemorrhagic fevers. Initial tests for Ebola viruses, Marburg virus, Rift Valley fever virus, and Crimean Congo hemorrhagic fever virus were negative. Unbiased PCR amplification of total RNA extracted directly from patient sera and next generation sequencing resulted in detection of yellow fever virus and generation of 98% of the virus genome sequence. This finding demonstrated the utility of next generation sequencing and a metagenomic approach to identify an etiological agent and direct the response to a disease outbreak.

Solid Organ Transplant–associated Lymphocytic Choriomeningitis, United States, 2011

Lymphocytic choriomeningitis virus (LCMV) is carried by rodents. In very rare instances, it has been transmitted from person-to-person by organ transplantation. In 2011, a total of 14 organ recipients were infected with the virus, of which 11 died in the United States. The 4 most recent patients received organs from the same donor, which resulted in 2 deaths. Only after these 4 organ recipients became sick was it discovered that the donor had been exposed to rodents. Had this exposure been known before transplantation, the organ recipients may have been more closely monitored. Early diagnosis and treatment might have improved their chances of survival. Although organ donor screening reduces the risk for transmission of some viruses, it is not possible to screen for all possible viruses, including LCMV. For patients who get severely ill after receiving a transplant, clinicians should add LCMV infection to their list of possible causes.