Paralytic Poliomyelitis in a Child With Hypogammaglobulinemia

8/10/2019 Paralytic Poliomyelitis in a Child With Hypogammaglobulinemia

1/5

PARALYTIC POLIOMYELITIS IN A CHILD WITH HYPOGAMMAGLOBULINEMIA:

PROBABLE IMPLICATION OF TYPE 1 VACCINE STRAIN

Although patients with hypo- oragammaglobulinemia are, in general, highly

susceptible to bacterial infections and fare poorly when affected by this tye of disease, they

behave, with few exceptions, in relatively normal fashion when they come in contact with

viruses. This may be attributed to the activity of interferon in the early stage of infections.

Lack of susceptibility to re-infections on exposure to viral agents which have previously

produced infections in such individuals is possibly related to the presence of minute serum

levels of specific neutralizing antibodies. Despite this, fatal disseminated vaccinia, severe

poliomyelitis, fulminant viral hepatitis, and severe generalized cytomegalic inclusion disease

have been reported in cases of significant gammaglobulin deficiency.

The purpose of this paper is to report a case hypogammaglobulinemia in which the

administration of live poliomyelitis virus vaccine orally was followed by the development of

paralytic disease from which the vaccine strain was isolated. The patient died subsequently,

shortly after developing pneumococcal meningitis.

CASE REPORT

M.D. (BFH No. 45507): The pstient was a year-old boy who was admitted to the

hospital on June 26, 1962, because his right hand had been weak for 4 days. Two weeks

earlier, he complained of transient hyperesthesia of the same hand which graduallv spread to

involve the entire arm. Eight hours before hospitalization, a shaking chill occurred and was

followed by severe pain in both hips.

Of note in the patients past history were the following. He had an episode of

etiologically undefined pneumonia 6 months earlier and made an uneventful recovery. As far

as could be ascertained, this was the only possible bacterial infection during the patients life.

Diphtheria-pertusis-tetanus immunization had been carried out at 1 year of age. When he was

immunized against smallpox and influenza virus, at the age of 6, he experienced systemic

reactions with high-grade fever. At 3 years of age, 3 doses of Salk type poliomyelitis vaccine

were administered; a booster injection was given yearly for the next 2 years. Seven weeks

prior to admission to the hospital, the youngster was given Type 1 poliomyelitis vaccine

(Sabin type) orally; 5 weeks later he received Type 3 of the same vaccine.

When the patient was admitted to the hospital he was found to be well developed and

well nourished and did not appear severely ill. His temperature was 99,4OF. (rectally), pulse

100, and respirations 30/min. The pharynx was inected but contained no exudate. Stiffness of

the neck was absent. There was lateral nystagmus. The lungs were clear to percussion and

ausculation. A highpitched blowing systolic murmur was audible over the entire precordium.

Liver and spleen were not palpable. Cranial nerve functions were intact. There was moderate

weakness of all of the muscle groups of the right shoulder, arm and hand. There were no

sensory abnormalities. The right triceps reflex was absent, the right biseps and radial

periosteal reflexes were reduced.


2/5

The hemoglobin level was 12 gm/100 ml and the hematocrit 39,5%. The white blood

count was 12,900 with 58% neutrophiles, 10% band froms, 24% lymphocytes, 6%

monocytes, and 2% eosinophiles. Urine examination revealed no abnormalities. Lumbar

puncture yielded spinal fluid at a pressure of 190 mm, the fluid contained 73 lymphocytes per

mm

2

, the protein and sugar levels were 40 and 101 mg/100 ml, respectively. Electrophoreticstudy of serum obtained on 2 separate occasions revealed the following : total protein, 6,2

gm/100 ml, albumin 3,7, alpha-1 globulin 0,4, alpha-2 globulin 0,9, beta-globulin 0,8,

gammaglobulin 0,3 gm/100 ml. Hinton, EGC dan BUN were normal. Cultures of the nose of

pharynx revealed no pathogens. The spinal fluid was sterile. Schick test was strongly positive

despite the fact that the patient had had primary immunization and, in addition, had had a

booster dose of toxoid 1 year prior to admission. Blood groups was A, antibodies to types A

and B were not detected.

