An analysis of the geographical distribution of Plasmodium ovale

Bull. Org. mond. Sante 1969, 40, 383-394Bull. Wid Hith Org. An Analysis of the Geographical Distribution of Plasmodium ovale A. JA. LYSENKO 1 & A. E. BELJAEV 1 For a long time Plasmodium ovale was considered a very rare causal agent of malaria, but recently it has been shown to be a fairly common parasite in Africa. The authors analyse all thefindings of P. ovale outside tropical Africa and describe its distribution. This species is distributed in 2 areas, the first confined to tropical Africa and the second to islands in the Western Pacific. The authors make a medico-geographical analysis of the distribution of P. ovale, and attempt to explain particular features of it. Plasmodium ovale Stephens 1922 was for a long time considered to be a very rare causal agent of malaria, but has recently been attracting greater attention. Ovale malaria has a number of distinguishing features, particularly the difficulty of detecting it, the length of its course, and its special area of distribu- tion. As yet it is not clear to what extent this form of malaria will yield to control measures, but it is probable that the same sort of difficulties may arise in clearing foci of ovale malaria as are already occurring with quartan malaria. The number of articles dealing with the distribu- tion of P. ovale and particularly the extensive review by Lacan 2 is evidence of the increasing interest in this species. In Lacan's review, the collection of a vast amount of factual material makes it possible for the first time to gain a clearer idea of the limits of distribution of this particular parasite in Africa. References given by Lacan 2 concerning the findings of P. ovale outside Africa suggest that this parasite has a world-wide distribution. The aim of our study is to assess the reliability of this conclusion. P. ovale has recently been diagnosed more frequent- ly in Africa, but hardly at all in other continents, despite the large increase in the number of blood slides examined in connexion with malaria eradi- 1 Marcinovskij Institute of Medical Parasitology and Tro- pical Medicine, Ministry of Health, Moscow, USSR. 2 Lacan, A. (1965) Plasmodium ovale Stephens 1922, sa distribution en Afrique (Unpublished document WHO/Mal/ 525.65). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. cation campaigns. Most of the findings of P. ovale outside Africa relate to the end of the 1930s and to the 1940s when this new species of parasite became, so to speak, fashionable. During these years, there were single findings which were not followed up from an epidemiological point of view and which were often described in such a way as to throw doubt on the correctness of the diagnosis. It is well known that some stages of P. ovale are similar to both P. vivax and P. malariae. The basic criteria for the differential diagnosis of P. ovale are the early appearance of James' stippling in infected erythrocytes, the compactness of the trophozoites and the specific shape of some of the infected red blood cells. These differences can be recognized only in thin films, properly stained. In the thick film the recognition of P. ovale is difficult and at times even impossible (James, Nicol & Shute, 1933; Lacan 3). In mass surveys, however, as a rule only thick films are used and, moreover, few microscopists are well acquainted with the morphology of P. ovale. Until recently, during mass surveys, most cases of ovale malaria have been incorrectly diagnosed, and the impression has been formed that the causal agent of this type of malaria is extremely rare. Thus Young & Johnson (1949) in a survey in Liberia, covering 10 128 persons, found P. vivax in 2% of cases. Bray (1957b), in a survey of 635 Liberians 3 Lacan, A. (1962) Plasmodium ovale in French-speaking countries in Africa (Unpublished document WHO/Mal/363). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organisation, 1211 Geneva, Switzerland. 2308 -383- 384 A. JA. LYSENKO & A. E. BELJAEV 8 years later, found P. vivax only once, whereas 4.4% of those examined were infected with P. ovale. It may be supposed that the parasites defined by Young & Johnson as P. vivax were in fact P. ovale. Diagnosis is also made more difficult by the fact that this species is found alone in only 38% of cases, being more commonly found in association with P. fakciparum (50 %), P. malariae (4 %), or with both species (8%) (Lacan, 1965). In ovale malaria the level of parasitaemia is as a rule low, so that in the presence of a mixed infection, it is easy to miss single parasites of P. ovale against a background of large numbers of ring forms of P. falciparum. In addition, when there is a mixed infection, P. ovale like P. vivax, is suppressed by P. falciparum. ANALYSIS OF FINDINGS OF P. 0 VALE OUTSIDE AFRICA Taking into account the special features of the morphology and ecology of the parasite, we have subjected the findings of