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A 3-year-old boy, who developed the signs and symptoms characteristic of Kawasaki disease, is described. The child also had an 8 cm tender hepatomegaly. Hydrops of the gallbladder could not be shown. Liver biopsy showed marked infiltration of inflammatory cells, including neutrophil and eosinophil leucocytes in the portal tracts involving the periphery of the portal arteries and veins, and acute inflammation of the bile ducts with neutrophil and eosinophil infiltration of the walls. Overt cholangitis has been described only once before in Kawasaki disease, when a viral agent was suggested as being important in the pathogenesis. Although the clinical and laboratory findings in cases of Kawasaki disease clearly suggest an acute infection--as they did in this case--no aetiological agent has yet been incriminated. The possibility of a drug-induced auto-allergic or hypersensitivity state is considered. Evidence for such a state includes a history of drug administration, pathological findings similar to peri-arteritis nodosa--a condition often associated with a hypersensitivity state--the presence of eosinophils in the lesions and a response to treatment with aspirin, a drug known to ameliorate hypersensitivity states.

In honouring the memory of Dr Alwyn Zoutendyk, a respected member of the staff of the South African Institute for Medical Research, attention is called to the studies of the immunological disorders. While investigating serum hepatitis affecting soldiers of the US army following the administration of yellow fever vaccine, an antigen similar to that later called the Australia antigen, now hepatitis B surface antigen, was found in the acute phase serum and the corresponding antibody was found in convalescence. This finding and subsequent studies suggested there was a group of disease, which we called the hyperreactive auto-allergic disorders, of which examples were to be found in every system. The obverse of these we called the hyporeactive immunologically deficient disorders resulting from defects of the cell or serum components of the immunological reactions, of which many examples have also been found.

Tick-bite fever in young children is usually a mild illness with few complications and no mortality. That it may assume a severe form is illustrated by the occurrence of 3 cases admitted to Johannesburg Hospital within 1 week in which 2 patients, 3 and 5 years old respectively, had severe involvement of the central nervous system with epileptiform fits and deep coma and loss of power of speech on recovering consciousness. The third patient, aged 5 years, developed an incipient haemorrhagic state as well as serious involvement of the central nervous system. The severe form of the disease in these patients appears to have been due to unusually virulent strains of Rickettsia conorii, probably acquired from dog ticks in their homes. All patients recovered on appropriate treatment. Two regained their normal speech after many weeks while the third patient's incipient haemorrhagic state rapidly resolved.

Virological investigations were carried out on 4 151 patients with respiratory disease hospitalized between May 1966 and April 1972. The groups examined were Black and White children and Black miners. Influenza viruses were more common among malnourished Black children and tended to cause more severe disease. This was also true of adenovirus and Herpesvirus hominis type 1 infections. Adenoviruses appear to be secondary invaders, frequently after a measles or influenza attack. A generalized epidemic of adenovirus type 7 occurred in 1967, the longest, coldest and most humid winter during the survey. The season of peak occurrence for respiratory syncytial (RS) virus is autumn, not winter as found elsewhere. The parainfluenza viruses differ from each other, types 1 and 2 being commoner in older children (12--48 months), mainly causing laryngotracheobronchitis (LTB), whereas type 3 is commoner in younger children (0--23 months), mainly causing pneumonia. The miners showed a preponderance of influenza A infections. The miners' origin from remote villages and high turnover rate create a situation where a given strain will persist at a moderate level for long periods, unlike in the general population where an outbreak lasts for only about 6--8 weeks. As opposed to other closed communities, adenovirus infections were rare. The reason for this is obscure.

Because of the occasional need for an alternative drug for the treatment of tick-bite fever, a study of the value of erythromycin for the variety of tick-borne typhus fever occurring in southern Africa was undertaken. In guinea-pigs erythromycin 125 mg/kg for 5 days largely prevented the fever and other signs of the infection, but did not prevent the serological reaction as determined by the rickettsial complement fixation test. A series of 17 human patients were treated for 4 days with erythromycin 500 mg 6-hourly for adults and 30-50 mg/kg/d in 4 divided doses for children. Eleven patients appeared to respond favourably. It was concluded that erythromycin does not have as specific a value as tetracycline in the treatment of tick-bite fever, but that when tetracycline is contraindicated erythromycin is a useful alternative drug.