Therapy consisted of bed rest, wet packs, and positioning of limbs to relieve

discomfort and prevent contractures. Defervescence took place in 72 hours. Passive andacyive physiotherapy was initiated. Weaknes of the left foot gradually decreased. The patient

was discharged form the hospital 6 weeks after he was admitted. Follow-up study revealed

gradual improvement so that, after approximately 1 mony\th, muscle activity in the right arm

and hand were considered normal.

On august 22 1962, the patient was admitted to the Morton Hospital in Taunton,

Massachusetts. He had been in good health until the morning of the day when he developed

fever, vomited, and had several generalized seizures. Physical examination was

unremarkable. Nuchal rigidity or other signs of meningeal irritation and muscle weakness

were not detected. All of the reflexes werw normal. The white blood count was 21,000 with51 % neurotrophiles, 46% dand form, and 3% monocytes. The temperature was 103 F three

hours after admission. The youngster had a generalized seizure at this poit and expired one

hour later. Treatment consisted of a single dose of 300,000 units of procaine penicillin

intramuscularly and 2 ml of gamma-globulin. Spinal fluid was not obtained.

PATHOLOGICAL STUDIES

(A-62-23, Morton Hospital): The brain was swollen and congested and a purulent inflamatory

exudate distended the leptomeninges. The cerebrospinal fluid within the ventricles was

cloudy. The lungs were atelectatic and congested. The spleen was unremarkable. There wasno local or systemic lymphadenopathy. The body cavities and other organs were considered

to be normal. On histological examination the leptomeninges were infiltrated by a rich

purulent inflammatory exudate composed of mature and immature leukocytes. This

inflammatory reaction in some areas extended superficially into the underlying cortex.

Smears of the exudate contained gram positive lancet-shaped diplococci. The histological and

gross findings were consistent with a very recent pneumococcal meningitis.

A finding of special interest was a subacute inflammatory reaction within the spinal

cord, brain stem, and midbrain that was quite distinct from the acute inflammatory reaction

throughout the meninges. Of the three areas involved the changes in the spinal cord were by


3/5

far the most striking and here the anterior horns were most seriously affected (Fig.1 and 2). In

these areas was an apparent focal asymmetrical fallaout of nerve cells, leaving the bordering

cells intact. There was edema, dissociation of the tissue, and a rich infiltration with lipid-

laden histiocytes. Capillaries were increased in number and many of the small vessels were

surrounded by a cuff of lymphocytes and histiocytes. There was a proliferation of bothfibrillary and protoplasmic astrocytes together with minute focal accumulations of granuler

calcified debris, suggesting remnants of necrotic neurons. Another finding in the gray matter

of the cord which has been occasionally observed in poliomyelitis, was the presence of

communicating perivascular cyst-like spaces filled with fluid, precipitate, and red blood cells

(fig.3). These spaces, unlike areas of recent infarction did not contain lipid-laden phagocytes

and were not surrounded by a margin of glial tissue. Occasionally, a swollen axone could be

followed as it crossed these cyst-like spaces. Nerves emerging from the ventral surface of the

cord adjacent to areas of neuronal damage were swollen, axones were fragmented and the

mylelin was interupted and infiltrated with lipid-laden phagocytes. In the brain stem and

midbrain the inflammatory changes were much less conspicuous. Here, there were scattred

perivascular collections of lymphocytes which formed dense celluler cuffs about some of the

vessels and there were focishowing glial cell hyperplasia infiltrated with macrophages (fig.4).

Nerve cells in the brain stem and midbrain were for the most part unchanged.

All of the lymph nodes examined showed a depletion of lymphocytes from the

medullary areas and all were entirely devoid of lymph follicle formation. In the intestines

lymphoid tissue was represented by very small nests of compact lymphocyctes. In the spleen

the number and size of the follicles had active germinal centers. The thymus was of average

size. There was a well-defined medulla and a narrow cortical zone of mature lymphocytes.the

lungs were atelectatic, congested and edematous. Small nests of lymphocytes were scattered

along the walls of the bronchi.

