|Year : 1953 | Volume
| Issue : 3 | Page : 71-88
Toxoplasmosis in India
Department of Ophthalmology, King Edward Memorial Hospital, Parel, Bombay, India
Department of Ophthalmology, King Edward Memorial Hospital, Parel, Bombay
|How to cite this article:|
Singh S. Toxoplasmosis in India. Indian J Ophthalmol 1953;1:71-88
Toxoplasmosis is a protozoal disease which has been recently studied more extensively in America. The history of the disease goes as far back as year 1900 when Levaran described the organism probably toxoplasma in Javanese paddybirds.
The genus Toxoplasma was created in 1909 by Nicolle and Manceaux for a parasite that they found in a small animal called gondi which habitate in North Africa around the Sahra Desert. Later it was found in the rabbit and still later in most domestic animals and birds, as a spontaneous disease.
The first recognised instance of its occurrence in the human being was in 1923 by Janku (1923), an Ophthalmologist in Prague who described encephalomyelitis and chorioretinitis with parasitic cysts in a boy who went blind at the age of 3 months and died at the age of 16 months of internal hydrocephalus with convulsive seizures. However not till Wolf, Cowen and Paige (1939) redescribed it, that interest was created about this disease in human infants. Pinkerton and Weinman (1940) demonstrated their presence in adults.
Till 1951, 78 cases of infantile or congenital human toxoplasmosis, proven or probable, with associated chorioretinitis had been recorded in the literature.-Hogan (1951). Since then, with increasing interest in the disease, several more cases have been recorded in various parts of the world both congenital and acquired. The frequency of this disease once considered rare has definitely been increasingly recorded and Helenor Wilder claims to have isolated toxoplasma-like organisms in granulomatous chorio-retinitis in 53 eyes. In 131 eyes with a diag nosis of a tuberculous lesion she found the protozoa in 30 eyes. This suggests that many cases diagnosed as tuberculous granulomata may be really cases of toxoplasmosis.
So far our country is concerned, the disease undoubtedly is present, as has been proved by this study, but has been overlooked till now.
| Morphology|| |
Toxoplasma is a highly organised protozoan parasite with distinct cytoplasm and nucleus. It is non-motile. The size and shape varies with the age and the mode of preparation.
In the fresh state the organism varies from 4 - 7 micra in length and 2 - 4 micra in breadth. A recently divided toxoplasma is crescentic and becomes more pyriform with age.
In Giemsa-stained films -- the cytoplasm is bluish and the nuclear chromatin takes up varying shades of red and purple.
The appearance in fixed tissues differs considerably. The organism appears only half as large and the staining reactions and morphology vary with the fixative and stains used. Iron hamatoxylin stain has been found to be of the greatest value in differentiating the organisms in sections ( Smith. 1953 ). It may be seen within mononuclear phagocytes, cells of reticulo-endothelial system, in visceral parenchyma) cells of liver, spleen, bone marrow, lung, brain, kidney, and heart, or be free in the tissues. [Figure - 1],[Figure - 2].
Although in the beginning at least two varieties of toxoplasma were distinguished depending upon the animal from which they were recovered, viz. t-gondii and t-cuniculi, now no such differentiation exists because Sabin and Olitsky ( 1937 ) have proved that morphologically no distinction is present, organisms from different sources cross imunize, i.e. there is no serological difference between the two strains, and the parasite is not host-specific, as a strain recovered from one animal can be successfully inoculated into other animals.
However there appears to be some difference in different strains, e.g. fresh strains are neurotropic and affect the central nervous system mainly, whereas those obtained after repeated transfers are viscerotropic and affect the various thoracic and abdominal viscera. Thus different tissue affinities may develop with the same strain and different strains with different tissue affinities may exist in nature.
Another organism Encephalitozoon cuniculi recovered from the brains of rabbits from encephalitis has been considered identical with toxoplasma from a study of experimental transmission of this organism into mice -- Hagan and Bruner (1951).
