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Biomedical subjects

S P Fisher-Hoch

Publications and source records attributed to S P Fisher-Hoch.

At least 19 recordsLinked to original sources

Type 2 diabetes and tuberculosis in a dynamic bi-national border population.

The epidemic of type 2 diabetes in the United States prompted us to explore the association between diabetes and tuberculosis (TB) on the South Texas-Mexico border, in a large population of mostly non-hospitalized TB patients. We examined 6 years of retrospective data from all TB patients (n=5049) in South Texas and northeastern Mexico and found diabetes self-reported by 27.8% of Texan and 17.8% of Mexican TB patients, significantly exceeding national self-reported diabetes rates for both countries. Diabetes comorbidity substantially exceeded that of HIV/AIDS. Patients with TB and diabetes were older, more likely to have haemoptysis, pulmonary cavitations, be smear positive at diagnosis, and remain positive at the end of the first (Texas) or second (Mexico) month of treatment. The impact of type 2 diabetes on TB is underappreciated, and in the light of its epidemic status in many countries, it should be actively considered by TB control programmes, particularly in older patients.

Adult↗

Lassa fever.

Explore the source record for details and available documents.

Adolescent↗

Human asymptomatic Ebola infection and strong inflammatory response.

BACKGROUND: Ebola virus is one of the most virulent pathogens, killing a very high proportion of patients within 5-7 days. Two outbreaks of fulminating haemorrhagic fever occurred in northern Gabon in 1996, with a 70% case-fatality rate. During both outbreaks we identified some individuals in direct contact with sick patients who never developed symptoms. We aimed to determine whether these individuals were indeed infected with Ebola virus, and how they maintained asymptomatic status. METHODS: Blood was collected from 24 close contacts of symptomatic patients. These asymptomatic individuals were sampled 2, 3, or 4 times during a 1-month period after the first exposure to symptomatic patients. Serum samples were analysed for the presence of Ebola antigens, virus-specific IgM and IgG (by ELISA and western blot), and different cytokines and chemokines. RNA was extracted from peripheral blood mononuclear cells, and reverse transcriptase-PCR assays were done to amplify RNA of Ebola virus. PCR products were then sequenced. FINDINGS: 11 of 24 asymptomatic individuals developed both IgM and IgG responses to Ebola antigens, indicating viral infection. Western-blot analysis showed that IgG responses were directed to nucleoprotein and viral protein of 40 kDa. The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals. Asymptomatic individuals had a strong inflammatory response characterised by high circulating concentrations of cytokines and chemokines. INTERPRETATION: This study showed that asymptomatic, replicative Ebola infection can and does occur in human beings. The lack of genetic differences between symptomatic and asymptomatic individuals suggest that asymptomatic Ebola infection did not result from viral mutations. Elucidation of the factors related to the genesis of the strong inflammatory response occurring early during the infectious process in these asymptomatic individuals could increase our understanding of the disease.

Antibodies, Viral↗

Apoptosis in fatal Ebola infection. Does the virus toll the bell for immune system?

In fatal Ebola virus hemorrhagic fever massive intravascular apoptosis develops rapidly following infection and progressing relentlessly until death. While data suggest that T lymphocytes are mainly deleted by apoptosis in PBMC of human fatal cases, experimental Ebola infection in animal models have shown some evidence of destruction of lymphocytes in spleen and lymph nodes probably involving both T and B cells. Nevertheless, we are able to conclude from the accumulated evidence that early interactions between Ebola virus and the immune system, probably via macrophages, main targets for viral replication, lead to massive destruction of immune cells in fatal cases.

Apoptosis↗

Effective vaccine for lassa fever.

