PubMed Health⌕ Search

Biomedical subjects

S R Zaki

Publications and source records attributed to S R Zaki.

At least 19 recordsLinked to original sources
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

Risk factors for Nipah virus infection among abattoir workers in Singapore.

During 10-19 March 1999, 11 workers in 1 of 2 Singaporean abattoirs developed Nipah-virus associated encephalitis or pneumonia, resulting in 1 fatality. A case-control study was conducted to determine occupational risk factors for infection. Case patients were abattoir A workers who had anti-Nipah IgM antibodies; control subjects were randomly selected abattoir A workers who tested negative for anti-Nipah IgM. All 13 case patients versus 26 (63%) of 41 control subjects reported contact with live pigs (P=.01). Swine importation from Malaysian states concurrently experiencing a Nipah virus outbreak was banned on 3 March 1999; on 19 March 1999, importation of Malaysian pigs was banned, and abattoirs were closed. No unusual illnesses among pigs processed during February-March were reported. Contact with live pigs appeared to be the most important risk factor for human Nipah virus infection. Direct contact with live, potentially infected pigs should be minimized to prevent transmission of this potentially fatal zoonosis to humans.

Abattoirs↗
PubMed2000

Pathogenesis of and immunity to avian influenza A H5 viruses.

In 1997 in Hong Kong, 18 human cases of respiratory illness were caused by an avian influenza A H5N1 virus. Although avian influenza viruses had not previously been known to cause respiratory illness in humans, the H5N1 viruses caused severe illness and death, primarily in individuals aged > 12 years. The introduction of H5N1 viruses into humans raised concerns about the potential of these viruses to cause a pandemic. We have used the BALB/c mouse to better understand the pathogenesis of and immunity to the H5N1 viruses in a mammalian model. Previously, we demonstrated that H5N1 viruses isolated from humans replicated efficiently in the lungs of mice without prior adaptation to this host. Two general phenotypes of pathogenicity of H5N1 viruses, based on high and low lethality for mice, were observed. We now demonstrate that in addition to a lethal outcome, H5N1 viruses with a high pathogenicity phenotype exhibit additional features that include rapid and uncontrolled replication in the lungs of infected mice, dissemination and replication of the virus in other organs, and depletion of peripheral blood leukocytes. The BALB/c mouse model was also used to better understand the parameters of protective immunity to the H5N1 viruses. Prior infection with H5N1 viruses of low pathogenicity or an antigenically related non-pathogenic H5N3 virus protected mice from death by infection with a highly pathogenic HK/483 virus. Serum hemagglutination-inhibition antibody titers of 40 or greater were associated with protection of mice from death. Immunization of mice with baculovirus-expressed recombinant H5 hemagglutinin protein or a previously defined HS-specific synthetic peptide induced MHC class II restricted CTL activity. Mice that had CTL activity but no serum hemagglutination-inhibition antibody were not protected from a lethal challenge with H5N1 virus. These results suggest that antibody is required for protection of mice against lethal challenge with H5N1 viruses of the high pathogenicity phenotype.

Animals↗
PubMed2000

Depletion of lymphocytes and diminished cytokine production in mice infected with a highly virulent influenza A (H5N1) virus isolated from humans.

Previously, we observed that several virulent influenza A (H5N1) viruses which caused severe or fatal disease in humans were also lethal in BALB/c mice following dissemination of the virus to solid organs, including the brain. In contrast, one particular human H5N1 virus was nonlethal in mice and showed no evidence of systemic spread. To compare H5N1 viruses of varying pathogenicity for their ability to alter the mammalian immune system, mice were infected with either influenza A/Hong Kong/483/97 (HK/483) (lethal) or A/Hong Kong/486/97 (HK/486) (nonlethal) virus and monitored for lymphocyte depletion in the blood, lungs, and lymphoid tissue. Intranasal infection with HK/483 resulted in a significant decrease in the total number of circulating leukocytes evident as early as day 2 postinfection. Differential blood counts demonstrated up to an 80% drop in lymphocytes by day 4 postinfection. In contrast, nonlethal HK/486-infected mice displayed only a transient drop of lymphocytes during the infectious period. Analysis of lung and lymphoid tissue from HK/483-infected mice demonstrated a reduction in the number of CD4(+) and CD8(+) T cells and reduced synthesis of the cytokines interleukin-1beta and gamma interferon and the chemokine macrophage inflammatory protein compared with HK/486-infected mice. In contrast, the cytokine and chemokine levels were increased in the brains of mice infected with HK/483 but not HK/486. Evidence of apoptosis in the spleen and lung of HK/483-infected mice was detected in situ, suggesting a mechanism for lymphocyte destruction. These results suggest that destructive effects on the immune system may be one factor that contributes to the pathogenesis of H5N1 viruses in mammalian hosts.

