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Biomedical subjects

C J Peters

Publications and source records attributed to C J Peters.

At least 19 recordsLinked to original sources
PubMed2002

Hemorrhagic fever viruses as biological weapons: medical and public health management.

OBJECTIVE: To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population. PARTICIPANTS: The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions. EVIDENCE: MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed. CONSENSUS PROCESS: Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft. CONCLUSIONS: Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.

Aerosols↗
PubMed2002

Hantavirus pulmonary syndrome: the new American hemorrhagic fever.

The recognition of hantavirus pulmonary syndrome (HPS) after the investigation of a cluster of unexplained respiratory deaths in the southwestern United States during the spring of 1993 showcased our ability to recognize new and emerging diseases, given the correct juxtaposition of a new clinical entity with circumscribed epidemiologic features that are analyzed with novel diagnostic methods. In less than a decade, HPS has become established as a pan-American zoonosis due to numerous viruses maintained by sigmodontine rodents with rodent- and virus-specific epidemiologic profiles. The classical features of the syndrome-acute febrile illness associated with prominent cardiorespiratory compromise after direct contact or inhalation of aerosolized rodent excreta-has been extended to include clinical variants, including disease with frank hemorrhage, that have confirmed that this syndrome is a viral hemorrhagic fever. Efforts are under way to refine prevention strategies, to understand the pathogenesis of the shock, and to identify therapeutic modalities.

Animals↗
PubMed2001

A reassortant bunyavirus isolated from acute hemorrhagic fever cases in Kenya and Somalia.

In late 1997 and early 1998, a large outbreak of hemorrhagic fever occurred in East Africa. Clinical samples were collected in Kenya and southern Somalia, and 27 of 115 (23%) hemorrhagic fever patients tested showed evidence of acute infection with Rift Valley fever (RVF) virus as determined by IgM detection, virus isolation, detection of virus RNA by reverse transcription-polymerase chain reaction (RT-PCR), or immunohistochemistry. However, two patients (one from Kenya and the other from Somalia) whose illness met the hemorrhagic fever case definition yielded virus isolates that were not RVF. Electron microscopy suggested these two virus isolates were members of the family Bunyaviridae. RT-PCR primers were designed to detect bunyavirus RNA in these samples. Regions of the S and L segments of the two isolates were successfully amplified, and their nucleotide sequences exhibited nearly complete identity with Bunyamwera virus, a mosquito-borne virus not previously associated with severe human disease. Unexpectedly, the virus M segment appeared to be reassorted, as the sequences detected exhibited 32-33% nucleotide and 28% amino acid differences relative to the corresponding M segment sequence of Bunyamwera virus. The association of this reassortant bunyavirus, proposed name Garissa virus, with severe disease is supported by the detection of the virus RNA in acute-phase sera taken from 12 additional hemorrhagic fever cases in the region.

Animals↗
PubMed2001

Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Antiviral Agents↗
PubMed2001

Low levels of interleukin-8 and interferon-inducible protein-10 in serum are associated with fatal infections in acute Lassa fever.

To investigate the role of inflammatory mediators in the pathogenesis of Lassa fever, the levels of a number of pro- and anti-inflammatory cytokines and chemokines in serum samples collected from hospitalized patients with fatal and nonfatal acute Lassa fever were compared with those from 2 control groups: patients with other febrile illnesses and uninfected individuals. Serum interleukin (IL)-8 and interferon (IFN)-inducible protein (IP)-10 levels were significantly higher in patients with acute nonfatal Lassa fever than in control subjects. In striking contrast, levels of these chemokines were low or undetectable in patients with fatal Lassa fever. IFN-gamma, IL-12, IL-6, and RANTES levels were elevated in all the febrile study groups. Tumor necrosis factor-alpha levels were not elevated in patients with fatal or nonfatal Lassa fever. These data indicate that acute nonfatal Lassa fever is associated with high levels of circulating IL-8 and IP-10 and that low levels or absence of these mediators correlates with a poor outcome.

