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Biomedical subjects

A J Shepherd

Publications and source records attributed to A J Shepherd.

At least 55 records · Page 3Linked to original sources

Epidemiologic and clinical features of Crimean-Congo hemorrhagic fever in southern Africa.

Following the diagnosis in 1981 of the first case of Crimean-Congo hemorrhagic fever (CCHF) in South Africa, an antibody survey was undertaken on cattle sera to determine the distribution of the virus and specific diagnostic tests were routinely applied to specimens from suspected cases of hemorrhagic fever to establish the medical significance of its presence. Antibody to CCHF virus was demonstrated by reversed passive hemagglutination-inhibition technique in 2,460/8,667 (28%) cattle sera and in 140/180 herds tested in South Africa, as well as in 347/763 (45%) cattle sera and in 32/34 (94%) herds tested in Zimbabwe. The antibody was found in all major cattle farming areas, but was of low prevalence along the southern coast where 2 of the 3 species of Hyalomma tick which occur in South Africa are absent. From February 1981 to January 1986, inclusive, 29 indigenous cases of CCHF were diagnosed in 16 outbreaks which arose in various locations throughout South Africa. A further 2 imported cases of CCHF arose in Zaire and Tanzania. The clinical features of infection conformed to the classical descriptions of CCHF in the Soviet Union. The fatal outcome in 11/31 cases indicates that the African disease is no less severe than that which occurs in Eurasia. It is inferred that the virus is widespread in all countries in Africa and Eurasia which lie within the limits of world distribution of ticks of the genus Hyalomma.

Animals↗

Antibody to Crimean-Congo hemorrhagic fever virus in wild mammals from southern Africa.

Crimean-Congo hemorrhagic fever (CCHF) virus is becoming increasingly recognized as an important human pathogen in southern Africa. In order to determine the role of wild mammals in the natural ecology of the virus, sera from 3,772 wild mammals of 87 species and from 1,978 domestic dogs collected in South Africa and Zimbabwe between 1964 and 1985 were tested for antibody to CCHF virus by reversed passive hemagglutination inhibition (RPHI) and by indirect immunofluorescence (IF). Antibody was found to be highly prevalent in large mammals in the Orders Artiodactyla and Perissodactyla such as giraffe, Giraffa camelopardalis (3/3 positive), rhinoceros, Ceratotherium simium and Diceros bicornis (7/13), eland, Taurotragus oryx (59/127), buffalo, Syncerus caffer (56/287), kudu, Tragelaphus strepsiceros (17/78), and zebra, Equus burchelli (16/93). In small mammals antibody was found in the sera of 40/293 hares, 22/1,305 rodents, and 1/74 wild carnivores, but not in 522 primates, 176 insectivores, or 19 hyrax. Antibody was also found in the sera of 118/1,978 domestic dogs. The species of wild mammal in which antibody was distributed (with highest antibody prevalence in hares and large herbivores) reflects the feeding preference of immature and adult ticks of the genus Hyalomma, suggesting that Hyalomma sp. are the principal CCHF vectors in the wild.

Animals↗

Preparation and use of monoclonal antibodies for identifying Crimean-Congo hemorrhagic fever virus.

Seven monoclonal antibodies were prepared against a South African strain of Crimean-Congo hemorrhagic fever (CCHF) virus and were found to be directed against viral nucleocapsid protein. Five of the monoclonal antibodies reacted to high titer in indirect immunofluorescence (IF) tests and enzyme-linked immunosorbent assays (ELISA) with 22 strains of CCHF virus and failed to cross-react with the closest antigenic relative of CCHF, Hazara virus, or with 4 other nairoviruses which need to be distinguished from CCHF virus in Africa. These antibodies, used in the IF technique, readily detected antigens induced by all strains of CCHF virus included in the study in cell culture monolayers and mouse brain tissue, which represent the systems commonly used for isolation of CCHF virus. The IF technique with monoclonal antibodies constitutes a rapid and specific means of identifying newly isolated strains of CCHF virus.

Animals↗

Comparative pathogenicity and antigenic cross-reactivity of Rift Valley fever and other African phleboviruses in sheep.

