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Biomedical subjects

D M Watts

Publications and source records attributed to D M Watts.

At least 55 records · Page 3Linked to original sources

Immunogenicity in Peruvian volunteers of a booster dose of oral cholera vaccine consisting of whole cells plus recombinant B subunit.

Forty-nine subjects received two doses of oral cholera vaccine consisting of whole cells plus recombinant B subunit; this was followed by a booster dose one year later. After the primary series, a significant (greater than twofold) increase in the levels of vibriocidal, anti-cholera toxin immunoglobulin G and anti-cholera toxin immunoglobulin A antibodies occurred in 54, 88, and 81% of the subjects, respectively. Within one year, titers decreased to levels close to baseline. A booster dose then induced rises to those which occurred after the initial vaccination. The results suggest that 1-year booster doses may be necessary to maintain immunity against cholera in Latin America.

Administration, Oral↗

Evaluation of the severe combined immunodeficient (SCID) mouse as an animal model for dengue viral infection.

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood lymphocytes (hu-PBL) were evaluated as an animal model for demonstrating dengue (DEN) viral infection. Reconstituted mice (hu-PBL-SCID) that demonstrated successful engraftment by the presence of serum titers of human immunoglobulin (Ig) were inoculated intraperitoneally with DEN virus serotype 1 (DEN-1). Serial blood samples were taken postinoculation and assayed for virus in C6/36 cells. The identity of all viral isolates was confirmed by an immunofluorescence antibody assay using DEN-1 monoclonal antibody. A total of six experiments were performed using different procedures of reconstitution and infection, and in three of these experiments, DEN-1 virus was recovered from the hu-PBL-SCID mice. In the first successful experiment, DEN-1 virus was recovered on postinoculation day (PID) 24 from blood, spleen, thymus, and lung tissues of one of eight hu-PBL-SCID mice. A second group of eight hu-PBL-SCID mice were inoculated with human monocytes infected in vitro with DEN-1 virus. Virus was recovered from the blood of mice between PID 15 and 23, and from lung tissue of one of these mice. In a third experiment, seven SCID mice were treated initially with anti-asialo GM1 antibody to eliminate natural killer cells, and then were injected simultaneously with a mixture of hu-PBL and DEN-1 virus. Virus was demonstrated in the blood of one mouse on PID 38, and in another mouse on PID 8, 12, 20, 24, and 36.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Coxiella burnetii antibody prevalences among human populations in north-east Africa determined by enzyme immunoassay.

Retrospective serosurveys were conducted to determine the prevalence of antibody to phase-I Coxiella burnetii among humans in various locations of north-east Africa. Sera were tested by the enzyme immunoassay (EIA). Initially the EIA was compared with the standard indirect fluorescent antibody (IFA) method for the detection of antibody to C. burnetii. Results indicated that the EIA was slightly less sensitive (88%), but highly specific (94%) and less subjective than the IFA technique. EIA was subsequently adopted for estimating prevalences in the studied human populations. Data obtained by EIA indicated that the prevalence of C. burnetii antibody among adult Egyptian blood donors was 20% (n = 358) in the Suez Canal area, 16% (n = 501) in the Nile Valley and 10% (n = 427) in the Nile Delta. Among adult patients with acute, undifferentiated fever in Egypt, the prevalence was 28% (n = 50) of acute sera, with seroconversion in 12% of convalescent sera. Antibody to C. burnetii was detected by EIA in the sera of 25% (n = 71) of cattle workers in Egypt, 10% (n = 100) of housewives in Sudan, and 37% (n = 104) of adults in north-west Somalia. Following a fever outbreak affecting all ages in northern Sudan, IgG antibody to C. burnetii was present in 54% of the febrile persons (n = 185) and in 53% of afebrile persons (n = 186). IgM antibody to C. burnetii was demonstrated in 29% of the febrile persons and 15% of the afebrile persons. These results implicate C. burnetii as a possibly important and under-reported cause of human disease and undiagnosed fevers in north-east Africa.

Adult↗

Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits.

