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Biomedical subjects

D B Hall

Publications and source records attributed to D B Hall.

At least 37 records · Page 2Linked to original sources

Rift Valley fever in rural northern Senegal: human risk factors and potential vectors.

To investigate past infection in and transmission of Rift Valley fever (RVF) virus to humans within an endemic focus, we undertook a retrospective cohort study of the seminomadic Peul people living in sub-Saharan northcentral Senegal. Residents of the rural settlement of Yonofere five years of age or older were studied during February-May 1989. Anti-RVF virus IgG was found in blood samples of 22.3% of 273 persons who responded to a standard questionnaire; none had IgM antibodies. Seropositivity was similar for males (25.4%) and females (21.1%), increased markedly with age for both sexes, and varied considerably among compounds (groups of huts) (0-37.5%). Risk factors for past RVF virus infection were nursing sick people, assisting animals during abortions/births, and treating sick animals. In all age groups, odds ratios (ORs) for RVF viral antibody among females who reported treating sick animals were three to six times greater than for those who did not. The ORs for males who reported assisting with animal births/abortions and nursing sick people were approximately five times those for males who did not. Serologic prevalence of RVF viral antibody among sheep averaged 30.1% overall (0.8% IgM), but varied among compounds (0-66.7%) in a manner different from that of humans. The seasonal abundance and relative density of potential mosquito vectors were estimated by monthly samples captured in Centers for Disease Control and Prevention-type traps. Mosquito abundance varied seasonally with rainfall (> 90% captures during four months). Species diversity was large (28 spp.), dominated by Aedes and Culex. Rift Valley fever virus was not isolated from 142 pools of 2,956 unengorged mosquitoes tested, although three other arboviruses were found. Results indicate that RVF is endemic in this region, people are at considerable risk of infection, and that a heretofore unrecognized mode of human infection under nonepizootic conditions may be transmission via contact with infected animals or humans.

Adolescent↗

Confidence intervals and controlled clinical trials: incompatible tools for medical research.

The probabilistic rationale for statistical design and analysis of clinical trials is random assignment. While arithmetic and mathematical formulations may be identical to those used with random samples, we should not indiscriminately borrow tools from survey sample methods. Specifically, the confidence interval should be used sparingly, if at all. Observations have an internal validity, within the clinical trial, with no basis for claims of quantitative external generalizability. Confidence intervals encourage an unnecessary dependence on statistical analysis when the careful design should allow the data to speak for itself. Confidence intervals encourage a statistical focus and statistical conclusions that ignore scientific context and misrepresent relationships among results from related research. The clinician is presented with information about population parameters when facing confidence intervals. These do not address questions about treatment and prognosis of an individual patient. Confidence intervals are particularly distracting when a clinical trial has failed to produce anticipated results. The clinical trial is the model research tool for clinical medical research, founded on randomization. The confidence interval is a statistical tool for parameter estimation based on population sampling concepts. These tools are incompatible.

Clinical Trials as Topic↗

Urban epizootic of rabies in Mexico: epidemiology and impact of animal bite injuries.

From 1 July 1987 to 31 December 1988, a total of 317 animals (91% of which were dogs) were confirmed to have rabies in Hermosillo, Mexico. The median age of rabid dogs was 1 year, 69% were male, and 98% were owned. The epizootic started in the southern areas of the city, rapidly involved the entire city, and persisted mainly in lower socioeconomic status areas. The area of the city and mean household size were significant predictor variables for the population density of rabid dogs around household clusters (Poisson linear regression, P < 0.001 and P = 0.03, resp). Approximately 2.5% of city residents were bitten by dogs in 1987, with the rate of reported dog bite injuries being positively correlated with mean household size and the proportion of households that owned dogs. Visits to the city health centre for evaluation of possible exposures to rabies increased by 135% after the start of the epizootic; approximately 273 per 100,000 city residents were administered a full or partial course of rabies post-exposure prophylaxis in 1987. Children were at greatest risk for exposures to rabies, accounting for 60% of all reported animal bite injuries evaluated at the health centre. Also they were more likely than older persons to have received bite injuries to the head, face, and neck (odds ratio = 21.6, 95% confidence interval = 5.4, 186.5).

