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Notes on endemic and acute malaria in central African natives
403 I'R ' ANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE.
Vol. 42. No. 4. January, 1949.
NOTES
ON ENDEMIC AND ACUTE MALARIA CENTRAL AFRICAN NATIVES
IN
BY
J. SCHWETZ.
Adults and children suffering from endemic malaria show wide quantitative and qualitative differences in their reaction to the disease. Quantitatively, in children the percentage of infection is much larger than in adults ; qualitatively, in children, in addition to Plasmodium falciparum, the dominating species, some P. malariae and even P. vivax are present, with gametocytes belonging to all three species. As a rule, in adults only the trophozoites of P. falciparum are found with, exceptionally, some very rare crescents. Different districts exhibit marked differences in the rate and progress of the infection. In districts with a high malarial endemicity--hyperendemic districts--the peak of the infection is already reached at the age of 1 or 2 years ; in districts with a low endemicity--hypoendemic districts--the most heavily infected children are much older, their age is 5 and even 7 or 8 years. The slowing down of the infective advance is accompanied by a slowing down of its retrogression. Moreover, the percentage of P. malariae infection in children is low, and P. vivax is almost completely absent in the hypoendemic districts.
,404
MALARIA IN CENTRAL AFRICA
Results of the examination of children soon after birth show : (a) No congenital malaria. (b) The first species to appear is P. falciparum (trophozoites and even: crescents). Later comes P. malariae (schizonts and gametocytes), and lastly, P. vivax (schizonts and gametocytes). (c) The retrogression of the infection follows in reverse: P. vivax disappearing first, followed later by P. malariae, leaving in the adults only P. falciparum. On treating a group of young children with quinine, in a post-natal health clinic for instance, there is a rapid, though temporary, disappearance of P. malariae and P. vfvax parasites (schizonts and gametocytes). P. fMciparum parasites, and especially the crescents, are much more resistant and only succumb to much more intense and prolonged treatment With quinine. I do not intend to discuss the controversial problem of malarial immunity, a subject which does not come within the scope of this study. It may be concluded from the foregoing observations that the parasites of P. malariae, and especially of P. vivax, belong to a stage of recent infection, from which the organism gradually and spontaneously frees itself. I now turn to the application of this deduction to the diagnosis of acute malaria. It is a well-known fact that cases of acute malaria arise from time to time even in districts where the disease is endemic; these must be due to a breakdown of the acquired immunity. This breakdown is more frequent in children, where immunity is most recent and therefore less stable than that of adults. But even among the latter acute attacks are to be found, due to lowered resistance from various causes such as fatigue, cold, removal from one district to another (superinfection, new strain, etc.). The diagnosis of acute malaria in an adult native living in a malarial district is not always easy. Indeed, the malarial parasites are present both in healthy apyretic natives and in those suffering from fever. The intensity of infection and the large number of parasites usually accompanying a feverish attack are not absolute proof of its malarial aetiology, for the parasites may sometimes be extremely numerous in healthy natives in certain hyperendemic districts, especially in children. Are these parasites survivals of a previous infection, or are they pathognomonic of a first infection ? Can this be ascertained by microscopical examination, or, at least, can the use of the microscope bring a valid contribution towards such a decision ? On the other hand, malaria does not extend in a continuous belt over the whole of Central Africa. In some districts, Or at least in some spots, no malaria at all is to be found, namely, at heights over 1,800, and especially 2,000 metres.