Duke Elder, Ashton and Geertruyden (1953) have pointed out that cellular debris or nuclear fragmentation may simulate the pseudo-cysts of toxoplasmas. Therefore, in the absence of confirmatory serological tests, mere histological appearances may be deceptive and should not be given any significance.
| Artificial Cultivation|| |
So far it has not been possible to cultivate the organism on any cell-free media, but Sabin and Olitsky succeeded in propagating it without loss of virulence on a medium consisting of minced chick embryo suspended in Tyrode's solution (Rivers-Li medium). For the several tests for toxoplasmosis it is necessary to have a continuous supply of these parasites. This is done most easily by injecting a strain intraperitonially into one of the experimental animals, preferably the mice. The animals die within three weeks, and their ascitic fluid should be injected into fresh animals in order to propagate the organism. It is evident that this can be done only if the work is centralised in a special laboratory.
| Mode of Transmission|| |
The mode of transmission of this parasitic infection from animals to animals or to human beings has yet not been demonstrated.
(i) Since the largest number of reported cases have occurred in newborn infants or within the early postnatal period, it is suggested that transmission of infection is from the mother to the foetus via placental circulation. The mothers in such cases are supposed to have an unrecognised infection at some period of their pregnancy which remains latent in then because of natural or acquired resistance to infection.
(ii) Ingestion : Sabin and Olitsky ( 1937 ) succeeded in infecting mice by feeding them with infected material.
When infection is transferred by feeding the animals, after a generalized parasitaemia, the disease becomes chronic, the animals become symptom-free and they do not die. The organisms become localized and walled off in pseudo-cysts in the organs which they have invaded.
Eichenwald (1948) has experimentally shown in the mice that if milk from infected mice is fed to healthy young mice, infection can be transmitted in about 20 per cent of the animals.
Eichenwald's interesting experimental study has yielded the following deductions.
Prenatal transmission occurred more readily than transmission through milk.
After birth, transmission of the disease by routes other than mother's milk would not appear to be important. Both Eichenwald and Hogan have actually seen toxoplasmas in small numbers in the mother's milk.
Much more diffuse and heavier parasitization was observed in animals infected in utero : no organ including the central nervous system escaped invasion.
With milk-infected animals, the digestive tract, liver, spleens and lungs were parasitized exclusively and a much smaller number of organisms was present.
From chronic carrier mothers, no transmission occurred in the offsprings either in utero or through lactation. In these chronic cases the organisms get bottled up in pseudocysts within the lung, heart and spleen and there is little or no tissue reaction.
This study offers an explanation why in many of the recorded cases as well as in our own cases (1 and 2) only one sibling was affected from a carrier mother, because the mother can transmit the disease only while an active, generalized infection is present and not while she is in the state of a chronic carrier.
This study also suggests that if the infant escapes intrauterine infection, it may still get infected from mother's milk if the mother gets infected during lactation.
There is a possibility of catching infection from infected unpasteurised milk of animals.
(iii) Contact kith domestic animals : Otten Westphal and Kajahan (1951) have recently investigated dogs in Germany, by means of Sabin Feldman dye test. They believe that dogs play an important role in the transmission of this disease.
Other domestic and laboratory animals have also been found to be naturally infected. This suggests the possibility that the disease may be transmitted from these animals, either by direct contact or by a vector, e.g. tick or by contamination of the eatables, at least in those cases who develop acquired type of toxoplasmosis and in those mothers who in turn transmit the disease to the foetus.
Experimental attempts to transfer the disease through insects have so far not been successful.
Magnusson (1951) has reported seven cases of adult infection, two of whom had been infected during their work in the bacteriological laboratory.
| Pathology|| |
Toxoplasma can invade practically every structure in the body and the pathological changes vary to some extent with the tissues involved.
In general the lesions are proliferative granulomata with nothing pathognomic in the histopathological appearances save for the parasites isolated in clumps or in cysts. In some areas particularly in the eye, brain and intestines there is a tendency to necrosis which is followed by resolution, scar tissue formation and in the brain by calcification.
In mice when infected in any other way than intracerebrally, the cerebral lesions are found along blood-vessels, indicating a spread through the blood stream, whereas with intracerebral inoculation the lesions are seen along the ventricles, indicating a spread through the cerebrospinal fluid.
In experimental animals the disease when transferred from a fresh isolated strain tends to be neurotropic and affects mainly the nerve-tissue of the central nervous system. Subsequent transfers make it viscerotropic, so that the abdominal organs get affected mostly.
In animals death occurs within three weeks, or may result some months later if the disease becomes chronic.
| Clinical Picture|| |
As a student of ophthalmology, I shall mainly emphasize the ocular aspects of this disease. Clinically four types of disease have been described in the literature;
1. Congenital type.
2. Acquired childhood type.
3. Acquired adult type.
4. Sub-clinical type.
Most of the cases encountered so far, fall in the first variety of congenital toxoplasmosis. It can be either acute, subacute or chronic. In its acute or subacute form it is characterised by encephalitis and almost invariably acute chorioretinitis which is much the commonest manifestation.
