Broad spectrum of time of detection, primary symptoms and disease progression in infants with HIV-1 infection.

The relationship between time of HIV-1 detection, appearance of symptoms and disease progression was studied in all 24 HIV-1-infected infants from a cohort of 117 children who were born to HIV-1-infected mothers and monitored from birth. HIV isolation from plasma and mononuclear cells, HIV-1 DNA PCR (polymerase chain reaction) and, retrospectively, a quantitative assay for HIV-1 RNA were used for virus detection. Two infants possibly exhibited a symptomatic primary HIV infection. More children with than without symptoms during the first year of life progressed to immunological class 3 (P=0.013) and to AIDS or death (P=0.003) during follow-up. HIV-1 was detected within 4 days of age in 4 of 16 infants: 3 of them became symptomatic within 1 year, as did 6 of the remaining 12 infants (not statistically significant). All four infants in whom virus was detected within 4 days of age progressed to severe immunosuppression, compared to 6 of 14 in whom the virus detection test was initially negative prior to the first positive result (n.s.). Two children with previous repeatedly negative HIV detection tests were diagnosed with HIV-1 infection at 8 and 9 months, respectively. Repeated blood sampling is needed for the diagnosis of HIV-1 infection in perinatally exposed infants, and virus detection tests for exclusion of HIV-1 infection must be used with caution.

Detection of urographic scars in girls with pyelonephritis followed for 13-38 years.

We report the detection and progression of renal scars in girls prospectively followed from their first recognized urinary tract infection. There were 107 infection-prone subjects with a median age of 7.1 years at the first and 21.7 years at the last urography. Of 51 females who ultimately had lesions, 38 had established scars at the first urography. In 18 subjects, new scars were found in previously undamaged kidneys, 5 already with unilateral scarring. There had been a normal urography after the 5th birthday in 8 of those with later scarring. Worsening of scarring was seen in 10 of the 38 subjects with established scars. The renal damage was in most cases slight or moderate. By stepwise logistic regression analysis, grade of reflux and number of pyelonephritic attacks correlated with scarring, and number of pyelonephritic attacks with new scars and worsening of the lesions. In summary, of the females who ultimately had renal lesions, one-third developed new scars. In most of those with established scars at the first urography, the focal character of lesions suggests that most were also acquired. Since reflux and number of pyelonephritic attacks were identified as risk factors, prevention of renal deterioration should be possible.

Long-term pattern of HIV-1 RNA load in perinatally infected children.

The objective of this study was to describe the natural history of HIV-1 RNA load in vertically HIV-1-infected children. HIV-1 RNA in 156 plasma or serum samples (1-14, median 4 from each child) from 32 vertically HIV-1-infected children was detected with the NASBA technique (Organon Teknika, The Netherlands). Twenty-one children were prospectively followed from birth, and 11 were identified and included at the age of 7-89 (median 61) months. The highest numbers of HIV-1 RNA copies were seen at 1.5-3 months of age. A quadratic curve model showed a reduction of HIV-1 RNA with increasing age up to approximately 8 years, and thereafter increasing numbers, p(age) = 0.002, p(age2) = 0.008. This pattern was not typical for individual children in whom a great variation in HIV-1 RNA numbers was seen over time. The interval from birth to the first HIV-1 RNA peak ranged from 1.5 months to more than 2 years. The HIV-1 RNA levels remained relatively high and fluctuating over the years in symptomatic as well as in long-term asymptomatic children. This makes HIV-1 RNA determination in children more difficult to use than in adults, as the only tool for prediction of disease progression and for initiation of therapy.

[The year of the world aids day: children in a world of AIDS]. / Arets världsaidsdag: barn i en värld med aids.

PIP: "Children living in a world with AIDS" was the theme of a UNAIDS campaign launched because 1 million children are infected with HIV and 9 million children have become orphans due to AIDS (90% in sub-Saharan Africa). During 1996 alone, 400,000 children were infected: 90% were infected during pregnancy, delivery, or while breast feeding; the remaining 10% were infected sexually or via blood or blood products. In Africa, only one-third of HIV-infected children survive their 3rd birthday, and 8% of all children in Zimbabwe have lost their mothers to AIDS. A similar situation is rapidly evolving in Asia and South America. In Spain and Italy, more than 600 children have AIDS; most of them were infected through drug-abusing mothers. In France the figure is comparable, but here a large segment is represented by children of mothers from African countries. The total number of children with AIDS in the European Community is 2800: 86% were infected through their mothers. Romania has 4000 children with AIDS, who were predominantly infected via nonsterile syringes and blood transfusion. The European Commission has a specific AIDS prevention program, which addresses the measurement of disease spread, counteracting the disease, information and education, support for persons with HIV/AIDS, and countering discrimination. The risk of mother-to-child HIV transmission can be reduced from 25% to 8% by zidovudine (AZT) treatment during pregnancy and delivery.^ieng

Girls prone to urinary infections followed into adulthood. Indices of renal disease.

