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Biomedical subjects

H C Whittle

Publications and source records attributed to H C Whittle.

At least 19 recordsLinked to original sources

Persistent hepatitis B virus infection and hepatoma in The Gambia, west Africa. A case-control study of 140 adults and their 603 family contacts.

To determine the incidence of persistent hepatitis B virus infection and its etiologic role as a cause of hepatoma, the authors carried out a case-control investigation of 70 persons with hepatoma, 70 controls, and their families in 1981-1982 in The Gambia, West Africa. The risk of developing hepatoma after the age of 39 years was 1.4% in men and 0.3% in women. Hepatoma occurred more than twice as frequently among persons who had four or more older siblings as among persons who had less than two older siblings. The attributable risk between persistent infection with hepatitis B virus and hepatoma was 78% for individuals aged less than 50 years and 37% for persons aged 50 years or more, with an overall risk of 53%. The high prevalence of hepatitis B surface antigen and hepatitis B e antigen antigenemia in children under 15 years of age (14% of 341 children) and the positive correlation between late birth order and risk of developing hepatoma suggest that postnatal early childhood exposure to hepatitis B virus is an important risk factor. The use of a hepatitis B virus vaccine which provides durable immunity in very young children will probably prevent most cases of hepatoma.

Adolescent

Single injection treatment of meningococcal meningitis. 1. Long-acting penicillin.

A single injection of a long-acting preparation of penicillin (Triplopen) was compared with a five-day course of crystalline and procaine penicillin in the treatment of meningococcal meningitis. The clinical response of patients treated with Triplopen was very similar to that of patients treated with crystalline penicillin and much more convenient to administer. However, four patients treated with Triplopen had a positive CSF culture 48 or 72 hours after their injection. One injection of Triplopen cannot, therefore, be recommended as an entirely safe form of treatment for meningococcal meningitis unless patients can be carefully followed.

Adolescent

Single injection treatment of meningococcal meningitis. 2. Long-acting chloramphenicol.

A single injection of a long-acting oily preparation of chloramphenicol (Tifomycine) was compared with a five-day course of crystalline and procaine penicillin in the treatment of 131 adult patients with meningococcal meningitis. The clinical response to treatment was similar in the two groups of patients. Serial lumbar punctures showed a parallel fall in CSF cell count, protein and lactate and all posttreatment cultures were sterile. Single injection chloramphenicol treatment was cheaper and much easier to administer than penicillin. Long-acting chloramphenicol is thus an effective form of treatment for meningococcal meningitis and is likely to prove of particular value in the management of epidemics in areas with limited medical resources.

Adolescent

An epidemic of meningococcal infection at Zaria, Northern Nigeria. 1. General epidemiological features.

In 1977 Zaria, in Northern Nigeria, was affected by a severe epidemic of group A meningococcal infection, 1,257 patients being admitted to hospital with the disease during a three-month period. The epidemic started towards the end of the dry season when it was hot, dry and dusty and finished shortly after the onset of the rains. The over-all attack rate was 3.6 per 1,000 but this varied considerably from area to area within the town. Few cases occurred amongst those belonging to the upper social classes. The disease was seen most frequently amongst those from five to 14 years old and there was a strong male preponderance. The over-all mortality was 8.3% but mortality was much higher (40.6%) amongst 67 patients with acute meningococcaemia.

Adolescent

An epidemic of meningococcal infection at Zaria, Northern Nigeria. 2. The changing clinical pattern.

1,003 patients with meningococcal disease admitted to a single hospital during the course of a three-month epidemic were studied. A progressive decline in mortality, especially among patients with acute meningococcaemia, and a falling incidence of systemic and severe neurological complications among patients with meningitis were observed. It is suggested that the virulence of the causative group A meningococcus declined as the epidemic progressed.

Acute Disease

An epidemic of meningococcal infection at Zaria, Northern Nigeria. 3. Meningococcal carriage.