j. SCHWETZ
405
In these districts there is no more immunity among the natives than there is among the whites. In consequence, when the native inhabitants of these high districts come down into lower regions, where endemic malaria exists, they are not slow in contracting malaria and in reacting in a manner similar to that of Europeans with fever and the different complications, haemoglobinuria included. The industrial development of the Central African colonies has led to much migration amongst the natives, and this has been followed by severe outbursts of acute malaria. This is especially true of Ruanda-Urundi, where foci of epidemic malaria have become established in recent years. The mean level of this country is high, but the land is very rough, the'high inhabited plateaux being intersected by deep and marshy valleys. To prevent drought and consequent famine, the Government has drained and cultivated these marshy valleys, and this has been followed by epidemics of acute malaria among the non-immune natives of these h!ghland regions. Our recent investigations in Ruanda-Urundi have disclosed a highly complicated situation. On one side, on high plateaux of 2,000 metres with slightly lower valleys, we found no malaria except a few sporadic infections obviously contracted on trips to distant and lower districts; whilst, in lower districts of 1,400 to 1,500 metres altitude, we found a light endemic malarial infection. In regions situated at the high level limit of malaria, at about 1,700 to 1,800 metres, we found, besides a high endemic malaria, a certain number of recent cases of the acute disease, dating from the draining of the neighbouring marshes. Lastly, we found plateaux of 1,800 to 2,000 metres altitude, where cultivation of the neighbouring marshes at 1,500 to 1,650 metres had'induced severe epidemics of acute malaria. In certain of these districts the epidemics were not recent but dated back 2 or 3 years. The malaria was now subacute or subchronic, and fever was absent. The unravelling of this situation is not easy, especially the determination of the stage of the infection. Moreover, in some of these foci the whole population had been more or less treated with quinine and it was necessary to determine whether natives with no parasites had never been infected, or whether the absence of parasites was due to treatment with quinine. The parasite rates we found there were quite peculiar, bearing no resemblance either to epidemic or endemic malaria. Two unusual phenomena had struck us and suggested the possibility of determining the " age " of a case of malaria by microscopical examination. (1) In two neighbouring villages on tile banks of Lake Edward (900 metres altitude), we found two entirely dissimilar malarial situations. In the first village the children were infected with P. falciparum + P. malariae ; the adults harboured only some rare P. falciparum (trophozoites). In the second village,
406
MALARIA IN CENTRAL AFRICA
a m o n g the adults we found P. falciparum, some cases with P. malariae and even P. vivax (schizonts and g a m e t o c y t e s ) . I t was only later that we found the solution of this puzzle. T h e natives of the first village had always lived on the banks of the lake. T h o s e of the second village had originally lived on the high plateaux dominating the western part of the lake, f r o m which they had come down 2 years before in order to start a fishery. D u r i n g the first year of their sojourn near the lake, these " immigrants " had suffered f r o m fever, and their death-rate had been inordinately high. At the t i m e we visited t h e m there was no longer a malaria epidemic, b u t merely the m o r e or less immediate consequences of one, i.e., subchronic malaria, and this explains our findings of P. malariae, and even P. vivax, a m o n g t h e adults. (2) As regards the trophozoites of P. falciparum which form the bulk of malarial infection in children as in adults, in b o t h endemic and epidemic malaria, I reproduce here a passage f r o m one of our p r e v i o u s studies, written in 1939 and printed in 1941.* After emphasizing the caution necessary in diagnosing fever of malarial origin in a district with endemic malaria, where the • parasites m a y only be commensals, we m a d e t h e following remarks : " Nevertheless in most cases a diagnosis may be made with a great deal of probability, especially among adults. If the pyretic patient shows no symptoms of any other disease, and if his blood at the same time contains a large number of very small trophozoites, a diagnosis of acute malaria may be made without any great risk of making a mistake. We insist upon the size of the trophozoites and upon the accompanying alterations of the red cells as a means of differential diagnosis between acute and chronic malaria, an adjuvant rather than an absolute means, to be sure. In this case there are numerous minute trophozoites, i.e., small thin rings, in normal red blood cells. Then, in chronic malaria we find more advanced trophozoites, with larger and thicker rings, in cells having already suffered the specific alterations--a general coppery colour with a certain number of Maurer's dots. These two morphological varieties have struck numerous observerS, and two or even more sub-species ofP. falciparum have been created accordingly. But in our opinion it is simply a question of age difference of the trophozoites. In acute malaria we encounter very young trophozoites which, owing to lack of time, have been unable to produce alterations in the red blood cell. In chronic malaria we are faced with more advanced stages." We m a y add that, even in children, a differential diagnosis m a y be m a d e b y a consideration of the morphological varieties of P. falciparum. But in certain h y p e r e n d e m i c districts of the Congo (in the M a y u m b e for instance), the n u m b e r of trophozoites (and this is equally valid for all malarial parasites) is very large in children whose state of health is nevertheless perfect. However, the t r o p h o zoites encountered are large and thick, the globular alterations are so m a r k e d that the infected cell can be picked out at a glance, because of its deeper, coppery e- j. SCHWETZet H. BAUMANN. Recherches sur le Paludisme dam les villages et les camps des mines d'or de Kilo Moto (Congo Belge). Mdmoire de l'Institut Royal Colonial Beige, 1941.