Some of these cases affected in early part of development are delivered as still horn babies very often with hydrocephalus or microcephalus.
Others, born with acute or subacute toxoplasmosis may either die within a short period after birth or may survive and show signs of previous infection. These are the cases of chronic or healed type of toxoplasmosis and are mainly characterised by chorioretinitis, cerebral calcification and convulsions. Other secondary manifestations in such cases described by various authors have been summarized by Hogan (1951). They are hydrocephalus and microcephalus in the brain; microphthalmos, microcornea and uveitis in the eyeball; nystagmus and squint as muscle anomalies and on ophthalmoscopic examination vitreous opacities, masses of proliferating vascular connective tissue in the vitreous, cataract secondary to uveitis, and optic atrophy, apart from the main feature of central chorioretinitis.
(2) Acquired childhood type : This is also mainly characterised by encephalitis as reported in two cases by Sabin ( 1941 ). He however mentions that encephalitis although fatal in one proved case is not characterised by destruction of the nervous tissue such as has been demonstrated in the congenital form. Ocular changes in such cases are not supposed to be characteristic. However a case is reported from Italy by Robinson (1947) in which the child had apart from neurological disturbances and fever, ocular lesions in the form of chorioretinitis.
The termination can be either by the death of the child or in case he or she survives, residual signs remain as in the congenital type.
(3) The third variety is again acquired and in adults which is characterised by an acute febrile illness with pulmonary symptoms and a generalised papillomacular eruption except for the face, palms of the hands and soles of the feet. The other lesions correspond to the viscerotropic type of toxoplasmosis described under experimental pathology and consist of enlargement of the lymph glands,
liver and spleen, ulcerations in the intestines with blood per rectum, and gradual emaciation and wasting.
(4) Lastly the infection may be subclinical in its manifestations and may be overlookea until attention is called to the loss of vision. This latent form may become active under the special stresses of hunger, pregnancy or disease. Then it is manifest in the eye as a central exudative retinitis. Four such cases are reported by Rieger (1951). There was involvement of the retinal vessels which suggests that some cases of perivasculitis of the retina which have been thought to be due to tuberculosis are probably toxoplasmotic in origin.
No doubt, thee main signs and symptoms described above are pertaining to the nervous system and the eyes, which are particularly affected in this disease, and are more so in acute and congenital cases. It will be of interest however, from the physician's point of view to note that other organs - lungs, liver, spleen, heart, bone-marrow, muscles, testes and ovaries may be as well affected by toxoplasma, and we may thus encounter certain other signs and symptoms like, fever, jaundice, gastrointestinal disturbances, enlarged liver and spleen, ana:mia and leucopxnia, and myopathy.
| Diagnosis|| |
It can be presumed on the basis of clinical findings which constitute a pathognomic triad, characterised by
(1) History of convulsions in infancy.
(2) Focal chorioretinitis of a destructive necrotic type, usually affecting the central areas of both fundii.
(3) Cerebral calcifications -- which usually measure 1 - 3 min. in diameter and can occur in all parts of cerebral cortex, basal ganglia and thalamus. In basal ganglia and thalamus it occurs as curved streaks which are said to be pothognomic. In some cases it may however appear like calcium dust and in a few, may even be absent.
Now if we analyse these three features, we will find that there is nothing characteristic about convulsions and convulsions occur so frequently during infancy that they by themselves cannot be evaluated. Cerebral calcifications occur in a variety of disease states as does also chorioretinitis. Moreover chorioretinitis of toxoplasmosis varies within wide limits.
Therefore it will be evident that it is not one particular feature but the combination of all these signs that points to the diagnosis of toxoplasmosis.
The diagnosis is further corroborated and confirmed by
(1) Morphological identification of toxoplasma from body fluids e.g. cerebrospinal fluid ( which may also show xanthochrornia and increased cells and protein content ) or from suspected tissues removed at biopsy or autopsy.
(2) Biological identification of toxoplasma by inoculation of suspected material into susceptible animals.
(3) Frenkel's toxoplasmin test: - performed by skin testing antigen. It is just like tuberculin hypersensitivity test. The ease of its performance and rapidity of reading make this test a useful procedure in population surveys.