Meningococcal carriage was studied in household contacts of patients with group A meningococcal disease and in controls. The carriage rate of group A meningococci among 1,098 household contacts was low (3.8%) and only slightly higher than the carriage rate found among 416 controls (2.6%). However, higher carrier rates were found among those in close contact with a patient. Carriage was found most frequently among children and young adults and was commoner in adult females than in adult males. Sulphonamides had no effect on carriage and all 60 strains tested in vitro were resistant to sodium sulphadiazine at a concentration of 10 micrograms/ml.

Adolescent

Severe ulcerative herpes of mouth and eye following measles.

Malnourished children in the north of Nigeria who had had a severe attack of measles were prone to deep ulcers of the mouth and eyes. Herpes simplex virus was isolated from 17 of 25 of the mouth ulcers which were erosive, slow to heal and caused much suffering and loss of weight. Herpes virus was also identified, either by immunofluorescent staining or viral culture, in the corneal scrapings of the eye ulcers from 16 of 34 children. These ulcers healed slowly in two to six weeks leaving damaging scars which impaired vision and caused blindness in some cases. It is suggested that measles leads to profound depression of cell mediated immunity in malnourished children with the consequence that secondary herpes simplex infections become abnormally severe and erosive.

Body Weight

Corneal ulceration following measles in Nigerian children.

Acute corneal ulceration in malnourished children is the commonest cause of childhood blindness in Northern Nigeria and usually develops after measles. Other severe diseases in malnourished children rarely precipitate corneal ulceration. A survey in a school for blind children showed that 69% of the children were blind from corneal disease, and a survey of children with corneal scars showed that at least 42% were caused by ulceration after measles. The clinical appearance of the active ulcers was very varied. The serum retinol-binding protein and prealbumin levels in children with corneal ulcers following measles were below normal, but a group of malnourished children without eye complaints following measles were found to have even lower levels. Thus a specific deficiency of vitamin A does not appear to be the primary cause of these ulcers, though it may be a contributory one. A specific measles keratitis and secondary herpes simplex infectious may be local factors contributing to this ulceration, and there is nearly always a background of protein calorie malnutrition. Racial factors may also be of some significance.

Blindness

Prevention of secondary cases of meningococcal disease in household contacts by vaccination.

Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.

Adolescent

Amoebiasis in northern Nigeria. An evaluation of the gel diffusion test.

Sera from 778 patients presenting a hospitals in Zaria and Kaduna, northern Nigeria, were tested for amoebic precipitins by the gel diffusion test; 106 (14%) were positive. Positive tests were obtained in 16 of 18 patients with an amoebic liver abscess, in 17 of 31 patients with amoebic dysentery and in three of 100 apparently healthy controls. Positive tests, and clinical cases of amoebiasis, were seen more frequently in the wet season than in the dry season.

Amoeba

Meningococcal infection and proteolytic control.

Cascade enzyme inhibitors (C1-esterase inhibitor, C3b inactivator, antithrombin III) and other major proteolytic enzyme inhibitors (alpha 1 trypsin inhibitor, alpha 1 chymotrypsin inhibitor, inter-alpha-trypsin inhibitor, alpha 2 macroglobulin) as well as C3 and alpha 1 acid glycoprotein, have been examined in the sera of Nigerian patients suffering from meningococcal infection of varied severity. Patients with meningococcaemia had lower serum concentrations of important inhibitors than did patients with localised meningitic infection. Within the coccaemic group, those who died had the lowest values, notably of antithrombin III and alpha 2 macroglobulin (and also of C3). The clinical end-result of meningococcal infection may be related to the degree of disequilibrium of the linked system of proteolytic control induced by the meningococcal endotoxin.

Antithrombin III

Cell-mediated immunity during natural measles infection.