J. SCIIWF.TZ
407
colour, even before the Stephens-Maurer dots and the trophozoites themselves are seen. On the contrary, in acute pyretic malaria the infected cells are not altered in the least and contain only minute trophozoites, very thin rings, but these are quite numerous, often several in one cell. Although differential diagnosis between acute pyretic malaria and endemic apyretic malaria is fairly easy, complications appear in the case of subacute malaria, a sequel to epidemic malaria, the epidemic dating back several months or even 2 or 3 years. Patients are already sub-pyretic or even apyretic, although patently still suffering from their recent infection, not having yet acquired a sufficient immunity. It is this post-epidemic stage we encountered in different Ruanda-Urundi districts. We must here distinguish between individual and collective examinations :
(a) Individual Examination.--Presence or absence of numerous minute trophozoites in a child or an adult. The presence in an adult of P. malariae forms, and especially of P. vivax forms, is proof of a recent infection, of a subacute or subehronie s t a g e . (b) Collective Examinations.--The results of the examination of a natural group of natives, such as a village, are clearer and easier to explain. In endemic malaria there is a sharp difference between children and adults, both quantitative and qualitative. This has already been discussed. No such difference is to be found between the different age groups in the case of epidemic or post-epidemic malaria. The number of infected individuals among adults is quite as large as, or even larger than, in children. The P. malariae and P. vivax parasites (schizonts and gametocytes) are found on the same scale in adults and children. This picture is found only in untreated epidemics. Medication alters, in proportion to its intensity, the parasite picture. In a group of villages, for instance, when the epidemic h a d begun a few months before, and where the patients were found to be obviously ill, with or without fever, the population had been collectively treated with totaquina and atebrin, but in a haphazard and quite inadequate manner. The parasite picture we found among the patients was very curious, though easily understood: 11o, or very few, trophozoites ; on the contrary, some rare or even fairly numerous P. malariae gametocytes, and especially P. falciparum (crescents, including young microgametocytes, circular in shape and red in colour). SUMMARY. Although in general the malaria extant among Central African natives is endemic, in certain districts, namely, in the high plateaux bordering on the Graben (Kivu-Ituri and Ruanda-Urundi), epidemic malaria has been observed during recent years. The microscopical blood picture can be a useful aid to G
408
MAI.ARIA IN CENTRAL AFRICA
the differential diagnosis of acute and endemic malaria. In the latter large and more or less thick trophozoites are encountered in cells with specific alterations ; in the case of acute malaria minute trophozoites are found which have not yet been able to cause alterations in the red cells. A notable distinction exists in endemic malaria as found in children and adults : in children there is a remarkable proportion of infected red cells with P. malariae and P. vivax ; in adults the number of infected cells is very much less and only trophozoites ofP. falciparum are encountered. In epidemic malaria, pyretic or even apyretic, the number of infected adults is the same as that of ehildren, and both groups show parasites of P. malariae and even of P. vivax.
Vol. 42. No. 4. January, 1949.
NOTES
ON ENDEMIC AND ACUTE MALARIA CENTRAL AFRICAN NATIVES
IN
BY
J. SCHWETZ.
Adults and children suffering from endemic malaria show wide quantitative and qualitative differences in their reaction to the disease. Quantitatively, in children the percentage of infection is much larger than in adults ; qualitatively, in children, in addition to Plasmodium falciparum, the dominating species, some P. malariae and even P. vivax are present, with gametocytes belonging to all three species. As a rule, in adults only the trophozoites of P. falciparum are found with, exceptionally, some very rare crescents. Different districts exhibit marked differences in the rate and progress of the infection. In districts with a high malarial endemicity--hyperendemic districts--the peak of the infection is already reached at the age of 1 or 2 years ; in districts with a low endemicity--hypoendemic districts--the most heavily infected children are much older, their age is 5 and even 7 or 8 years. The slowing down of the infective advance is accompanied by a slowing down of its retrogression. Moreover, the percentage of P. malariae infection in children is low, and P. vivax is almost completely absent in the hypoendemic districts.
,404
MALARIA IN CENTRAL AFRICA
Results of the examination of children soon after birth show : (a) No congenital malaria. (b) The first species to appear is P. falciparum (trophozoites and even: crescents). Later comes P. malariae (schizonts and gametocytes), and lastly, P. vivax (schizonts and gametocytes). (c) The retrogression of the infection follows in reverse: P. vivax disappearing first, followed later by P. malariae, leaving in the adults only P. falciparum. On treating a group of young children with quinine, in a post-natal health clinic for instance, there is a rapid, though temporary, disappearance of P. malariae and P. vfvax parasites (schizonts and gametocytes). P. fMciparum parasites, and especially the crescents, are much more resistant and only succumb to much more intense and prolonged treatment With quinine. I do not intend to discuss the controversial problem of malarial immunity, a subject which does not come within the scope of this study. It may be concluded from the foregoing observations that the parasites of P. malariae, and especially of P. vivax, belong to a stage of recent infection, from which the organism gradually and spontaneously frees itself. I now turn to the application of this deduction to the diagnosis of acute malaria. It is a well-known fact that cases of acute malaria arise from time to time even in districts where the disease is endemic; these must be due to a breakdown of the acquired immunity. This breakdown is more frequent in children, where immunity is most recent and therefore less stable than that of adults. But even among the latter acute attacks are to be found, due to lowered resistance from various causes such as fatigue, cold, removal from one district to another (superinfection, new strain, etc.). The diagnosis of acute malaria in an adult native living in a malarial district is not always easy. Indeed, the malarial parasites are present both in healthy apyretic natives and in those suffering from fever. The intensity of infection and the large number of parasites usually accompanying a feverish attack are not absolute proof of its malarial aetiology, for the parasites may sometimes be extremely numerous in healthy natives in certain hyperendemic districts, especially in children. Are these parasites survivals of a previous infection, or are they pathognomonic of a first infection ? Can this be ascertained by microscopical examination, or, at least, can the use of the microscope bring a valid contribution towards such a decision ? On the other hand, malaria does not extend in a continuous belt over the whole of Central Africa. In some districts, Or at least in some spots, no malaria at all is to be found, namely, at heights over 1,800, and especially 2,000 metres.