(4) Finally the serological investigation for the presence of antibodies. This forms a very important procedure in the diagnosis of this disease:
Three different tests have been used
(a) Serum neutralisation test - in which the antigen (standard suspension of fresh toxoplasmas) mixed with varying dilutions of patient's serum is injected intradermally into the skin of the rabbit. There occurs either a local reaction -- necrosis, erythema, or there is no change and is compared with that produced by a similar mixture containing control serum from a normal person.
(b) Complement fixation test - which is also performed with a similar antigen. Titres as low as 1 : 2 are said to be specific
(c) and lastly Sabin's methylene blue dye test - which is a simple, most satisfactory and quantitative method for the laboratory diagnosis of toxoplasmosis. So far as intepretation of dye test is concerned, according to Beverley and Beattie (1952), levels of positive titres which may be regarded as significant, are:
Under 10 years........... 1 : 16 or over
10 -- 19 years......... 1 : 32 or over
Over 20 years............ 1 : 64
Here the staining of extracellular toxoplasmas with alkaline methylene blue is used to indicate whether or not a serum contains neutralising antibodies. If it does, the protoplasm of the parasites which have been exposed to the serum remains unstained and parasites have crescentic shape whereas with normal serum the cytoplasm is deeply stained and the parasites are rounded or oval.
Here I would like to point out that we have so far no arrangements in India to do any of these tests. Dr. Hogan of California University has very kindly agreed to send us a carrier guineapig which will enable us to perform these tests in our hospital, but the difficulty is of importing such a guineapig.
Our only hope lies in recovering the living protozoa from infected animals or man and then transferring the same continuously through generations of mice.
| Differential Diagnosis|| |
1. Chorioretinitis - Differential diagnosis of chorioretinitis should include: -
(i) Metastatic chorioretinitis especially that associated with acute infections of the upper respiratory tract, and acute exanthems.
(ii) Meningitis - particularly of tuberculous form.
(iii) Granulomata -- of syphilitic, tuberculous or leprous origin.
(iv) Congenital coloboma.
(v) Scars of birth injuries and
(vi) Hereditary macular degeneration
2. Cerebral Calcification: As already stated, the possibility of toxoplasmosis should be suggested by intracerebral calcilications. However these are occasionally observed radiologically with
(a) Non-neoplastic pathology as in
(1) the aged in the internal carotid artery: (2) aneurysms: (3) the Sturge Weber syndrome More Details: (4) within subdural and intracerebral haematomas, (5) tuberculomas, (6) cysticercosis, torulosis and trichinosis, (7) cerebral atrophy (including facial hemiatrophy ), (8) parathyroid deficiency, (9) as a normal as well as abnormal finding in the penial gland, choroid plexus, in the falx and in petrospheroid ligament.
(b) Tumours - such as craniopharyngioma, oligodendroglioma, meningeoma, cerebral dermoid and in ependymoma.
(c) Intracranial foreign bodies and radiopaque material may simulate foreign bodies of inflammatory origin.
3. Sabin-Feldman Syndrome : This syndrome can be very well included in conditions described under the differential diagnosis of chorioretinitis.
Sabin and Feldman (1949) have described a syndrome which is most probably congenital and of which chorioretinopathy is one manifestation, which clinically simulates healed congenital toxoplasmosis. They have also observed that this syndrome is more frequent than congenital toxoplasmosis. We too agree with them in their observation from our very limited experience.
They studied 43 children who exhibited chorioretinopathy associated with various other manifestations of cerebral damage and have come to the conclusion that their cases fall in two distinct groups, (1) serologically compatible with a diagnosis of congenital toxoplasmosis and (2) without serologic evidence of toxoplasmosis.
Apart from serological differentiation, a very interesting correlation with reference to the incidence of cerebral calcification appeared when they analysed those cases.
Among the 23 children with positive serological evidence of toxoplasmosis 87 per cent. had cerebral calcification associated with chorioretinopathy while among the other 20 children with negative tests for toxoplasmic antibodies --only 5 per cent. had cerebral calcification.
Sabin therefore suggests a useful guide for ophthalmologists that if the chorioretinopathy of presumable congenital origin is associated with cerebral calcification, the chances are approximately 9 : I that serologic tests will prove to be due to congenital toxoplasmosis. On the other hand if it is not associated with cerebral calcification the chances are approximately 9:1 that it is not due to toxoplasmosis. He however stresses that in individual cases the diagnosis must still be made by the serological tests.
| Prognosis|| |
Prognosis depends on accurate diagnosis.