Lassa fever has been estimated to cause 5,000 deaths annually in West Africa. Recently, war in the zone where Lassa fever is hyperendemic has severely impeded control and treatment. Vaccination is the most viable control measure. There is no correlation between antibody levels and outcome in human patients, and inactivated vaccines produce high titers of antibodies to all viral proteins but do not prevent virus replication and death in nonhuman primates. Accordingly, we vaccinated 44 macaques with vaccinia virus-expressed Lassa virus structural proteins separately and in combination, with the object of inducing a predominantly TH1-type immune response. Following Lassa virus challenge, all unvaccinated animals died (0% survival). Nine of 10 animals vaccinated with all proteins survived (90% survival). Although no animals that received full-length glycoprotein alone had a high titer of antibody, 17 of 19 survived challenge (88%). In contrast, all animals vaccinated with nucleoprotein developed high titers of antibody but 12 of 15 died (20% survival). All animals vaccinated with single glycoproteins, G1 or G2, died, but all those that received both single glycoproteins (G1 plus G2) at separate sites survived, showing that both glycoproteins are independently important in protection. Neither group had demonstrable antibody levels prior to challenge. We demonstrate that in primates, immune responses to epitopes on both glycoproteins are required to protect against lethal challenge with Lassa virus without having untoward side effects and that this protection is likely to be primarily cell mediated. We show that an effective, safe vaccine against Lassa virus can and should be made and that its evaluation for human populations is a matter of humanitarian priority.

Animals↗

Diagnosis of Ebola haemorrhagic fever by RT-PCR in an epidemic setting.

This study reports the first field evaluation of a new diagnostic technique for Ebola virus disease with sensitivity and specificity. Ebola virus causes rare but fulminating outbreaks in Equatorial Africa. Rapid differentiation from other infections is critical for timely implementation of public health measures. Patients usually die before developing antibodies, necessitating rapid virus detection. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed, implemented and evaluated at Centre International de Recherches Médicales de Franceville (CIRMF) in Gabon, to detect Ebola viral RNA in peripheral blood mononuclear cells (PBMC). Twenty-six laboratory-confirmed patients during and 5 after the acute phase of Ebola haemorrhagic fever, 15 healthy controls and 20 febrile patients not infected with Ebola virus were studied. RT-PCR results were compared with ELISA antigen capture, and Ebola specific IgM and IgG antibody detection. Ebola virus RNA was amplified from 26/26 specimens from the acute phase, 3/5 during recovery, 0/20 febrile patients and 1/15 negative controls. Sensitivity of RT-PCR in identifying acute infection and early convalescence compared with antigen or IgM detection was 100% and 91% respectively, and specificity compared with antigen detection and IgM assay combined was 97%. Antigen capture detected only 83% of those identified by PCR, and IgM only 67%. Ebola virus RNA was detected in all 13 fatalities, only 5 of whom had IgM and none IgG. RT-PCR detected Ebola RNA in PBMC one to three weeks after disappearance of symptoms when antigen was undetectable. RT-PCR was the most sensitive method and able to detect virus from early acute disease throughout early recovery.

Disease Outbreaks↗

Household members of hepatitis C virus-infected people in Hafizabad, Pakistan: infection by injections from health care providers.

Household members of people with hepatitis C are at increased risk of HCV infection. The prevalence and routes of transmission of HCV to household members in Hafizabad, Pakistan were investigated. Household members of 24 index cases were given a risk factor questionnaire, tested for HCV infection, and the risk factors between the infected and uninfected were compared. Twelve of 74 household members (16.2%) were seropositive for HCV antibody. This was 2(1/2) times the rate of infection in the general population (OR = 2.8; P = 0.01). None of the routes of transmission studied within the household was associated with an increased risk. Household members who received more than 4 injections per year were 11.9 times more likely to be infected than those who had not (P = 0.016). In Hafizabad, the greatest risk for HCV infection to household members of infected people is injections given by health-care workers rather than household contact with infected persons.

Adolescent↗

Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients.

Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients. We compared the immune responses of patients who died from Ebola virus disease with those who survived during two large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells, which was indicated by the upregulation of FasL, perforin, CD28 and gamma interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal infection was characterized by impaired humoral responses, with absent specific IgG and barely detectable IgM. Early activation of T cells, indicated by mRNA patterns in peripheral blood mononuclear cells and considerable release of gamma interferon in plasma, was followed in the days preceding death by the disappearance of T cell-related mRNA (including CD3 and CD8). DNA fragmentation in blood leukocytes and release of 41/7 nuclear matrix protein in plasma indicated that massive intravascular apoptosis proceeded relentlessly during the last 5 days of life. Thus, events very early in Ebola virus infection determine the control of viral replication and recovery or catastrophic illness and death.

Antibodies, Viral↗

Risk factors for typhoid fever in an endemic setting, Karachi, Pakistan.

We conducted a study to evaluate risk factors for developing typhoid fever in a setting where the disease is endemic in Karachi, Pakistan. We enrolled 100 cases with blood culture-confirmed Salmonella typhi between July and October 1994 and 200 age-matched neighbourhood controls. Cases had a median age of 5.8 years. In a conditional logistic regression model, eating ice cream (Odds ratio [OR] = 2.3; 95% confidence interval [CI] 1.2-4.2, attributable risk [AR] = 36%), eating food from a roadside cabin during the summer months (OR = 4.6, 95% CI 1.6-13.0; AR = 18%), taking antimicrobials in the 2 weeks preceding the onset of symptoms (OR = 5.7, 95% CI 2.3-13.9, AR = 21%), and drinking water at the work-site (OR = 44.0, 95% CI 2.8-680, AR = 8%) were all independently associated with typhoid fever. There was no difference in the microbiological water quality of home drinking water between cases and controls. Typhoid fever in Karachi resulted from high-dose exposures from multiple sources with individual susceptibility increased by young age and prior antimicrobial use. Improving commercial food hygiene and decreasing unnecessary antimicrobial use would be expected to decrease the burden of typhoid fever.

Adolescent↗

Cholera in a developing megacity; Karachi, Pakistan.

Despite rapid urbanization and increasing affluence in Karachi, cases of cholera are frequent. We analysed computerized isolation data from the AKUH Clinical Microbiology Laboratory, Karachi, from 1990-6 to examine microbiological, temporal and demographic trends in Vibrio cholerae infections. During this period 888 strains of V. cholerae (566 V. cholerae serogroup O1, and 204 V. cholerae serogroup O139) were isolated from specimens from 886 patients; 214/464 were adult inpatients, and 250/464 paediatric inpatients, the remaining 422 outpatients. Isolations peaked between June and August. Overlapping epidemics occurred in 1993 and 1994 of serogroup O1 (May to August), and serogroup O139 (August to October). All ages and social and economic strata were affected. Forty-four percent of all isolates were from children under the age of 5 years. The mean age of all patients with serogroup O1 infections was 19.6 years (+/-0.9) compared with 367 (+/-1.7) for serogroup O139 infections (P < 0.0001, t test). More than a quarter (27%) of all serogroup O1 isolates were from babies under 2 years of age. One patient had a serogroup O1 infection followed by a serogroup O139 infection 1 year later. Another patient was infected with serogroup O1 strains 5 years apart. Emergence of resistant strains was observed, but by 1996 serogroup O139 had disappeared. An aquatic organism, cholera nevertheless continues to take its toll in this city of 11 million situated in a desert.

Adolescent↗

Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice.