Adult↗

Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children.

From January, 1988, to March, 1989, a widespread outbreak (118 cases) of poliomyelitis type 1 occurred in Oman. Incidence of paralytic disease was highest in children younger than 2 years (87/100,000) despite an immunisation programme that recently had raised coverage with 3 doses of oral poliovirus vaccine (OPV) among 12-month-old children from 67% to 87%. We did a case-control study (70 case-patients, 692 age-matched controls) to estimate the clinical efficacy of OPV, assessed the immunogenicity of OPV and extent of poliovirus spread by serology, retrospectively evaluated the cold chain and vaccine potency, and sought the origin of the outbreak strain by genomic sequencing. 3 doses of OPV reduced the risk of paralysis by 91%; vaccine failures could not be explained by failures in the cold chain nor on suboptimum vaccine potency. Cases and controls had virtually identical type 1 neutralising antibody profiles, suggesting that poliovirus type 1 circulation was widespread. Genomic sequencing indicated that the outbreak strain had been recently imported from South Asia and was distinguishable from isolates indigenous to the Middle East. Accumulation of enough children to sustain the outbreak seems to have been due to previous success of the immunisation programme in reducing spread of endemic strains, suboptimum efficacy of OPV, and delay in completing the primary immunisation series until 7 months of age. Additionally, the estimated attack rate of infection among children aged 9-23 months exceeded 25% in some regions, suggesting that a substantial proportion of fully vaccinated children had been involved in the chain of transmission.

Case-Control Studies↗

Risk factors for Crimean-Congo hemorrhagic fever in rural northern Senegal.

The extent of infection among 722 residents of an enzootic focus of Crimean-Congo hemorrhagic fever (CCHF) virus in rural northern Senegal and putative modes of transmission were studied by a cross-sectional seroprevalence survey done from February through May 1989. Anti-CCHF virus IgG was found in 13.1% of 283 persons who completed a standard questionnaire and provided blood samples. Seropositivity rates were similar between sexes and increased significantly with age among nomadic persons. Behavior patterns providing exposure to multifactorial risk factors were gender-based. Male risk factors, primarily associated with herding activities, included sleeping outside during seasonal migrations (also a risk factor for nomadic women), bite by a tick (adult male Hyalomma truncatum), tick bite during the cool dry season, and contact with sick animals. Human infection of CCHF occurred more frequently or with less mortality in the region studied than has been found elsewhere in Africa; however, the rate of seroconversion-associated illness is undetermined. Hyalomma ticks appear to be the primary transmission mode.

Adolescent↗

Occupational risk of human parvovirus B19 infection for school and day-care personnel during an outbreak of erythema infectiosum.

Human parvovirus B19, the cause of erythema infectiosum, has recently been associated with adverse fetal outcomes. During a large outbreak of erythema infectiosum in Connecticut, a survey was conducted on 571 (90%) of 634 school and day-care personnel to determine the risk of acquiring B19 infection. Serologic evidence of B19 infection was determined by using an enzyme-linked immunosorbent assay. Of the school and day-care personnel, 58% had evidence of previous B19 infection. The minimal rate of B19 infection in susceptible personnel during the outbreak was 19%. The risk was increased for teachers and day-care providers who had contact with younger children and with greater numbers of ill children. These results suggest that B19 infection is an occupational risk for school and day-care personnel.

Adult↗

Duration of immunogenicity and efficacy of hepatitis B vaccine in a Yupik Eskimo population.