(a) Cases of healed toxoplasmosis although ocularly and mentally crippling in some degrees, will not be as marked from the standpoint of educational potentialities as it will be in those infants and children with congenital developmental cerebral and ophthalmic defects of non-toxoplasmic origin.
(b) Secondly we can tell the parents that the outlook for a subsequent normal child is good when the diagnosis of congenital toxoplasmosis can be confirmed while in non-toxoplasmic group where chorioretinopathy is associated with other evidence of cerebral damage. we still do not know enough about familial and other underlying factors to be able to say anything.
| Treatment|| |
Prophylaxis:- (1) The experimental findings of Eichenwald indicate that breastfed infants possibly should not be fed from the mother if possibility of toxoplasmosis exists.
(2) If a pregnant woman is strongly positive with dye test, there is a good possibility that she is undergoing an acute infection with this organism and in such a case this is an indication for giving sulphonamides in the hope of preventing congenital toxoplasmosis in the infant. Sabin (1950).
(3) Avoiding contact or contamination from supposedly infected domestic or laboratory animals.
Curative Treatment : Number of drugs have been tried but the results so far are not encouraging.
1. The antiprotozoal drugs like antimony, arsenic and quinine groups while effective in vitro are useless in animal infections.
2. Drugs of the sulphonamide group have given slightly more promising results but it has been found that animals cured in this way may remain as carriers. However, sulphonamides with fever therapy has been found useful for uveitis of toxoplasmosis.
3. Antibiotics - Penicillin, Streptomycin, Aureomycin and Chloromycetin are also found ineffective in the control of experimental toxoplasmosis in mice.
4. Lastly Frenkel advocates a systematic desensitisation of the patient or rather raising of the level of his humoral antibodies by injections of increasing doses of toxoplasmin.
He has treated a group of nine patients with chorioretinitis on these lines and reports that in eight cases the lesions became inactive as indicated by disappearance of vitreous exudate, subsidence of chorioretinal lesions and improved visual acuity.
5. Sabin and Olitsky working with monkeys, which frequently recover, were able to show that they become immune to reinoculation. They showed that the serum from recovered monkeys had the power of protecting other monkeys. Studying with mixtures of organismal suspension and antisera and injecting the same in experimental animals, mice, they found that the latter did not contract the disease. However separating the mixture of organisms and serum by centrifugation, they recovered the organisms with full virulence. Thus antiserum does not destroy the organisms but it somehow inhibits infectivity.
This suggests a line of treatment, that is to make use of the serum of an infected chronic case for reducing the toxic effect of a fresh infection in another person but that will not kill the organisms in him.
6. So far as chronic healed cases are concerned there is however no treatment.
| Analysis of Cases|| |
Although we have diagnosed, clinically as well as serologically, only one case of congenital healed toxoplasmosis associated with chorioretinitis and one carrier, the following report includes all those cases observed and investigated from the point of this disease, in one year.
Case No. 1 : S. Y., a male child, aged 9 years, first reported in the Ophthalmic Outpatient department on September 17, 1951.
Chief complaint : Diminished vision in both eyes, since 8 years.
History : The mother was well throughout her pregnancy. She had fever after delivery for which she was treated in the hospital for two months.
The child was delivered at full term and was healthy. One month after birth, the child started getting fits, occurring twice or thrice a week. These fits persisted till he was of about six months, when the mother noticed that he had also defective vision and slight squinting tendency in both eyes. Later there was spontaneous recovery from fits till four months prior to his reporting in the hospital when he again got an attack of fit.
All these years he had been treated by household remedies, and indigenous drugs without improvement in his vision, and so he was brought to the hospital.
His general development and progress in the school was poor.
There was no history, in the child or his mother, of contact with domestic animals.
His parents were healthy. He had one elder sister, one younger brother and three younger sisters, who were all healthy.
General Examination : He was of an average build, but showed mental retardation. [Figure - 3].
Ocular Examination : The eyes were of normal size. There was exotropia and right hypertropia with fine nystagmus in both eyes. The visual acuity was reduced to finger counting at two meters in each eve, which could not be improved with any optical correction.
The cornae were smaller in size, being 10 x 11 mm. in the right eve and 9.5 x 10.5 mm. in the left eye. The anterior chambers were of normal depth. In the right eve, the iris was normal and pupil showed full dilatation under atropine. while in the left eye pupil showed poor dilatation under atropine. The lenses were clear.
Ophthalmoscopic Examination : The media were clear in both eyes.
