Kuru and "new variant" CJD.

Acquired transmissible spongiform encephalopathies in humans include Kuru (a disease which was associated with ritualistic cannibalism in Papua New Guinea), iatrogenic Creutzfeldt-Jakob disease and a newly recognized variant form of Creutzfeldt-Jakob disease (nvCJD). Clinical and neuropathological features of nvCJD are reminiscent of Kuru: early and progressive cerebellar ataxia and numerous characteristic Kuru-type amyloid plaques surrounded by spongiform change. In contrast to typical cases of sporadic CJD, Kuru and nvCJD affect young patients. The newly recognized form of CJD has been identified in ten young people in the UK in 1996, approximately 10 years after the beginning of the bovine spongiform encephalopathy (BSE) epidemic in the UK. Molecular analysis has shown that nvCJD has strain characteristics that are distinct from other types of CJD but similar to those of BSE. In the UK an estimated half a million BSE-infected cows entered the human food chain before the bovine offal ban of 1989. To be effective the oral route probably requires high-infectivity titers which are encountered only in the brain, spinal cord and eyes of naturally infected cows. In patients with Kuru, titers of more than 10(8) infectious doses per gram were reported in the brain tissues. As a result of the estimated very long incubation period of nvCJD (10 to 30 years or more) the predicted nvCJD epidemic will have the shape of a normal distribution curve with a peak expected in 2009. The epidemic may extend until 2030. There is already an example to illustrate such a curve in its descending line: the decline of Kuru deaths following the interruption of ritual cannibalism.

Localized permanent epidemics: the genesis of chloroquine resistance in Plasmodium falciparum.

Localized permanent epidemics occur when, for an indefinite period of time, there is a temporary but continuous introduction of unprotected non-immunes into the same locality of a hyperendemic area. The main epidemiological factors involved in the genesis of localized permanent epidemics were encountered in Pailin (Cambodia) the epicenter of drug resistance in Southeast Asia: a very efficient vector, Anopheles dirus, exophilic and of limited distribution with, therefore, adjacent hyperendemic and non-endemic areas; a permanent pole of attraction in the hyperendemic area: Pailin's sapphires and rubies; a temporary but continuous influx of non-immunes into the pole of attraction: continuous influx of non-immunes into the Pailin gem mining area. In the gem-mining Pailin village drug pressure was considerable: mass drug administration, a medicated salt project and permanent self-medication with very high doses, much higher doses being required to cure non-immunes with heavy infections and severe clinical attacks in epidemic situations. It appears, therefore, that the emergence of chloroquine resistance in Southeast Asia was the consequence of the localized permanent epidemics in Païlin. High level resistance was the result of continuous and intensive serial passages of P. falciparum in the non-immune subjects, large numbers of parasites being exposed to a high level of drug pressure at each passage. Similar epidemiological conditions are encountered in some parts of South America where the exophilic vector is An. nuneztovari. In Colombia, whose eastern mountains bordering Venezuela yield the most highly prized emeralds in the world, chloroquine resistance was detected at about the same time as in Southeast Asia.(ABSTRACT TRUNCATED AT 250 WORDS)

[AIDS. Hypothesis on the origin and emergence of HIV]. / SIDA. Hypothèses sur l'origine et l'émergence du VIH.

Cross-species transfer of simian immunodeficiency viruses (SIV) may occur accidentally. This transfer, with the possible exception of the virus of the sooty mangabey monkey, leads to a biological dead-end. Thus, only serial passages of the virus from man to man, through blood inoculation, could explain its progressive evolution from SIV to HIV. Such an artificial cycle may have been initiated, in the 1910s, following the introduction of syringes and needles into the region of the African Great Lakes, a region where some communities were considering that the inoculation of blood from certain individuals or from monkeys was a very powerful magical remedy. The first HIV-1 infection may have emerged in the 1940s, in one of these isolated communities among which the virus remained at first confined before spreading to other populations.

[Angkor. The mystery of the dead city and Anopheles dirus]. / Angkor. Le mystère de la ville morte et Anophèles dirus.