The cholera epidemic in South America has reinforced the need for safe and effective oral vaccines. In a randomised, double-blind, placebo-controlled efficacy trial among 1563 Peruvian military recruits we have investigated the protective efficacy of an oral inactivated whole-cell/recombinant-B-subunit (WC/rBS) cholera vaccine. Participants were given two oral doses of cholera vaccine or Escherichia coli K12 placebo, with an interval of 7-14 days. 1426 (91%) subjects received the two prescribed doses and were followed up for a mean of 18 weeks (median 21 weeks). After vaccination, Vibrio cholerae O1 El Tor Ogawa was isolated from 17 subjects with diarrhoea. 16 of the cholera cases occurred 2 weeks or longer after the second dose of vaccine (14 placebo recipients, 2 vaccinees). We also detected 14 symptomless infections (11 [7 placebo recipients, 4 vaccinees]) 2 weeks or longer after the second dose. The vaccine had significant protective efficacy against cholera (86% [95% CI 37-97], p < 0.01) but not against symptomless infection (42% [-96 to 85]). All cholera cases were in people of blood group O, who made up 76% of the study population (p < 0.01). Two doses of WC/rBS vaccine, given 1 to 2 weeks apart, provide rapid, short-term protection against symptomatic cholera in adult South Americans, who are predominantly of blood group O. Long-term efficacy studies in Peruvian adults and children are under way.

ABO Blood-Group System↗

A rapid method for detection and identification of flaviviruses by polymerase chain reaction and nucleic acid hybridization.

A polymerase chain reaction (PCR) technique was developed and evaluated for the detection of flaviviruses. A set of sense and antisense oligomeric DNA primers were constructed from nucleotide sequences of the conserved region of the genome of several different flaviviruses. Virus specific complementary DNA (cDNA) was prepared by reverse transcription of total RNA extracted from infected cell cultures. Amplified cDNA was identified by nucleic acid hybridization with specific oligomeric internal probes. Various conditions, such as number of cycles and annealing temperature were examined to optimize the detection of viral RNAs from infected cell cultures. Slot blot hybridization with a radioactive probe was used to evaluate the sensitivity of PCR amplification. The PCR amplified RNA sequences of dengue 2 (DEN-2), West Nile (WN), St. Louis encephalitis (SLE) and Kunjin (KUN) virus and detected 0.1 to 1 pg of viral RNA. Japanese encephalitis (JE), Yellow Fever virus (YF), DEN-1, 3, and 4 viruses were not amplified. The more frequent occurrence of mismatches in the 3' primer binding site may explain the failure to amplify cDNA of these viruses.

Aedes↗

Arthropod-borne viral infections associated with a fever outbreak in the northern province of Sudan.

An outbreak of acute febrile illness occurred during August and September 1989 in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies. An investigation was conducted to determine whether arboviruses were associated with human illness during this outbreak. Sera were obtained from 185 febrile individuals and tested for IgG and IgM antibody to selected arboviruses by enzyme immunoassay (EIA). The prevalence of IgG antibody was 59% for West Nile (WN), 53% for Sandfly Fever Sicilian (SFS), 32% for Sandfly Fever Naples (SFN), 39% for Yellow Fever (YF), 24% for dengue-2 (DEN-2), 23% for Rift Valley Fever (RVF), 12% for Chikungunya (CHIK) and 5% for Crimean-Congo haemorrhagic Fever (CCHF) viruses. Antibody prevalences tended to increase with age for WN and YF viruses. Antibody rates were about the same for males and females for most of the viruses tested. The prevalence of IgM antibody to SFN was 24% and reciprocal IgM titre exceeded 12,800 for some individuals suggesting that this virus was the cause of recent infection. The prevalence of IgM antibody for the other viruses did not exceed 5%. The study indicated that several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan.

Acute Disease↗

Detection of immunoglobulin A in urine specimens from children with Campylobacter-associated diarrhea by a chemiluminescent indicator-based western immunoblot assay.

A Western blot (immunoblot) assay was used to detect Campylobacter-specific immunoglobulin A in urine. Acute-phase urine samples from six children with Campylobacter diarrhea had titers ranging from 2 to 8. The highest titer was detected 4 days postonset. Campylobacter-specific immunoglobulin A was undetectable in the paired convalescent-phase specimens and urine samples from three control children.

