Ralph E. Haynes

THE ETIOLOGY OF INFECTIOUS DIARRHEA IN INFANCY, WITH SPECIAL REFERENCE TO ENTEROPATHOGENIC E. COLI

Bacterial pathogens including Salmonella, Shigella, and enteropathogenic Escherichia coli (EPEC) have been accepted as causative agents of gastroenteritis for many years. These pathogens, however, have not been recovered from more than 38% of infants less than two :rears of age with diarrhea in any perennial study conducted in North America and Europe since 1955 (TABLE 1 ) . The calculated mean isolation rate of pathogenic bacteria recovered from infants less than two years of age with diarrhea as reported in the above studies is 18.5% (TABLE 1) . This leaves a mean of at least 81.5% of all moderate or severe cases of gastroenteritis unexplained bacteriologically. The assumption has been that the majority of the cases of gastroenteritis in infancy and early childhood is due to viral agents. However, proof of the etiologic association of viruses with gastroenteritis has been difficult to establish and studies to date have not accounted for a large percentage of the cases of gastroenteritis on this basis. As early as 1931, McLean speculated on the viral origin of winter epidemics of vomiting and abdominal pain among children in the United States. Seven years later, an epidemic of diarrhea in California was ascribed for the first time to viral agents.’ From 1943 on, various groups of investigators 3-6 attempted to produce diarrhea in experimental animals by exposure to bacteria-free filtrates of stool suspensions from patients with diarrhea. The experiments were successful only in calves and cats. Human volunteer experiments with such filtrates carried out in the 1940’s did not yield uniform results. By the oral route, gastroenteritis was produced in 50% of Japanese Reimann * reported a gastroenteritis attack rate of 53 % among volunteers who had inhaled filtrates of garglings or stools from diarrhea patients, as compared with an incidence of 9% of naturally occurring gastroenteritis in a matched control group. In one study conducted in New York,O in spite of the absence of demonstrable pathogenic bacteria. only the ingestion of unfiltered throat wayhings and the ingestion of filtered feces from patients with gastroenteritis resulted in a similar illness in volunteers. The inoculation of bacteria-free filtrates of throat and anal specimens from infants with stomatitis and diarrhea into the corneas of rabbits was an ingenious anticipation of modern cell culture techniques.lO.

ECHO virus type 3 infections in children: Clinical and laboratory studies+

ECHO virus type 3 was recovered from 29 children during the summer of 1970. Twenty-four children had aseptic meningitis which was similar to the same illness caused by other enteroviruses. Two children had undifferentiated febrile illnesses associated with a short generalized convulsion. ECHO virus type 3 was also recovered from three children with illnesses not previously associated with this virus: concomitant aseptic meningitis, pericarditis, and myocarditis, a severe generalized neonatal infection, and a fatal illness fulfilling the criteria for Reyes syndrome.

INTRACRANIAL PRESSURE IN REYE'S SYNDROME

During the past 3 years the intracranial pressure(ICP)of 17 children with Reyes Syndrome(RS)has been monitored. The epidural monitor was placed in patients whose level of coma was III or deeper(Sherard Stages I-VI). The cerebrospinal fluid pressure or ICP was measured on 15 patients on admission to the hospital. The pressure was 200mm H2O or less in 7 patients and 300mm H2O or less in 13 patients. In survivors maximum ICP was recorded at 8-24 hours after admission and correlated with the level of coma. An ICP of 400-800 mm H2O was associated with coma level of IV or deeper. In one child the ICP was greater than 1300mm H2O. In 8 patients abrupt increases in ICP to 700mm HpO or greater occurred and preceded any clinical evidence of increasing ICP. These episodes lasted 20-30 minutes, and were treated with hyperventilation and/or mannitol. In 4 patients these episodes were repetitive, being separated by intervals of 2-12 hours. Most of our patients were admitted to the hospital during the early hours of their illness and were in Stage II or III coma. During this phase, the level of consciousness does not appear to be directly related to the ICP, however if the level of coma deepens during the next 24 hours after admission the ICP correlates with the stage of coma. Continuous ICP monitoring is essential for the optimal management of intracranial hypertension associated with RS and serves as an objective criteria for the administration of hyperosmolar agents in patients with coma Stage III or deeper.

Reye syndrome in siblings.

Reye syndrome in siblings was seen in three of 85 families; the incidence of RS in these family groups appears to exceed that of the general population. The interval between development of RS in the first and second siblings was two to 11 days and related to the incubation period of the initial viral infection. In five of the children this infection was chickenpox and in two, an unspecified upper respiratory illness. To assess the role of genetic factors, HLA typing was performed on these siblings; a common genetic marker indicating susceptibility to RS was not identified. All families resided in rural and suburban areas; exposure to a common environmental toxin was not identified.

