Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part I. Clinical and neurological observations.

Four laboratory workers from the same vaccine-packing facility developed at different times over an 8-year period an illness characterised by encephalitis (in 3 workers) and uveochorioretinitis (in 4). Low complement fixation titres were detected in all 4 patients to African horsesickness (AHS) virus and enzyme immunoassay and plaque reduction neutralising tests were positive, the latter against both serotypes 1 and 6. Five of 15 laboratory workers from the same facility who were healthy on clinical and ophthalmological examination showed positive plaque reduction neutralising tests but none to both serotypes 1 and 6. It is postulated that the encephalitis with the predominant temporal lobe involvement was caused by an airborne transnasal route of infection of the neurotropic AHS virus released in dried powder form, secondary to the accidental breaking of vaccine bottles. This is possibly the first report of subclinical and probable clinical neurotropic AHS infection in man.

Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part IV. Experimental infection of the vervet monkey (Cercopithecus pygerythrus).

Neurotropic vaccine strains of African horsesickness (AHS) virus types 1 and 6 were implicated as the possible aetiological agents in 4 cases of encephalitis and uveochorioretinitis in laboratory workers accidentally exposed to the freeze-dried vaccine preparations of the virus. To date, AHS virus has not been known to infect man. To ascertain whether or not primates were susceptible to infection with AHS virus, vervet monkeys (Cercopithecus pygerythrus) were inoculated, either transnasally or intraconjunctivally, with vaccine strains of AHS virus types 1 and 6. The course of infection was monitored using parameters such as behavioural changes, febrile reaction, cerebrospinal fluid pleocytosis, serology, magnetic resonance imaging and autopsy. Encephalitis, manifested by varying degrees of fever, behavioural changes and pleocytosis, but no chorioretinitis was detected in all 6 transnasally infected monkeys. This was confirmed by autopsy, where a meningo-encephalitis affecting the medial temporal lobe but no lesions in the eyes was demonstrated. Neither virus appeared to infect the animals after intraconjunctival inoculation. These findings support the theory that the patients were infected by the inhalation of freeze-dried vaccine preparations. The pathogenesis of the eye lesions, however, remains uncertain.

An experimental assessment of the tampan tick Ornithodoros moubata as vector of hepatitis B virus.

Wild-caught and colonized tampan ticks, Ornithodoros moubata (Murray), were fed on hepatitis B virus (HBV)-positive blood-means in a series of four experiments. Hepatitis B surface antigen (HBsAg) persisted in nymphal and adult ticks for up to 779 days, while the epsmark antigen (HBeAg) persisted in mature nymphs up to 13 days, in adult males up to 11 days and in adult females up to 16 days. HBsAg was transmitted trans-stadially through two moults during the life cycle but transovarial transmission did not occur. The surface antigen was transmitted by two out of fifteen single ticks into 0.4 ml aliquots of HBV-negative blood, although six groups of ticks failed to transmit into 5.5 ml aliquots of blood: this antigen was not transmitted to hamsters. HBsAg was detected in samples of the ticks' coxal and rectal fluid secretions always at the infecting feed and usually at the second feed. HBeAg was only detected in one of two samples of coxal fluid collected at the infecting feed. The results as a whole indicate that no biological multiplication of virus occurs in O.moubata but that mechanical transmission from ticks to man could occur by: (i) contamination of a person when crushing infected ticks; (ii) infection by bite; (iii) contamination with coxal fluid, especially by scratching bites. This is thought to take place among the Kavango tribe in their village huts in north-eastern Namibia where infestations of infected O.moubata occur.

Rubella--a case for immunising male adolescents.

An outbreak of rubella at a training institution for predominantly adolescent males is described. The cost and inconvenience of the outbreak furnish evidence that immunisation in its own right is worth while, and should not be seen only as a means of protecting susceptible females of child-bearing age.

The spectrum of complement-fixing antinuclear antibodies in patients with hepatocellular carcinoma.