In 1981, a hepatitis B virus vaccine demonstration project was conducted in 1630 Yupik Eskimos in southwest Alaska. Levels of antibody to hepatitis B surface antigen and markers for hepatitis B virus infection in vaccinees were monitored yearly for 5 years. After 5 years of follow-up, 19% of those who initially had an immune response to vaccine of 10 sample ratio units or greater subsequently had levels of antibody to hepatitis B surface antigen lower than 10 sample ratio units. During the 5 years after the first dose of vaccine, in three responders and one person with an antibody to hepatitis B surface antigen response lower than 10 sample ratio units, antibody to hepatitis B core antigen developed, and the level of antibody to hepatitis B surface antigen was boosted. Hepatitis B surface antigen did not develop in any subjects, and none had clinical hepatitis. In the 5 years following the demonstration project, the annual incidence of hepatitis B virus infection decreased from 50 cases per 1000 population before the vaccine trial to 0.45 per 1000.

Adolescent↗

Analysis of surveillance data: a rationale for statistical tests with comments on confidence intervals and statistical models.

In the examination of differences between subgroups in surveillance data, whether through simple counting or through sophisticated statistical modelling, the comparison is not between simple random samples from two or more populations. The rationale for statistical tests rests on an appeal to a model of random permutation of demographic and disease factors for the observed population during the surveillance period. The testing evaluates chance as a possible explanation for the observed results. In the analysis of internal structure in a surveillance data set, statistical tests produce a conceptually simple result that lends itself to concise presentation and flexible interpretation. Tests limit emphasis on probabilistic manipulation and on parameter estimates. They cannot stand alone, and thus encourage descriptive presentation of observations. In contrast, statistical models and confidence intervals emphasize parameters rather than distributions and compete with the data for limited space.

Data Interpretation, Statistical↗

An epidemic of acute hemorrhagic conjunctivitis in American Samoa caused by coxsackievirus A24 variant.

Between May 25 and July 5, 1986, an epidemic of acute hemorrhagic conjunctivitis affected an estimated 47% of the population on American Samoa. Coxsackievirus A24 variant was isolated from 18 of 22 patients. This is the first documented outbreak of acute hemorrhagic conjunctivitis due to coxsackievirus A24 variant outside of Southeast Asia and the Indian subcontinent. When this outbreak was compared with an outbreak on the island in 1981-1982 caused by enterovirus 70, conjunctival hemorrhage or injection and the severity of hemorrhage were less prevalent among cases in 1986, while upper respiratory and systemic symptoms were more common. Residents of traditional housing had significantly higher attack rates (48%) than residents of government housing (23%). Serum specimens collected from the residents of Samoa in 1985, before the outbreak, unexpectedly revealed the presence of neutralizing antibodies against coxsackievirus A24 variant. The presence of these antibodies correlated with protection against coxsackievirus A24 variant infection in this outbreak.

Adolescent↗

Pharyngeal carriage and acquisition of anticapsular antibody to Haemophilus influenzae type b in a high-risk population in southwestern Alaska.

Haemophilus influenzae type b disease in Alaskan Eskimos is characterized by greatly increased disease incidence at younger ages. This suggests that Eskimo infants have increased exposure to the disease. Exposure was studied in 1982-1983 in children less than age three years who lived in four Eskimo villages, as well as in a random sample of their family members (354 people from 132 households). During a 12-month period, up to four pharyngeal cultures and two serum specimens were obtained from each participant. Colonization with H. influenzae type b was relatively uncommon (overall 2.5% of cultures, 6.8% of individuals) and was not associated with age, sex, season, or prior incidence of disease in the village. Biotyping and outer-membrane-protein typing of H. influenzae type b isolates revealed homogeneity within villages, with differences between villages. Matched sera revealed a significant decline in H. influenzae type b capsular antibody in the course of the study year. However, pharyngeal carriage of H. influenzae type b was associated with increases in antibody for carriers and members of their households. Antibody levels were positively associated with age. Only one case of H. influenzae type b disease developed during the study. Low carriage of H. influenzae type b was coincident with low incidence of disease and declining levels of capsular antibody in these villages. Mechanisms for increased exposure which would not be reflected in high carriage rates may exist for these young children.