Right fundus : showed an area of healed chorioretinitis in the central area measuring approximately 4 x 5 disc diameters. The central portion was atrophic with choroidal vessels seen traversing through it, while the periphery showed a ring of proliferated pigment. The whole patch was clearly demarcated from the rest of the fundus. The disc showed marked temporal pallor. The background was tesselated. [Figure - 4].
Left Fundus : showed an area of healed chorioretinitis of the size of macular area. From this a band of connective tissue extended down to the inferior quadrant of the fundus. [Figure - 5].
Examination of other systems : did not show anything abnormal. He had enlarged tonsils and some nasal discharge.
Special Investigations : Kahn's floculation test for blood was negative. Intradermal tuberculin reaction was mildly positive.
X-ray of the skull showed multiple areas of calcification, particularly in the left parietal region. [Figure - 6],[Figure - 7].
Electroencephalogram showed evidence of cerebral dysrrhethmia.
Serological investigations were done at the Medical Centre, University of California, San Francisco, and at the National Microbiological Institute, Bethesda. At California University only dye test was performed and was positive in titres of 1 :8 and 1:16 in the child only. At Bethesda both complement fixation and dye tests have been done -- both of which were positive in the mother; while in the child only dye test was positive. Quantitatively mother's blood was positive in titre of 1 :128 and of child in titre of 1 :16.
Comment : The characteristic triad of chorioretinitis, fits and cerebral calcifications with other features like mental retardation, squint, nystagmus and microcornea were highly suggestive of congenital healed toxoplasmosis.
Positive serological report for dye test in the child as well as in the mother - confirmed the diagnosis.
Case No. 2: S. B., the mother of the above patient, but for the positive serological tests showed no abnormality of any kind, and may rightly he called a carrier. As reported above the complement fixation test was positive, so also the dye test which was positive in titre of 1 :128.
Case No. 3: H.S., an old man of 55 years, reported in Ophthalmic O.P.D. on September 9, 1951.
Chief complaint : Diminished vision in both eyes.
History : The patient noticed defective vision in both eves, since childhood, which had gradually deteriorated. He consulted a number of doctors and had been undergoing various lines of treatment but without any relief. However some eye specialist had told him that there were "Spots" in his eyes which were responsible for his defective vision and that glasses could not he fitted to him.
He did not remember any history of fever or fits. There was no history of contact with domestic animals. There was no history of fits or similar defect in vision in any other member of the family.
General Examination : He was of an average build and was fairly intelligent.
Ocular Examination : The vision in each eye was reduced to finger counting at two metres and did not improve with glasses.
Anterior segment showed no abnormality of either eye.
Ophthalmoscopic examination : The vitreous was dear in both eyes.
Right Fundus: showed tesselated background. There was a well-defined, punched-out like area of healed, central chorioretinitis. The size was approximately 4 x 4 disc diameters. It showed atrophy of the retina and the choroid in the centre and a border of proliferated pigment.
Left Fundus : showed almost a similar picture.
Examination of other systems : did not reveal any abnormal feature.
Special Investigations : Kahn's floculation test for blood was negative.
Tuberculin test was negative.
No septic focus could he detected.
X-ray of the skull showed normal markings of the sutures and blood-vessels, Sella was larger than normal, wall was thinned out.
Cerebral calcifications were noticed besides that in the Pineal gland.
Comment:- Presence of bilateral, central, and symmetrical healed chorioretinitis in otherwise normal fundii, with cerebral calcifications were suggestive of toxoplasmosis. Patient came only on two occasions in the hospital and then could not be contacted, so serological investigations for toxoplasma antibodies could not he done.
Case No. 4: P. S., a boy of 14 years, was brought by his father in Ophthalmic O.P.D. on October 26, 1951.
Chief complaints : (i) Defective vision in both the eyes. (ii) Mental instability.
History : Before the illness, the child was healthy and was studying in a class in consonance with his age. Three months prior to his reporting in the hospital, he had an attack of fever which lasted for three weeks. Subsequently he was alright for about two weeks but then started showing mental instability. He could not understand things and stopped going to school. At times he became restless and started shouting. Parents noticed that he also developed squint in right eve and diminished vision in both the eyes.
There was no history of contact with domestic animals. There was no family history of fits, defective vision or mental sickness.
General Examination : He was thin, undernourished and showed mental instability.