P. ovale outside tropical Africa to a critical analysis; some of these findings are quoted by Lacan.1 The results of our analysis are shown in the accompanying table. Other authors have also had doubts about the authenticity of finding of P. ovale outside Africa. Sinton, Hutton & Shute (1939) wrote that at least in some of the cases in which the parasite had been found outside Africa, unusual forms of P. vivax and P. malariae had been mistaken for P. ovale. Nikolaev (1951) demonstrated the doubtful authenticity of all 4 findings of P. ovale in the USSR (cases 7, 12, 13 and 19 in the accom- panying table), although these are still quoted as authentic by many workers (Russell et al., 1963; Lacan 1). Later, Young, Eyles & Burgess (1948) and Young & Eyles (1949) warned against the incorrect diagnosis of P. ovale among soldiers returning from the Pacific theatre of operations, stating that when P. vivax from New Guinea was passaged, ovale-like forms appeared from time to time in blood. The erroneous identification of local cases of P. ovale may be due not only to the shortcomings of a laboratory diagnosis. In the absence of an epi- demiological follow-up, some cases regarded as local could, in fact, have been cases of imported or induced malaria. Moreover, the possibility of the 1 Lacan, A. (1965) Plasmodium ovale Stephens 1922, sa distribution en Afrique (Unpublished document WHO/Mal/ 525.65). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. infection of man by simian malaria cannot be considered out of the question. Already 5 species of simian plasmodium are known which can be transmitted to man (P. cynomolgi, P. knowlesi, P. simium, P. inui and P. brasilianum) and in the case of the first 3 species, infection has occurred under natural conditions.2 Some simian parasites are very similar to human plasmodia. In particular, P. fieldi, P. simiovale, and according to some classifications P. simium, belong to the same group as P. ovale. It is therefore quite possible that in some of the reported cases one of the simian parasites has been mistaken for P. ovale. In view of the possibility that ovale-like forms may occur in human malaria plasmodia, we consider that a local case of ovale malaria recorded outside tropical Africa can be considered as authentic only if it fulfils the following conditions: (1) that an experimental study of the detected strain has been made by passage in human beings, proving that it is indeed P. ovale; (2) that, in the patient concerned, a series of blood preparations taken at various periods of the illness have been studied, without any change being found in the morphological characteristics of the parasite; and (3) that, in the area concerned, several cases of ovale malaria have been detected, and that the patients have been studied with sufficient care (by examination of a series of blood preparations, and by a clinical follow-up). If these criteria are adopted, the cases given in the accompanying table may be divided into the follow- ing groups: (A) Cases known to be unreliable: (a) cases in which the identity of the parasite with P. ovale was not confirmed by experimental study (cases 3 and 7); (b) cases with mixed P. vivax and P. ovale infection in which there was no proof that it was not ovale-like forms of P. vivax that were present (cases 8, 17 and 20). (B) Very doubtful cases not properly described (cases 2, 4, 6 and 19). 2 Bruce-Chwatt, J. L. (1966) Malaria as a zoonosis (Unpublished document WHO/Zoon/66.90, WHO/Mal/ 66.578). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. AN ANALYSIS OF THE GEOGRAPHICAL DISTRIBUTION OF PLASMODIUM O VALE 385 ANALYSIS OF FINDINGS OF P. OVALE OUTSIDE TROPICAL AFRICA Author and place Assumed place Diagnosis Method of establishing A of description of infection by the author the diagnosis Analysis of the cases 1. Craig (1900), Philippines First, P. vivax var., Identified as P. ovale Although the diagnosis was established also Craig & the P. vivax var. minu- after re-examination retrospectively, without epidemiological Faust (1951)- tum, finally P. ovale of the preparations in investigation, it is possible that this USA 1933 really was a case of P. ovale in view of later findings (case 21) 2. Heydon (1923) Duke of York Forms reminiscent of Retrospectively by According to McMillan & Kelly (1966), -Rabaul, Island, Bismarck P. vivax var. minutum study of the prepara- Heydon, having learnt of Stephens' New Britain Archipelago (Emin); later P. ovale tion obtained during a discovery, identified the parasite he mass survey found as P. ovale. No description or illustrations of the parasite were ever published 3. Plehn (1924)- Palestine An unusual strain of Passages in persons Identified with P. ovale by many authors Germany malaria parasite dis- suffering from general (e.g. Brumpt, 1949; Lacan a). According tinguished by its paralysisoftheinsane to Brumpt (1949) this strain after 20 diurnal periodicity passages