Adolescent↗

Invasive Haemophilus influenzae type b disease in Alaska: background epidemiology for a vaccine efficacy trial.

In a previous study we demonstrated that Alaskan Eskimos had the highest endemic incidence of invasive Haemophilus influenzae type b (Hib) disease. In 1980 we established a prospective surveillance program for all invasive Hib disease throughout Alaska to characterize additional epidemiological features of disease in Native Alaskans to plan for a vaccine efficacy trial and define the epidemiology of Hib disease in all population groups in the state. For the three-year period, 1980-1982, 287 confirmed episodes of invasive Hib disease occurred. For children less than five years of age, the incidences for Eskimos, Indians, and non-Natives were 705, 401, and 129 cases per 100,000 population, respectively. The Native population represents only 16% of the population of Alaska but has 51% of all invasive Hib disease. Disease differed significantly among Eskimos, Indians, and non-Natives with regard to risk, age of onset, disease type, antibiotic susceptibility of strains, and regional incidence, but mortality and seasonal occurrence were similar. For Native Alaskans the cumulative Hib disease risk for the first two years of life was 4% (range, 1%-7% by region). This high endemic disease risk, concentrated in the first two years of life, provides a unique opportunity to prospectively evaluate the protective efficacy of a vaccine in a randomized, blinded, and placebo-controlled trial. Such a trial was initiated in December 1984.

Adolescent↗

Uridine monophosphate kinase 3: a genetic marker for susceptibility to Haemophilus influenzae type B disease.

Alaskan Eskimos have the highest known prevalence of invasive Haemophilus influenzae type b (Hib) disease, primarily meningitis, affecting 1-5% of all children in the first two years of life. In this population a polymorphic genetic variant of the pyrimidine pathway enzyme, uridine monophosphate kinase-3 (UMPK-3), was found to be positively associated with invasive Hib disease (relative risk 3.3) and a tendency towards a younger age at onset of illness. There was no difference in levels of naturally acquired Hib anticapsular antibody between persons with Hib disease and healthy controls in this population. This suggests that UMPK-3 may have a role in mediating non-humoral immunity to Hib. However, unlike other enzyme variants in the nucleoside synthesis pathways which result in syndromes of severe immunodeficiency, this gene appears to confer a more subtle disease susceptibility.

Age Factors↗

Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state.

Yupik Eskimos of southwestern Alaska have the highest known prevalence of hepatitis B virus infection of any general population in the United States. Prospective serological surveys of 1,280 seronegative Yupik Eskimos, performed between 1971 and 1976, identified 189 (14.8%) who developed serological evidence of hepatitis B virus infection. Twenty-six (13.8%) developed clinical hepatitis during the interval when seroconversion occurred. The proportion of patients with clinically apparent hepatitis increased with age (P less than .01), ranging from 9.5% of infections in patients who were four years of age or less to 33.3% of infections in patients who were 30 years of age or older. Twenty-five (13.3%) of the 188 individuals who were studied became chronic carriers of hepatitis B surface antigen. The risk of becoming a carrier was inversely related to the age of the patient at the time of infection (P = .02). Among patients who were four years of age or less when infected, 28.8% became chronic carriers of hepatitis B, as compared with 7.7% of those who were 30 years of age or older.

Acute Disease↗

The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma.

One hundred fifty asymptomatic patients who were carriers of hepatitis B surface antigen (HBsAg) were studied serologically for up to 11.3 years (mean, 6.1 years). Only 9 (6.0%) lost HBsAg during the study period, for a mean annual clearance rate of 1.0%. We found no difference in the clearance of HBsAg by age, but a higher percentage of females lost HBsAg than did males (P less than .02). Hepatitis B e antigen (HBeAg) was found in 102 (68.5%) of the 149 carriers of HBsAg who were tested. Carriers of HBsAg who were seropositive for HBeAg were younger than those who were seronegative for HBeAg (P less than .01). The prevalence of HBeAg was not affected by the patients' sex. The clearance of HBeAg was gradual; 9.6% of the HBsAg carriers lost HBeAg each year. Females were more likely to clear HBeAg than were males (P less than .01), and those who cleared HBeAg were older than those who did not (P less than .01). Three (2.0%) of the HBsAg carriers developed primary hepatocellular carcinoma during the study period.

