Hendrik J. Koornhof

Emergence of Multiply Resistant Pneumococci

Multiple antimicrobial resistance in pneumococci was detected in Johannesburg in July, 1977, and prompted an investigation of the prevalence of resistant strains in two hospitals. Carriers of Types 6A and 19A penicillin-resistant pneumococci, resistant to antibiotic concentrations ranging between 0.12 and 4 microgram per milliliter were found in 29 per cent of 543 pediatric patients and 2 per cent of 434 hospital staff members. Multiply resistant Type 19A strains, resistant to beta-lactam antibiotics, erythromycin, clindamycin, tetracycline and chloramphenicol, were isolated from 128 carriers, and were responsible for bacteremia in four patients. Isolates from 40 other carriers were resistant to penicillin alone or to penicillin and chloramphenicol or to penicillin, chloramphenicol and tetracycline. Pneumococci can be screened for penicillin resistance with a modified Kirby--Bauer technic; the strains with zones of less than 35 mm around 6-microgram penicillin disks or less than 25 mm around 5-microgram methicillin disks should be tested for sensitivity to penicillin by measurements of minimum inhibitory concentration.

Immunogenicity, efficacy and serological correlate of protection of Salmonella typhi Vi capsular polysaccharide vaccine three years after immunization

The protective efficacy and immunogenicity of Vi capsular polysaccharide vaccine against typhoid fever was measured 3 years after its administration in a double-blind randomized trial. Vaccine efficacy was not significantly different during each year of the trial and was 55% (95% CI: 30-71%) over the 3 year period. In a case-control study at 3 years after vaccination, recipients of Vi had higher levels of Vi antibodies than controls, as measured by radio-immunoassay (GMT 1.28 vs 0.76 microgram ml-1, P = 0.0004) and by passive haemagglutination assay (GMT 10.46 vs 3.52, P = 0.0001). The serological correlate of protection has been estimated using the relative risks of typhoid fever in the 2 groups and the relative ratio of antibody levels. The estimated protective level is 1 microgram ml-1 suggesting that at a mean age of 9 years, 64% of vaccinates and 40% of controls had protective antibody against typhoid fever in this endemic area.

Epidemiology of rheumatic heart disease in black shcoolchildren of Soweto, Johannesburg.

A survey to determine the prevalence of rheumatic heart disease (R.H.D.) in Black children was conducted in the creeches and primary schools of the South Western Townships of Johannesburg (Soweto). A total of 12 050 Black children were examined by 10 cardiologists in May to October 1972. The overal prevalence rate of R.H.D. was 6.9 per 1000, with a peak rate of 19.2 per 1000 in children of the seventh school grade. The maximal age incidence was 15-18 years and there was a female preponderance of 1 6:1. A rise in prevalence occurred with increasing family size. Most children (92%) were asymptomatic, and in 82.5% R.H.D. was diagnosed for the first time during the school survey. The commonest valve lesion was mitral regurgitation, which was present in 93% and occurred as an isolated lesion in 47.5%. Lancefields group A beta-haemolytic streptococcus was isolated from the throats of 52 per 1000 Soweto children. The auscultatory features of a non-ejection systolic click and late systolic murmur were prevalent (13.9 per 1000) and had several epidemiological factors in common with R.H.D. A comprehensive preventative campaign is urgently needed in South Africa, directed at both primary and secondary prophylaxis of R.H.D. The socioeconomic status of the community must be improved if optimal prevention is to be achieved.

Carriage of penicillin resistant pneumococci.

A survey of 303 urban and 156 rural children showed nasopharyngeal carriage of relatively resistant Streptococcus pneumoniae organisms in 14.2% and 19.2% of children, respectively. These organisms have minimum inhibitory concentrations for penicillin in the range of 0.12-1 microgram/ml. An analysis of 40 relatively resistant S. pneumoniae strains showed resistance to co-trimoxazole in 47.5%, trimethoprim in 42.5%, fusidic acid in 20%, tetracycline in 2.5%, and rifampicin in 5%. All the strains were susceptible to chloramphenicol and vancomycin, while the minimum inhibitory concentrations of third generation cephalosporins and imipenem were comparable with or lower than those of penicillin. Eighty three per cent of the strains tested belonged to serogroups 6 and 19. These findings are discussed in relation to the poor clinical response to treatment with penicillin for relatively resistant S. pneumoniae meningitis, and the minimum inhibitory concentrations of alternate agents under review for treatment of systemic pneumococcal disease are presented.

High Human Immunodeficiency Virus Type 1 RNA Load in the Cerebrospinal Fluid from Patients with Lymphocytic Meningitis

Thirty-seven matched cerebrospinal fluid (CSF) and plasma samples from 34 human immunodeficiency virus type 1 (HIV-1)-infected patients with suspected meningitis were analyzed for levels of HIV-1 RNA and markers of inflammation. Patients with tuberculous (n = 9) or cryptococcal (n = 6) meningitis had the highest CSF virus loads, which in many cases exceeded the levels in plasma, compared with patients with meningococcal meningitis (n = 3), aseptic meningitis (n = 8), tuberculoma (n = 2), or AIDS dementia complex (n = 4) or with normal lumbar punctures (n = 3). CSF virus load correlated significantly with the number of infiltrating lymphocytes (r = .60, P < .001) but not with plasma virus load, the levels of beta2-microglobulin in the CSF, or the integrity of the blood-brain barrier. These data suggest significant intrathecal HIV-1 replication in patients with lymphocytic meningeal infections such as tuberculous and cryptococcal meningitis.

