Poxviruses

 

The global eradication of smallpox through the WHO campaign is the most outstanding example of what could be achieve through international cooperation. As a result, poxviruses have been relegated to the position of relatively unimportant human pathogens.

A. Properties

The family of poxviridae is divided into 6 genera, with species within each genera closely related.
Poxviruses are the largest viruses known
dsDNA enveloped virus, bricked shaped virions 200-250 * 250-300 nm in diameter. 2 morphological forms are seen: M (mulberry) and C (capsule) forms that are interconvertable. Internally, poxviruses have a biconcave "nucleoid" and 2 lateral bodies.
Inside the cell, the virion often has a double membrane. The lateral bodies contain various enzymes essential for virus replication.
>100 polypeptides have been demonstrated in vaccinia.
Poxviruses are very easy to isolate and will grow in a variety of cell cultures and will produce pocks on the chick chorioallantoic membrane (CAM)

Electronmicrograph of molluscum contagiosum particles. (Courtesy of Linda M. Stannard, University of Cape Town)

 

B. Smallpox

Smallpox was transmitted by respiratory route from lesions in the respiratory tract of patients in the early stage of the disease. During the 12 day incubation period, the virus was distributed initially to the internal organs and then to the skin. Variola major caused severe infections with 20-50% mortality, variola minor with <1% mortality. Management of outbreaks depended on the isolation of infected individuals and the vaccination of close contacts. The vaccine was highly effective. If given during the incubation period, it either prevented or reduced the severity of clinical symptoms. The origin of the vaccine strain is not known, it is thought that it may have been horsepox which is now an extinct disease.

The eradication of smallpox

Smallpox was eradicated from most countries in Europe and the US by 1940s. By the 1960s, smallpox remained a serious problem in the Indian subcontinent, Indonesia and much of Africa. The WHO listed smallpox as the top on the list for eradication in 1967. There were certain features of smallpox which made it a highly eradicable disease. (see table below). The WHO smallpox eradication unit was set up in 1967. The initial strategy was separated into 3 phases;

  1. Attack phase - This applied to areas where the incidence of smallpox exceeded 5 cases per 100,000 and where vaccination coverage was less than 80%. Attention was given to mass vaccination and improvement in case surveillance and reporting. This phase lasted from 1967-1973. A large amount of financial resoureces were provided for setting up surveillance centres and reference centres. Priority was given to Brazil, sub-saharan African, S.Asia and Africa. Brazil and Indonesis were thought to be the easiest countries to eradicate the virus from. In fact by 1973, smallpox had been eradicated from Braziland Indonesia. It was decided it was time to go on to the consolidation phase.
  2. Consolidation Phase - In areas where the incidence was less than 5 cases per 100,000 and vaccination coverage exceeded 80%, the objective was the elimination of smallpox. Vaccination uptake was to be maintained and surveillance improved. Facilities should be made available for isolation.
  3. Maintenance Phase - once smallpox had been eliminated, it was essential it was not reintroduced. This phase was entered in 1978. In 1980, the world was declared to be free of smallpox.

It soon became clear that smallpox could not be eradicated with mass vaccination alone. In some countries, it was not possible to achieve a smallpox vaccination uptake rate of 80%. More attention was therefore paid to case tracing and isolation procedures. Experience in West Africa and Indonesia had shown that smallpox can be eliminated without mass vaccination, provided that a high rate of case detection was achieved. The Indian subcontinent was a special problem because of its large size and population. It provided a reservoir for variola major infection. Extra attention was paid to search out unnotified cases that proved to be highly effective. The last cases of variola major occurred in the Indian subcontinent in 1975. The last case of variola minor occurred in Somalia in 1977. The last cases of smallpox occurred in a Birmingham laboratory in 1979. It was estimated that the smallpox eradication campaign costed US $312 million. If smallpox had not been eradicated, routine efforts to control smallpox would have costed US $1000 million. The success of smallpox eradication was due to the involvement of an international agency which was able to cross national barriers. The following were features that made smallpox an eradicable disease;

1. A severe disease with morbidity and mortality
2. Considerable savings to developed non-endemic countries
3. Eradication from developed countries demonstrated its feasibility
4. No cultural or social barriers to case tracing and control
5. Long incubation period
6. Infectious only after incubation period
7. Low communicability
8. No carrier state
9. Subclinical infections not a source of infection
10. Easily diagnosed
11. No animal reservoir
12. Infection confers long-term immunity
13. one stable serotype
14. Effective vaccine available
 

 