Homologous and heterologous haemagglutination-inhibition (HAI), complement-fixation (CF), immunodiffusion (ID) and mouse neutralization tests were performed with the Lunyo (LUN) and a Zimbabwean strain of Rift Valley fever (RVF) virus, the prototype and a South African strain of Arumowot (AMT) virus and prototype strains of Gordil (GOR), Saint-Floris (SAF) and Gabek Forest (GF) viruses, using immune mouse ascitic fluids prepared against these viruses. Reactions of identity occurred in all tests between LUN and the Zimbabwean strains of RVF and between the two strains of AMT virus. Otherwise, cross-reactions occurred between all the phleboviruses in HAI tests, while reactions in CF, ID and neutralization tests were monospecific for virus serotypes, except that weak cross-reaction occurred between GOR and SAF viruses in CF and ID tests. Four sheep infected subcutaneously with the Zimbabwean strain of RVF virus developed transient fever, viraemia, leucopaenia, relative thrombocytopaenia, haemoconcentration and raised serum enzyme levels, which indicated that the sheep had developed necrotic hepatitis. Disseminated focal necrotic hepatitis was confirmed in a sheep killed for examination on day 4 post-infection. The other three sheep recovered uneventfully after only mild depression and anorexia. Groups of three sheep infected with SAF, GOR, AMT and GF viruses had no demonstrable viraemia or other sign of infection or illness, except that the sheep infected with AMT developed mild fever lasting less than 24 h. Antibody responses were monitored at intervals over a period of 24 weeks in all sheep by homologous and heterologous HAI, CF and cell culture neutralization (CPENT) tests. Homologous antibody responses were marked in the RVF-infected sheep and their sera cross-reacted strongly in HAI tests with antigens of the other viruses. The sera of the RVF-infected sheep cross-reacted less markedly in CF and CPENT tests. Homologous antibody responses were poor in all the sheep infected with phleboviruses other than RVF, and the cross-reactivity of their sera for RVF antigen or virus was negligible. All sheep were challenged with RVF virus 48 weeks after their initial infection. The sheep which had originally been infected with RVF virus were immune and developed neither fever nor viraemia. All other sheep developed fever, viraemia and antibodies to RVF virus. It was concluded that the African phleboviruses, other than RVF, are unlikely to cause disease in livestock or to induce antibodies which could cause confusion in the diagnosis of RVF.

Animals↗

Experimental plague infection in South African wild rodents.

Susceptibility studies were undertaken to determine the response of some South African wild rodent species to experimental plague (Yersinia pestis) infection. A degree of plague resistance was found in three gerbil species captured in the plague enzootic region of the northern Cape Province, these being the Namaqua gerbil, Desmodillus auricularis, (LD50 1 X 10(6) organisms), the bushveld gerbil, Tatera leucogaster, (LD50 9.1 X 10(5)) and the highveld gerbil, T. brantsii (LD50 4 X 10(2)). Animals from a population of the four-striped mouse, Rhabdomys pumilio, captured in the plague area of Port Elizabeth, proved moderately resistant to experimental plague infection (LD50 1.3 X 10(4)) while those from another population of the same species captured in a plague-free area of the Orange Free State were extremely susceptible (LD50, 5 organisms). The response of both populations however was a heterogeneous one. Marked differences in susceptibility were also found between two populations of multimammate mice, Mastomys natalensis (2n = 32) although both originated from areas outwith the known distribution of plague in southern Africa. The 50% infectious dose was relatively high in T. leucogaster (3.2 X 10(2)) and D. auricularis (1.7 X 10(3)), but was low (2-16 organisms) in the other rodent species tested. The plague antibody response, determined by enzyme-linked immunosorbent assay (ELISA), was extremely short-lived in T. leucogaster, only 10% of inoculated animals remaining seropositive at low titres after 11 weeks. Antibodies persisted for only slightly longer in the sera of T. brantsii which were reinoculated with 2 X 10(3) plague organisms 6 weeks after initial challenge. The demonstration of the existence of both susceptible and resistant populations of R. pumilio and M. natalensis indicates that these species must be considered as potential plague reservoir hosts in parts of South Africa. The results suggest that resistance to plague infection in previously epizootic hosts in the northern Cape Province such as Tatera sp. and D. auricularis has arisen through continual selective pressure of the organism. If the findings are applicable to gerbil populations in other plague enzootic regions of South Africa it is probable that acquired plague resistance has been responsible for the absence of gerbil epizootics and consequently for the dramatic decline in human plague outbreaks in South Africa since 1950.

Animals↗

Comparison of methods for isolation and titration of Crimean-Congo hemorrhagic fever virus.

The fluorescence focus assay and the plaque assay in CER cells were compared with mouse inoculation for the isolation and titration of Crimean-Congo hemorrhagic fever virus. The fluorescence focus assay and the plaque assay were of similar sensitivity, but both produced 10- to 100-fold lower titers than did mouse inoculation. For specimens from 26 Crimean-Congo hemorrhagic fever patients in South Africa, virus was isolated from 20 by mouse inoculation and from only 11 by cell culturing. Although cell cultures were less sensitive for the isolation of virus from clinical specimens, they produced diagnostic results much more rapidly.

Animals↗

Comparative tests for detection of plague antigen and antibody in experimentally infected wild rodents.