Acute Disease↗
PubMed2001

Enzyme-linked immunosorbent assays for detection of antibodies to Ebola and Marburg viruses using recombinant nucleoproteins.

The full-length nucleoprotein (NP) of Ebola virus (EBO) was expressed as a His-tagged recombinant protein (His-EBO-NP) by a baculovirus system. Carboxy-terminal halves of NPs of EBO and Marburg virus (MBG) were expressed as glutathione S-transferase-tagged recombinant proteins in an Escherichia coli system. The antigenic regions on the NPs of EBO and MBG were determined by both Western blotting and enzyme-linked immunosorbent assay (ELISA) to be located on the C-terminal halves. The C-terminal 110 and 102 amino acids of the NPs of EBO and MBG, respectively, possess strong antigenicity. The full-length NP of EBO was strongly expressed in insect cells upon infection with the recombinant baculovirus, while expression of the full-length NP of MBG was weak. We developed an immunoglobulin G (IgG) ELISA using His-EBO-NP and the C-terminal halves of the NPs of EBO and MBG as antigens. We evaluated the IgG ELISA for the ability to detect IgG antibodies to EBO and MBG, using human sera collected from EBO and MBG patients. The IgG ELISA with the recombinant NPs showed high sensitivity and specificity in detecting EBO and MBG antibodies. The results indicate that ELISA systems prepared with the recombinant NPs of EBO and MBG are valuable tools for the diagnosis of EBO and MBG infections and for seroepidemiological field studies.

Animals↗
PubMed2001

Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells.

Sin Nombre virus (SNV) and Hantaan virus (HTN) infect endothelial cells and are associated with different patterns of increased vascular permeability during human disease. It is thought that such patterns of increased vascular permeability are a consequence of endothelial activation and subsequent dysfunction mediated by differential immune responses to hantavirus infection. In this study, the ability of hantavirus to directly induce activation of human lung microvascular endothelial cells (HMVEC-Ls) was examined. No virus-specific modulation in the constitutive or cytokine-induced expression of cellular adhesion molecules (CD40, CD54, CD61, CD62E, CD62P, CD106, and major histocompatibility complex classes I and II) or in cytokines and chemokines (eotaxin, tumor necrosis factor alpha, interleukin 1beta [IL-1beta], IL-6, IL-8, MCP-1, MIP-1alpha, and MIP-1beta) was detected at either the protein or message level in hantavirus-infected HMVEC-Ls. Furthermore, no virus-specific enhancement of paracellular or transcellular permeability or changes in the organization and distribution of endothelial intercellular junctional proteins was observed. However, infection with either HTN or SNV resulted in detectable levels of the chemokines RANTES and IP-10 (the 10-kDa interferon-inducible protein) in HMVEC-Ls within 72 h and was associated with nuclear translocation of interferon regulatory factor 3 (IRF-3) and IRF-7. Gamma interferon (IFN-gamma)-induced expression of RANTES and IP-10 could also be detected in uninfected HMVEC-Ls and was associated with nuclear translocation of IRF-1 and IRF-3. Treatment of hantavirus-infected HMVEC-Ls with IFN-gamma for 24 h resulted in a synergistic enhancement in the expression of both RANTES and IP-10 and was associated with nuclear translocation of IRF-1, IRF-3, IRF-7, and NF-kappaB p65. These results reveal a possible mechanism by which hantavirus infection and a TH1 immune response can cooperate to synergistically enhance chemokine expression by HMVEC-Ls and trigger immune-mediated increases in vascular permeability.

Animals↗
PubMed2001

Multiplex analysis of cytokines in the blood of cynomolgus macaques naturally infected with Ebola virus (Reston serotype).

