Commonwealth Health

Smallpox: the lethal, scarring killer
Professor Alimuddin Zumla

Professor Alimuddin Zumla Director of the Centre for Infectious Diseases at the University College London celebrates the global eradication of the disease in 1977 with a cautious hint on how the forgotten horrors could be revived by use of the virus as a biological weapon.

Historical accounts of smallpox date back to 1580 BC in Egyptian mummies. Over centuries, smallpox was apparently a devastating illness characterised by extensive, profuse vesicular skin rashes and with a high mortality rate. Survivors were left with severe disfiguring facial scars. Smallpox was a disease with characteristic clinical signs. It caused dramatic and disastrous epidemics which became the subject of myths and superstitions around the world. The human smallpox virus was one of the most fatal of all viral infections. If a sufferer survived the attack, a lifelong immunity ensued. A textbook printed in 1988 by the World Health Organisation in 1988
(ISBN:9241561106) is one of the most comprehensive available on the subject. While hard copies are not available, it is viewable on the internet at website.

Smallpox in Africa
The earliest presumptive evidence of smallpox anywhere in the world is in Egyptian mummies over 3000 years old. Later, smallpox swept along the North African coast during the great expansion of Islam in the 8th century. The disease became endemic around the Mediterranean region. The slave trade in the 18th and 19th centuries provided excellent conditions for the spread of smallpox. With traders penetrating deep into the interior, the overland caravans carried smallpox far and wide into central Africa. The Portuguese established a settlement in Luanda, Angola in 1484 and probably introduced smallpox into the area shortly after that.

Over the next two centuries, smallpox and the slave trade combined to take a terrible toll on the population. In 1713 smallpox was imported into South Africa through a ship that docked at Cape town on a return trip from India. In the 19th century, Arab slave trade expanded from the east coast ports into central Africa. Smallpox was brought into Uganda by slave caravans in the 1840s. Meanwhile, smallpox continued to be a severe endemic disease in coastal towns in north
Africa. Six epidemics were reported in Ethiopia and Sudan: in 1811-1813; 1838-1839; 1865-1866; 1878-1879; 18885-18887 and 1889-1890.

Smallpox in Southern Africa
In 1967 when the World Health Organisation (WHO) smallpox eradication programme began, the disease didn't appear to be a major problem throughout southern Africa. Political problems made it difficult for WHO to co-operate with governments. Only 4 countries with a population of 10.4 million in 1970 were member-states of WHO with full voting rights. Angola and Mozambique were
pre-occupied with their respective civil wars. Nevertheless rapid results were achieved in central and western Africa and steady progress occurred in eastern and southern Africa. By 1976 the only remaining endemic country in Africa was Ethiopia and Somalia. By the end of 1977 smallpox had been totally eradicated in Africa.

Indeed, smallpox is one of the few infectious diseases that has been eradicated globally. There was one host, one virus and one vaccine and thus the eradication of smallpox was a straightforward matter. The success of this eradication programme was based on several factors:
1. Human beings were the only hosts.
2. An effective vaccine inducing solid immunity was available to it.
3. Governments were committed to the vaccination programmes. This was backed up by the WHO's search and containment campaigns where cases were isolated and contacts were traced and vaccinated. The last case of endemic smallpox occured in Somalia in 1977 and eradication of the disease was declared in 1980. The world has been free of small pox for the past two decades and the eradication campaign is heralded as one of the most successful carried out by the WHO.

Clinical manifestations
A recent review in the New England Journal of Medicine gives a succinct updated summary of the clinical features and diagnosis of smallpox (Breman et al,2002). The pox viruses are double-stranded DNA molecules of 130-375 kb pairs and are shaped like bricks on the electron micrograph pictures measuring 250 x 200 x 300 nm. Due to strain variation, two clinical forms of the disease are expressed: Variola major causes the more serious form of the diseases and forms the majority of cases. Variola minor causes a less sever form of smallpox. The virus enters the respiratory tract and seeds onto the mucous membranes and spreads into the regional lymph nodes.