j. SCHWETZ
405
In these districts there is no more immunity among the natives than there is among the whites. In consequence, when the native inhabitants of these high districts come down into lower regions, where endemic malaria exists, they are not slow in contracting malaria and in reacting in a manner similar to that of Europeans with fever and the different complications, haemoglobinuria included. The industrial development of the Central African colonies has led to much migration amongst the natives, and this has been followed by severe outbursts of acute malaria. This is especially true of Ruanda-Urundi, where foci of epidemic malaria have become established in recent years. The mean level of this country is high, but the land is very rough, the'high inhabited plateaux being intersected by deep and marshy valleys. To prevent drought and consequent famine, the Government has drained and cultivated these marshy valleys, and this has been followed by epidemics of acute malaria among the non-immune natives of these h!ghland regions. Our recent investigations in Ruanda-Urundi have disclosed a highly complicated situation. On one side, on high plateaux of 2,000 metres with slightly lower valleys, we found no malaria except a few sporadic infections obviously contracted on trips to distant and lower districts; whilst, in lower districts of 1,400 to 1,500 metres altitude, we found a light endemic malarial infection. In regions situated at the high level limit of malaria, at about 1,700 to 1,800 metres, we found, besides a high endemic malaria, a certain number of recent cases of the acute disease, dating from the draining of the neighbouring marshes. Lastly, we found plateaux of 1,800 to 2,000 metres altitude, where cultivation of the neighbouring marshes at 1,500 to 1,650 metres had'induced severe epidemics of acute malaria. In certain of these districts the epidemics were not recent but dated back 2 or 3 years. The malaria was now subacute or subchronic, and fever was absent. The unravelling of this situation is not easy, especially the determination of the stage of the infection. Moreover, in some of these foci the whole population had been more or less treated with quinine and it was necessary to determine whether natives with no parasites had never been infected, or whether the absence of parasites was due to treatment with quinine. The parasite rates we found there were quite peculiar, bearing no resemblance either to epidemic or endemic malaria. Two unusual phenomena had struck us and suggested the possibility of determining the " age " of a case of malaria by microscopical examination. (1) In two neighbouring villages on tile banks of Lake Edward (900 metres altitude), we found two entirely dissimilar malarial situations. In the first village the children were infected with P. falciparum + P. malariae ; the adults harboured only some rare P. falciparum (trophozoites). In the second village,
406
MALARIA IN CENTRAL AFRICA
a m o n g the adults we found P. falciparum, some cases with P. malariae and even P. vivax (schizonts and g a m e t o c y t e s ) . I t was only later that we found the solution of this puzzle. T h e natives of the first village had always lived on the banks of the lake. T h o s e of the second village had originally lived on the high plateaux dominating the western part of the lake, f r o m which they had come down 2 years before in order to start a fishery. D u r i n g the first year of their sojourn near the lake, these " immigrants " had suffered f r o m fever, and their death-rate had been inordinately high. At the t i m e we visited t h e m there was no longer a malaria epidemic, b u t merely the m o r e or less immediate consequences of one, i.e., subchronic malaria, and this explains our findings of P. malariae, and even P. vivax, a m o n g t h e adults. (2) As regards the trophozoites of P. falciparum which form the bulk of malarial infection in children as in adults, in b o t h endemic and epidemic malaria, I reproduce here a passage f r o m one of our p r e v i o u s studies, written in 1939 and printed in 1941.* After emphasizing the caution necessary in diagnosing fever of malarial origin in a district with endemic malaria, where the • parasites m a y only be commensals, we m a d e t h e following remarks : " Nevertheless in most cases a diagnosis may be made with a great deal of probability, especially among adults. If the pyretic patient shows no symptoms of any other disease, and if his blood at the same time contains a large number of very small trophozoites, a diagnosis of acute malaria may be made without any great risk of making a mistake. We insist upon the size of the trophozoites and upon the accompanying alterations of the red cells as a means of differential diagnosis between acute and chronic malaria, an adjuvant rather than an absolute means, to be sure. In this case there are numerous minute trophozoites, i.e., small thin rings, in normal red blood cells. Then, in chronic