The origin of registry-based medical research and care.

During the last decades, registers comprising medical data have played an increasingly important role in medicine, both in health care and research. It is reasonable to expect that their importance will also increase in the future. Thus, a search for the origin of register-based medicine seems meaningful. Admittedly, collections of individual data on a number of patients may have occurred way back in history (Tidsskr Nor Laegeforen, 96, 1976:295). However, if we accept WHO's definition of a register, it implies more than a number of notifications. A register requires that a permanent record be established, that the cases be followed up and that basic statistical tabulations be prepared both on frequency and survival (Epidemiological Methods on the study of chronic diseases, Geneva, WHO Expert committee on Health Statistics, 1967). Thus, a register should aim at improving surveillance, health care and research. If we apply these criteria, we find the origin of register-based medicine in Norway in terms of the National Leprosy Registry, representing the world's first national patient register for any disease, established 1856 (Int J Epidemiol, 2, 1973: 81).

Acid-fast bacilli found in sphagnum vegetation of coastal Norway containing Mycobacterium leprae-specific phenolic glycolipid-I.

In the grey layer of sphagnum vegetation originating from former leprosy-endemic regions of coastal Norway, acid-fast bacilli (AFB) containing Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) on the surface have been found. These AFB survived in foot pads of nude mice with multiplication but without swelling. This contrasts to experimental leprosy with clinically derived M. leprae where swelling and unlimited multiplication takes place. The naturally occurring AFB may be of a lower pathogenicity than M. leprae obtained from clinical cases. The possibility of M. leprae surviving in sphagnum vegetation was assessed by inoculation of clinically derived M. leprae into the grey layer of the sphagnum. It multiplied more than tenfold and retained its pathogenicity in nude mice for 16 weeks, the duration of the experiment. The lack of pathogenicity of sphagnum-derived, M. leprae-like mycobacteria may be relevant to the decline of leprosy in Norway.

Leprosy in Portugal 1946-80: epidemiologic patterns observed during declining incidence rates.

Compulsory notification of leprosy in Portugal formed the basis for the establishment of a national patient registry used in an epidemiological study. Highest incidence rates were observed in the coastal counties in the middle of Portugal and particularly in the municipalities with a high annual rainfall. Peak incidence rates in males was observed at the age of 25-29 years against 50-59 in females. A continuous and increasing decline in incidence rates was observed throughout the observation period, 1946-80. Towards the end of the period the slopes of the incidence curves seemed to be identical with those observed in other countries where leprosy has previously been eradicated. This is consistent with the notion that towards the end of an endemic situation no new transmission of the disease occurs, and the incidence curve takes the shape of the right part of the distribution of incubation periods which apparently is uniform in leprosy, irrespective of time and place. The pattern observed in other areas during declining incidence rates, of an increase in age at onset by year of onset together with a lack of increase in age at onset by year of birth was confirmed by the Portuguese data, also consistent with a break in the transmission of the disease a long time before the final termination of the endemic situation.

Geographical variations in the occurrence of leprosy: possible roles played by nutrition and some other environmental factors.

The considerable variation in leprosy prevalence among 35 villages and field areas in South India was compared with variations in their socioeconomic and nutritional conditions. Using villages/field areas and aggregates thereof as observational units, leprosy prevalence rates were found to be significantly lower in field areas than in villages. Moreover, there was a significant correlation between the occurrence of malnutrition in children 1 to 4 years of age and the prevalence of leprosy. The possible association between the occurrence of malnutrition in childhood and leprosy is discussed in light of the present knowledge of leprosy, immunocompetence, and malnutrition. Strategies for further illumination of the hypothesized importance of malnutrition among children are discussed.

Secular trends in age at onset, sex ratio, and type index in leprosy observed during declining incidence rates.

Epidemiologic surveillance in Norway, the United States, Nigeria, Japan, Venezuela, India, and China, covering periods from 1851 to 1981, demonstrates a consistent decline in incidence rates of leprosy. At the same time, secular trends have been observed which imply an increasing age at onset, an increasing male excess, and an increasing fraction of new cases represented by multibacillary leprosy. Theoretically, an increasing age at onset may be caused by two mechanisms, namely postponement of infection to a later age and/or an increasing fraction of patients with long incubation periods. Cohort analyses have shown no increase in age at onset in subsequent birth cohorts, but rather have shown a decrease. The latter mechanism, the increasing importance of long incubation periods, is consistent with the shift toward multibacillary cases in which the incubation period is longer than that in paucibacillary cases. Apparently, this mechanism has also been present during the decline of tuberculosis. An increasing fraction of new patients with long incubation periods, resulting in an increasing age at onset, is proposed as a general principle to be expected in any disease in rapid decline which also has a long and varying incubation period. This theory offers a basis for assessment of secular trends.

The discovery of Mycobacterium leprae. A medical achievement in the light of evolving scientific methods.

The discovery of M. leprae by G. H. Armauer Hansen (1841-1912) in 1873 represents a link in a chain of development in international medicine that was influenced by two main concepts, namely, that germs may be causes of disease and that social conditions may be related to disease, either as causes or consequences or both. Hansen's work is also a link in a chain of research on leprosy in Norway. Hansen met with serious challenges in addition to those that were purely scientific. To prove the causative effect of the microorganism according to principles that later came to be known as Koch's postulates, Hansen felt compelled to conduct experiments that were deemed illegal by the authorities. At the same time, he was fighting to establish priority for his discovery. Later, Hansen was honored as the discoverer of the bacillus of leprosy and was privileged to see benefits in the public health as a consequence of the discovery. Hansen's epoch-making achievements may serve as an inspiration to all who aspire to combat disease by seeking answers to questions about causes of disease, modes of prevention, and social consequences of disease.

Conditions relevant to the occurrence of acid-fast bacilli in sphagnum vegetation.

Biotopes with intact sphagnum vegetation were studied in Naustdal, West Norway: the health district with the former highest leprosy incidence rates in Norway. Concentration of acid-fast bacilli and concentration of non-cultivable acid-fast bacilli found in the vegetation fluid were compared with a series of variables related to the local environment and to the samples of vegetation. In bivariate analyses high concentrations were found in biotopes with orientation toward South, with a high coverage of vascular plants and with presence of Ericaceae. High concentrations were also found where dry weight of a vegetation was high, where pH in the fluid was low and where dry weight of the fluid was high. In a multivariate analysis, log-linear model, based on concentration of acid-fast bacilli as the dependent variable and orientation, pH, dry weight of vegetation and dry weight of fluid as the independent variables, all two-factor effects including the dependent variable were retained in the model. Furthermore, orientation versus dry weight of vegetation and dry weight of fluid versus dry weight of vegetation were retained.

Isolation of non-cultivable acid-fast bacilli in sphagnum and moss vegetation by foot pad technique in mice.

In the former leprosy-endemic coastal area of Norway, 122 samples of sphagnum and moss vegetation were collected from 6 biotopes and examined for non-cultivable AFB by foot pad inoculation. Of the 759 foot pads examined, 20% contained non-cultivable AFB. A significantly higher frequency was found in a habitat where Sphagnum cuspidatum was preponderant, the sphagnum species from which the maximum yield was obtained. The bacteria were polymorphous, solidly staining AFB, which multiplied in passage in foot pads while they could not be cultivated on the conventional media for mycobacteria. Efforts are continuing to identify these AFB by biochemical methods and by inoculation into nine-banded armadillos.