1.5.1 Congenital toxoplasmosis
Three pathologists - Wolf, Cowen, and Paige, from New York, USA - first conclusively identified T. gondii in an infant girl who was delivered full term by Caesarean section on 23 May 1938 at Babies' Hospital, New York (Wolf et al., 1939a, 1939b). The girl developed convulsive seizures at 3 days of age, and lesions were noted in the maculae of both eyes through an ophthalmoscope. She died when a month old, and an autopsy was performed. At post mortem, brain, spinal cord, and right eye were removed for examination. Free and intracellular T. gondii were found in lesions of encephalomyelitis and retinitis of the girl. Portions of cerebral cortex and spinal cord were homogenized in saline and inoculated intracerebrally into rabbits and mice. These animals developed encephalitis, T. gondii was demonstrated in their neural lesions, and T. gondii from these animals was successfully passaged into other mice.
Wolf, Cowen, and Paige reviewed in detail their own cases and those reported by others, particularly Janku (1923) and Torres (1927), of T. gondii-like encephalomyelitis and chorioretinitis in infants (Wolf and Cowen, 1937, 1938; Wolf et al., 1939a, 1939b, 1940; Cowen et al., 1942; Paige et al., 1942). Joseph Janku (1923), an ophthalmologist from Czechoslovakia, was credited earlier with finding a T. gondii-like parasite in a human eye (Janku, 1923). The following description of the case of Janku is taken from the English translation published by Wolf and Cowen (1937):
The patient was born with left microphthalus and became blind at the age of 3 months, and had hydrocephalus. The child died when 11 months old. The eyes and brain were removed at autopsy. Grossly, the child had internal hydrocephalus but the brain was not available for histopathological examination. Chorioretinitis was present in both eyes and cyst-like structures [termed sporocysts by Janku] were seen in the right eye.
Janku (1923, reprinted 1959) thought that this parasite was Encephalitozoon (a microsporidium).
The material from this case is thought to have been destroyed in World War II bombing, and so confirmation of these findings is not possible. Torres (1927) found protozoa in lesions of encephalitis in a 2-day-old infant in Rio de Janeiro, Brazil. Numerous organisms were seen, but these were thought to be a new species of Encephalitozoon. This patient also had myocarditis and myositis. In the Netherlands, de Lange (1929) found protozoa in sections of the brain of a 4-month-old child that was born with hydrocephalus. These sections were reexamined by Wolf and Cowen, and a lull account was reviewed by Sabin (1942).
Sabin (1942) summarized all that was known of congenital toxoplasmosis in 1942, and proposed typical clinical signs of congenital toxoplasmosis: hydrocephalus or microcephalus, intracerebral calcification, and chorioretinitis. These signs helped in the clinical recognition of congenital toxoplasmosis. Frenkel and Friedlander (1951) published a detailed account of five fatal cases of toxoplasmosis in infants that were born with hydrocephalus; T. gondii was isolated from two. They described the pathogenesis of internal hydrocephalus as a blockage of the aqueduct of Sylveus due to ventriculitis resulting from a T. gondii antigen-antibody reaction. This lesion is unique to human congenital toxoplasmosis, and has never been verified in other animals (Dubey, unpublished). This report was the first in-depth description of lesions of congenital toxoplasmosis not only in the central nervous system but also in other organs. Hogan (1951) also provided the first detailed clinical description of ocular toxoplasmosis.