The desertion of Angkor, which during more than five centuries was the center of a glorious civilization, has long been a matter of mystery and conjecture. The discovery of the vectorial capacity of the jungle mosquito Anopheles dirus, its epidemiological importance in the emergence and spread of multidrug resistance in Plasmodium falciparum malaria, the wiping out of large populations after transfer or deportation of non-immune Khmers into forest areas can now easily explain the desertion of Angkor. In 1431, Angkor Thom, the capital of the Khmer kingdom surrendered to the Thai conquerors. Soon afterwards, the young king left the city in search of a new capital. As a result of the population decrease large surfaces of rice fields were abandoned and reinvaded by the jungle, the typical biotope of Anopheles dirus. Severe epidemics of Plasmodium falciparum then occurred in the non-immune population with very high mortality decreasing again the number of workers and, thus, creating a vicious circle resulting in the progressive but complete desertion of Angkor.

Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia.

A review is presented of the development of drug-resistant malaria in Païlin on the Thai-Kampuchean border and its spread to other parts of the region and beyond. Resistance of P. falciparum to chloroquine appears to have emerged in this area in the early 1960s and evidence of resistance to the combination of sulfadoxine and pyrimethamine and to the combination of diaphenylsulfone and pyrimethamine came from the same area towards the end of the same decade. The factors leading to the emergence and increase of drug resistance appear to have been: the continuous introduction of non-immune migrants to a hyperendemic malaria area, an increase in already intense transmission resulting from the living and working conditions of the migrants and prolonged drug pressure resulting from individual drug consumption and mass drug administration, particularly from the medicated salt project which covered the area in which resistance emerged. These conditions lead to the selection of resistant mutants. Moreover, resistant parasites were exposed to multiple and increasing doses of chloroquine, pyrimethamine and sulfathiazole during repeated passages through non-immune hosts who were being treated for primary attacks, early recrudescences and reinfections. This probably resulted in increasing the degree of resistance and in the selection of parasites resistant to sulfathiazole with cross-resistance to other sulfonamides. In Irian Jaya, Indonesian New Guinea, where there had been a chloroquinized salt project, the level of chloroquine resistance was much lower than in Païlin; this is associated with the absence of a non-immune population and the lower dose of chloroquine base used in the salt. The spread of chloroquine resistance is then discussed. At first resistance was found only in three foci in South-East Asia where A. balabacensis is the vector of malaria. It then spread to all A. balabacensis areas, and finally to areas outside the area of distribution of A. balabacensis. The spread of resistance is found to be favoured by the presence of the vector A. balabacensis and by the introduction of a non-immune population.

Epidemiology of emergence and spread of drug-resistant falciparum malaria in Southeast Asia.

In Southeast Asia the medicated salt project of Pailin, on the Kampuchea-Thai border, demonstrated that drug resistance, especially chloroquine resistance, can develop when a large population of P. falciparum parasites is exposed to intense transmission under intense drug pressure. The selection of resistant parasites being activated by the introduction of non-immune groups. Emergence of drug resistance was the result of continuous and prolonged mass exposure of P. falciparum to pyrimethamine and chloroquine resulting in the selection of resistant mutants. This selection was associated with multiple exposures of the parasites to much higher drug doses, during repeated passages through the non-immune hosts, increasing the degree of resistance. Resistances spread to the receptive areas of Kampuchea and other neighbouring countries through the movements of the temporary migrants who, by then, had become carriers infected with drug resistant falciparum parasites. The rapid and early spread of chloroquine resistance in A. balabacensis areas was not a coincidence but the result of the biological advantages of this species complex in relation to malaria transmission. In Australasia the medicated salt project carried out in Irian Jaya, on the border with Papua New Guinea, also resulted in the development of drug resistance in P. falciparum.

Chloroquine-resistant falciparum malaria in East Kalimantan, Indonesia.

Following the discovery of four imported chloroquine-resistant P. falciparum infections in the Province of Yogyakarta (Island of Java) sensitivity tests were carried out in the Province of East Kalimantan Island of Borneo). Twenty subjects were given 25 mg. of chloroquine base per kilogram of body weight over three days. Two infections were found resistant at the RII level and a third at the RI level with early recrudescence on day 7. In the other 17 cases followed up to day 21, six were found again with asexual parasites between day 9 and day 14 and a seventh on day 21. These results confirm the presence of chloroquine resistance in P. falciparum in East Kalimantan and, together with previous findings, suggest a widespread distribution of chloroquine-resistant falciparum malaria in this Province of Indonesia. It is particularly interesting to note that chloroquine-resistant falciparum malaria has now been detected in almost all the area of dispersion of A. balabacensis.