Animals↗
PubMed2000

Immunohistochemical and in situ hybridization studies of influenza A virus infection in human lungs.

Influenza viruses are responsible for acute febrile respiratory disease. When deaths occur, definitive diagnosis requires viral isolation because no characteristic viral inclusions are seen. We examined the distribution of influenza A virus in tissues from 8 patients with fatal infection using 2 immunohistochemical assays (monoclonal antibodies to nucleoprotein [NP] and hemagglutinin [HA]) and 2 in situ hybridization (ISH) assays (digoxigenin-labeled probes that hybridized to HA and NP genes). Five patients had prominent bronchitis; by immunohistochemical assay, influenza A staining was present focally in the epithelium of larger bronchi (intact and detached necrotic cells) and in rare interstitial cells. The anti-NP antibody stained primarily cell nuclei, and the anti-HA antibody stained mainly the cytoplasm. In 4 of these cases, nucleic acids (ISH) were identified in the same areas. Three patients had lymphohistiocytic alveolitis and showed no immunohistochemical or ISH staining. Both techniques were useful for detection of influenza virus antigens and nucleic acids in formalin-fixed paraffin-embedded tissues and can enable further understanding of fatal influenza A virus infections in humans.

Adolescent↗
PubMed1999

Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia.

BACKGROUND: Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died. METHODS: Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses. FINDINGS: The three pig-farmers presented with fever, headache, and altered level of consciousness. Myoclonus was present in two patients. There were signs of brainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSF of two patients after 5 days; the virus stained positively with antibodies against Hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. Inclusion bodies likely to be of viral origin were noted in neurons near vasculitic blood vessels. INTERPRETATION: The causative agent was a previously undescribed paramyxovirus related to the Hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the Hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in Malaysia.

Adult↗
PubMed1999

Outbreak of Nipah-virus infection among abattoir workers in Singapore.

BACKGROUND: In March 1999, an outbreak of encephalitis and pneumonia occurred in workers at an abattoir in Singapore. We describe the clinical presentation and the results of investigations in these patients. METHODS: Clinical and laboratory data were collected by systemic review of the case records. Serum and cerebrospinal fluid (CSF) samples were tested for IgM antibodies to Nipah virus with an IgM capture ELISA. Reverse-transcriptase PCR was done on the CSF and tissue samples from one patient who died. FINDINGS: Eleven patients were confirmed to have acute Nipah-virus infection based on raised IgM in serum. Nipah virus was identified by reverse transcriptase PCR in the CSF and tissue of the patient who died. The patients were all men, with a median age of 44 years. The commonest presenting symptoms were fever, headache, and drowsiness. Eight patients presented with signs of encephalitis (decreased level of consciousness or focal neurological signs). Three patients presented with atypical pneumonia, but one later developed hallucinations and had evidence of encephalitis on CSF examination. Abnormal laboratory findings included a low lymphocyte count (nine patients), low platelet count, low serum sodium, and high aspartate aminostransferase concentration (each observed in five patients). The CSF protein was high in eight patients and white-blood-cell count was high in seven. Chest radiography showed mild interstitial shadowing in eight patients. Magnetic resonance imaging (MRI) showed focal areas of increased signal intensity in the cortical white marker in all eight patients who were scanned. The nine patients with encephalitis received empirical treatment with intravenous aciclovir and eight survived. INTERPRETATION: Infection with Nipah virus caused an encephalitis illness with characteristic focal areas of increased intensity seen on MRI. Lung involvement was also common, and the disease may present as an atypical pneumonia.

Abattoirs↗
PubMed1999

Concepts and transformational knowledge.

The effect of exposure to principled change in concept formation was investigated in four experiments. In Experiment 1, participants were trained on either patterns that transformed systematically or control patterns that were distorted randomly. Training on transformational patterns produced concepts that were more resistant to false intrusions and decay. Experiment 2 separated the relative influences of transformational knowledge and pairwise similarity. Participants were able to identify the next pattern in a transformational sequence even though the foils were closer to the training patterns. Experiment 3 investigated whether participants use transformational information in a speeded categorization task. Participants were faster at classifying patterns that continued a transformational path than patterns that fell off the path, only if they had trained on the transformational patterns in a systematic order. Experiment 4 used multidimensional scaling to explore the psychological structure of transformational knowledge following training. Analyses revealed clear evidence of a transformational path with systematic training. Implications for theories of similarity and categorization are discussed.