1.5.2 Acquired toxoplasmosis
Sabin (1941) reported toxoplasmosis in a 6-year-old boy from Cincinnati, Ohio. An asymptomatic child (initials RH) was hit with a baseball bat on 22 October 1937. He developed a headache 2 days later and convulsions the day after. He was admitted to hospital on the seventh day, but without obvious clinical signs. Except for lymphadenopathy and an enlarged spleen, nothing abnormal was found. He then developed neurological signs and died on the thirtieth day of illness. The brain and spinal cord were removed for histopathological examination and bioassay. Because of the suspicion of polio virus infection, a homogenate of cerebral cortex was inoculated into mice. T. gondii was isolated from the inoculated mice, and this isolate was given the initials of the child, becoming the famous RH strain. Only small lesions of nonsuppurative encephalitis were found microscopically in the brain of this child; neither gross lesions nor any viral or bacterial infections were found. This child most likely had acquired T. gondii infection recently, and the blow to the head was coincidental and unrelated to the onset of symptoms. It is noteworthy that some mice infected with the original RH strain did not die until day 21 post-inoculation, but by the third passage mice died 3-5 days after inoculation. The RH strain of T. gondii has since 1938 been passaged in mice in many laboratories. After this prolonged passage, its pathogenicity for mice has been stabilized (Dubey, 1977) and it has lost the capacity to produce oocysts in cats (Frenkel et al., 1976).
Pinkerton and Weinman (1940) identified T. gondii in the heart, spleen, and other tissues of a 22-year-old patient who died in 1937 in Lima, Peru. The patient exhibited fever and concomitant Bartonella sp. infection. Pinkerton and Henderson (1941) isolated T. gondii from the blood and tissues of two individuals (aged 50 and 43) who died in St Louis, Missouri. Recorded symptoms included rash, fever, and malaise. These were the first reports of acute toxoplasmosis in adults without neurological signs.
Lymphadenopathy Siim (1956) drew attention to the fact that lymphadenopathy is a frequent sign of acquired toxoplasmosis in adults and these findings were confirmed by Beverley and Beattie (1958), who reported on the cases of 30 patients. A full appreciation of the clinical symptoms of acquired toxoplasmosis was achieved when outbreaks of acute toxoplasmosis were reported in adults in the USA (Teutsch et al., 1979) and in Canada (Bowie et al., 1997).
Ocular disease Before 1950, virtually all cases of ocular toxoplasmosis were considered to result from congenital transmission (Perkins, 1961). Wilder (1952) identified T. gondii in eyes that had been enucleated. The significance of this finding lies in the way this discovery was made. These eyes were suspected of being syphilitic, tuberculous, or of having tumors. Wilder was a technician in the registry of Ophthalmic Pathology at AFIP, and she routinely microscopically examined the sections that she prepared. She put enormous effort into identifying microbes in these 'tuberculous' eyes, but never identified bacteria or spirochetes by special staining. Then she found T. gondii in the retinas of these eyes. She subsequently collaborated with Jacobs and Cook and found most of these patients with histologically confirmed T. gondii infection had low levels of dye test antibodies (a titer of 1:16), and in one patient antibodies were demonstrable only in undiluted serum (Jacobs et al., 1954a). Jacobs et al. (1954b) made the first isolation of T. gondii from an eye of a 30-year-old male hospitalized at the Walter Reed Army Hospital. The eye had been enucleated because of pain associated with elevated intraocular pressure. A group of ophthalmologists from southern Brazil initially discovered ocular toxoplasmosis in siblings. Among patients with postnatally acquired toxoplasmosis who did not have retinochoroidal scars before, 8.3 percent developed retinal lesions during a 7-year follow-up (Silveira et al., 1988, 2001). Ocular toxoplasmo-sis was diagnosed in 20 of 95 patients with acute toxoplasmosis associated with the Canadian waterborne outbreak of toxoplasmosis in 1995 (Burnett et al., 1998; see also Holland, 2003).
AIDS epidemic Before the epidemic of the acquired immunodeficiency syndrome (AIDS) in adults in the 1980s, neurological toxoplasmosis in adults was rarely reported and was essentially limited to patients treated for tumors or those given transplants. Luft et al. (1983) reported acute toxoplasmosis-induced encephalitis that was fatal if not treated. In almost all cases, clinical disease occurred as result of reactivation of chronic infection initiated by the depression of intracellular immunity due to HIV infection. Initially, many of these cases of toxoplasmosis in AIDS patients were thought to be lymphoma.
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