Adolescent↗

Respiratory disease among military personnel in Saudi Arabia during Operation Desert Shield.

OBJECTIVES: The purpose of this study was to determine whether respiratory disease due to crowded living conditions and high levels of suspended and blowing sand had a major adverse impact on US military personnel during Operation Desert Shield. METHODS: A questionnaire survey was administered to 2598 combat troops stationed in Northeast Saudi Arabia for a mean of 102 days. Samples of surface sand from seven different locations were analyzed by scanning electron microscopy and x-ray diffraction. RESULTS: Among surveyed troops, 34.4% reported a sore throat, 43.1% complained of a cough, 15.4% complained of chronic rhinorrhea, and 1.8% were unable to perform their routine duties because of upper respiratory symptoms. Evaluation of sleeping accommodations indicated that complaints of a sore throat and cough were most closely associated with sleeping in air-conditioned buildings; in contrast, complaints of rhinorrhea were associated with exposure to the outdoor environment while living in tents. Sand samples consisted mostly of quartz, with just 0.21% by weight of respirable size (< 10 microns in diameter). CONCLUSIONS: These findings indicate that upper respiratory complaints were frequent among Operation Desert Shield troops and were related both to the troops' housing and to their exposure to the outside environment.

Adolescent↗

Acute sporadic hepatitis E in an Egyptian pediatric population.

A study was conducted to determine the etiology of acute hepatitis among 261 children (age range 1-11 years) living in Cairo, Egypt. A blood sample was obtained from each subject when initially evaluated and a questionnaire was used to collect demographic and risk factor data. Sera were tested by enzyme immunoassay for acute hepatitis A (anti-hepatitis A virus IgM), hepatitis B (anti-hepatitis B core antigen IgM and hepatitis B surface antigen [HBsAg]), hepatitis C (total anti-HCV), delta hepatitis (total anti-delta), and cytomegalovirus infection (anti-CMV IgM). In addition, hepatitis E virus (HEV) infection was diagnosed using a new Western blot technique to test patients with non-A, non-B hepatitis for anti-HEV IgM. Among 261 children, acute hepatitis A was diagnosed in 85 (32.6%) patients, acute hepatitis B in 19 (7.3%), delta hepatitis in 3 (1.1%), mixed hepatitis A and B infection in 2 (0.8%), CMV infection in 1 (0.4%), hepatitis E in 58 (22.2%), and non-A, non-B hepatitis of unknown type in 51 (19.5%). Forty-two (16.1%) subjects had HBsAg without other markers of acute infection. Risk factor analysis indicated that patients living in homes not connected to a municipal source of water were at increased risk of hepatitis E infection. These data provide additional evidence that hepatitis E virus is a common cause of acute sporadic hepatitis in children living in Egypt.

Acute Disease↗

Vertical transmission of West Nile virus by Culex and Aedes species mosquitoes.

Experiments were conducted to determine whether West Nile (WN) virus was transmitted vertically by colonized strains of Aedes albopictus, Ae. aegypti, and Culex tritaeniorhynchus. Female mosquitoes were infected by intrathoracic inoculation with WN virus, and the F1 progeny were tested for virus by the fluorescence antibody technique and the newborn mouse assay. Each of the three mosquito species transmitted WN virus to F1 adults derived from immature forms reared at 26 degrees C. The minimal filial infection rate (MFIR) ranged from 1:124 to 1:138 for Ae. albopictus, from 1:62 to 1:172 for Ae. aegypti, and from 1:325 to 1:859 for Cx. tritaeniorhynchus. The MFIR for Cx. tritaeniorhynchus reared at 20 degrees C was 1:213 for larvae and 1:390 for pupae, and 1:208 for larvae and 1:554 for pupae reared at 26 degrees C. These data are the first reported evidence of vertical transmission of WN virus by mosquitoes, and therefore warrant further studies to determine whether vertical transmission occurs among WN viral-infected mosquitoes in nature.

Aedes↗

Prevalence of hepatitis C viral antibody in transfused and nontransfused Egyptian children.