suddenly changed its pro- and lack of gameto- perties and turned into ordinary P. vivax cyte production 4. Muhlens 1934 West coast of P. ovale Retrospectively, on No description or illustration of the pa- -Germany South America the basis of the pre- rasite is given. No epidemiological paration in the collec- survey was carried out and the place of tion infection remains obscure 5. Mageed (1936) Near Zagazig, P. ovale Retrospectively on the Description very brief. Some characters -Egypt Lower Egypt basis of a slide taken not typical of P. ovale. No epidemiologi- during a mass survey cal survey 6. Muhlens 1938 Iran P. ovale ? Described as a " case of ovale malaria from Persia ". No description or illustra- tion of the parasite is given and there is no indication as a whether there was an epidemiological investigation 7. Eskin (1938)- Neighbourhood To begin with P. vivax Passages in blood The strain differed from P. ovale mor- Tashkent, of Ufa in + P. ovale; later P. and through phologically and biologically (see Niko- USSR Bashkiria, USSR ovale mosquitos laev, 1951). In an editor's note to the article by Lisova et al. (1946), summing up the study of ihe strain, doubt is ex- pressed as to it being P. ovale 8. Shieber (1939) Neighbourhood P. vivax + P. ovale Blood-slide examina- In view of the possibility of the occur- -Palestine of Haifa, tion rence of ova/e-like forms in P. vivax, it Palestine seems improbable that such a difficult task as the establishment of a correct diagnosis of a mixed infection with P. vivax and P. ovale would have been correctly carried out in the initial period of study of P. ovale. In subsequent years no cases of ovale malaria of local origin were described from Palestine 9. Papafigou First case from P. ovale Retrospective Some features in the parasites described (1939)-Greece E. Macedonia, diagnosis from blood- are nottypical of P. ovale. No epidemiolo- second from slide examination gical survey S. Epirus 10. Mendez Venezuela P. ovale ? Original paper not seen (1939) Venezuela A. JA. LYSENKO & A. E. BELJAEV ANALYSIS OF FINDINGS OF P. OVALE OUTSIDE TROPICAL AFRICA (continued) Author and place of description 11. Raman (1940) -India 12. Matevosjan (1940)- Armenia, USSR 13. Gvelisiani (1940)- Georgia, USSR 14. Garcia (1941) -Manila, Philippines 15. Yao & Wu(1941)- Kungming, Yunnan, China 16. Ganov (1941) -Bulgaria 17. de Zulueta (1942)- Colombia 18. Jackson (1944)- New Guinea- 2 cases 19. Fridman (1946)- Tvilisi, Georgia, USSR Assumed place of infection Vizagapatam, Andhra-Pradesh, India Armenia, USSR Georgia, USSR Manila, Philippines Southern China South-eastern frontier of Bulgaria Colombia Neighbourhood of Port Moresby, Papua Diagnosis Method of establishing by the author the diagnosis P. ovale Blood-slide examination P. ovale P. ovale P. ovale Retrospectively, on the basis of one preparation On the basis of sever- al preparations made at one and the same time Blood-slide examina- tion. Clinical observa- tions P. falciparum + Retrospectively on forms reminiscent of the basis of several P. ovale smears P. ovale P. vivax + P. ovale P. ovale P. ovale On the basis of slides taken during 4 hours on the same day (a) First case-series of preparations taken on various days of the illness in the absence of specific therapy (b) Second case- blood-slide examina- tion on a single occa- sion and clinical ob- servation Blood-slide examination Analysis of the cases Despite the author's assertions, the photomicrographs printed do not con- firm his diagnosis. Some of the parasites are P. falciparum Judging from the description and the illustrations, the parasite found differs somewhat from P. ovale. The case cannot be considered as reliable since no epidemiological investigation was car - ried out A sufficiently complete description of the parasite is not available. There are a number of features uncharacteristic of P. ovale. The case was not investigated Judging from the description, the author was probably dealing with P. ovale of local origin. The discovery of the Do- naldson strain (see case No. 21) con- firms Garcia's finding A most careful description of a parasite which resembles P. ovale, although it possesses some features not characte- ristic of that parasite. No additional blood examination or epidemiological follow-up. It is not impossible that this may be an infection with simian malaria in a human patient Original paper not seen The author's statement that intermediate forms between P. vivax and P. ovale were present in the blood preparations and the absence of any evidence other than morphological, makes it doubtful wheth- er the patient's blood contained P. ovale Both cases are undoubtedly of local origin. The first of them was studied very carefully. It is quite probable that the author was dealing with P. ovale The description is extremely short and it is impossible to know what species of parasite was involved 386 387AN ANALYSIS OF THE GEOGRAPHICAL