Other Poxviruses

1. Monkeypox

Monkeypox was first isolated from monkeys in 1958, but it was not until 1970 that it was associated with human disease. To date, over 400 cases have been investigated, mainly from Zaire. The pathogenesis and clinical features for monkeypox is the same as for smallpox. The main differences are a greater degree of lymphadenopathy and a lower capacity for case-to-case spread. Most cases occur in unvaccinated children. The mortality in human monkeypox is appreciable, being in the order of 10%. The management of human monkeypox is the same as for smallpox. Human monkeypox has not been detected outside West Africa. Although monkeypox was first isolated from monkeys, there is no evidence that African monkeys act as the reservoir. The most likely candidate for reservoir is the African squirrel. One important difference between human monkeypox and smallpox is the lower capacity for human spread. The attack rate among unvaccinated contacts is 9% in contrast to >37% for smallpox. Laboratory workers studying monkeypox should be vaccinated.

2. Vaccinia

Vaccination with vaccinia was associated with certain risks. Complications ranged from mild reactions and fatal encephalitis. The overall incidence of complications was around 1/800 although the more severe forms occurred only in 15 per million vaccinees. Recent interest has focused on the possible usage of vaccinia as a vector for immunization against other viruses. It is possible that certain changes can be made to the vaccinia genome which makes it less likely to develop side effects.

 3. Cowpox

Cowpox is a relatively unimportant zoonosis which has only been isolated in Britain and Europe. Infection has been described in humans, cows and cats. Infection in humans usually remain localized, often producing a lesion which is similar to that caused by vaccination, although the inflammatory response is greater and general constitutional symptoms such as fever and myalgia may be present in some cases. In humans, lesions are usually restricted to the hands, but may also be transferred to the face. EM is generally used for the diagnosis of infection. The virus will also grow well on CAM. Human cowpox usually respond to treatment with antivaccinia immunoglobulin, but its use should be restricted to the most severe cases. Although cowpox was first isolated form cattle and farm workers. There is no evidence that cattle serve as the reservoir. In fact, cowpox is very rare in cattle. It has been suggested that the reservoir is actually a small rodent but this is not proven.

4. Parapoxviruses

Parapoxvirus infections are widespread in sheep, goats and cattle and relatively unimportant but common human infections occur. Infections in cattle and humans are usually referred to as pseudocowpox, paravaccinia or milker's nodes. Those in sheep and goats as orf. The viruses are closely related and the nomenclature of the human disease is based on the identity of the host form which the infection was acquired. (orf from sheep and pseudocowpox from cattle). Infection occurs via small cuts and abrasions in all hosts and is usually localized. Although the lesions are similar to the early lesions of cowpox and vaccinia, true macrovesicles do not form. In humans, lesions usually occur on the hand but may be transferred to the face. The laboratory diagnosis is usually made by EM. The virus may also be isolated in human, bovine and ovine cells but such investigations are not part of routine diagnostic virology. Parapoxvirus infections occur worldwide, and are of considerable importance. A survey carried in New Zealand showed that 1.4% of workers in the meat industry became infected in 1 year. The lesions are surprisingly painless and thus there is probably substantial under-reporting. Idoxuridine had occasionally been prescribed for treatment but no trials have been carried out to prove the efficacy of treatment. Prevention of human infection is difficult. Reasonable precautions should be undertaken when handling infected animals.

5. Molluscum Contagiosum

Molluscum contagiosum is a specifically human disease of worldwide distribution. The incubation period varies from 1 week to 6 months. The lesion begins as a small papule and gradually grows into a discrete, waxy, smooth, dome-shaped, pearly or flesh-coloured nodule. Usually 1-20 lesions but occasionally they may be present in hundreds. In children, the lesions are found on the trunk and the proximal extremities. In adults they tend to occur on the trunk, pubic area and thighs. Individual lesions persist for about 2 months, but the disease usually lasts 6 to 9 months. Constitutional disturbance is rare. The disease occurs world-wide and is spread by direct contact or fomites. In general it tends to occur in children. The disease by may transmitted from skin to skin after sexual intercourse. A diagnosis can usually be made on clinical appearance alone. The diagnosis can be supported by EM. Unlike other poxviruses, molluscum have not been demonstrated to grow in cell culture. Infection is usually benign and painless, with spontaneous recovery in most cases. Where treatment is required for cosmetic reasons, various procedures are available such as curretage, cryotherapy with liquid nitrogen, silver nitrate etc. which are routinely used for the removal of warts.

6. Tanapox

Tanapox is a poxvirus infection first recognized in 1957 in the Tana River area of Kenya. It is a zoonosis, human cases have only been seen in the Tana valley and Zaire. The distribution of the virus and the real extent of the human infection is not known, as is the method of transmission of infection. The virus produces a mild febrile illness with one or two skin lesions. The virus does not grow in CAM but will grow in a variety of cell lines.