The enzyme-linked immunosorbent assay (ELISA) was compared with other standard tests for detection of plague (Yersinia pestis) antibody and antigen in multimammate mice (Mastomys coucha and M. natalensis) which were experimentally infected and then killed at daily intervals postinoculation. For detection of antibody in sera from M. natalensis, the immunoglobulin G (IgG) ELISA was equivalent in sensitivity to passive hemagglutination and more sensitive than the IgM ELISA and complement fixation. Antibody was first detected on postinfection day 6 by all four tests, but IgM ELISA titers had declined to undetectable levels after 8 weeks. For detection of fraction 1 Y. pestis antigen in rodent organs, the ELISA was less sensitive than fluorescent antibody but more sensitive than complement fixation or immunodiffusion. Plague fraction 1 antigen was detected in 16 of 34 bacteremic sera from M. coucha and M. natalensis. The threshold sensitivity of the ELISA was approximately 10(5) Y. pestis per ml.

Animals↗

A nosocomial outbreak of Crimean-Congo haemorrhagic fever at Tygerberg Hospital. Part V. Virological and serological observations.

A nosocomial outbreak of Crimean-Congo haemorrhagic fever occurred in Tygerberg Hospital near Cape Town in September 1984 when 7 medical personnel became ill after admission of an index patient. The disease was fatal in the index and 1 secondary case, and was confirmed in the index and 6 secondary cases by isolation of the virus. An antibody response was demonstrated in the remaining patient, thought to be a tertiary case, but the fact that the patient received immune plasma therapy raises doubts about the validity of the diagnosis. The index case had contact with ticks and horses but his infection could not be related to a specific incident.

Antibodies, Viral↗

A common-source outbreak of Crimean-Congo haemorrhagic fever on a dairy farm.

An outbreak of Crimean-Congo haemorrhagic fever (CCHF) on a dairy farm in the Orange Free State in 1984 is described. Forty-six cows were purchased from the western Cape Province in January 1984; 2 died from the tick-borne disease anaplasmosis in March and a labourer who helped butcher the carcasses became ill a few days later. Another cow died at the end of April and within 9 days 4 people who had come into contact with its blood became ill. Antibodies to CCHF virus were found in the sera of the 5 patients but not in other residents of the farm. Three patients recovered from a severe influenza-like illness without seeking medical attention; 1 patient, who was admitted to hospital, recovered from illness marked by haematemesis, epistaxis and amnesia and the 5th patient died of complications of surgery for brain haemorrhage. Antibody studies indicated that many of the cows became infected with CCHF after their arrival on the farm. It can be deduced that animals reared in tick-free, or relatively tick-free, circumstances, which are then moved to where they are subject to heavy parasitization by ticks, can acquire common tick-borne diseases of livestock plus CCHF infection simultaneously. In such circumstances there is a definite risk of human exposure to CCHF-infected blood or other tissues.

Adolescent↗

Investigations following initial recognition of Crimean-Congo haemorrhagic fever in South Africa and the diagnosis of 2 further cases.

Sera from 124 cattle herds were tested, and antibodies to Crimean-Congo haemorrhagic fever (CCHF) were found in 93 herds. The prevalence of antibodies was high in the interior of the country, in excess of 90% in some herds, but was less than 4% in cattle along the coast from Cape Town to East London. Only 17 out of 1109 (1,5%) human residents of 55 farms had antibodies to CCHF, while none of 164 veterinary research workers or 98 veterinarians engaged in farm animal practice had them. Specimens from 130 suspected cases of viral haemorrhagic fever were examined and CCHF was diagnosed only in the patient previously reported as the first case of the disease to be recognized in this country. A further 2 cases of CCHF were diagnosed by examining 318 specimens from patients with nonfatal febrile illness. Both patients had contact with livestock. Increasing awareness of the disease will probably lead to an increase in the number of cases diagnosed, but there are no grounds for concluding that the disease is on the increase.

Adult↗

Nuchal cord as a cause of neonatal anemia.

Nuchal cord was documented in 437 neonates consecutively admitted to the newborn nursery at The University of Texas Medical Branch Hospital, Galveston. The prevalence of anemia in the nuchal cord group (venous hemoglobin level of less than 13.2 g/dL or hematocrit of less than 39.2%) was compared with that in a control group. None of the controls was anemic. Five of 27 neonates with tight nuchal cord and four of 30 with loose nuchal cord were anemic. Anemia in the tight nuchal cord group was usually observed early, and in three infants was manifest by hypotension, necessitating transfusion. Anemia associated with loose nuchal cord occurred later and was asymptomatic. This study emphasizes the increased risk of anemia associated with nuchal cord and demonstrates the need for hemoglobin and hematocrit determinations in neonates with this obstetrical complication.

Anemia, Neonatal↗

A comparison of serological techniques for plague surveillance.