DISTRIBUTION OF PLASMODIUM 0 VALE ANALYSIS OF FINDINGS OF P. OVALE OUTSIDE TROPICAL AFRICA (concluded) Author and place Assumed place Diagnosis of description of infection by the author 20. Gurevitch & Neighbourhood P. vivax + P. ovale Laufer (1952) of Mosul, Iraq -Israel 21. Jeffery, Young & Willcox (1954)-USA 22. Quoted by Mukherjea, Chatterjee & Paul (1966). Original paper pub- lished in 1960-India 23. Jevtic & Bokic (1965) -Yugoslavia Luzon, Philippines Calcutta, India East Pakistan P. ovale P. ovale P. ovale IMethod of establishingthe diagnosis Blood-slide examination Passages in blood and through mosq uitos Two slide taken 2 and 17 hours respec- tively after an attack Analysis of the cases There is no description or illustration of the parasite. The case was not in- vestigated in detail and it is possible that this was a case of induced malaria. The possibility of establishing a correct diagnosis of mixed infection with P. vivax and P. ovale after such a short investiga- tion is also doubtful Careful experimental study of the strain isolated (the Donaldson strain) demon- strated that it belonged to P. ovale Original paper not seen It is most probable that infection did not occur in Pakistan where the patient had been 15 months before the illness, but in Togoland which he had left 34 months earlier. Long-term relapses of this kind have been described by other authors in regard to ovale-malaria: in these other cases 20 and 44 months (Trager & Most, 1963) and 52 months (Dixit, 1958) had elapsed since the patients' return from malarious areas 24. Mukherjea, East Pakistan or P. ovale Retrospectively, on The description given is very brief. Some Chatterjee & West Bengal the basis of one pre- features of the parasite are not typical of Paul (1966)- (India) paration P. ovale. No epidemiological survey Calcutta, India 25. McMillan & Eastern part of P. ovale Blood-slide examina- Kelly (1967)- New Guinea tion and clinical ob- New Guinea sei vation Case 25 was studied in sufficient detail. In cases 26 and 27 there was no epide- 26. McMillan & Eastern part of P. ovale Thin film miological survey. No additional para- Kelly (1967)- New Guinea sitological examinations were made. In New Guinea view of the fact that case 25 is territo- rially linked with case 18, the authors _m _ _may have encountered P. ovale 27. McMillan & Solomon Islands P. ovale On the basis of a col- Kelly (1967)- lection preparation New Guinea made by Price in 1942 28. Alves, Neighbourhood P. ovale On the basis of pre- Two cases, apparently linked epidemio- Schinazi & of Puerto Prin- parations made logically. The correctness of the identi- Aniceto cesa, Palawan, during mass survey of fication has been confirmed by Professor (1968)- Philippines prison population Garnham Philippines a Lacan, A. (1965) Plasmodium Ovale Stephens 1922, sa distribution en Afrique (Unpublished documentWHO/Mal/525.65). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. A. JA. LYSENKO & A. E. BELJAEV (C) Doubtful cases: (a) cases in which there was retrospective de- termination on the basis of one preparation, or of several taken at the same time, without epi- demiological investigation or a series of parasito- logical examinations. In some cases the parasite possessed characteristics not typical of P. ovale (cases 5, 9, 11, 12, 13, 15, 18b, 24, 25, 26, and 27); (b) cases in which the precise place where infection occurred was not known (case 23). (D) Probable cases: (a) cases in which the description of the parasite fits P. ovale and in which epidemiological in- vestigations and a series of parasitological ex- aminations were carried out (case 18a); (b) cases in which the description of the parasite fits P. ovale and which occurred in areas where the existence of P. ovale has been proved (cases 1, 14, and 28). (E) Reliable cases in which the parasite has been proved experimentally to be P. ovale (case 21). (F) Cases which cannot be classified because of the inadequacy of the information available (cases 10, 16 and 22). Thus, it may be said with confidence that in addition to tropical Africa, P. ovale is encountered in the Philippines (Fig. 1) and possibly in New Guinea also. It may also be found in some areas of South-East Asia, although this is less likely. There is no clear evidence that it is endemic in other areas in FIG. 1 SITES AND CLASSIFICATION OF FINDINGS OF PLASMODIUM OVALE OUTSIDE TROPICAL AFRICA e Clearly unreliable and very doubtful 0 Doubtful (group C)(groups A and B) * Reliable and probably correct 0 Cases for which there is no information (group F)(groups D and E) a The numbers by the sites on the map correspond with the numbers in the table. 