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THE PROBLEM OF RICKETTSIOSES IN THE USSR
AND CURRENT TASKS CONCERNING IT
Zhurnal 1~?Y.robiolor;ii, hpidemiologii,
i Irrmunot,iolo~;ii? No '%
Moacow, Jul 1954
The stuffy of rickettsiae and rickettsioses is at present being set apart as
a new and independent subdivision oi' the branch oi' medicsl sciences which deals
with infectious diseases. Accordingly, the new discipline of rickettsiology is
being differentiated as a subdivision of medical microbiology and has been added
to the older subdivisions of protozoology, bacteriology, and virology. (The
editor oi' the periodical says here in a i'ootr,ate comment that it is hardly ex-
pedient at present to separate the theory oi' rickettsioses into an independent
discipline.] It is therefore natural that in plans made for research, the stuffy
of rickettsioses has also been separateu in the Porm of sn independent problem.
The separation oi' the study of rickettsiae and rickettsioses into a special
subdivision of the medical science on infectious uiseases is expedient and timely.
Specifically, this separation is based on the characteristics which typify the
biology of rickettsiae as that of an individual group of intracellular micro-
organiems, the worr. on which required the application of special laboratory
meti:ous. This separation is also justified by the specific characteristics of the
clinical and puthomorohological aspects of rickettsisl diseases, by *.he consider-
able spread of these diseases, and by the presence among them of forms which are
of great significance frora the standpoint of public health, such as typhus, Q
fever, tsutsugarnushi fever, and Rocgy Mountain spotted fever. Furthern;ore, the
separation oi' rickettsioses into a special group is based on the peculiar traits
oi' their epidemiolorGy, which, as a rule, is associated with the presence of blood-
sucking transmitters such as lice, fleas, ticks, or mites. Often, the identical
infection is present among; animals i:r the focus oi' the disease in question. in
accordance with this, the study of rickettsioses is connected with the appropriate
subdivisions of parasitology and medical patholoSy, including; the study of natural
foci of transmissive infection, as this subject is understood by Ye. N. Pavlovskly.
As a result, the attempt to g;eneraiize and summarize the data on rickett-
sioses which had been accumulated reyuired the publication of an extensive mono-
graph and ;csnual, which, in turn, illustrates the extent and specific character-
istics of the subject under discussion (P. F. Zdrodovskiy, Ye. M. Golinevich,
Uchenive o Rikketsivai:h i Rikketsioza}:h [The Science of RicketL-siae and R!ckett-
sioses], hiedgiz, Moscow, 1953, 440 pp).
At the same time, one must tare into consideration that the study of
r?ic}cettsioses is still in a period of initial development which has not been
completed and that it is being; continuously supplemented by new facts and discov-
eries, while the increased importance of rickettsioses in the infectious pathology
of humans is becoming clearer. As far as the actual significance of rickettsioses
for the regional patholoDy of ttre USSR is concerned, it is determined bp.?the fol-
lowing data. During; the past 1'7 years (1936-1953), Soviet investi[;ators have
detected or discovered on the territory of the USSR the i'ollowing endemic rickett-
sioses: marine typhus, vesicular rickettsioses or rickettsisl pox, boutonneuse
fever, the tici: rickettsioses of Central Asia, paroxysmal tick rickettsioses, and
6',-fever or pulmonary rickettsioses. Ir: addition to that, residual forr.,s of epi-
demic typhus are still found, and locally there is occurrence of trench fever.
T}rus, the existence oi' eight different forms of rickettsioses has been es-
tablished in the USSR, among them six endemic rickettsioses connected with cor-
responding enzootics among wild or domestic animals. One nmst particularly
emphasize that in recent times, foci of Q fever have been discovered in some
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localities of the USSR. Q fever is a disease which affects Loth human beings
and farm animals. It has been suddenly discovered everywhere in Europe and
in a number of regions of Asia adjacent to the USSR.
Let us now discuss the research problems and particular organizational
problems which arise in connection with rickettsioses. Within the Framework
of the present review, we will limit ourselves to a discussion of the most
important problems of a general type and will not touch on special laboratory
research. One of the most important tasks is further investigation of the
geographic distribution of endemic rickettsioses which are already Y.nown and
the existence of which has been established. This investigation should be
accompanied by a more thorough study of the regional epidemiology of these
rickettsioses. This refers particularly to marine typhus and to the whole
group of tick rickettsioses (North Asiatic rickettsiosis, vesicular rickett-
siosis, and boutonneuse fever) and must be particularly stressed in relation
to Q fever. In addition to this, the search for new types and varieties of
rickettsioses is indicated,
For the precise diagnostics in territorially new foci of endemic
rlckettsioses end for the differentiation of new types of rickettsiosis, the
isolation oi' the causative factors (rickettsiae) from patients is required
and also detection of these factors in the corresponding links of the epide-
miological chain, i.e., in the blood-sucking parasite vectors, in wild animals
on which the blood-sucking transmitters parasitize, and among domestic animals,
if the latter as such form a source and reservoir of the infection. It i.s well
known that from the standpoint of the methods applied, this task is carried
out by infecting experimental animals with the material in question. This work
is conducted, as a rule, with the use of guinea pigs, and the causative factor
is lister detected in them according to the beneral rules for the detection of
rickettsiae.