Summer diarrhoea in African infants and children.

Of 70 black South African infants and children with acute summer diarrhoea, 30 (43%) were infected with enteropathogenic serogroups of Escherichia coli (EPEC), 13 (19%) with enterotoxigenic Gram-negative bacilli, 12 (17%) with Salmonella sp., 6 (9%) with Shigella sp., and 3 (4%) with rotaviruses. 13 (19%) patients were infected simultaneously with more than one enteropathogen, and no pathogen was detected in 22 (31%). In addition, 6 (15%) of 41 unselected patients were excreting Campylobacter fetus. Of 30 age-matched controls drawn from the same population, 5 (17%) were infected with EPEC serotypes, and 1 each with Salmonella sp. and rotavirus. This study stresses the polymicrobial nature of paediatric diarrhoea in a developing community and shows the continued importance of EPEC in this setting.

Antibiotic-resistant pneumococci in hospitalized children.

A search for nasopharyngeal carriers of Streptococcus pneumoniae was conducted in 573 children hospitalized in Durban, South Africa. Study subjects were divided into two groups, comprising 305 new admissions and 268 patients who had been hospitalized for more than 24 h. Of the 573 children 178 (31%) yielded pneumococci on nasopharyngeal culture; 99 (32%) and 79 (29%) children in the new admission and in-patient categories respectively. Twenty-one (12%) pneumococci were resistant to penicillin, including 11 strains that were resistant to more than one antibiotic. Resistant pneumococci belonged exclusively to serotypes 6 and 19 (Danish nomenclature), which were also the commonest serotypes among penicillin-sensitive strains. Factors that correlated with carriage of penicillin-resistant pneumococci were hospitalization for more than 24 h, young age and recent exposure to beta-lactam antibiotics.

Klebsiella pneumoniae bacteraemia at an urban general hospital

Of 47 patients with Klebsiella pneumoniae bacteraemia admitted to the Hillbrow Hospital, Johannesburg during a period of 18 months, 31 were males and 16 were females. Features predisposing to illness were found in 89.4% patients, chronic alcoholism, neoplastic disease and diabetes mellitus being the most common. Twenty-five infections were acquired in hospital and 22 in the community. Most patients (59.6%) had pneumonia. All isolates of K. pneumoniae were resistant to ampicillin (100%); several (42.6%) were resistant to other antibiotics also. The overall mortality rate was 55.3%. A higher mean initial blood pressure and lower concentrations of serum urea and bilirubin were found in survivors. None of the 28 patients, surviving more than 48 h who received combined therapy with an aminoglycoside and a beta-lactam antibiotic (to which the organism was susceptible) died. Among the remaining patients treated with either an appropriate beta-lactam agent alone, an appropriate aminoglycoside alone or ciprofloxacin the combined mortality rate was 83.3% (P = 0.007).

Defective neutrophil motility in children with measles

The random migration and chemotactic ability of neutrophils from ten patients with uncomplicated measles was found to be grossly impaired when compared to a group of normal children. Chemotaxis to endotoxin activated serum and to hydrolysed casein was markedly depressed, but serum from measles patients, when activated by endotoxin, generated and chemotactic activity and did not contain leukotactic inhibitors. The defect in neutrophil motility was confirmed in vivo by abnormal Rebuck skin windows. The defect was temporary, and recovery of normal chemotaxis was observed by the eleventh day after the onset of the rash.

Meningitis in a community with a high prevalence of tuberculosis and HIV infection.

OBJECTIVES To evaluate the spectrum of aetiologies, and distinguishing clinical and laboratory features, of meningeal infection in a community with a high prevalence of tuberculosis (TB) and HIV infection. SETTING A hospital serving mineworkers, originating from rural areas of Southern Africa. DESIGN Prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis. MEASUREMENTS Clinical history and examination; concurrent cerebrospinal fluid (CSF) and blood samples; mortality status six months after entry to study. RESULTS 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis (TBM) and two had tuberculomas; four developed disease while on TB therapy. There was one case of multidrug, and two of isoniazid-resistant TBM. There were nine episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis, two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were significantly younger (p=0.004). All patients with tuberculous, cryptococcal (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive. Within six months, 19 patients had died. Death was associated with HIV positivity (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis, CNS TB or ADC. CONCLUSION HIV has a major impact on the burden of disease and mortality, with a predominance of opportunistic chronic meningitides, despite a meningococcal outbreak, in this community. Of concern is the development of TBM despite therapy, and the emergence of drug-resistant strains.