Hepatitis C (HCV) virus is recognized as the major cause of what was previously referred to as parenterally acquired (blood-mediated) non-A, non-B hepatitis. A study involving 252 transfused and nontransfused Egyptian children was conducted from November 1990 through February 1991 to determine the prevalence of HCV and the role of blood and blood and blood product transfusions in the spread of the virus. Serum specimens were assayed by a second generation enzyme immunoassay and were considered reactive only after supplemental testing using the second generation recombinant immunoblot assay. Prevalence among 84 young study subjects with hematologic disorders was 55% (46 of 84), while no HCV antibodies were detected among the two nonhematologic pediatric populations studied: 84 hospital admissions and 84 acutely ill but otherwise healthy outpatients (seeking treatment for symptoms associated with a new condition less than three weeks old in the absence of any chronic health problem). Ninety-two percent (77 of 84) of the hematology-related cases had medical histories of multiple transfusions. Positive antibody responses (46) were significantly associated with increased duration of illness (P < 0.001) and the volume and number of transfusions (P < 0.01) when compared with negative ones (38). However, prior hospitalization and/or surgery were not related to HCV antibody status. The high prevalence of HCV antibody among multiply transfused infants and children suggests that blood and blood product supplies should be regularly screened for HCV antibody.

Adolescent↗

HIV infection among secondary school students in Djibouti, horn of Africa: knowledge, exposure and prevalence.

A study of HIV infection among secondary school students was conducted in Djibouti in February 1990 during a national hepatitis survey. Serology was negative for HIV and syphilis among 294 students (ages 14 to 20 years) in spite of a dramatic increase of HIV seropositivity (as high as 41%), and a high level of syphilis positive serology (up to 46%) among adult high-risk groups such as street prostitutes. Results of a face-to-face interview of these pupils indicated that 64% had a basic knowledge of AIDS. As expected, a much better knowledge of AIDS was found among those who recently received AIDS education. However, 80% of secondary school teenagers did not consider themselves at risk for acquiring HIV. Transmission of HIV among school-children would be possible through sexual activity (22% stated to be sexually active) or parenteral therapy (75% had received at least one intramuscular injection), and not likely through blood transfusion or intravenous drug abuse. Results, close to those of a similar study in Zimbabwe, suggest that AIDS education programme should be given to all secondary school pupils and include public health lectures on syphilis, tuberculosis, and HIV infection.

Adolescent↗

Prevalence of HIV infection and AIDS in Egypt over four years of surveillance (1986-1990).

Serosurveys were conducted from April 1986 to March 1990 to determine the prevalence of HIV-1 infections among Egyptians and foreigners. Sera from 29,261 high risk individuals and blood or blood product donors in Egypt, and from 10,326 foreigners were tested for HIV-1 antibodies by a recombinant HIV-1 and a recombinant combination HIV-1/HIV-2 enzyme immunoassay (EIA). Any serum found to be repeatedly reactive by EIA was tested by Western blot for confirmation of HIV-1 infection. The overall prevalence of HIV-1 infection among the Egyptians was 0.18% (54/29,261); of which 4.8% (28/582) were blood and factor VIII recipients, 0.15% (3/1961) drug addicts, 0.18% (3/1650) fever of unknown origin patients, 0.23% (6/2602) sexually transmitted disease patients, 1.9% (5/269) HIV-1 contacts, 0.07% (7/9778) international travellers, and 0.02% (2/12,070) blood/product donors. Evidence of HIV-1 infection was not demonstrated among 349 prostitutes. The prevalence of HIV-1 antibody among foreigners was 0.97% (100/10,326), who were mainly (94%) from other African countries. Among the total 54 HIV infected Egyptians, 20 developed AIDS, and at least 12 have died. Only one of the 100 infected foreigners was diagnosed with AIDS. While the number of AIDS cases has increased in Egypt over 18 months October 1988-March 1990, the overall prevalence of new HIV infections has decreased since 1988 and endemic transmission has not been documented in Egypt.

Acquired Immunodeficiency Syndrome↗

Acute sporadic hepatitis E in children living in Cairo, Egypt.