388 AN ANALYSIS OF THE GEOGRAPHICAL DISTRIBUTION OF PLASMODIUM OVALE 389 FIG. 2 AREA OF DISTRIBUTION OF PLASMODIUM OVALE AND THE ORIGINAL AREA OF DISTRIBUTION OF MALARIA ///7 > Area of distribution of malaria S Area of distribution of P. ova/e /Area of distribution of malaria Area of distribution of P. ovale the world. On the basis of what has been stated we suggest that the distribution of P. ovale is confined to tropical Africa and to islands in the Western Pacific (Fig. 2). MEDICO-GEOGRAPHICAL ANALYSIS OF THE DISTRIBUTION OF P. O VALE As will be seen from Fig. 1 the area of distribution of P. ovale is peculiar in extent, shape and structure. In size it is much smaller than the area of distribution of any of the other species of human malaria parasites. In shape it is discontinuous, with a break in the Indian subcontinent, and there is no doubt that tropical Africa should be considered as its " centre of abundance ".I 1" Centre of abundance " (centr obilija): the part of the area of distribution where the species in question is most commonly encountered (Voronov, 1963). Although nowhere in Africa does P. ovale occupy a dominant position among the species of malaria parasites, in some foci (e.g., in Liberia) the pre- valence does reach 10%. In the islands of the Western Pacific only sporadic cases of ovale malaria occur. We have attempted to prepare a map showing the distribution of P. ovale in Africa, by using data from original sources and from Lacan's review 2 (Fig. 3). In compiling the map we found that data for the various areas were rarely comparable. In the first place, the earlier sources always gave figures that were too low; secondly, prevalence is given for 2Lacan, A. (1965) Plasmodium ovale Stephens 1922, sa distribution en Afrique (Unpublished document WHO/Mal/ 525.65). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. 390 A. JA. LYSENKO & A. E. BELJAEV FIG. 3 AREA OF DISTRIBUTION OF PLASMODIUM OVALE IN AFRICA Area of distribution of P. ovals Percentage prevalence based on mass surveys I >2% S 1%-2% <1% different population groups in different papers, and thirdly, the standards of diagnosis differed in the different areas. Otherwise it would be impossible to explain the fact that in the north-eastern areas of Liberia, on the borders with Guinea, the prevalence of P. ovale among the population is very high, rising to 4.400 (Bray, 1957b), whereas in Guinea itself not a single finding of the parasite has been reported. However, P. ovale is in fact quite often encountered in Guinea, as is shown by the fact that out of 55 imported cases of ovale malaria recorded in the USSR in the 1963-67 period, 21 originated in Guinea (figures supplied by the Malaria Prophylaxis De- partment of the Marcinovskij Institute of Medical Parasitology and Tropical Medicine). Cases of ovale malaria have also occurred in the USSR which had been imported from Portuguese Guinea and Mali, also countries in which, according to Lacan,1 P. ovale has never been recorded. The study of imported cases has enabled us to determine more precisely the limits of the distribution of P. ovale. The incidence of P. qvale remains unknown in some extensive areas, with different natural conditions such as the Democratic Republic of the Congo, Mozambique, etc. Despite the numerous gaps, however, the main features of the distribution of P. ovale are clear. In Africa the " centre of abundance " is close to the northern coast of the Gulf of Guinea while the area of distribution covers the rest of tropical Africa. The portion of the area of distribution in the Pacific may be considered as an area where the infection was introduced. It is of interest to analyse possible links between the component parts of the area of dis- tribution of P. ovale and the factors which may determine them. Relation with climate Regions with comparatively high prevalence of P. ovale (>2% of the population) are confined to the area of equatorial forest and savanna woodland. The prevalence of P. ovale in West Africa decreases regularly from south to north of the region in accordance with the decrease in the rainfall (cf. Fig. 3 and Fig. 4). In woodland savanna areas it is often as wide- spread as in the neighbouring forests (Lacan & Peel, 1958; Choumara 2) and this indicates that the distribution of P. ovale is not directly influenced by the type of vegetation, but by climatic conditions. However, although the centre of abundance lies in the tropical forest zone, with its hot humid climate, the parasite is also found far beyond its limits, along the lower course of the River Senegal almost to the borders of the desert. On the other hand, in areas of the world with roughly identical climatic conditions, prevalence ranges from comparatively high in Africa to sporadic in the Western Pacific and to zero in the tropical areas of South and Central America. I Lacan, A. (1965) Plasmodium ovale Stephens 1922, sa distribution en Afrique (Unpublished document WHO/Mal/ 525.65). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. 