Adult↗
PubMed1999

Reversal of virus-induced systemic shock and respiratory failure by blockade of the lymphotoxin pathway.

At present, little is known about the pathogenesis of acute virus-induced shock and pulmonary failure. A chief impediment in understanding the underlying disease mechanisms and developing treatment strategies has been the lack of a suitable animal model. This study describes a mouse model of virus-induced systemic shock and respiratory distress, and shows that blockade of the lymphotoxin beta receptor pathway reverses the disease.

Animals↗
PubMed1999

Hantavirus pulmonary syndrome in pregnancy.

This comprehensive case review of hantavirus pulmonary syndrome (HPS) during pregnancy in 5 women characterizes the effect of Sin Nombre virus infection on maternal and fetal outcomes. Histopathologic, serological, and clinical information were evaluated for evidence of vertical transmission. Maternal ages ranged from 20 to 34 years and gestational ages from 13 to 29 weeks. Symptoms, physical findings, and laboratory values other than those related to pregnancy were not noticeably different from those of nonpregnant patients with HPS, although fevers were somewhat lower. One maternal death and 2 fetal losses occurred. Gross, microscopic, and immunohistochemical examination for hantavirus antigen were done on 2 fetal autopsies and 3 placentas showing no evidence of transplacental hantavirus transmission. There was no serological evidence of conversion in the 3 surviving children. Maternal and fetal outcomes of HPS appear similar to those of nonpregnant HPS patients and of pregnant patients with other causes of acute respiratory distress syndrome. No evidence of vertical transmission of Sin Nombre virus was found.

Adult↗
PubMed1999

Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease.

Rocky Mountain spotted fever (RMSF) is the most severe tickborne infection in the United States and is a nationally notifiable disease. Since 1981, the annual case-fatality ratio for RMSF has been determined from laboratory-confirmed cases reported to the Centers for Disease Control and Prevention (CDC). Herein, a description is given of patients with fatal, serologically unconfirmed RMSF for whom a diagnosis of RMSF was established by immunohistochemical (IHC) staining of tissues obtained at autopsy. During 1996-1997, acute-phase serum and tissue samples from patients with fatal disease compatible with RMSF were tested at the CDC. As determined by indirect immunofluorescence assay, no patient serum demonstrated IgG or IgM antibodies reactive with Rickettsia rickettsii at a diagnostic titer (i.e., >/=64); however, IHC staining confirmed diagnosis of RMSF in all patients. Polymerase chain reaction validated the IHC findings for 2 patients for whom appropriate samples were available for testing. These findings suggest that dependence on serologic assays and limited use of IHC staining for confirmation of fatal RMSF results in underestimates of mortality and of case-fatality ratios for this disease.

Adult↗
PubMed1999

Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL-10, and tumor necrosis factor-alpha associated with fatal Ebola virus infection.

The role of immune mechanisms in the pathogenesis of Ebola hemorrhagic fever (EHF) remains to be elucidated. In this report, the serum cytokine levels of patients who died of EHF were compared with those of patients who recovered and those of control patients. A marked elevation of interferon (IFN)-gamma levels (>100 pg/mL) was observed in sequential serum samples from all fatal EHF cases compared with patients who recovered or controls. Markedly elevated serum levels of interleukin (IL)-2, IL-10, tumor necrosis factor (TNF)-alpha, and IFN-alpha were also noted in fatal EHF cases; however, they had a greater degree of variability. No differences were noted in serum levels of IL-4 and IL-6. mRNA quantitation from blood clots of the same patients showed relatively elevated levels of TNF-alpha and IFN-alpha in samples from EHF patients. Taken together, these results suggest that a high degree of immune activation accompanies and potentially contributes to a fatal outcome in EHF patients.

Cytokines↗
PubMed1999

Isolated case of Ebola hemorrhagic fever with mucormycosis complications, Kinshasa, Democratic Republic of the Congo.