Seventy-three pediatric patients with acute hepatitis and 19 control patients without liver disease living in Cairo, Egypt, were evaluated with a newly developed Western blot assay for IgM antibody to hepatitis E virus (IgM anti-HEV). The mean age of acute hepatitis patients was 6.4 years (range, 1-13 years); 56% were male. Among the 73 acute cases, hepatitis A was diagnosed in 30 (41%), possible acute hepatitis B in three (4%), hepatitis E in nine (12%), and by exclusion, non-A, non-B hepatitis in 29 (40%). Two additional acute cases were positive for both IgM anti-HAV and IgM anti-HEV. None of the 19 control subjects had IgM anti-HEV. Parenteral risk factors were associated with cases of non-A, non-B hepatitis but were not associated with acute hepatitis E. Contact with a family member with jaundice was associated with acute hepatitis A. In contrast to prior epidemics of enterically-transmitted non-A, non-B hepatitis, HEV was found to be a common cause of acute hepatitis in a pediatric population. This study provides additional evidence that HEV may be a frequent cause of acute sporadic hepatitis among children living in some developing countries.

Adolescent↗

Geographic diversity of human immunodeficiency virus type 1: serologic reactivity to env epitopes and relationship to neutralization.

The antibody recognition of the major neutralization epitopes of human immunodeficiency virus type 1 (HIV-1) in 829 HIV-1-seropositive subjects from North America (106), Europe (241), Africa (342), and Asia (100) was investigated. Peptides derived from diverse published V3 loop sequences were used as antigen, and serum reactivity was detected by sensitive ELISAs. Antibody binding to peptides derived from the V3 loop sequence of HIV-1 isolates varies considerably depending on the geographic origin of the antibody and is associated with neutralization titer against homologous isolates. Serotype reactivity to peptides may be a simple and rapid approach to investigation of HIV-1 env diversity worldwide and may assist the choice of immunogen for development of future AIDS vaccines.

Africa↗

Evaluation of a competitive enzyme immunoassay for detection of Coxiella burnetii antibody in animal sera.

A competitive enzyme immunoassay (CEIA) was established and compared with other serological techniques for detecting Coxiella burnetii antibody in camels, goats, and sheep. This technique was evaluated because a conjugated anti-camel immunoglobulin was not available to serve as a direct signal for the demonstration of antigen-antibody reaction. A C. burnetii antibody-positive human serum and a peroxidase-conjugated anti-human immunoglobulin G were used as an indicator system competing against antibody in animal serum or as an indicator of the absence of antibody. Sera were considered antibody positive when the A414 of the test sera plus the competing positive antibody was less than or equal to 50% of the A414 of the negative-control serum plus the competing antibody. Antibody to C. burnetii was repeatedly demonstrated in 66% of camel serum samples (n = 200) by the CEIA. Among 48 camel serum samples, 71% were positive for antibody by CEIA versus 65% by EIA using peroxidase-labeled protein A. The CEIA detected C. burnetii antibody in 63% of sheep serum samples (n = 40) and in 50% of goat serum samples (n = 96), while the indirect fluorescent-antibody technique detected antibody in 38% of sheep and 34% of goat serum samples and the EIA detected antibody in 50% of sheep and 35% of goat serum samples. These data indicate that the CEIA is a reliable and sensitive technique for demonstrating C. burnetii antibody in camels, sheep, and goats.

Animals↗

A serosurvey for HTLV-I among high-risk populations and normal adults in Egypt.

The prevalence of antibodies to human T-cell lymphotropic virus type I (HTLV-I) was determined in high-risk groups and normal adults in Egypt. Among 647 individuals tested, 6 (0.9%) were confirmed positive by western blot analysis. These included 2 (0.7%) of 279 drug addicts, 1 (3.3%) of 30 patients with sexually transmitted diseases, and 3 (2.2%) of 133 healthy individuals. Antibody was not detected in 47 blood recipients or 158 prostitutes. There was no correlation between sex or geographical location and HTLV-I infection. Fifty-three of the 647 sera (8%) were initially reactive by ELISA, but only 12 sera were repeatedly reactive. Since only 4 of these repeatedly reactive sera were confirmed by the western blot, the frequency of false positives using the DuPont screening ELISA was 1.2% (8/643). Two additional sera, confirmed positive by western blot, had been reactive, but not repeatedly, by ELISA. In comparison to the prevalence of HTLV-I antibody among risk groups in many parts of the world, the prevalence in Egypt was low.

Adolescent↗