The handling of potentially lethal and highly infective material in a routine clinical pathology laboratory and in a viral diagnostic unit is detailed. Extensive precautions were taken at each step of the receiving, processing and disposal cycle. Disposable protective clothing and apparatus were used whenever possible. Laboratory tests were limited to those essential for the clinical management and diagnosis. Technologists who handled infective material were limited to minimal numbers of experienced, non-pregnant, informed volunteers. They wore special protective clothing, including gloves, caps, gowns and masks. When possible, specimens were handled under special protective hoods. Potentially infective material was processed through automated apparatus, and care was taken to prevent contamination of its exterior. The effluent from the machines was collected into viricidal agents (glutaraldehyde, sodium hypochlorite). After processing, the machines were flushed extensively with viricidal solution. This procedure has caused no damage to the automated equipment and has been adopted as a routine laboratory safety measure. The protective procedures adopted were successful in that there was no outbreak of the viral infection among the associated laboratory workers.

A description of the postmortem pathological findings in a case of Marburg virus disease emphasizes the findings of focal necrosis in the liver, spleen and lymphoid tissue, disseminated intravascular coagulation and acute tubular necrosis. These features are compared and contrasted with those of other potentially fatal viral haemorrhagic fevers to help pathologists make an early diagnosis wherever possible.

In considering the diagnosis of a patient admitted to the Johannesburg Hospital, suffering from an illness characterized by high fever and complicated by a hemorrhagic state from which he died, a list of possible causes of his illness was drawn up. This list included the arthropodborne viral infections prevalent in southern Africa, namely, chikungunya fever, Sindbis fever, West Nile fever, yellow fever, and Rift Valley fever; viral infections associated with rodents, such as Lassa fever; the viral infection associated with monkeys, Marburg virus disease; the rickettsial infections; tick-bite fever (the variety of spotted fever of tick typhus occurring in southern Africa) and Q fever; the bacterial infections, especially the coccal infections, plague septicemia, and meningococcal, staphylococcal, and streptococcal septicemia; and the blood protozoal infections malaria and trypanosomiasis. In addition, rubella, Gasser's syndrome, Henoch-Schönlein purpura, and viperine snakebite were briefly described in this review. All of these conditions may be complicated by the development of a hemorrhagic state. The circulation of large numbers of infecting organisms, by they viruses, rickettsiae, bacteria, or protozoa, may initiate the coagulation cascade, the formation of fibrin and its deposition in the finer blood vessels, and the aggregation and entanglement of platelets resulting in marked thrombocytopenia and bleeding. This bleeding tendency is greatly aggravated when the infection specifically involves the parenchymal cells of the liver; such a condition results in defective formation of coagulation factors such as prothrombin. The proper care of patients in whom a hemorrhagic state has developed requires urgent and accurate diagnosis followed by immediate and appropriate treatment that will combat the infection and alleviate the hemorrhagic state and liver disorder. If the hemorrhagic state is due to one of the dangerous infectious fevers, adequate protection of the medical, nursing, and laboratory staff concerned is also vital.

A 13-year-old boy, after having spent a week at a camp in a nature reserve in the western Transvaal, developed an acute illness of sudden onset characterized by chills, severe headache, muscle pains and high fever. On the 3rd day he developed a haemorrhagic state with profuse bleeding from the gastro-intestinal tract and other mucous membranes and petechial haemorrhages into the skin, from which he died on the 6th day after onset of the illness. A tick, identified as a species of Hyalomma, was found attached to his scalp. The provisional clinical diagnosis of Congo virus fever was confirmed in the laboratory by the isolation of the virus in newborn mice inoculated with the patient's blood. This is the first incrimination of Congo virus as the cause of a fatal case of haemorrhagic fever in South Africa, although it is known to occur in several countries in the tropical region of Africa and in south-eastern Europe and Asia.

Biopsy material, from a patient with an esophageal carcinoma of a type occurring relatively frequently in Africans in some regions of Southern Africa, has been adapted to cell culture conditions and has developed into a continuously growing tumor cell line. The cells have a squamous pattern of growth which they maintain, without piling up, even in heavily confluent cultures.