Sera from 230 hepatocellular carcinoma patients were tested for antinuclear antibodies by anticomplement immunofluorescence in 16 types of transformed, diploid or primary cells of human, monkey, chimpanzee or rat origin. As controls, we tested 85 sera from patients with chronic liver diseases, 48 sera from patients with nonhepatic cancers and 164 sera of normal controls. Exactly 11.2% of all cancer patients but only 3.6% of noncancer patients had complement-fixing antinuclear antibody that reacted with all substrates. Only sera from hepatocellular carcinoma reacted with subsets of the tumor cell substrates. These sera reacted with hepatocellular carcinoma cells and nonhepatic cancer cells (antitumor) or only with one or more of the human hepatocellular carcinoma cell lines, PLC/PRF/5, Hep3B and Mahlavu, that were derived from HBsAg-positive patients (antihepatocellular carcinoma). Three of these reacted only with hepatitis B virus DNA-positive cells (PLC/PRF/5 and Hep3B) that contained "hepatitis B-associated nuclear antigen," 1 reacted only with hepatitis B virus DNA-negative Mahlavu cells, 1 reacted with PLC/PRF/5 and Mahlavu and 3 reacted with all 3 cells. The nuclear antigen in Mahlavu was expressed as a homogeneous fluorescence that spared the nucleoli, was present in a lower percentage of cells than hepatitis B-associated nuclear antigen and was more thermostable than hepatitis B-associated nuclear antigen. However, it resembled hepatitis B-associated nuclear antigen in kinetics of expression and susceptibility to digestion with DNase, RNase and proteinase K. The nature of the nuclear antigens in the hepatocellular carcinoma cells is poorly understood but one possibility is that they may represent the expression of viral or tumor-related genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of hepatitis virus and some arbovirus infections in Kavango, northern SWA/Namibia.

A survey of the frequency of hepatitis B markers in 258 subjects from Kavango, northern South West Africa/Namibia, was undertaken during February - May 1983. The hepatitis B surface antigen and hepatitis B e antigen carrier rates were 13,6% and 2,7% respectively. Only 1,9% of the subjects were negative for all the markers tested, indicating that infection had been present at some stage in 98,1% of the sample. No known transmission method of the virus seems to fit this high exposure rate. The possibility that arthropod transmission of the virus may play a role in the epidemiology of the disease in Kavango is being investigated. All subjects tested for antibodies to hepatitis A virus were found to give a positive result. Of the arboviruses tested for, West Nile virus was usually predominant and was probably responsible for most of the arbovirus infections. Antibodies to the Sindbis, Chikungunya, Germiston and Rift Valley fever viruses were also found.

Diagnosis of viral hepatitis. Experience in a South African laboratory.

Analysis of results in 14 250 specimens assayed for the diagnosis of viral hepatitis at one laboratory shows that hepatitis A and B are endemic in South Africa and that an important part of the diagnostic workload of virology laboratories now consists of determining their markers. The results fall into previously described patterns, but some anomalies were detected which indicated that unintentional parenteral transfer may occur even when testing for hepatitis B markers has been done. Furthermore, simultaneous hepatitis A and B infections or superinfection of carriers were found to be not as uncommon as one would expect. A progression flow-chart was drawn up to show how the markers change in retested patients, and this may serve as a guide for clinicians dealing with viral hepatitis in South Africa.

Baseline epidemiological studies for a hepatitis B vaccine trial in Kangwane.

Hepatitis B markers were determined by radioimmunoassay of serum samples from 1 495 Black subjects representative of the resident population of Kangwane, a rural area with a high incidence of chronic liver disease and hepatocellular carcinoma. Pregnant women formed an important part of the study group, since it was intended to assess the frequency of perinatal transmission and the passive immunity of their infants, two factors which would markedly influence an infant immunization programme. A high overall marker positivity rate was found, indicating that hepatitis B is endemic. The hepatitis B surface antigen (HBsAg) carrier rate was 14,6% in adult males and 4,6% in adult females, while 82.6% of adult males and 69,4% of adult females were positive for at least one marker, indicating that infection had been present at some stage. Of infants under 1 year of age 34,5% were positive for antibodies to HBsAg (anti-HBs), compared with 9,3% at 13-24 months, which indicates that transplacental transfer of anti-HBs is frequent. Other markers were acquired even in the 1st year of life, with the sharpest increase at 3-11 years. Perinatal transmission was not common, however, and horizontal transmission during early childhood seemed to play an important role. It was concluded that the risk and frequency of infection justified a vaccine trial in this population and that the target group for vaccination should be infants under 1 year of age.