2 Choumara, R. (1963) Note on Plasmodium ovale in South Cameroon (Unpublished document WHO/Mal/387). A limited number of copies of this document is available to persons officially or professionally interested on request to Distribution and Sales, World Health Organization, 1211 Geneva, Switzerland. AN ANALYSIS OF THE GEOGRAPHICAL DISTRIBUTION OF PLASMODIUM 0 VALE 391 FIG. 4 AREA OF DISTRIBUTION OF PLASMODIUM OVALE IN AFRICA AND DISTRIBUTION OF RAINFALL mm Area of distribution of P. ovale 1 Isohyets (mm) Relation with the vector fauna It is possible that these differences may be ex- plained by the different species-composition of the mosquito-vector fauna in different parts of the world. In tropical Africa, the main vector of malaria is Anopheles gambiae, and to a lesser extent A. funes- tus. It may be assumed that A. gambiae is a more effective vector of P. ovale than A. minimus flavi- rostris and A. punctulatus, which are the main malaria vectors in the Philippines and New Guinea respectively. Differences in prevalence in Africa could be ascribed to the fact that A. gambiae repre- sents a species complex, different constituents of which may behave differently in respect of P. ovale. The range of one of the species in the complex, A. gambiae sp. A, roughly corresponds to the area with the greatest prevalence of P. ovale.1 In addition a secondary vector such as A. moucheti, which is widespread in the forest areas of Africa, may play a role in the transmission of P. ovale. This suggestion contradicts the experimental findings, however, since it is well known that mosquito vectors from other zoogeographical regions are susceptible to infection with P. ovale. The Liberian strain and the Donaldson strain of P. ovale have been successfully transmitted through vectors from America-A. albimanus and A. quadrimaculatus (Jeffrey, Willcox & Young, 1955) and A. freeborni (Chin, Contacos & Buxbaum, 1966). The same applies to vectors from the Palaearctic region- A. maculipennis atroparvus, which has more than once been successfully infected with P. ovale from Africa (James, Nicol & Shute, 1932; Garnham et al., 1955) and A. maculatus (Chin, Contacos & Buxbaum, 1966). It should be noted, however, that the number of oocysts in non-African mosquitos has always been small. Possibly, although P. ovale is not strictly tied to one particular species of vector, not all the known species of Anopheles can ensure its endemic existence. Relation with host susceptibility The racial composition of the population is similar in both parts of the area of distribution of P. ovale. On the African continent it coincides with the settlements of the Negro race and in New Guinea with the settlements of the Melanesian race (Fig. 5). According to Soviet anthropologists these 2 races, which make up the equatorial race, are of closely related origin (Debec, 1955; Nesturh, 1960; Rogins- kij, 1962). As regards the Philippines and Madagas- car, the Mongoloid population of those islands has a strong admixture of the equatorial race, and in the Philippines, in addition, groups of pygmies, belonging directly to the equatorial race, have survived. It is known that resistance to certain diseases may be a racial character. Thus, the bulk of the Negroid population in Africa possess a congenital resistance to P. vivax, as has been demonstrated experimentally (Bray, 1958). This resistance has been retained by the American Negroes. Bray (1957a) considers that 1 Davidson, G. (1966) Distribution records of member species of the Anopheles gambiae complex (identifications up to May 1966) (Unpublished document WHO/Mal/66.570; WHO/Vector Control/66.215). A limited number of copies of this document is available to persons officially or profes- sionally interested on request to Distribution and Sales, World I-ealth Organization, 1211 Geneva, Switzerland. 5 A. JA. LYSENKO & A. E. BELJAEV FIG. 5 AREA OF DISTRIBUTION OF PLASMODIUM OVALE AND DISTRIBUTION OF PEOPLE BELONGING TO THE EQUATORIAL RACE a / o-, %% Area of distribution of P. ovale A Equatorial race-African 11_ .01 branch ______ Mixed and transitional forms 11I1I Mixed and transitional f4 - between equatorial and l l 'Mongoloid racs - - - europeoid races I I I mongoloid races a Based on Atlas of the world's peoples, Moscow, 1964. P. vivax cannot exist in a purely Negro environment, although a few individuals of the Negro race do not possess resistance to it. In places where the pre- valence of P. ovale is greatest (Nigeria, Ghana, Cameroon, Liberia and Gambia) P. vivax is practi- cally absent. It is regularly found only in East Africa, where there is a Europeoid element (Arabs, Indians, Europeans and the peoples of the Ethiopian transitional race), and in Madagascar, which is mainly peopled by Mongoloids. In accordance with this, the prevalence of P. ovale, as far as can be judged, is lower in those territories than in West I I I . Equatorial race-OceanicI I& branch Drms between equatorial and Africa. The peoples belonging to the Melanesian race, and the rest of the population of the islands of the Pacific Ocean, show no resistance to P. vivax, and P. ovale is encountered there