During an epizootic of Rift Valley fever in South Africa in 1974/1975, mainly affecting sheep and cattle, a large number of human cases occurred. The majority of the patients, mostly farmers, farm labourers and veterinary surgeons, acquired the infection while handling the carcasses of animals which had died of Rift Valley fever. Some gave no history of contact with infected animals and it is presumed that they were infected by mosquitoes. Complications were common. Retinitis clinically associated with defective vision occurred in about 20% of patients investigated. In others, meningo-encephalitis developed; 1 patient died and the brain showed perivascular cuffing and round-cell infiltration. In 110 cases the diagnosis was confirmed in the laboratory, in 17 by isolation of the virus and in 93 by the finding of an antibody response in serological tests. In 3 fatal cases the virus was isolated from the liver, and in a further 4 fatal cases in which virus isolation was not attempted, there was clinical and epidemiological evidence of the diagnosis; in each case a haemorrhagic state associated with hepatitis had developed. In 1978, follow-up studies showed that immune rates among residents on affected farms varied from 10% in children to 17,1% in adult males, with an overall immunity rate of 14,5%.

Forty-five human malignant tumour specimens were cultivated in vitro in an attempt to determine the necessary conditions for tumour cell maintenance and to establish permanently-growing cell lines. Continuously-growing cultures were derived from five tumours, including carcinomas of the oesophagus and colon, a hepatoma, a mesothelioma and a retroperitoneal sarcoma. The carcinoma of the oesophagus and the hepatoma, which have adapted fully to in vitro conditions, can be regarded as established cell lines.

Three hemorrhagic fevers occur in southern Africa: Rift Valley fever, Marburg virus disease, and Crimean-Congo hemorrhagic fever. The patient's history of travel in Africa, visits to rural areas, contact with sick animals or their carcasses, or contact with a tick-infested environment or tick bites is important. Rift Valley fever is characterized by an incubation period of approximately 3 or 4 days, sudden onset of fever with a biphasic course, and signs and symptoms of liver and kidney disorder. The commonest complication is retinitis with a central scotoma. Severe cases may develop a hemorrhagic state, which may be fatal. Marburg virus disease was studied in two Australian students after a tour of Rhodesia (now Zimbabwe) and in a nurse who cared for them. The incubation period of approximately 7 days is followed by sudden onset of fever (typically lasting 7 days) and the appearance of a maculopapular petechial rash on the 5th day. A hemorrhagic state develops about the same time and may be fatal. Crimean-Congo hemorrhagic fever is widespread in South Africa; it may be transmitted by tick bite of the species Hyalomma, by contact with the tissues of animals, or by contact with infected patients.

In a study of patients with suspected poliomyelitis, but from whom poliovirus was not isolated, a variety of causes of the paralysis was found. Injury of the spinal column sometimes followed by periostitis or osteomyelitis was relatively common. Exotic causes included paralysis due to snake bite, spider bite, scorpion sting, and tick bite and schistosomiasis involving the spinal cord. Chemical poisons, such as arsenic, triorthocresyl phosphate, and organophosphorus insecticides, were responsible for paralysis affecting groups of people. Paralysis in individual patients with porphyria followed the administration of anesthesia and certain drugs. Normal clinicopathologic findings in hospital nurses with Iceland disease suggested a psychological component. The Guillain-Barré syndrome in some patients resulted from virus infection of the nerve tissue, in others it was related to a hyperreactive autoallergic state. Enterovirus infections, especially coxsackieviruses A9 and A23 (echovirus 9) and group B coxsackieviruses, frequently caused meningoencephalitis often associated with transient paralysis. Coxsackievirus A7 infection occasionally resulted in permanent paralysis. Clearly it is important to maintain surveillance of these infections.

A man was admitted to the Johannesburg Hospital with a history of fever, diarrhoea, and dry cough for four days. He began to produce bloodstained sputum and was found to have severe arterial hypoxaemia. Radiography showed widespread opacification over both lung fields, and the clinical and haemodynamic features were consistent with the adult respiratory distress syndrome. Serology for Leptospira canicola was positive. Despite antibiotics, supportive therapy, and ventilation the patient died. Necropsy excluded cardiac disease. This case shows that leptospirosis may cause the adult respiratory distress syndrome.

In tropical thrombophlebitis the leg veins are most often involved, but in some patients thrombosis of the visceral veins may be fatal. As its cause is unknown, attention is called to outbreaks of relapsing fever in the Transvaal which effects labourers on citrus and maize farms and which often develops into thrombophlebitis. Appropriate tests for relapsing fever should be done in patients who develop this complication. Passengers on long overnight journeys by air are liable to deep vein thrombosis and should exercise to avoid it.

