Surveillance and research

Surveillance and research by Svetlana Marennikova (!] nly two years after the world's last case of endemic smallpox occurred in Somalia, in Oc- tober 1977, WHO was able to make the official declaration of global smallpox eradication. Throughout this period a continuous search was undertaken for possible hidden cases in the areas where the disease had previously been endemic. This thorough and comprehen- sive search relied heavily on laboratory investigations of all sus- pect cases , since it was often only the laboratory that could show whether the disease was smallpox or not. Thousands of such investiga- tions were carried out on smallpox suspects from dozens of countries at the two institutions supremely qual- ified in the laboratory diagnosis of pox infections , namely , the WHO Collaborating Centres in Moscow (Moscow Research Institute for Viral Preparations) and in Atlanta , USA (Centers for Disease Con- trol) . These investigations gave negative results for all suspected cases: not a single case of smallpox has been revealed. The data obtained provided the major premise that enabled the Global Commission for the Certifi- cation of Smallpox Eradication, which had been created by WHO , to confirm that the whole planet was "clean". In the Commission's re- port , recommendations for the post-eradication era occupy a spe- cial place, because of the need to give the public evidence that small- pox will never reappear and that mankind is not endangered by other poxviruses. ••••••••••••••••••••••••••• • • : Dr Svetlana MARENNIKOVA : • • : is Chief. WHO Collaborating : : Centre on Smallpox and Re- : : lated Infections. Laboratory of : : Viral Vesicular Infections. : : Moscow Research Institute : : for Viral Preparations . : • • ••••••••••••••••••••••••••• Laboratory work combining both diagnosis and research formed a substantial element in this post- eradication surveillance pro- gramme. The diagnostic part was in effect a continuation of similar work carried out during the closing stages of the eradication campaign, when it related to patients sus- pected to be smallpox cases. In the past decade we at the Moscow Collaborating Centre were involved in investigating rumours about smallpox, some of which reached the press and thus aroused the natural concern of the public. In all these cases , WHO was eager to obtain from the collaborating centres the results of laboratory study of materials taken from the patients in question . To our general satisfaction, the rumours have never been proved true . It is appropriate here to make a small digression. During the cam- paign the laboratories performing the diagnostic work that was needed in order to identify new viral isolates used to use laboratory strains of the variola virus. At our laboratory and elsewhere, the peculiarities of variola virus strains isolated in different geographical regions were studied. This work not only enlarged our knowledge of the variola virus but also made it possi- ble to explain the difference in the clinical course of the so-called " Asian " smallpox and " African " smallpox. The research undertaken in other laboratories involved a comparative analysis of variola and other orthopox (especially monkey- pox) virus genomes. As a result of this long-term work with variola virus, a vast collection of its strains was gathered in some laboratories . After smallpox transmission stop- ped , the stocks of strains preserved in laboratories turned out to be a real potential hazard for the reap- pearance of smallpox. The small number of laboratory- acquired smallpox cases testify to the fact that work with variola virus without appropriate precautions al- ways presents a danger for those who handle it as well as for other people. A threatening reminder was Sealed refrigerator at the WHO Col- laborating Centre in Moscow where variola virus strains are stored. Besides a lock and a seal, it is fitted with a sound alarm. Photo W HO/S. Marennikova W oRLD HEALTH, Aug./Sept. 1987 the tragic episode that occurred in 1978 in Birmingham, England, when a woman working one floor above a laboratory where variola virus strains were being studied contracted smallpox and died . Her mother , too, was infected but recovered. The abandonment of vaccination after smallpox eradication naturally increases the risk of infection spreading if the virus ever escapes from a laboratory. That is why WHO has undertaken a complex of mea- sures to exclude such a possibility. The first step in this direction was to reduce the number of laboratories maintaining variola virus strains. This process started even before the campaign was completed. In 1976 there were 76 such laboratories , but today there are only two , both act- ing as WHO Collaborating Centres. The stocks in other laboratories have either been destroyed (in most cases) or transmitted to one of the two centres. Besides this , in 1977 WHO began to develop biological safety require- ments for laboratories dealing with or preserving variola virus. After some improvements , these require- ments provided appropriate safe- guards both for people handling the virus and for those in the vicinity. WHO inspection teams regularly check that these requirements and virus storage regulations are fulfil- led . It should be added that re- search into variola virus has actually stopped within the last two years. Now the question arises whether we must continue maintaining stocks of variola virus or destroy them. A no less important part of laboratory research in the post- eradication era was the study of human monkeypox , a disease " dis- covered" in Equatorial Africa in 1970. Its striking feature is the similarity of the clinical picture to that of smallpox. This very fact accounts for the close attention paid to this disease and the need for it to be investigated in the framework of a special WHO project. Some ques- tions still remain to be answered about the development of infection in human beings , the ecology of the virus and the potential danger of monkeypox under conditions of a steadily vanishing immunity to smallpox. As a result of activities organized and coordinated by WHO between surveillance teams in some African countries and laboratory W oRLD HEALTH, Aug ./Sept. 1987 work at the collaborating centres , it has been established that human monkeypox is a rare zoonotic dis- ease, but the geographical area where it can be encountered is a large one and covers the tropical rain forests of Equatorial Africa. Most patients (75.1 per cent) get infected from animals-the natural carriers of the virus. In 18.6 per cent of cases, the source of human monkeypox under conditions of close contact was the infected per- son (second infection generation). Transmission to the third genera- tion was very rare (less than seven per cent), and only once in 17 years was a fourth generation infection found. Results obtained so far con- firm the initial data showing the small contagiousness and transmis- sibility of monkeypox in compari- son with smallpox. An important step in the mon- keypox study was the detection of a natural reservoir of this infection. For a number of years, efforts in this direction failed to give any perceptible results. Only by the end of 1985 did the combined investi- gations carried out by WHO epidemiologists and virologists from the collaborating centres re- sult in the discovery of the virus reservoir. It turned out to be some species of tropical squirrels. The long-term (17-year) study of monkeypox isolates obtained from patients in various African coun- tries showed the pathogen to be quite stable and not prone to any substantial variability. However, it seems reasonable to maintain Laboratory technicians in the Moscow centre which played a key role in eradicating smallpox. Photo WHO/Novosti periodical control of the properties of this virus in the future. Among other orthopoxviruses (besides vaccinia virus), the cowpox virus is pathogenic for humans. During the years of post-eradica- tion surveillance, our knowledge of the ecology of this virus was ex- tended. The most interesting thing here is that we had to change our opinion about the natural reservoir of this infection. It has been proved that the carriers of the virus in nature are small rodents. It also appeared that the cowpox virus possesses a wide range of pathogenicity and can affect indi- viduals of the majority of tax- onomic groups of animals. Recently the possibility of human cowpox infection caused by contact with sick rodents was demonstrated. The feature of this infection and its contagiousness has not changed since Jenner's time , and it is only harmful to human health in special cases , for instance , when it affects the eye. The overall conclusions of the surveillance and research into orthopoxvirus infections conducted during the post-eradication period are that smallpox itself has com- pletely disappeared and that other orthopoxviruses, including mon- keypox, do not present a danger for public health. • 23