very rarely. Although a comparison of the Liberian strain and the Donaldson strain of P. ovale showed that both Negroes and Caucasians are equally susceptible to both strains (Jeffrey, Willcox & Young, 1955), this does not exclude the possibility that under natural conditions very fine, almost undetectable, differences in the susceptibility of the host to the parasite, and in the formation of immunity, may come into play. 392 AN ANALYSIS OF THE GEOGRAPHICAL DISTRIBUTION OF PLASMODIUM 0 VALE Relation with simian malaria The features of the distribution of ovale malaria have suggested to some investigators that the disease is a zoonosis. Brumpt (1949), believing that P. ovale was distributed in all continents, but was encountered very rarely, wondered whether P. ovale was not an abrupt mutation of P. vivax or a malaria parasite of a vertebrate species with universal distribution. When it became clear that P. ovale was not so rare, but that its range was confined to certain tropical areas, Languillon (1957) suggested that P. ovale might be a normal parasite of apes, particularly chim- panzees. The possibility of transmission of P. ovale to chimpanzees, by passage through A. gambiae, has been experimentally proved (Bray, 1957b). Although P. ovale has a wider range than the chimpanzee, and one which partly overlaps with the range of the lower catarrhine monkeys, this does not altogether exclude the possibility of the circulation of this malaria parasite between man and ape. The fact that so far no analogues of human P. ovale, such as are known in P. vivax and P. malariae, have been found in the anthropoid apes, does not mean that they are absent in nature, since the biological features of P. ovale make it difficult to detect, particularly in apes. As already suggested, it may be that in some cases ovale-like plasmodia of the lower primates have been mistaken for P. ovale. The possibility of P. ovale becoming entrenched out- side its known area of distribution A number of biological features of P. ovale, particularly the long period of sporogony (15-16 days at 25°C, as against 10 days at the same temperature in the case of P. vivax), the very low and inconsistent rate of parasitaemia, the scanty production of gametocytes, and the low degree of infection of the vector create serious obstacles to its spread in areas with low temperatures and seasonal malarial trans- mission, with ineffective vectors or an insufficiently high population density of the vector. Some of these features are also found in P. malariae, but in P. ovale they are much more clear-cut. They may apparently be responsible for the special type of patchy distribution of both parasites inside the area of distribution of the disease. The greater duration of the course of infection in quartan and ovale malaria is apparently an evolutionary adaptation compensating for features in their biology which are unfavourable to the existence of the parasites. In view of what has been said, when single carriers of P. ovale enter a region free from ovale malaria the probability of transmission from a sick to a healthy person is practically nil and this may explain to some degree why P. ovale has not spread out of Africa, that citadel of malaria, and why it is absent from America, where all types of malaria were imported on a huge scale with African slaves and where a number of parasitic diseases, including tropi- cal and quartan malaria, have become entrenched. Jeffery, Young & Willcox (1954), who studied the Donaldson strain, expressed anxiety lest the P. ovale imported from the islands of the Pacific Ocean should become endemic in the USA, in which case great difficulties would arise in its detection and eradication. In the light of what has been said these fears seem to be exaggerated. CONCLUSION In conclusion it must be pointed out that not one of the factors considered (climate, vector fauna, area of distribution of simian species and racial features of the population) is sufficient by itself to explain the special features of the range of P. ovale. Obviously the explanation must be sought in a complex inter- action of the factors listed and possibly of others. There are grounds for supposing that the medico- geographical approach to the study of the dis- tribution of P. ovale will promote the successful solution of this problem. SUME ANALYSE DE LA RtPARTITION GEOGRAPHIQUE DE PLASMODIUM OVALE Plasmodium ovale Stephens 1922, considere autrefois comme un parasite rare du paludisme, retient davantage l'attention depuis quelque temps. La presente etude a pour objet d'evaluer le bien-fonde des rapports signalant sa presence hors d'Afrique, de determiner les limites de sa zone de repartition et d'analyser les parti- cularites de celle-ci. Les auteurs, examinant une serie de rapports affirmant l'existence de cas indigenes de P. ovale survenus ailleurs qu'en Afrique tropicale, estiment que l'identification de P. ovale n'est certaine