In summary, the significant histopathology in this case was characterized by (a)acute

pneumococcal meningitis, (b)subacute or healing inflammatory reaction in the spinal cord,

brain stem, and midbrain consistent histologically and topographically with the recovery or

reparative phase of poliomyelitis, and (c) a conspicuous absence of lymph follicles

throughout the body.

VIROLOGICAL STUDIES

Virologic studies carried out in the laboratories of the Massachusetts Department of

Health, the Communicable Disease Center Service of the New England Center Hospital all

revealed Type I poliomyelitis virus in throat washings and stools collected on the day the

patient was admitted to the hospital.

Identification of the isolated virus was carried out at the Communicable Disease

Center. The strain was classified as vaccine-like on the basis of the results of two different

intratypic sero-differential tests. The mean percentage plaque breakthrough (MPB) was found

to average 5,4%; strains with values less than 10% are considered vaccine-like, those with

values of 10 to 20% are classified as intermediate, and those with values higher than 20% are


4/5

considered non-vaccine-like. The McBride test (the ratio of values reflecting the kinetics of

neutralization of an unknown and the homologous vaccine strain) gave a NK average of 86;

strains with values greater than 70 are classified as vaccine-like.16,17 Rct (the reproductive

capacity at 36 and 40C) was found to be negative. A difference greater than 105 is

considered to be a characteristic of vaccine-like strains.

18

The TCID50of the isolated strainwas 10-7,5at 36C and 10

-1,5 at 40C.

Throat washings and stools were mixed with ppoliomyelitis antiserums and inoculated

into monkey kidney and human amnion cell cultures and into infant mice. No enteroviruses

were isolated.

Serums obtained 3, 26, and 32 days after admission to the hospital were examined for

antibody to a number of viruses, using complement fixation, antihemagglutination, and

neutralization tests. Antibodies to the following agents were not demonstrated: types 1,2, and

3 poliomyelitis, mumps, herpes simplex, lymphocytic choriomeningitis, eastern and westernequine encephalitis, types A, A1, A2 and B influenza, types 9,10,16, and 27 ECHO, and

Cosackie A9and B2.

Attempts to isolate poliomyelitis virus from the spinal cord were unsuccessful; this

was probably due to the fact that the cord had inadvertently been placed in formalin solution

for a short time before it was obtained for culture.

COMMENT

On the basis of the clinical, histological, and virological findings, there appears to be

little doubt that the patient described in this paper had paralytic poliomyelitis. Although

absolute proof of thr involvement of poliomyelitis virus could not be established because of

failure to demonstrate a significant level of specific neutralizing antibody, it is important to

stress the fact that this patient had deficient gamma-globulin and that administration of 3 dose

of killed virus vaccine followed by 2 boosters had failed to evoke an antibody response. For

this reason, isolation of poliomyelitis virus from pharyngeal washings and stool was

considered highly presumptive evidence of infection by this agent. Additional support for this

possibility was provided by the absence of other recognized cases of poliomyelitis in tha

community and failure to demonstrate involvement of other enteroviruses.

However, the incubation period is more plausible for type 3 vaccine virus disease

than type 1, and the possibility exists that type 1 and 3 could coexist in the alimentary tract

and one could outlast the other but not be the agent of CNS disease. Furthermore, the type

vaccine virus is considered to be more genetically unstable than type 1. On the other hand, it

is equality possible that type 1 vaccine virus had persisted in the alimentary tract of this

unusual child and exerted its interference effect on the subsequent type 3 vaccine virus

infection.

The possibility that other enterovirus was responsible for the paralytic disease is not

likely since the distribution of lesions in the brain was characteristic of poliomyelitis and thesearch for other enteroviruses was not revealing.


5/5

Documents

Paralytic Poliomyelitis in a Child With Hypogammaglobulinemia