Cephalexin: Treatment of streptococcal pharyngitis

Twenty-five children with group A streptococcal pharyngitis were treated withcephalexin, an acid stable semisynthetic derivative of cephalosporin C. All patients responded clinically. Bacteriologically, two patients had recurrence of the group A streptococci following the cessation of therapy. Cephalexin can be considered as effective alternate therapy to penicillin in individuals who are allergic to the latter.

Treatment of herpesvirus encephalitis with iododeoxyuridine

Three children developed severe, rapidly progressive encephalitis, with the clinical picture of a mass lesion in the brain. In each patient the electroencephalogram, brain scans, and carotid angiograms revealed findings consistent with focal disease. Diagnosis was proved by recovery of herpesvirus from biopsy specimens of brain tissue. The outcome of treatment with iododeoxyuridine appears to be related to the duration of illness. A 3-year-old, girl, ill for five days, recovered with permanent sequelae. A 14-year-old boy, ill for only two days, recovered completely. A 9-year-old boy, ill for nine days, remained comatose until death.

Thymidine Kinase Activity in Cerebrospinal Fluid of Rabbits with Herpesvirus hominis Encephalitis

Extract: The rabbit model of Herpesvirus hominis (HVH) encephalitis was utilized to determine whether thymidine (TdR) kinase (EC. 2.7.1.2.1), an early enzyme in the HVH replicative cycle, is present in the cerebrospinal fluid (CSF) of rabbits with HVH encephalitis. The mean TdR kinase activity in CSF from infected rabbits was 2.30 ± 1.69 pmol product/120 min/100 μl CSF, while the mean TdR kinase activity of uninfected CSF was 0.34 ± 0.25. The enzyme appeared to be cell associated since the TdR kinase activity in the sedimented cell suspension was 5.08 ± 2.93 (seven values) while the supernatant activity was 0.14 ± 0.31 (seven values). To allow a comparison of TdR kinase from infected rabbit CSF with HVH and rabbit mononuclear cell TdR kinase, the mean ratio of TdR kinase activity at pH 6.0/pH 8.0 was calculated. The mean ratio of thymidine kinase activity, pH 6.0/pH 8.0, for infected rabbit CSF is intermediate between the ratio for HVH TdR kinase (P < 0.001) and rabbit mononuclear cell TdR kinase (P < 0.05).Speculation: The presence of TdR kinase in CSF from HVH-infected rabbits with biochemical properties intermediate between HVH and mononuclear cell TdR kinase suggests that abortive HVH infection occurs in CSF mononuclear cells during the course of HVH encephalitis.

Escherichia Coli Osteomyelitis in an Infant with Sickle-cell Disease

* Instructor, Department of Pediatrics. ** Associate Professor, Department of Pediatrics. From the Department of Pediatrics, Ohio State University, College of Medicine, and Children’s Hospital Research Foundation. Supported by the Children’s Hospital Research Foundation. Correspondence to 561 South Seventeenth Street, Columbus, Ohio 43205 (Dr. Haynes). CHILDREN ~vith sickle-cell and related anemias have a higher incidence of osteomyelitis than normal children.1-4 This paper presents a sevenmonth-old Negro infant in whom diffuse osteomyelitis due to Escherichia coli developed and was treated successfully with antibiotics.

TYPHOID FEVER IN CHILDREN

ConclusionsTyphoid fever in children occurs commonly in this region. It is not difficult to recognise the disease if the condition is borne in mind when dealing with a child suffering from fever of some days duration realising that the clinical picture as seen in children is markedly different from the descriptions found in text-books of internal medicine.One looks with some degree of satisfaction at the progress mad e during the last two decades in the control of typhoid fever in children. However, this control is restricted narrowly to combating the infection contracted by the child because, at least in this region, it has not been possible effectively to control the spread of infection which is due to the unfortunate circumstances of scocioeconomic conditions and sanitary habits of a large proportion of the population which do not permit eradication of the disease.The successful use of anti-typhoid drugs have brought in its wake problems of sequelae in children surviving from severe infections, especially if the nervous system is also involved. Such problems were encountered very infrequently in the past because the severe infections of this type almost invarialy terminated fatally.Eradication of typhoid fever from this land is not going to be an easy task. Country wide vaccination does not appear to be practicable at present. Public health measures and clean water supply by themselves would not solve the problem until the living conditions and sanitary habits of the population as a whole improve to the extent of preventing the spread of the disease through human discharges.Typhoid fever in children occurs commonly in this region. It is not difficult to recognise the disease if the condition is borne in mind when dealing with a child suffering from fever of some days duration realising that the clinical picture as seen in children is markedly different from the descriptions found in text-books of internal medicine.