OBJECTIVE: To investigate two hospital outbreaks of Lassa fever in southern central Nigeria. SETTING: Hospitals and clinics in urban and rural areas of Imo State, Nigeria. DESIGN: Medical records were reviewed in hospitals and clinics in both areas. Patients with presumed and laboratory confirmed Lassa fever were identified and contracts traced. Hospital staff, patients, and local residents were questioned, records were carefully reviewed, and serum samples were taken. Serum samples were assayed for antibody specific to Lassa virus, and isolates of Lassa virus were obtained. RESULTS: Among 34 patients with Lassa fever, including 20 patients, six nurses, two surgeons, one physician, and the son of a patient, there were 22 deaths (65% fatality rate). Eleven cases were laboratory confirmed, five by isolation of virus. Most patients had been exposed in hospitals (attack rate in patients in one hospital 55%). Both outbreak hospitals were inadequately equipped and staffed, with poor medical practice. Compelling, indirect evidence revealed that parenteral drug rounds with sharing of syringes, conducted by minimally educated and supervised staff, fuelled the epidemic among patients. Staff were subsequently infected during emergency surgery and while caring for nosocomially infected patients. CONCLUSION: This outbreak illustrates the high price exacted by the practice of modern medicine, particularly use of parenteral injections and surgery, without due attention to good medical practice. High priority must be given to education of medical staff in developing countries and to guidelines for safe operation of clinics and hospitals. Failure to do so will have far reaching, costly, and ultimately devastating consequences.

Clinical Competence↗

Crimean Congo-haemorrhagic fever treated with oral ribavirin.

Crimean-Congo Haemorrhagic Fever (CCHF) is an often-lethal haemorrhagic fever caused by a tick-borne virus. There are no published data on ribavirin treatment of CCHF-infected patients, despite established in-vitro and in-vivo sensitivity. We report three health workers--two surgeons and a hospital worker--infected with CCHF virus in Pakistan who were treated with oral ribavirin 4 g/day for four days, then 2.4 g/day for six days. Intravenous ribavirin was unavailable. All three patients were severely ill with low platelet and white-cell counts, raised aspartate transaminase and evidence of impaired haemostasis. Based on published reports, all had an estimated probability of death of 90% or more. The patients became afebrile, and their haematological and biochemical abnormalities returned to normal within 48 h of ribavirin treatment; all made a complete recovery, and developed IgG and IgM antibody to CCHF virus. Our experience with ribavirin treatment is encouraging, but does not constitute evidence of efficacy. Given the difficulties in gathering adequate treatment data, we propose a consensus protocol for both intravenous and oral treatment of CCHF. This protocol could be distributed to key medical personnel in areas endemic for CCHF and used to provide a firm basis for effective treatment recommendations.

Acute Disease↗

Opportunistic candidiasis: an epidemic of the 1980s.

Hospital discharge data from 1980 to 1989 from the National Center for Health Statistics, National Hospital Discharge Survey (NHDH), and two commercially generated hospital discharge data sources (PAS and McAuto) were analyzed to document nationally the increased rate of opportunistic candidal infections among hospitalized patients in the 1980s and to identify the major risk factors. National projections were made by year. Age-, sex-, race-, and disease-specific denominators were generated from NHDS data. ICD-9-CM codes derived from discharge diagnoses were used to identify patients with oropharyngeal candidiasis, disseminated candidiasis, human immunodeficiency virus (HIV) infection/AIDS, or malignancies and transplants. Between 1980 and 1989, rates of oropharyngeal candidiasis increased 4.7 times (from 0.34 to 1.6 cases per 1,000 admissions per year), and the number of deaths among patients with oropharyngeal candidiasis increased fivefold. Although the highest rates were among pediatric patients (3 cases per 1,000 pediatric admissions), the greatest rate increases were among 15- to 44-year-old patients (13-fold) and males (fivefold). Between 1983 and 1989, the rates of oropharyngeal candidiasis among patients with HIV infections/AIDS rose more than 22 times (from 0.02 to 0.45 case per 1,000 admissions; NHDS data). Over the whole decade, the rates of disseminated candidiasis increased 11 times (from 0.013 to 0.15 case per 1,000 admissions). Between 1985 and 1989, the rate of this complication among patients with HIV infection/AIDS increased 10-fold, compared with only a twofold rate increase among patients with malignancies or transplants. The rate of debilitating and life-threatening candidiasis among hospitalized patients increased considerably over the 1980s. This rate increase was significant among patients with HIV infection/AIDS and patients undergoing transplantation or immunosuppressive therapy for malignancies.

AIDS-Related Opportunistic Infections↗

A serotypic study of hemorrhagic fever with renal syndrome in rural China.