Mollaret's meningitis or the benign recurrent meningitis syndrome is a rare disorder not previously described in Africa. The syndrome has a characteristic clinical presentation with spinal fluid pleocytosis, often with unusual 'epithelial' cells. With contemporary techniques no causative organism has been incriminated. The aetiology remains speculative, but we report on a patient found to have a cerebrospinal fluid leak, which may represent a factor in the pathogenesis of this disorder.

In this review of studies on the hemorrhagic fevers of Southern Africa carried out in the South African Institute for Medical Research, attention has been called to occurrence of meningococcal septicemia in recruits to the mining industry and South African Army, to cases of staphylococcal and streptococcal septicemia with hemorrhagic manifestations, and to the occurrence of plague which, in its septicemic form, may cause a hemorrhagic state. "Onyalai," a bleeding disease in tropical Africa, often fatal, was related to profound thrombocytopenia possibly following administration of toxic witch doctor medicine. Spirochetal diseases, and rickettsial diseases in their severe forms, are often manifested with hemorrhagic complications. Of enterovirus infections, Coxsackie B viruses occasionally caused severe hepatitis associated with bleeding, especially in newborn babies. Cases of hemorrhagic fever presenting in February-March, 1975 are described. The first outbreak was due to Marburg virus disease and the second, which included seven fatal cases, was caused by Rift Valley fever virus. In recent cases of hemorrhagic fever a variety of infective organisms have been incriminated including bacterial infections, rickettsial diseases, and virus diseases, including Herpesvirus hominis; in one patient, the hemorrhagic state was related to rubella. A boy who died in a hemorrhagic state was found to have Congo fever; another patient who died of severe bleeding from the lungs was infected with Leptospira canicola, and two patients who developed a hemorrhagic state after a safari trip in Northern Botswana were infected with Trypanosoma rhodesiense. An illness manifested by high fever and melena developed in a young man after a visit to Zimbabwe; the patient was found to have both malaria and Marburg virus disease.

The first recognised outbreak of Marburg virus disease in Africa, and the first since the original epidemic in West Germany and Yugoslavia in 1967, occurred in South Africa in February 1975. The primary case was in a young Australian man , who was admitted to the Johannesburg Hospital after having toured Rhodesia. Two secondary cases occurred, one being in the first patient's travelling companion, and the other in a nurse. Features of the illness included high fever, myalgia, vomiting and diarrhoea, hepatitis, a characteristic maculopapular rash, leucopenia, thrombocytopenia, and a bleeding tendency. The first patient died on the seventh day from haemorrhage resulting from a combination of disseminated intravascular coagulation and hepatic failure. The other two patients were given vigorous supportive treatment and prophylactic heparin and recovered after an acute phase lasting about seven days. During this period on developed pancreatitis, the serum amylase remaining raised until the 32nd day after the onset of the illness. The other developed unilateral uveitis after having been asymptomatic for two months. This persisted for several weeks and Marburg virus was cultured from the anterior chamber of the eye.

Patients usually provisionally diagnosed as having typhoid fever or pneumonia are regularly admitted to the Rietfontein Fever Hospital suffering from psittacosis. The main symptoms are intense headache, chills and fever and an irritating non-productive cough. Later most patients develop signs of pneumonitis most clearly seen on radiographic examination. An important clue to the diagnosis is a history of contact with birds, most often budgerigars and more recently cockatiels. The diagnosis may be confirmed by the isolation of Chlamydia psittaci, the causative organism, but more usually reliance is placed on the results of serological tests revealing the development of chlamydial antibodies. None of the patients in this series developed serious complications, but if not treated psittacosis sufferers may develop severe pneumonitis, hepatitis and gastro-enteritis; the mortality rate is up to 20%. A rare but fatal complication is chlamydial endocarditis, presenting with the signs and symptoms of subacute bacterial endocarditis, but giving repeated negative blood cultures. The illness responds specifically to treatment with tetracycline antibiotics within 48 hours. Chlamydial infections are widespread among avian species. In the RSA most cases of psittacosis have resulted from contact with budgerigars and cockatiels, but outbreaks have been associated with imported batches of birds including South American parrots and Australian finches, emphasizing the need for vigilance at seaports.