A patient with undiagnosed Ebola (EBO) hemorrhagic fever (EHF) was transferred from Kikwit to a private clinic in Kinshasa, Democratic Republic of the Congo. A diagnosis of EHF was suspected on clinical grounds and was confirmed by detection of EBO virus-specific IgM and IgG in serum of the patient. During the course of the disease, although she had no known predisposing factors, the patient developed a periorbital mucormycosis abscess on eyelid tissue that was biopsied during surgical drainage; the abscess was histologically confirmed. Presence of EBO antigen was also detected by specific immunohistochemistry on the biopsied tissue. The patient survived the EBO infection but had severe sequelae associated with the mucormycosis. Standard barrier-nursing precautions were taken upon admission and upgraded when EHF was suspected; there was no secondary transmission of the disease.

Adult↗
PubMed1999

The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit.

In May 1995, an international team characterized and contained an outbreak of Ebola hemorrhagic fever (EHF) in Kikwit, Democratic Republic of the Congo. Active surveillance was instituted using several methods, including house-to-house search, review of hospital and dispensary logs, interview of health care personnel, retrospective contact tracing, and direct follow-up of suspect cases. In the field, a clinical case was defined as fever and hemorrhagic signs, fever plus contact with a case-patient, or fever plus at least 3 of 10 symptoms. A total of 315 cases of EHF, with an 81% case fatality, were identified, excluding 10 clinical cases with negative laboratory results. The earliest documented case-patient had onset on 6 January, and the last case-patient died on 16 July. Eighty cases (25%) occurred among health care workers. Two individuals may have been the source of infection for >50 cases. The outbreak was terminated by the initiation of barrier-nursing techniques, health education efforts, and rapid identification of cases.

Adolescent↗
PubMed1999

Long-term disease surveillance in Bandundu region, Democratic Republic of the Congo: a model for early detection and prevention of Ebola hemorrhagic fever.

After the large-scale outbreak of Ebola hemorrhagic fever (EHF) in Bandundu region, Democratic Republic of the Congo, a program was developed to help detect and prevent future outbreaks of EHF in the region. The long-term surveillance and prevention strategy is based on early recognition by physicians, immediate initiation of enhanced barrier-nursing practices, and the use of an immunohistochemical diagnostic test performed on formalin-fixed skin specimens of patients who die of suspected viral hemorrhagic fever. The program was implemented in September 1995 during a 4-day workshop with 28 local physicians representing 17 of 22 health zones in the region. Specimen collection kits were distributed to clinics in participating health zones, and a follow-up evaluation was conducted after 6 months. The use of a formalin-fixed skin specimen for laboratory confirmation of EHF can provide an appropriate method for EHF surveillance when linked with physician training, use of viral hemorrhagic fever isolation precautions, and follow-up investigation.

Adult↗
PubMed1999

A novel immunohistochemical assay for the detection of Ebola virus in skin: implications for diagnosis, spread, and surveillance of Ebola hemorrhagic fever. Commission de Lutte contre les Epidémies à Kikwit.

Laboratory diagnosis of Ebola hemorrhagic fever (EHF) is currently performed by virus isolation and serology and can be done only in a few high-containment laboratories worldwide. In 1995, during the EHF outbreak in the Democratic Republic of Congo, the possibility of using immunohistochemistry (IHC) testing of formalin-fixed postmortem skin specimens was investigated as an alternative diagnostic method for EHF. Fourteen of 19 cases of suspected EHF met the surveillance definition for EHF and were positive by IHC. IHC, serologic, and virus isolation results were concordant for all EHF and non-EHF cases. IHC and electron microscopic examination showed that endothelial cells, mononuclear phagocytes, and hepatocytes are main targets of infection, and IHC showed an association of cellular damage with viral infection. The finding of abundant viral antigens and particles in the skin of EHF patients suggests an epidemiologic role for contact transmission. IHC testing of formalin-fixed skin specimens is a safe, sensitive, and specific method for laboratory diagnosis of EHF and should be useful for EHF surveillance and prevention.

Adolescent↗
PubMed1999

Family cluster of Rocky Mountain spotted fever.

Soon after a patient from Tennessee died of Rocky Mountain spotted fever (RMSF), several family members developed symptoms suggestive of the disease and were treated presumptively for RMSF. Fifty-four persons visiting the index patient's home were interviewed; serum samples were collected from 35. Three additional cases of RMSF were confirmed, all of which occurred in first-degree relatives. Time spent at the family home and going into the surrounding woods were significantly associated with developing antibodies to Rickettsia rickettsii. Ticks were collected and examined for rickettsiae by polymerase chain reaction analysis. Because hyperendemic foci and family clusters of RMSF can occur, when a case is suspected clinicians should be vigilant for signs and symptoms consistent with R. rickettsii infection in other persons who may have been similarly exposed.

Antibodies, Bacterial↗