Ebola virus (EBO) causes the most severe form of viral hemorrhagic fever in humans and nonhuman primates with up to 90% of infections culminating in death. The requirement of maximum containment laboratories for Ebola virus research has limited opportunities to study the pathogenesis of EBO infections. While tissue damage does occur, often it would appear not to be sufficient to explain death, indicating that soluble mediators play an important role in disease progression. In previous studies, fatal human infections with the Zaire subtype of Ebola (EBO-Z) were associated with an increase in the levels of inflammatory cytokines. In this investigation, a new multiplex assay was developed and used to measure circulating levels of cytokines and chemokines in cynomolgus macaques infected with the Reston subtype of EBO (EBO-R). Increased levels of IL-6, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-8, IL-10, and GM-CSF were detected in infected animals, and the increase in circulating cytokines correlated with an increase in circulating viral antigen. Blood samples from animals showing high levels of cytokines were also tested for the chemokines: MCP-1, IL-1beta, MIP-1alpha, MIP-1beta, IP-10, and RANTES. High levels of MCP-1 and MIP-1beta, and RANTES were found in infected primates and, while levels were more variable, IL-1beta was detected only in infected animals.

Amino Acid Sequence↗
PubMed2000

Hantavirus pulmonary syndrome in Panama: identification of novel hantaviruses and their likely reservoirs.

Hantavirus pulmonary syndrome (HPS), a severe respiratory disease with high mortality caused by rodent-borne hantaviruses, has previously been identified in the United States and Canada as well as central and southern South America. In late 1999 and early 2000, an outbreak of acute illness compatible with HPS was reported in Los Santos, Panama, with the death of 3 of the 12 (25%) suspected cases. Hantavirus-specific antibodies were detected in patient sera, and virus RNA was detected by reverse transcriptase-polymerase chain reaction. Sequence analysis of virus genome N-, G1-, and G2-encoding fragments showed this to be a novel hantavirus, Choclo virus. Serologic and virus genetic analyses of rodents trapped in the area showed Oligoryzomys fulvescens to be the likely reservoir for the HPS-associated Choclo virus. In addition, Zygodontomys brevicauda rodents were shown to harbor another genetically unique hantavirus, Calabazo virus.

Animals↗
PubMed2000

Nipah virus: a recently emergent deadly paramyxovirus.

A paramyxovirus virus termed Nipah virus has been identified as the etiologic agent of an outbreak of severe encephalitis in people with close contact exposure to pigs in Malaysia and Singapore. The outbreak was first noted in late September 1998 and by mid-June 1999, more than 265 encephalitis cases, including 105 deaths, had been reported in Malaysia, and 11 cases of encephalitis or respiratory illness with one death had been reported in Singapore. Electron microscopic, serologic, and genetic studies indicate that this virus belongs to the family Paramyxoviridae and is most closely related to the recently discovered Hendra virus. We suggest that these two viruses are representative of a new genus within the family Paramyxoviridae. Like Hendra virus, Nipah virus is unusual among the paramyxoviruses in its ability to infect and cause potentially fatal disease in a number of host species, including humans.

Animals↗
PubMed2000

Transmission of Black Creek Canal virus between cotton rats.

Black Creek Canal (BCC) virus is a hantavirus associated with hantavirus pulmonary syndrome in southeastern North America. The virus was isolated from the spleen of a cotton rat (Sigmodon hispidus) trapped in southern Florida. Our previous studies have shown that we could consistently infect male cotton rats with BCC virus in the laboratory. These animals became persistently infected and virus could be detected in salivary glands, urine, and feces. In this report we show: (1) female and male cotton rats are equally susceptible to BCC virus infection, (2) susceptibility to infection was not influenced by age, (3) all inoculated rats transmitted the infection to uninoculated cage mates, and (4) offspring of infected rats became infected despite the presence of high maternal antibodies. The course of BCC virus infection, as determined by antibody response and the ability to isolate or detect virus, appeared to be similar regardless of whether the rats obtained their infection by inoculation or contact with inoculated rats. J. Med. Virol. 60:70-76, 2000. Published 2000 Wiley-Liss, Inc.

Animals↗
PubMed2000

Hantavirus infection in Taiwan: the experience of a geographically unique area.