Inactivation of hepatitis A virus and indicator organisms in water by free chlorine residuals.

Hepatitis A virus (HAV) and selected indicator organisms were mixed together in chlorine-demand-free buffers at pH 6, 8, or 10 and exposed to free chlorine residuals, and the survival kinetics of individual organisms were compared. HAV was enumerated by a most-probable-number dilution assay, using PLC/PRF/5 liver cells for propagation of the virus and radioimmunoassay for its detection. At all pH levels, HAV was more sensitive than Mycobacterium fortuitum, coliphage V1 (representing a type of phage common in some sewage-polluted waters), and poliovirus type 2. Under certain conditions, HAV was more resistant than Escherichia coli, Streptococcus faecalis, coliphage MS2, and reovirus type 3. It was always more resistant than SA-11 rotavirus. Evidence is presented that conditions generally specified for the chlorine disinfection of drinking-water supplies will also successfully inactivate HAV and that HAV inactivation by free chlorine residuals can reliably be monitored by practical indicator systems consisting of appropriate combinations of suitable indicators such as coliform and acid-fast bacteria, coliphages, the standard plate count, and fecal streptococci.

Immune response to hepatitis B vaccine in newborns.

Three injections of 10 microgram/ml hepatitis B vaccine (Merck) given in the first week after birth, a month later and again at the age of six months to 63 neonates in a rural African population, elicited an antibody response in 93 per cent. The initial hepatitis B marker status of the babies and mothers did not influence the results at nine months. Side-effects were minor and we conclude that the vaccine can effectively and safely be used from birth in endemic situations.

Immunological abnormalities in South African homosexual men.

Immunological tests of cell-mediated immunity (CMI), serological tests for antibodies to sexually transmitted and possibly immunosuppressive viruses, determination of serum immunoglobulin levels, full blood counts and serotyping for the HLA-DRw5 antigen were performed in 10 homosexual men with a mean age of 35 years (range 21-59 years). Five of these were associates of a patient who had died of confirmed acquired immunodeficiency syndrome (AIDS). At the time of investigation 9 of the men were apparently healthy and 1 had active pulmonary tuberculosis. Only in 2 subjects were no abnormalities of CMI found; they were 23 and 28 years of age and, interestingly, were also the only 2 whose sera were negative for antibodies to cytomegalovirus (CMV) and for the other viruses investigated. Of the remainder, 1 was lymphopenic, 6 had increased numbers of circulating suppressor T lymphocytes, 4 had reduced delayed-type hypersensitivity skin responses to recall antigens, and in 6 mitogen-induced lymphocyte transformation was decreased. Of these 8 subjects, 4 and 2 had antibodies to hepatitis B surface and core antigens respectively and 1 was positive for hepatitis B surface antigen and HBe antigen. The most severe abnormalities were observed in individuals who were seropositive for both CMV and hepatitis B virus. These findings indicate the existence of acquired immunosuppression in some members of the South African homosexual community. On the basis of these findings an immunological classification of potential sufferers of AIDS in the male homosexual community is proposed.

Acquired immunodeficiency syndrome. A report of 2 South African cases.

This report documents the first 2 cases of the acquired immunodeficiency syndrome in male homosexuals identified in South Africa. Both patients died of Pneumocystis carinii pneumonia and both had cytomegalovirus infection. Neither had peripheral lymphadenopathy and in both cases the lymph nodes showed cortical and paracortical atrophy with marked plasma cell and histiocytic infiltration. It is suggested that this lymph node pattern represents the morphological expression of the immunological defect in this syndrome.