Ocular Examination : Visual acuity could not he recorded because the patient was not co-operative and not in a fit state of mind. He had convergent squint in his right eye. The anterior segment of the eyeball was normal in both the eyes.
Ophthalmoscopic Examination revealed that vitreous was clear in both the eyes.
Right Fundus : showed a linear patch of chorioretinitis of the size of ½ x 2 disc diameters, in the macular area.
Left Fundus : showed diffuse retinitis and marked pallor of the optic disc.
Examination of other systems: Central Nervous System: Reflexes were brisk. Condition of cranial, motor and sensory nerves could not be elicited. Other systems did not reveal anything abnormal.
Special Investigations : Kahn's floculation test for blood was negative.
Tuberculin reaction was negative.
X-ray of the skull did not show anything abnormal.
Course : On the advice of Honorary Psychiatrist, he was referred to the Mental Hospital, Thana, for further investigation and treatment.
On enquiry from the mental hospital we found that the child was not taken to that hospital at all and incidentally we lost contact of this case.
Comment : Because of ocular findings and mental disturbances we suspected that it was a case of toxoplasmosis. There was however no cerebral calcification. As the child was healthy before this illness, we feel that if it was a case of toxoplasmosis it was of an acquired variety of childhood type.
Case No. 5: L. Z., a boy aged 17 years, was referred from the Medical Outpatient department on October 10, 1951, for the chief complaint of defective vision in both the eyes.
History : There was no history of illness in the mother during pregnancy or labour. He was born at full term.
Very shortly after birth the parents noticed squint in his left eye and fine movements of both eyeballs (Nystagmus). His vision in both eyes was subsequently found to be diminished.
At the age of six years, he started his studies and his progress in the school was quite good inspite of defective vision. However the vision gradually deteriorated and was more marked in the last four years.
Three years prior to reporting in the hospital, he started getting fits for which he came to the Medical ORD. He was diagnosed as a case of epilepsy for which he was treated as an outdoor as well as an indoor patient till 10th November 1951 when he was referred to the Ophthalmic department for defective vision.
His vision was diminished to such an extent that he had to discontinue his studies. There was no contact with domestic animals.
His father died of some prolonged illness. His mother, one elder brother and one elder sister were living and were healthy.
General Examination : He was thin and poorly built. He showed mental retardation. The head appeared small in size suggestive of microcephaly but on actual measurements showed that it was only flattened from sides. [Figure - 9].
Ocular Examination : On external examination the eyeballs were normal and equal in size. There was exotropia in right eye with fine nystagmus in both the eyes.
The visual acuity in the right eye was finger counting at three metres which improved to finger counting at six metres with + 1.0 cylinder axis 120°. The vision in the left eye was finger counting at three metres but showed no improvement with any optical correction.
The anterior segment of the eyeball was normal in either eye.
Right Fundus: showed multiple, minute spots of atrophy and pigmentation in the central area of the fundus.
Left Fundus: showed an extensive area of healed chorioretinitis, in the central area, approximately 5 x 6 disc diameters in size. Centre showed white patches of exposed sclera indicating atrophy of retina and choroid while the periphery was bordered by proliferated pigment.
Examination of other systems : did not show any abnormal feature: except brisk reflexes.
Special Investigations : Kahn's floculation test for blood was negative.
Tuberculin reaction was negative.
Septic foci:- Teeth showed pyrrhoea with early carries.
E.N.T.:-No septic focus was detected.
X-ray of the skull showed no evidence of increased intracranial tension or calcification.
Electroencephalogram showed cerebral dysrrhythmia suggestive of grand mal.
Serological report:- (a) die rest : showed mildly positive result in 1 :12 titre.
(b) Complement Fixation Test : Negative.
Course : He was taking regular treatment for fits and was at the same time under the care of Occupational Therapy Centre of our hospital. On enquiry from Mrs. Nimbkar, the Director of the Centre. we were told that the patient's mental condition seemed to he very gradually deteriorating.
He went to his native place for some time where unfortunately he got a convulsive seizure on one occasion and expired. An autopsy was not performed.
Comment : Because of bilateral chorioretinitis and fits with other defects lake squint, nystagmus and mental retardation we supected this to be a case of congenital healed toxoplasmosis. However on receipt of serological report from London, we revised our diagnosis. Because of absence of definitely positive serological evidence and so also of calcification, we feel that it comes under the category of Sahin-Feldman syndrome - a condition which has been mentioned in the differential diagnosis of toxoplasmosis.