Hantaviruses are rodent-borne viruses, and they, mainly the Hantaan (HTN) serotype, are the causative agents of a group of febrile nephropathies known as "hemorrhagic fever with renal syndrome (HFRS). " Despite the fact that HFRS is frequently reported in China, with an annual incidence of 50,000-100,000 cases, one puzzling observation that no local case of HFRS has been confirmed in Taiwan has yet to be explained. We hypothesized that the hantavirus strain prevailing in Taiwan mainly belongs to the mild strain, the Seoul (SEO) strain, and the absence of severe disease was related to the absence of HTN. To test these hypotheses, this epidemiologic study was performed, including a seroprevalence survey and phylogenetic analysis on hantavirus isolated from the rodent population trapped in major seaports, rural, and mountainous areas of Taiwan. This study also included rodents and viruses from two isolated islands, Kinmen and Matzu, which are geographically adjacent to the east coast of mainland China. There were a total of 5,461 rodents of 16 species captured, and R. norvegicus was the most common species, with an antibody prevalence much higher in international seaports (20%) than in rural regions (approximately 5%) and intermediate in some domestic seaports. By reverse transcriptase polymerase chain reaction (RT-PCR), 33.9% of the seropositive R. norvegicus were found to have amplifiable hantavirus sequences in their lung tissues, and subsequent phylogenetic analyses indicated that almost all hantavirus in Taiwan was most closely related to the prototype SEO strain, and no HTN strain was recovered from any rodent species indigenous to Taiwan. The seroprevalence of SEO infection in R. norvegicus on Kinmen and Matzu was also different from that in southern provinces of China but closely resembled that in seaports in Taiwan, and the SEO identified was genetically linked to Taiwanese SEO strains. These results substantiate our hypotheses, and suggest that the epidemiology of hantavirus infection in Taiwan are different from that in China, where the HTN and SEO strains and HFRS concurrently prevail.

Animals↗
PubMed2000

Cerebral near infrared spectroscopy for the measurement of indocyanine green elimination in cirrhosis.

BACKGROUND: Indocyanine green (ICG) clearance is a useful indicator of hepatic function but most measurement methods are invasive. AIM: To validate a less invasive technique using cerebral near infrared spectrophotometry (NIRS) to measure ICG elimination, and to compare it with the established methods for the determination of ICG clearance in a group of normal controls and patients with cirrhosis. METHOD: NIRS was used to measure ICG elimination in 41 cirrhotic patients and nine healthy volunteers. The first 13 of the cirrhotic patients also had their ICG clearance measured by the conventional spectrophotometric technique. RESULTS: NIRS ICG elimination rate (ICG-k) and spectrophotometry ICG-k values correlated strongly (r= 0. 828, P < 0.001, n=13). There was a significant reduction in the mean NIRS-k in cirrhotic patients and within Child-Pugh classes A, B, and C (P < 0.001). CONCLUSION: Measurement of ICG elimination by the NIRS method is at least as reliable as the conventional spectrophotometric technique in normals and in patients with cirrhosis. This technique merits further development for use as a bedside, less invasive liver function test.

Coloring Agents↗
PubMed2000

Crimean-congo haemorrhagic fever: a seroepidemiological and tick survey in the Sultanate of Oman.

In 1995 and 1996, 4 persons from the Sultanate of Oman were confirmed with clinical Crimean-Congo haemorrhagic fever (CCHF). To assess the prevalence of CCHF virus infection in Oman, a convenience sample of imported and domestic animals from farms, abattoirs and livestock markets was examined by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to CCHF virus. Ticks were collected from selected animals, identified, pooled by species, host and location and tested for evidence of infection with CCHF virus by antigen-capture ELISA. Serum samples from individuals working in animal and nonanimal contact-related jobs were also tested for CCHF antibodies. Serological evidence of infection was noted in 108 (22%) of 489 animals. Most of the ticks collected (618 of 912) from all species of sampled livestock were Hyalomma anatolicum anatolicum, a competent vector and reservoir of CCHF virus. 243 tick pools were tested for CCHF antigen, and 19 pools were positive. Of the individuals working in animal contact-related jobs, 73 (30.3%) of 241 non-Omani citizens and only 1 (2.4%) of 41 Omani citizens were CCHF antibody-positive. Butchers were more likely to have CCHF antibody than persons in other job categories. The presence of clinical disease and the serological results for animals and humans and infected Hyalomma ticks provide ample evidence of the presence of CCHF virus in yet another country in the Arabian Peninsula.