The differentiation of the rickettsia strains isolated in this manner
is carried out by methods which make possible a comparative characterization.
These methods are cytomos?phological, involving multiplication in the cyto-
plasm and in the nuclei of affected cells; cultural, involving propagation
in egg cultures; experimental, involving experiments on animals; and sero-
immunological, involving testing for direct serological reactions and cross
reactions and carrying out experiments on the imesunization of animals. In
the course of this work, the strains under investigation must be preserved
by passing them through animals (this is a method which is only of relative
importance), ox still better, by culturing these strains. It is best to
preserve the Rickettsia strains (egg cultures or rickettsial material from
animals) in a dessicated form.
One must note particularly that in the process of a preliminary search
for the foci of these rickettsioses, as well as in the subsequent study of
these foci, it is of great importance to apply methods of serological inves-
tigation on sick humans and animals suspected oi' having rickettsioses.
Generally speaking, it is important to keep in mind that serological
methods of investigation, under application of specific rickettsial antigens,
play a most prominent :?ole in contemporary wor;c on the detection and differen-
tiation of rickettsial infections among humans and animals. It is essential
to take recourse to these methods in carryying out such work. The methods in
question, which comprise the agglutination reaction and quite particularly the
reaction of compliment fixation, make it possible to recognize with certainty
among humans and animals the occurrence of a rickettsiosis infection either in
the past or at present, while at the same time, the croup and type specificity
of the causative factor of the infection can be established.
_ _ _ _. _ . ,
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Accordingly, the specific serological diagnosis of rickettsioses is the
principal method for identifying these diseases among patients at hospitals.
This method of diagnosis is absolutely indispensable in all types of epide-
miological and epizoological investigations of rickettsioses, including their
retrospective investigation.
Specific serological diagnosis as a preliminary and orienting method of
investigating suspicious patients is particularly indicated in the detection of
and search for new endemic rickettsioses, in view of the fact that the serolo-
gical detection of rickettsiosis of some group or type in human beings is a
good index of the presence in the region in question of natural foci of the
rickettsiosis in question.
Advisable also are serological investigations of wild and domestic animals
to find enzootic sources of the rickettsiosis infection in the region where
infections c,ccur among humans. On the other hand, the Pact that the infection
is present in humans may indicate that wild or domestic animals are also affected.
Generally speaking, specific serological diagnosis which is supported by
the isolation of the causative factor either in work on the detection of new
foci or in connection with special tasks is one of the basic and obligatory
methods for the detection of rickettsioses. Any procedures used for the mass
investigation of humans and animals with a view to detecting rickettsioses are
completely valid only when serological tests are applied. At the same tiiae,
the serological characterization of rickettsiae according to their. antigenic
structure is the basic prerequisite for the differentiation and classification
of these organisms.
As has already been stated, the application of the reaction of complement
fixation is particularly indicated for purposes of the specific serological
diagnosis of rickettsioses. In addition to the clarity of the results obtained
and the possibility of their application in retrospective serological diagnosis,
the reaction of complement fixation with the use of the so-called full antigens
(GOlinevich) makes certain the diagnosis of all types of rlckettsioses, including
those of the tick-transmitted group. The possibility of diagnosing tick-trans-
mitted rickettsioses is particularly important because no corpuscular antigens
exist for them, so that the reaction of agglutination can not be carried out.
Furthermore, the experience acquired at our laboratory has shown that the re-
action of complement fixation can be carried out with serum dried on paper and
sent from the foci being investigated to the central laboratories (Yablonskaye).
Finally, one must take into consideration the possibility of supplying full
antigens for the reaction of complement fixation at s very low cost, which ie not
a matter of indifference in the case of mass investigations, because the corpus-
cular antigens used in the reaction of agglutination have a very high primary cost.