Sera collected from 691 dogs and 231 rodents in South Africa were tested in parallel by the passive haemagglutination (PHA) and enzyme-linked immunosorbent assay (ELISA) for antibodies to the Fraction 1 antigen of the plague bacillus (Yersinia pseudotuberculosis subsp. pestis). There was a high degree of correlation between the tests, both in over-all numbers positive and in serum titres. 42 dog sera were positive by PHA and 41 by ELISA, 40 sera being positive by both tests. However, using ELISA the numbers of non-specific reactors in dog sera were cut by almost two thirds compared to PHA. The results of tests on rodent sera were identical: only one rodent was positive in both tests. The findings suggest that the ELISA test may have advantages over PHA for large scale serological surveillance.

Animals↗

Plague in South African rodents 1972-1981.

Sera from 3012 rodents of 24 species captured in South Africa during the period 1972-81 were tested for antibody to the Fraction 1 antigen of Yersinia pestis by passive haemagglutination. Antibodies were found in seven (0.23%) rodents of three species. These were Desmodillus auricularis and Tatera brantsii in the northern Cape Province and Rhabdomys pumilio in the eastern Cape Province. Rodents were found positive in 1972, 1974, 1975 and 1979, indicating that plague continues to circulate in rodent populations apparently without causing human cases. The significance of the results is discussed in relation to plague outbreaks in neighbouring countries and to the 1982 outbreak in South Africa.

Animals↗

Studies on plague in the eastern Cape Province of South Africa.

Investigations were carried out in the area of a human plague outbreak in March 1982 at Coega in the eastern Cape Province of South Africa. Trapping revealed that rodent populations were high owing primarily to a population increase of the four-striped mouse, Rhabdomys pumilio. Flea populations were low and had been declining in the eastern Cape Province since October 1981. The results of a serological survey from March to October 1982 showed haemagglutinating antibody to Yersinia pestis in 0.35% of 5938 dog sera and 0.53% of 1132 small mammal sera. Plague antibody was detected in two small mammal species, R. pumilio and the vlei rat, Otomys irroratus. There was thus evidence that a small, limited rodent epizootic preceded the human plague cases and it appears that at least one human case was contracted from an infected domestic cat. The extent of the enzootic area was confined to a coastal belt north of Port Elizabeth and showed a close correlation with river courses. It was concluded that the Port Elizabeth-Uitenhage focus was in an inter-epidemic phase and that the human plague outbreak was an isolated incident.

Animals↗

Crimean-congo hemorrhagic fever in South Africa.

Crimean-Congo hemorrhagic fever virus was isolated for the first time in South Africa in February 1981, from the blood of a 13-year-old boy who died in Johannesburg after attending a camp in a nature reserve in the western Transvaal. Virus was isolated from 21/120 pools of questing ticks from the nature reserve, the infected species being Hyalomma marginatum rufipes and H. truncatum. Virus was also isolated from 4/38 pools of partially engorged ticks and other ectoparasites collected off hosts, the infected species being H.m. rufipes, H. truncatum and Rhipicephalus evertsi. Antibodies were found in the sera of 5/74 humans, 8/26 wild vertebrates, 74/270 sheep, and 109/170 cattle from the reserve and surrounding farms. Antibodies were also found in 28/200 hares from various locations in the country. It was concluded that the virus is widely prevalent in South Africa, but the full medical and veterinary significance of its presence has yet to be determined.

Adolescent↗

Isolation of Pasteurella pneumotropica from rodents in South Africa.

Four thousand, five hundred and sixteen rodents of 27 species were captured in widely separated localities in South Africa over a period of ten years. Samples of spleen, lung, heart, liver and rectal tissue with faeces were tested for the presence of zoonotic bacteria and 109 isolations of Pasteurella pneumotropica were made from 11 species. Latent infection with the organism was found to be widespread although there were temporal fluctuations in prevalence. Field and laboratory evidence suggest that P. pneumotropica may be associated with, but not the primary cause of, rodent epizootics in the wild.

Animals↗

Defective platelet lipid peroxidation in myeloproliferative disorders: a possible defect of prostaglandin synthesis.

Platelet lipid peroxidation induced by the sulphydryl blocking reagent n-ethylmaleimide [NEM] was measured by production of malonyldialdehyde [MDA]. Lipid peroxidation was decreased in five of 10 patients with proven myeloproliferative disease. The low levels of lipid peroxidation correlated well with in vitro and in vivo tests of platelet function and the bleeding and bruising problems. The reduction in lipid peroxidation with NEM may be due to one or more of the following: [i] an aged platelet population; [ii] an abnormal cell line; [iii] a reduction of the cyclo-oxygenase enzyme activity in the platelet prostaglandin synthetic pathway; [iv] a reduction of the substrate for platelet prostaglandin synthesis, Arachidonic acid; and [v] an abnormality of phospholipase A activation.

Blood Platelet Disorders↗