After a brief period of viraemia there is a latent period during which time the virus multiplies in the reticuloendothelial system. During this prodromal phase mucous membranes in the mouth and pharynx are infected. The virus then enters the capillary epithelium of the dermal layer in skin and mucous membranes, leading to the development of papules, vesicles and pustules. The lesions contain abundant viral particles. Since every organ of the body becomes infected with the virus the disease is systemic. The urine, saliva and tears of the sufferer are also teaming with virus particles. The incubation period for smallpox is 7 to 17 days (mean 10 to 12). The prodromal phase is non-specific and lasts for two or three days and is characterised by a headache, backache, and fever beginning abruptly.

The skin rash begins as a small reddish macule, which becomes a papule with a diameter of around 2-3mm over a period of one or two days. After an additional one or two days the papules become vesicles with a diameter of 2 to 5mm. The lesions occur first on the face and extremities but gradually cover the whole body. Pustules of around 4-6mm in diameter develop about four to seven days after the onset of the rash and remain for up to to eight days. If the patient is still alive, the lesions then umbilcate and then crust which then falls off leaving a scar. Death from smallpox is due to toxaemia, immune complexes and hypotension. After a smallpox, pockmarks or pitted lesions are seen in 65-80 per cent of survivors.

The diagnosis of smallpox is usually a clinical one. As the skin manifestations are similar to those of other cutaenous viral exanthemata, clinically the smallpox can be mistaken with many skin illnesses such as severe chickenpox, monkeypox, molluscum contagiosum, severe herpes, simplex infections and drug skin reactions. Clinical samples for virological confirmation (by several methods including viral culture, immunoflourescence, ELISA and polymerase chain reaction) should be handled very carefully and be processed in category 4 laboratory where staff members have been vaccinated.

Significance of smallpox today
Given that smallpox disappeared worldwide over two decades ago, its significance in public health today is nought. However, the disease has of late aroused extensive interest and debate throughout the world due to its potential as a biological weapon. Smallpox is highly contagious and could spread rapidly by direct contact with an infected person and could potentially kill millions. Following the attack on the New York twin towers in September 2001 the media has reviewed the threats of biological warfare, causing much anxiety to the public.

Strategies to prevent smallpox threat
In light of the growing threats of bio-terrorism and the fragile nature of global politics, developing public health strategies to counter bio-terrorism threats from smallpox is a high global priority. In the event of an emergency consequential upon a smallpox outbreak, there are insufficient stocks of smallpox vaccine (vaccinia virus) available to vaccinate the population of the USA or UK, let alone everyone globally.

What to do if there is a smallpox outbreak
Any clinical suspicion of a case of smallpox is a public health emergency and is of international concern. When a health worker suspects smallpox, the case must be reported immediately to relevant authorities who should immediately get in touch with the World Health Organization Department of Communicable Diseases in Geneva, Switzerland or the Centres for Disease Control (CDC) in Atlanta, USA. The patient should be immediately isolated and contacts be identified. The contacts and all health personnel should be vaccinated as soon as possible. All governments and health systems must be prepared for a smallpox outbreak.

Reading material
Breman JG, Henderson DA. Diagnosis and management of smallpox. New England Journal of Medicine 2002; 346: 17: 1300- 1308.

Fenner F, Hendersen DA, Arita I, Jezek Z, Ladni ID. Smallpox and its eradication. WHO CSR website:

Kaplan J. CDC's startegic plan for bioterorrism preparedness and response. Public Health Report 2001;116 suppl 2:9-16

For more information Email:

Table 1:
A classification of clinical types of smallpox (variola major)

Clinical type Clinical Features

Ordinary type

Modified type
Variola sine eruptione
Flat type Pustules remain flat:
Haemorrhgic type

Raised pustular skin lesions
Three sub types:
a) Confluent: confluent rash on face/forearms
b) Semiconfluent: semiconfluent rash on face, discrete elsewhere
c) Discrete: areas of nomal skin between pustules, even on face
As above but has an accelerated course
Fever without rash caused by variola virus

usually confluent Usually fatal
Widespread haemorrhages in skin and mucous membranes.
Two subtypes:
a) early with purpuric rash -always fatal
b) late, with haemorrhages into base of pustules - usually fatal.

Based on Ramchandran Rao (1972)

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