que dans quelques cas, tous observ6s aux Philippines et en Nouvelle-Guinee. Les autres cas signales ne correspondent pas aux normes. diagnostiques et dpidemiologiques proposdes dans le 393 394 A. JA. LYSENKO & A. E. BELJAEV present document. II ressort de ces etudes que la zone de repartition de P. ovale se limite a I'Afrique tropicale et a des iles du Pacifique occidental. Les auteurs procedent ensuite 'a une analyse medico- geographique de la zone de repartition de P. ovale en fonction du climat, des especes de moustiques vecteurs et de la receptivite de l'hote. Ils envisagent egalement la possibilite d'une relation avec le paludisme simien. Ils concluent qu'aucun des facteurs consideres ne suffit par lui-meme a expliquer les caracteres particuliers de la r6partition de P. ovale, et que la solution du pro- bleme doit faire appel 'a l'interaction complexe de ces facteurs et peut-etre d'autres encore. On a des raisons de penser que la methode medico-geographique permettra de planifier les nouvelles recherches qui sont necessaires pour expliquer les particularites de la r6partition geogra- phique de P. ovale. REFERENCES Alves, W., Schinazi, L. A. & Aniceto, F. (1968) Bull. Wld HIth Org., 39, 494 Atlas of the World's Peoples (1964) Moscow Bray, R. S. (1957a) Amer. J. trop. Med. Hyg., 6, 638 Bray, R. S. (1957b) Amer. J. trop. Med. Hyg., 6, 961 Bray, R. S. (1958) J. Parasit., 44, 371 Brumpt, E. (1949) Pr&is de parasitologie, Paris Chin, W., Contacos, P. G. & Buxbaum, J. N. (1966) Amer. J. trop. Med. Hyg., 15, 5, 690 Craig, C. F. (1900). In: Report of the Surgeon-General, U.S. Army, Government Printing Office, Washington, D.C., p. 59 Craig, C. F. & Faust, E. C. (1951) Clinical parasitology, 5th ed., Philadelphia, Lea & Febiger, p. 243 Debec, G. F. (1955) [Races]. In: Large Soviet Encyclopae- dia, vol. 36, Moscow Dixit, N. S. (1958) Brit. med. J., 2, 1578 Eskin, V. A. (1938) Med. Parasit. (Mosk.), 7, 40 Fridman, M. M. (1946) Trudy Tbilisskoj klinicYeskoj bol'nicy ZKBfd, Tbilisi [Transactions of the Tbilisi Clinical Hospital ofthe Transcaucasian Railways, Tbilisi] Ganov, V. (1941) Bdlg. Klin., 18, 9 (Quoted from Med. Parazit. (Mosk.), 1948, 17, 187) Garcia, E. Y. (1941) Acta med. philipp., 2, 341 Garnham, P. C. C. et al. (1955) Trans. roy. Soc. trop. Med. Hyg., 49,158 Gurevitch, J. & Laufer, A. (1952) Ann. trop. Med. Parasit., 46, 238 Gvelisiani, I. D. (1940) Sovetsk. Med., 3, 43 Heydon, G. A. M. (1923) Hlth Bull. (Melbourne), 1, 249; Med. J. Aust., 2, 625 Jackson, A. V. (1944) Med. J. Aust., 2, 278 James, S. P., Nicol, W. D. & Shute, P. G. (1932) Ann. trop. Med. Parasit., 26, 139 James, S. P., Nicol, W. D. & Shute, P. G. (1933) Para- sitology, 25, 27 Jeffery, G. M., Willcox, A. & Young, M. D. (1955) Trans. roy. Soc. trop. Med. Hyg., 49, 168 Jeffery, G. M., Young, M. D. & Willcox, A. (1954) Amer. J. trop. Med. Hyg., 3, 628 Jevtid, M. & Bokic, P. (1965) Glasnik zavoda za zdravstve- nu zagitu SRS, Beograd, 14, 40 Lacan, A. (1965) Note sur la distribution de Plasmodium ovale en Afrique. In: Rapportfinal de la Ve Conference technique de I'OCCGE, Bodo-Dioulasso, vol. 1, p. 19 Lacan, A. & Peel, E. (1958) Bull. Soc. Path. exot., 51, 167 Languillon, J. (1957) Bull. Soc. Path. exot., 50, 587 Lisova, A. I., Sofiev, M. S. & Eskin, V. A. (1946) Med. Parazit. (Mosk.), 15, 40 McMillan, B. & Kelly, A. (1967) Trop. geogr. Med., 19, 172 Mageed, A. A. A. (1936) J. Egypt med. Ass., 19, 229 Matevosjan, 9. M. (1940) Med. Parazit. (Mosk.), 9, 291 Mendez, C. (1939) P. ovale, relacion delprimer caso obser- vado en Venezuela, Maracay, Divisi6n de la Malario- logia, Venezuela Muhlens, P. (1934) Arch. Schiffs-u. Tropenhyg., 38, 367 Muhlens, P. (1938) Malaria. In: Ruge, R., Miuhlens, P., & Zur Verth M., ed., Krankheiten und Hygiene der warmen Ldnder, Leipzig Mukherjea, A. K., Chatterjee, P. K. & Paul, S. C. (1966) Bull. Calcutta Sch. trop. Med., 14, 3, 88-89 Nesturh, M. F. (1960) [Primatology and anthropogenesis], Moscow Nikolaev, B. P. (1951) Zool. 2., 30, 211 Onori, E. (1967) Bull. Wld Hlth Org., 37, 665 Papafigou, T. (1947) Bull. Soc. Path. exot., 61, 161 Plehn, A. (1924) Dtsch. med. Wschr., 50, 136 Raman, T. K. (1940) J. Indian med. Ass., 9, 583 Roginskij, Ja. Ja. (1962) [Races]. In: Large Soviet Medi- cal Encyclopaedia, vol. 27, Moscow Russell, P. F. et al. (1963) Practical malariology, London, Oxford University Press Shieber, C. (1939) Harefuah, 16, 122 (Trop. Dis. Bull., 1939, 36, 809) Sinton, J. A., Hutton, E. L. & Shute, P. G. (1939) Trans. roy. Soc. trop. Med. Hyg., 32, 751 Trager, W. & Most, H. (1963) Amer. J. trop. Med. Hyg., 12, 837 Voronov, A. G. (1963) Biogeografija, Moscow Yao, Y. T. & Wu, C. C. (1941) Chin. med. J., 60, 178; J. trop. Med. Hyg. (1942), 45, 9 Young, M. D. & Johnson, T. H. J. (1949) J. nat. Malar. Soc., 8, 247 Young, M. D., Eyles, D. E. & Burgess, R. W. (1948) J. nat. Malar. Soc., 7, 171 Zulueta, J. de (1942), Rev. Fac. Med. vet. (Bogotd), 10, 487 (Trop. Dis. Bull., 39, 809)