Thus, the detection and investigation of rickettsioses is impossible
locally without the application of contemporary methods of specific serological
investigation, among which diagnosis with the aid of the reaction of complement
fixation is the most important from every standpoint. This leads to two impor-
tant requirements. First, the Ministry of Health USSR must secure the mass
production of all types of rickettsiosis antigens, including full antiaena for
the reaction of complement fixation. Secondly, the laboratories located in the
regions affected must familiarize themselves with the methods of the specific
serological diagnosis of rickettsioses, particularly the reaction of complement
fixation. 1?lithout practical organizational solution of the problems involved,
both from the standpoint of methods and that of technology, one cannot solve
the problems of the geographic distribution of rickettsiosis and of their group
and type differentiation, combined with a precise clarification of the elements
of their regional epidemiology and epizootology.
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lately-in some ~regioasoofdtheoUSSRfoci of Q-fever have been discovered
-was infection with Q-fever of cattle andtothercflities in question, there
Chumalcov, et al; Khodukin and Lysunkinn; Kulagin8a daKekcheyeva)friThe ??
findings relative to Q-fever imposed on medical and veterinary workers the task
of carrying ou+c investigations with a view to clarifying the actual distribution
of the Q-fever.? rickettsiosis and establishing precisely the nature of its
epidemiology (the presence of the infection among domestic animals and in
natural foci, i,e., among ticks and wild animals),
Initially the investigations in question, primarily serological investiga-
tiona.with the aid of the reactions oP agglutination or of complement fixation,
should be carried out at mayor meat combines in various regions, so that if
@-fever is discovered among the workers at the meat combines and among the?
cattle that are being slaughtered, one may transfer the investigation to the
regions where the sick animals have been bred. One should also carry out serolo-
gical investigations aiming at the discovery of the Q-fever rickettsiosis among
patients having atypical pneumonias or lingering influenza. This applies
particularly to persons who are associated with some activity in the field of
animal breeding or an activity involving the processing of raw material of
animal origin, particularly wool.
It is quite clear that in addition to epidemiological and enzoological?
investigations, wort. should be done at rickettsiosis laboratories with a view
to a comprehensive investigation of any new rickettsiosis which may occur,
one should pay particular attention to the study of the distribution of
having inpmindatheobasinscofrtheeg~ckcSeaf the Caspian Sea, andtthe lowease,
lying lands in the valleys of the rivers within these basins, as well as the
coastal regions of the Far-mast, In addition to this, thorough research on
the tick rickettsiosis of the Northern Asiatic type must be carried out in the
regions of Central Asia. It is also necessary to carry out comprehensive
investigations of the paroxysmal tick rickettsiosis described by Ukrainian
authors (Sirotinin, Ruchkovskiy, Padalka et,al.), since the position occupied-
by this particular rickettsiosis uitki refation to other rickettsioses is not
clear, because the characteristics of the causative factor are not known.- In
addition, it is advisable to conduct cork reviewing the nature of the eo-called
hemorrhagic fever from the standpoint of the possibility that this disease may
have ricketteial etiology, at least in some areas of western Siberia. This ~
problem can perhaps be successfully solved with the aid of a serological inves-
tigation of patients, involving application of a complete selection of rickett-
siosis antigens.
While .limiting ourselves to tasks which are primarily of a regional charac_ r
ter, as far as the endemic rickettsioses discussed above are concerned, we will
now consider the tasks connected with the problem of the residual forms 'of
typhus, which, to a ma,~or degree, coincide with those raised by the problem of
recurrent typhus.
As a discussion conducted in 1952 has shown, the ma,~ority cf Soviet
specialists qualified to interpret the nature of residual or recurrent forms
of typhus adheres to the concepts oi' the classical epidemiology of typhus,
cihirh r?r_ognizes the significance of the louse factor and of the loss of irmsunity
in those who have been repeatedly infected (see the articles on the subject
published in Zhurnal Diikrobiolo ii E idemiolo?13 i Irununobiolo ii during 1952).
In contradistinction to the prevalent view, K. N. Toknrevich and G. S.
