BSE and vCJD: Their biology and management
BSE and vCJD: Their biology and management

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BSE and vCJD: Their biology and management

1.3 Pre-existing human TSEs

Before BSE was recognised, several distinct human TSEs were already known, the most significant of which are outlined below. Human TSEs can have incubation periods of several decades between initiation of the disease and recognition of its early symptoms. Following provisional diagnosis, all these TSEs inevitably culminate in the patient's death after varying periods of decline. Definitive diagnosis required post-mortem examination of the brain. Although in all TSEs brain tissue has a pathological and usually spongy appearance similar to that seen in BSE, the different human TSEs affect different parts of the brain (Figure 3) and this influences the symptoms observed. Figure 4 shows the microscopic appearance of human cerebral cortex in individuals who have died of CJD.

Figure 3
Figure 3 Different human TSEs mainly affect different parts of the brain: Creutzfeldt-Jakob disease (CJD), the cerebral cortex; Gerstmann-Sträussler-Scheinker syndrome (GSS) and kuru, the cerebellum; fatal familial insomnia (FFI), the thalamus. (In BSE, the main effect is on the brainstem.)
Figure 4
Courtesy of Dr J W Ironside, National CJD Surveillance Unit ©
Courtesy of Dr J W Ironside, National CJD Surveillance Unit
Figure 4 (a) Thin section through a normal human cerebral cortex, stained with a red dye. (b) A stained, thin section through the cerebral cortex of an individual with the original form of CJD; note the widespread spongiform changes. (c) A stained, thin section through the cerebral cortex of an individual with vCJD, showing local spongiform changes

An important human TSE is Creutzfeldt-Jakob disease (CJD), the annual incidence of which throughout the world is approximately 1 case per million of the population.

Question 4

The current population of the UK is about 60 million. How many CJD cases would therefore be expected in a typical year in the UK? [R]

Answer

About 60. This does emphasise the comparative rarity of CJD.

The fact that the annual incidence of CJD among Libyan Jews is about 25 cases per million suggested that there might be something fundamentally different about the development of CJD in this group. Intriguing clusters of cases (in either time or space) have been reported from Slovakia, Hungary, England, the USA and Chile. Since in 85-90% of CJD cases no specific cause can be identified, these are referred to as sporadic CJD. Typically, victims of sporadic CJD are in their 50s or 60s and die within a year of onset of the illness (although they may have been incubating the disease for much longer). Symptoms include muscular spasms, dementia, loss of higher brain functions and behavioural abnormalities. Inherited or familial CJD is another form of the disease which accounts for the remaining 10-15% of cases. Worldwide, about 100 families are known to carry one of the genetic mutations responsible for it. In the past, CJD was acquired occasionally by transmission as a consequence of medical procedures involving biological material (e.g. concentrated human growth hormone or transplanted corneas) derived from people with undiagnosed CJD. This form is known as iatrogenic CJD (which literally means 'CJD caused by the doctor'). [R]

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a dementia known to be genetically inherited in about 50 families worldwide. Although GSS is otherwise similar to CJD, the age of onset is more variable and so is the duration of the disease (two to six years). Worldwide, about 10 families are known to carry a genetic mutation that gives rise to fatal familial insomnia (FFI), in which death occurs about one year after the onset of complete insomnia and other symptoms. Clearly, GSS and FFI are even rarer than CJD. However, detailed genetic studies of these families have contributed to our understanding of the cause(s) of human TSEs.

Kuru is a TSE disease that was formerly quite common in the Foré people of the Eastern Highlands of Papua New Guinea. Kuru's symptoms include uncoordinated movement, paralysis and an irrational laughter, which gave rise to the disease's alternative name, 'the laughing death'. Dementia is uncommon in kuru (in marked contrast to CJD). Death usually occurs within 12 months.

Question 5

The annual disease-specific mortality from kuru was about 3%. How much more common was kuru among the Foré people than CJD worldwide? [R]

Answer

3% is equivalent to 3 in 100 or 0.03. The annual incidence of CJD worldwide is 1 in a million, which is equivalent to 0.000 001. Dividing the former by the latter tells us that kuru was about 30 000 times more common among the Foré than CJD is on a worldwide basis.

Kuru affected mainly women, and children of both sexes. In fact, at one stage most deaths in women were caused by this disease and men came to outnumber women by 3 to 1. The few men who died from the disease had probably contracted it when young. Although never witnessed by outsiders, the Foré reportedly held mortuary feasts in which they ate their dead as a mark of respect. Women and children were believed to have eaten the ground-up and heated brain of the dead tribal member as a kind of grey soup, while men ate the muscle tissue. This difference presumably reflected differences in status within the social group. Kuru began to decline in the mid-1950s, after mortuary feasts were banned by the Australian authorities which then governed Papua New Guinea. By this time, the American virologist Carleton Gajdusek and others had worked out that kuru must have been contracted by eating infected human brain tissue. For this work, Gajdusek was awarded the Nobel Prize in Physiology or Medicine in 1976.

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