Adolescent↗

The control of hepatitis B virus infection with vaccine in Yupik Eskimos. Demonstration of safety, immunogenicity, and efficacy under field conditions.

In 1981, a hepatitis B vaccine demonstration project was initiated among Yupik Eskimos of southwest Alaska to demonstrate that, under field conditions, the vaccine was safe, immunogenic, and efficacious. Laboratory tests for serologic markers of hepatitis B virus infection (HBsAg, anti-HBs, and anti-HBc) performed on sera collected in May 1981 from 3,988 residents of 17 remote Eskimo villages revealed that 2,645 (66.3%) had no evidence of hepatitis B virus infection. Because of a limited supply of vaccine, specific criteria for selection were used so that those at highest risk of infection would be immunized first. In November 1981, the first dose of vaccine was administered to 1,693 carefully selected individuals. The second dose was administered to 1,678 (99.1%) of those who received the first dose, and the final dose was administered to 1,630 persons (96.3%). Serologic follow-up showed the vaccine to be safe (0.4% experienced minor adverse reactions) and immunogenic (97.4% developed antibody). Vaccine-induced antibody levels were significantly higher for persons less than 30 years of age (p less than 0.001) and for females (p less than 0.001). Vaccine recipients were also protected from hepatitis B virus infection (p = 0.002). This public health measure proved to be feasible and effective in this remote arctic population despite difficult conditions for delivery and administration of this temperature-sensitive vaccine. This strategy for immunization is now being applied on a larger scale in Alaska as part of a program for the primary prevention of this infection and its sequelae.

Adolescent↗

High prevalence of myopia among young adult Yupik Eskimos.

Myopia is common in Western populations but is considered rare in nonindustrialized population groups. However, studies in undeveloped areas of the Arctic and sub-Arctic have demonstrated increased rates of myopia among young Inuit adults indigenous to the region. We examined the refractive status of Yupik Eskimos, a group that had not previously been evaluated. Our subjects were young adults born between November 1960 and December 1962 to persons living in 10 villages in southwestern Alaska. The refractive status was obtained for 92% of these persons. The prevalence of myopia (refractive error -0.50 D or greater) was 68%, a rate among the highest reported for a general population anywhere in the world. The young women were significantly more myopic than the young men (mean refractive errors -1.91 and -1.36 D respectively). Astigmatism and myopia were positively correlated (r = 0.20, p less than 0.01). The etiology of myopia in this population is under study.

Alaska↗

Prevalence of hepatitis B in selected Alaskan Eskimo villages.

Sera collected in 1973-1975 from 3053 residents of 12 selected Alaskan Eskimo villages were tested for evidence of hepatitis B virus infection. Overall, hepatitis B surface antigen (HBsAg) was found in 6.4% of those tested. Evidence of hepatitis B infection (positive for HBsAg or antibody to hepatitis B surface antigen (anti-HBs] varied considerably by village, from 4.6% to 69.9%, and increased with advancing age. The proportion with HBsAg was significantly higher in those under the age of 13 years, and the male/female ratio varied from 0.9 to 1.5 to 1.5 in the prepubertal, postpubertal-premenopausal, and postmenopausal age groups, respectively. The prevalence of hepatitis B e antigen (HBeAg) in HBsAg-positive persons decreased with advancing age, and conversely, the prevalence of antibody to hepatitis B e antigen (anti-HBe) increased with age. Hepatitis B infection was found to be sporadically distributed, with great village-to-village variation and further variation by household within most villages. The high HBsAg and HBeAg seropositivity observed in children suggests that children are both more recently infected with hepatitis B and are more involved in hepatitis B transmission in these villages.

Adolescent↗