Natural measles causes prolonged depression of cell-mediated immunity yet little is known as to how the infection influences lymphocyte function. Therefore, we studied the properties and function of lymphocytes during and after measles. The number and proportion of circulating thymus-derived lymphocytes was low during the acute stage of measles, and at this time 37% of these cells showed positive immunofluorescent staining for measles virus after stimulation with phytohemagglutinin. 7% of B cells were shown to contain virus but their numbers did not alter during the infection. Acute-phase lymphocytes, when stimulated, yielded infective virus and half were killed on incubation with autologous serum and complement. In acute measles the increase in [(3)H]-thymidine uptake of lymphocytes when stimulated with an optimal dose of PHA was normal in media with 10% fetal calf serum and low in media containing 10% autologous serum: the mean values were 56.8+/-34.1 and 23.7+/-25.9 cpm x 10(3) per 10(6) lymphocytes, respectively. Stimulation of acute-phase lymphocytes by Candida antigen was also low in media containing autologous serum averaging 1.2 x 10(3) cpm per 10(6) lymphocytes. On recovery 4-6 wk later this rose significantly to 18.9+/-19.8. The mean migration index of leukocytes to heat-killed candida cells in acute measles was 0.84+/-SD 0.08, and this fell significantly to 0.75+/-SD 0.08 4 wk later. Thus, depletion of T cells, an inhibitor of lymphocyte proliferation in the serum and a possible defect in antigen processing, interacts to depress cell-mediated immunity in measles.

Antigens, Fungal

Persistent measles infection in malnourished children.

Thirty malnourished and 25 well-nourished children were studied six to 31 days after the onset of a measles rash. Evidence of the virus was found in 40% of the malnourished children but in none of the well-nourished controls. Giant cells were found in the nasal secretions of five out of 17 malnourished children and measles antigen was detected in the lymphocytes of eight out of 28. The malnourished children showed depressed cell-mediated immunity to measles and candida antigens and a low response to meningococcal vaccine. Fifteen died from intercurrent infections. Malnutrition was thought to have depressed the immune response in these children, resulting in a severe and prolonged attack of measles. This, in turn, led to further damage to the immune system and more severe malnutrition. Thus these children were made susceptible to intercurrent infection.

Antigens, Viral

Comparative study of group A and group C meningococcal infection.

114 patients with meningococcal infection were studied; 72 had group C infection and 42 group A infection. 14 patients had acute meningococcaemia, all of whom had group C infection and 9 of whom died. Clinical and laboratory findings were similar in patients with meningitis due to a group A and C organisms, but arthritis and cutaneous vasculitis were more common in patients with group C infection. The overall mortality was 22% in patients with group C infection, and 12% in patients with group A infection, but was the same in both groups when cases of acute meningococcaemia are excluded.

Adolescent

Cerebrospinal fluid immunoglobulins and complement in meningococcal meningitis.

Cerebrospinal fluid (CSF) immunoglobulins (IgA, IgG, IgM) were measured in 107 patients with meningococcal meningitis. Levels were correlated significantly with CSF total protein, and both CSF immunoglobulin and protein increased with age. C3 was measured in the CSF of 38 patients and was also closely correlated with the CSF protein level. C3 breakdown products were found in all six CSFs tested. The CSF immunoglobulin and complement were thought to have leaked from the plasma due to inflammation of the meninges and had little value in diagnosis or prognosis.

Adolescent

IgM and antibody measurement in the diagnosis and management of Gambian trypanosomiasis.

Serum and cerebrospinal fluid (CSF) IgM were measured in 182 patients at various stages of Gambian sleeping sickness and correlated with antibody levels measured by enzyme-linked immunosorbent assay (ELISA). Each of these tests in serum gave a 30% false negative result, but when both were used this fell to 12%. Measurements of IgM in CSF were raised in 87% of patients with advanced disease and in none of the early cases. The IgM levels fell slowly to normal by 12 months after treatment. A high level at this time, or a rise after treatment, was helpful in diagnosing relapsed patients. Antibody levels in CSF were of no use in diagnosis or prognosis, and were raised in many controls.

Antibodies

Mortality from pneumococcal meningitis.

The records of 207 patients with pneumococcal meningitis admitted to Ahmadu Bello University Hospital, Zaira, northern Nigeria, between February, 1971 and June, 1976 have been reviewed. Mortality was 51%. Death was more likely in patients with a short history, impaired consciousness on admission, and an associated pneumonia. Cerebrospinal fluid levels of protein, lactate, fibrin degradation products, and polysaccharide antigen were higher in patients who died than in survivors.

Adult