Mosing.expressed agreement with the views of Zinsser and Parrot, which have
received wide recognition abroad, and advanced the hypothesis of recrudescence
in recurrent typhus. They consider that at least in a certain number of cases,
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typhus assumes a latent form of indefinite duration, and recrudescence takes
place under certain conditions, so that the clinical characteristics of re-
cu?'rent typhus appear again, `
Finally, our laboratory (Zdrodovakiy, Colinevich, and Kulagin), on the basis
of characteristics of the epidemiology of sporadic forma of typhus and the
detection in these forms of a new intermediate variant of Prowazek rickettsia
(R, prowazeki var, intermedin, Golinevich 195 0 , expressed the opinion that
these forms are produced by a special variety of rickettsia which perhaps
does not arise within the chain man-louse-man but~in some other epizootologirr7
connection. The assumption was made that the modified causative factor of
typhus circulates within a chain formed by Gamasidae mites and domestic rodents
(Zdrodovskiy, Kulagin), In other words, the question was advanced as to~whether
there isn't, a reservoir of the causative factor of typhus outside of human
beinRS similar to that present in all other rickettsioses, with the exception
of trench fever.,
All the assumptions expressed remain hypothetical and require further
research and precise proof, This refers particularly to the interpretation of
data on residual or recurrent forms of typhus frog the standpoint of classical
epidemiology, because, in a number of cases, the origin of sporadic typhus can-
not be explained satisfactorily from this standpoint.
This applies to a still greater degree to the hypothesis assuming recru-
descence of recurrent typhus, because precise proofs are often net given and
purely speculative discussions and reasoning by analogy are substituted for
these proofs. Without factual data, this very important hypothesis, which
inactivates practical measures, can not be accepted, From the standpoint of
this hypothesis, the search for the causative factor of typhus in persons who
recovered from typhus a long time ago must be conducted. With this aim in
view, one may utilize to some extent material obtained in surgical operations,
In other cases, one may perhaps apply for the same purpose the method of punc-
turing bones and investigating samples of bone marrow obtained in this manner,
This is a method used in hematology and in investigations dealing with leish-
maniasis, Finall;~, one may use material obtained in autopsies carried out on
persons who had had typhus, It, is obvious that the investigations in question
must be carried out with the application of the most sensitive method, namely,
that of the infection of clothes lice,
The same requirements must be put to the adherents of classical epidemiology,
who must supply objective proof of the applicability of the factor louse-man-
louse to the cases of sporadic typhus which are observed and who must also refute
conclusively the epidemiological basis on which the hypothesis of recrudescence
rests.
To summarize, the problem of residual or recurrent sporadic forms of
typhus must be subjected to many-sided investigations and a number of postulates
of classical epidemiology must be revised in that connection. These concepts
were forr.:ulated in the relatively distant past, when the sensitive methods of
investigation which are available to contemporary rickettsiology had not yet
been developed. ,
+..iy+..or. u~.uG+l1Vti1J,
ii' only by applying one of the simplified methods of microagglutination, The
use of a simplified method is permissible unless differentiation between epidemic
typhus and~murine typhus is to be carried out. For this particular purpose, they
ordinary reaction of agglutination or the reaction of complement fixation should
be used,
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With regard to the prophylaxis of rickettsioses, one may recommend the
following line of research.
First, it is advisable to clarify the question as to whether it would be
profitable to pursue work on the prophylaxis by vaccination of the most impor-,
taut endemic rickettsioses, particularly marine typhus, the Northern Asiatic
tick rickettsiosis, and Q-fever, with consideration of the possibilities that
human beings and farm animals be inoculated. Obviously, the work on the subject
will require preliminary experimentation on animals.
Through investigation under practical conditions of the effectiveness of
sanitary-antiepidemic measures for the control of endemic rickettsioses, accom-
panied by experiments on the elimination of individual foci after their compre-
hensive study Prom the epidemiological standpoint, are absolutely necessary.
In this subdivision of research, one must specifically take into consideration
measures for the control of blood-sucking transmitters and of animals, partic-
ularly rodents, which form a reservoir of the infection at the foci (for instance,
rats and mice in cases of marine typhus and vesicular rickettsiosis). In the
same subdivision, one must develop the moat effective methods of personal hy-
giene for purposes of prophylaxis, as far as transmission of the infection by
insect parasites (ticks and fleas) is concerned.
Finally, one must carry out n number of clinical investigations on endemic
rickettsioses, primarily on the clinical forms of Q-fever, an infection which
is new to clinicists and which apparently needs very thorough study. In addi-
tion to acquiring a thorough knowledge of the clinical aspects of the diseases
involved, one must svb~ect to earnest study the chemotherapy of rickettsioses
by means of Soviet antibiotics (syntouyycin, levom;~cetin, and biougrcin). In
this respect, one should pay particular attention to the investigation of the
possibility of combined therapy, using antibiotics together with specific
vaccines.
In our opinion, these are the most important tasks in research work to be
done on rickettsioses.- In conclusion, one may remark that work on rickettsioses
must be curried out by microbiologists specializing in rickettsiology and work-
ing in cooperation with immunologists, infectionists, epidemiologists, and para-
sitologists. One must particularly emphasize that collaboration between epide-
miologists and parasitologists will lead to good results in this field.
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