Apodemus agrarius was trapped in the fields and Rattus norvegicus was trapped within the houses in the villages of Jiande County, a region in the Zhejiang Province of China endemic for hemorrhagic fever with renal syndrome (HFRS). Antibodies to hantaviruses were detected in three (16.7%) of 18 A. agrarius and 12 (13.5%) of 89 R. norvegicus, whereas hantavirus antigens were detected in the lung tissues of four (22.2%) of 18 and nine (10.1%) of 89 of these rodents, respectively. Three hantaviruses, one from A. agrarius and two from R. norvegicus, were isolated and found to be antigenically similar to Hantaan and Seoul serotype viruses, respectively. A serologic study of 437 clinically defined HFRS patients conducted in Jiande County in 1988 revealed that the ratio of Hantaan (72.5%) to Seoul (26.8%) serotype virus infections was 2.7:1. Two epidemic seasons were found, with a major peak in November and a minor peak in June, and both were associated with Hantaan serotype virus infections that coincided with two seasonal peaks of the A. agrarius population and local agricultural activities in the fields. Seoul serotype virus infections occurred with a small peak during the months of December through May, in which in-house activities were dominant. All data suggested that Jiande County was an area endemic for HFRS, predominantly of the Hantaan virus serotype, combined with Seoul serotype virus infections.

Animals↗

Retrospective and prospective studies of hemorrhagic fever with renal syndrome in rural China.

Residents of two villages in Zhejiang Province, China, were interviewed and serum samples were collected to assess prevalence of hantavirus infection. Antibody prevalence was 12% (219/1811), with a ratio of illness to infection of 1.0:5.4. Seroprevalence increased with age, but no association was found with sex. There was also no evidence of vertical transmission. One year later, 2.3% (30/1325) of seronegative subjects had seroconverted including 2 who had hemorrhagic fever with renal syndrome. Peak incidence of infection occurred in those 15-39 years old. Hantaan was the dominant serotype; Seoul serotype was less common (5:1). Host reservoirs were Apodemus agrarius in agricultural fields and Rattus norvegicus in houses. Risk factors for infection were traces of rat-contaminated food, travel to other areas for farm work, direct rodent contact, camping in grain fields, living in a house on the periphery of a village, stacking straw stacks outside houses, and keeping cats. All may provide exposure to infectious rodent reservoirs.

Adolescent↗

Evaluation of the polymerase chain reaction for diagnosis of Lassa virus infection.

We evaluated the polymerase chain reaction (PCR) and hybridization procedures for diagnosis of Lassa fever. Primers were derived from a region of the small RNA segment of Lassa virus coding for the glycoprotein. Serum samples stored for a 14-year period from patients in Sierra Leone, West Africa were examined retrospectively. Blinded samples were then tested prospectively. Eighty-eight virus isolation-negative control sera were negative by PCR and hybridization. In the retrospective study, virus was isolated from 51 of 98 specimens from patients with Lassa fever, and 33 of these were positive for Lassa virus RNA by PCR, and 42 by PCR and hybridization. Fifteen were positive by PCR and hybridization but isolation-negative, and nine were positive by isolation but PCR/hybridization-negative. Thirty-two were negative by all methods (sensitivity by PCR/hybridization compared with virus isolation 0.82, specificity 0.68). In a prospective blinded study of 195 patient sera, 51 were positive by PCR and virus isolation, and 24 were PCR positive but virus isolation-negative (sensitivity 0.66, specificity 0.71). After hybridization, 66 virus isolation-positive sera were positive. The sensitivity was 0.86 and the specificity was 0.59, and the probability of false-positive results compared with virus isolation was 32%, (chi 2 = 21.9, by McNemar's test). Since some specimens may not have contained viable virus, we re-analyzed the data of individual patients using laboratory-confirmed case definitions for Lassa fever. All specimens from patients in whom Lassa fever was excluded by serologic tests were negative by PCR/hybridization.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