Adolescent↗
PubMed2000

Diagnosis and clinical virology of Lassa fever as evaluated by enzyme-linked immunosorbent assay, indirect fluorescent-antibody test, and virus isolation.

The Lassa virus (an arenavirus) is found in West Africa, where it sometimes causes a severe hemorrhagic illness called Lassa fever. Laboratory diagnosis has traditionally been by the indirect fluorescent-antibody (IFA) test. However, enzyme-linked immunosorbent assays (ELISAs) for Lassa virus antigen and immunoglobulin M (IgM) and G (IgG) antibodies have been developed that are thought to be more sensitive and specific. We compared ELISA and IFA testing on sera from 305 suspected cases of Lassa fever by using virus isolation with a positive reverse transcription-PCR (RT-PCR) test as the "gold standard." Virus isolation and RT-PCR were positive on 50 (16%) of the 305 suspected cases. Taken together, Lassa virus antigen and IgM ELISAs were 88% (95% confidence interval [CI], 77 to 95%) sensitive and 90% (95% CI, 88 to 91%) specific for acute infection. Due to the stringent gold standard used, these likely represent underestimates. Diagnosis could often be made on a single serum specimen. Antigen detection was particularly useful in providing early diagnosis as well as prognostic information. Level of antigenemia varied inversely with survival. Detection by ELISA of IgG antibody early in the course of illness helped rule out acute Lassa virus infection. The presence of IFA during both acute and convalescent stages of infection, as well as significant interobserver variation in reading the slides, made interpretation difficult. However, the assay provided useful prognostic information, the presence of IFA early in the course of illness correlating with death. The high sensitivity and specificity, capability for early diagnosis, and prognostic value of the ELISAs make them the diagnostic tests of choice for the detection of Lassa fever.

Antibodies, Viral↗
PubMed2000

Genetic diversity among Lassa virus strains.

The arenavirus Lassa virus causes Lassa fever, a viral hemorrhagic fever that is endemic in the countries of Nigeria, Sierra Leone, Liberia, and Guinea and perhaps elsewhere in West Africa. To determine the degree of genetic diversity among Lassa virus strains, partial nucleoprotein (NP) gene sequences were obtained from 54 strains and analyzed. Phylogenetic analyses showed that Lassa viruses comprise four lineages, three of which are found in Nigeria and the fourth in Guinea, Liberia, and Sierra Leone. Overall strain variation in the partial NP gene sequence was found to be as high as 27% at the nucleotide level and 15% at the amino acid level. Genetic distance among Lassa strains was found to correlate with geographic distance rather than time, and no evidence of a "molecular clock" was found. A method for amplifying and cloning full-length arenavirus S RNAs was developed and used to obtain the complete NP and glycoprotein gene (GP1 and GP2) sequences for two representative Nigerian strains of Lassa virus. Comparison of full-length gene sequences for four Lassa virus strains representing the four lineages showed that the NP gene (up to 23.8% nucleotide difference and 12.0% amino acid difference) is more variable than the glycoprotein genes. Although the evolutionary order of descent within Lassa virus strains was not completely resolved, the phylogenetic analyses of full-length NP, GP1, and GP2 gene sequences suggested that Nigerian strains of Lassa virus were ancestral to strains from Guinea, Liberia, and Sierra Leone. Compared to the New World arenaviruses, Lassa and the other Old World arenaviruses have either undergone a shorter period of diverisification or are evolving at a slower rate. This study represents the first large-scale examination of Lassa virus genetic variation.

Africa, Western↗