Case No. 6: R. K., a male child, aged 8 years, was brought in Ophthalmic O.P.D., on January 2, 1952.
Chief complaint : Diminished vision in both eyes.
History : The mother was well during pregnancy and labour. The child was born full term, but at the time of delivery, there was a history of fall on the floor. There was no apparent sign of injury at that time.
Shortly after birth, the parents noticed that the child had defective vision and since then it had persisted. There was no history of fever or fits.
The parents were healthy. He had five elder brothers and one younger brother who were healthy.
There was no history of contact with domestic animals either in the mother or in the child.
General Examination : He was of average build but showed some mental retardation.
Ocular Examination : Visual acuity was reduced to finger counting at three metres in both eyes, and showed no improvement with glasses. The eyeballs were of normal size and showed fine nystagmus. Anterior segment of the eyeball was normal in either eye.
Ophthalmoscopie Examination revealed that the media were clear.
Right Fundus : showed an area of healed, central, chorioretinitis of the size of 4 x 4 disc diameters clearly demarcated from the rest of fundus which was otherwise normal.
Left Fundus : showed more or less similar picture. [Figure - 12],[Figure - 13].
Examination of other systems showed no abnormal feature.
Special Investigations : Kahn's floculation test for blood was negative.
Tuberculin reaction was mildly positive.
Septic foci: as reported from E.N.T. department, he had enlarged tonsils and discharge from nose.
X-ray Skull: showed silver beaten appearance. [Figure - 14].
Serological investigation for antibodies:-
(a) Dye test ... ... ... ... Negative
(b) Complement fixation test ... Negative
Comment : Bilateral symmetrical chorioretinitis, clearly demarcated from the rest of the fundii which were absolutely normal otherwise, was suggestive of some focal lesion rather than due to birth injury which might be thought of in this case.
On the basis of bilateral central chorioretinitis in a child with X-ray changes in the skull, we made provisional diagnosis of toxoplasmosis. However on receipt of negative serological report we revised our diagnosis. We feel that ocular and cerebral changes with mental retardation are more of developmental nature and as such we are inclined to group this case also in Sabin Feldman syndrome.
Cases Nos. 7 and 8: Besides these were two other cases (1) of perivasculitis and (2) of disseminated chorioretinitis where after ruling out various aetiological factors, confirmatory serological evidence for toxoplasma was sought. This was done in view of Rieger's recorded cases, mentioned earlier,; where he had observed perivasculitis in the retina. Since the serological report has come negative in the first case and the serum got spoiled during transit in the second, these cases are not reported.
| Conclusions and Summary|| |
1. Toxoplasmosis in human beings is a comparatively rare condition. Hitherto no case has ever been recorded in India either in animals or man. Our study has revealed the presence of at least one confirmed case and one confirmed carrier in man.
2. A brief description of the protozoa, its staining and cultural properties is given.
3. The mode of infection is discussed. It is possible for only one child to be infected, although the mother may be a carrier.
4. The avenues of transmission of the disease with the clinical peculiarities in the mode of transmission have been described.
5. Four clinical types: (1) congenital, (2) acquired childhood, (3) acquired adult and (4) sub-clinical types have been described. The clinical diagnosis is done by the presence of the triad fits, chorioretinitis and cerebral calcification.
6. Various laboratory tests for toxoplasmosis have been described.
7. Confirmatory Serological tests have been carried out in foreign laboratories which specialise in toxoplasma work, as we have no materials to test with.
8. The differential diagnosis particularly from Sabin-Feldman syndrome is discussed.
9. Six case reports are given - one confirmed case, one confirmed carrier, two cases highly suspicious clinically but serologically unconfirmed, and two cases of Sabin-Feldman syndrome.
10. It is a disease that should interest not only the ophthalmologist, but also the physician, pediatrician, neurosurgeon, psychiatrist, obstetrician, radiologist, pathologist, and the veterinary physician.
| Acknowledgement|| |
I express my gratitude to my teacher Dr. S. N. Cooper with whose inspiration and guidance I could study this problem and all my colleagues who helped me in this study.
I am also indebted to Drs. M. J. Hogan and A. Lewis of California, Drs. Leon Jacobs, John E. Tobie and John Bozicevich of Bethesda, and Dr. Norman Ashton of London who have taken the trouble of doing serological investigations of our cases. My thanks are also due to Mr. Kalgutkar who has made drawings with great accuracy and skill.
| References|| |
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11], [Figure - 12], [Figure - 13], [Figure - 14]