malaria we find more advanced trophozoites, with larger and thicker rings, in cells having already suffered the specific alterations--a general coppery colour with a certain number of Maurer's dots. These two morphological varieties have struck numerous observerS, and two or even more sub-species ofP. falciparum have been created accordingly. But in our opinion it is simply a question of age difference of the trophozoites. In acute malaria we encounter very young trophozoites which, owing to lack of time, have been unable to produce alterations in the red blood cell. In chronic malaria we are faced with more advanced stages." We m a y add that, even in children, a differential diagnosis m a y be m a d e b y a consideration of the morphological varieties of P. falciparum. But in certain h y p e r e n d e m i c districts of the Congo (in the M a y u m b e for instance), the n u m b e r of trophozoites (and this is equally valid for all malarial parasites) is very large in children whose state of health is nevertheless perfect. However, the t r o p h o zoites encountered are large and thick, the globular alterations are so m a r k e d that the infected cell can be picked out at a glance, because of its deeper, coppery e- j. SCHWETZet H. BAUMANN. Recherches sur le Paludisme dam les villages et les camps des mines d'or de Kilo Moto (Congo Belge). Mdmoire de l'Institut Royal Colonial Beige, 1941.
J. SCIIWF.TZ
407
colour, even before the Stephens-Maurer dots and the trophozoites themselves are seen. On the contrary, in acute pyretic malaria the infected cells are not altered in the least and contain only minute trophozoites, very thin rings, but these are quite numerous, often several in one cell. Although differential diagnosis between acute pyretic malaria and endemic apyretic malaria is fairly easy, complications appear in the case of subacute malaria, a sequel to epidemic malaria, the epidemic dating back several months or even 2 or 3 years. Patients are already sub-pyretic or even apyretic, although patently still suffering from their recent infection, not having yet acquired a sufficient immunity. It is this post-epidemic stage we encountered in different Ruanda-Urundi districts. We must here distinguish between individual and collective examinations :
(a) Individual Examination.--Presence or absence of numerous minute trophozoites in a child or an adult. The presence in an adult of P. malariae forms, and especially of P. vivax forms, is proof of a recent infection, of a subacute or subehronie s t a g e . (b) Collective Examinations.--The results of the examination of a natural group of natives, such as a village, are clearer and easier to explain. In endemic malaria there is a sharp difference between children and adults, both quantitative and qualitative. This has already been discussed. No such difference is to be found between the different age groups in the case of epidemic or post-epidemic malaria. The number of infected individuals among adults is quite as large as, or even larger than, in children. The P. malariae and P. vivax parasites (schizonts and gametocytes) are found on the same scale in adults and children. This picture is found only in untreated epidemics. Medication alters, in proportion to its intensity, the parasite picture. In a group of villages, for instance, when the epidemic h a d begun a few months before, and where the patients were found to be obviously ill, with or without fever, the population had been collectively treated with totaquina and atebrin, but in a haphazard and quite inadequate manner. The parasite picture we found among the patients was very curious, though easily understood: 11o, or very few, trophozoites ; on the contrary, some rare or even fairly numerous P. malariae gametocytes, and especially P. falciparum (crescents, including young microgametocytes, circular in shape and red in colour). SUMMARY. Although in general the malaria extant among Central African natives is endemic, in certain districts, namely, in the high plateaux bordering on the Graben (Kivu-Ituri and Ruanda-Urundi), epidemic malaria has been observed during recent years. The microscopical blood picture can be a useful aid to G
408
MAI.ARIA IN CENTRAL AFRICA
the differential diagnosis of acute and endemic malaria. In the latter large and more or less thick trophozoites are encountered in cells with specific alterations ; in the case of acute malaria minute trophozoites are found which have not yet been able to cause alterations in the red cells. A notable distinction exists in endemic malaria as found in children and adults : in children there is a remarkable proportion of infected red cells with P. malariae and P. vivax ; in adults the number of infected cells is very much less and only trophozoites ofP. falciparum are encountered. In epidemic malaria, pyretic or even apyretic, the number of infected adults is the same as that of ehildren, and both groups show parasites of P. malariae and even of P. vivax.