This study describes blood pressure and renal function, as well as indices of renal disease, in females with and without renal scarring followed from their first urinary tract infection (UTI) in childhood. Of the 111 patients with a median follow-up time of 15 years, 54 had renal scarring (reflux nephropathy) on urography, which was severe in 19 and moderate in 35. The glomerular filtration rate was lower in patients with severe renal scarring and correlated with renal area on urography. However, the filtration rate was decreased below the lower reference limit in only 7 patients, with a lowest value of 70 ml/min per 1.73 m2. The diastolic blood pressure was higher in women with severe scarring. Hypertension of at least 140/90 mmHg was diagnosed in 3 of 54 (5.5%) females with renal scarring, 2 before and 1 at the follow-up examination. The excretion of albumin in urine was low and not correlated to filtration rate. Tubular enzymes in urine were similar in all groups. Thus the renal function was well preserved and the incidence of hypertension low. Within this range of renal function, the level of albumin in urine did not predict the degree of renal scarring.

Urinary infection, reflux and renal scarring in females continuously followed for 13-38 years.

This study describes the pattern of urinary tract infections (UTI) in 87 females prospectively followed for a median of 23 years from their first recognized symptomatic infection in childhood. At 16 years of age they were selected for follow-up into adulthood because of renal scarring (reflux nephropathy) in 45 and recurrent UTI in 42. The attack rate (number of urinary tract infections per individual per observation year) was highest during the 1st year of life (1.9), with a gradual decrease to the lowest rate (0.2) at age 11-15 years. A moderately increased attack rate (0.4), was seen in the late teens, extending through to the mid twenties. The proportion of infections having a pyelonephritic character decreased with age and number of infection episodes, but not in females with severe renal scarring. Pyelonephritic infections were correlated with vesicoureteric reflux, and renal scarring to low age at the index infection, total number of pyelonephritic episodes and reflux. Females with renal scarring continued to have a high proportion of pyelonephritic recurrences after 10 years of age, implying that they risk progressive renal disease and should be closely followed into adulthood.

Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

The mucosal and systemic interleukin-6 (IL-6) response to urinary tract infection was analyzed in women with acute pyelonephritis or asymptomatic bacteriuria. Urine and serum samples were obtained at diagnosis and after treatment. IL-6 activity was elevated in urine samples from most bacteriuric women, regardless of the severity of infection. Urinary levels greater than 20 units/mL occurred in 25 of 29 women with acute pyelonephritis and in 36 of 42 women with asymptomatic bacteriuria. Elevated serum IL-6 levels were found mainly in patients with acute pyelonephritis: Levels greater than 20 units/mL occurred in 14 of 28 women with acute pyelonephritis compared with 0 of 28 women with asymptomatic bacteriuria. These results suggest that bacteriuria is accompanied by elevated urinary IL-6 levels and that this IL-6 is locally produced. The spread of IL-6 to the circulation in patients with acute pyelonephritis may contribute to the elevation of fever and C-reactive protein characteristic of the disease.

Resident colonic Escherichia coli strains frequently display uropathogenic characteristics.

Bacterial factors associated with long-term persistence in the colon have not been defined. Individual Escherichia coli strains in the colonic flora of 13 schoolgirls with asymptomatic bacteriuria were identified by electromorphic typing of chromosomally encoded enzymes and defined as resident or transient. The strains were characterized as to serotype, receptor specificity, and adherence to the human colonic epithelial cell line HT-29. Colonic resident strains expressed P fimbriae, adhered to colonic epithelial cells via a mannose-resistant mechanism, and expressed the uropathogenic serotypes O1, O2, O6, O7, O18, O25, or O75 more often than did the transient strains, which were often nontypeable. The serotype and hemagglutination pattern were generally retained during intestinal carriage, in contrast to the loss of such properties upon prolonged colonization of the urinary tract. P fimbriae with Gal alpha 1----4Gal beta-specific adherence may, in fact, have evolved to increase persistence in the colon.

Persistence of Escherichia coli bacteriuria is not determined by bacterial adherence.

The role of bacterial adherence in the persistence of bacteria in the human urinary tract was analyzed. Women with chronic symptomatic urinary tract infections were subjected to deliberate colonization with nonvirulent Escherichia coli, after eradication of their current infections. E. coli organisms were instilled into the bladder through a catheter. The strain used for colonization, E. coli 83972, was isolated from a patient with stable bacteriuria. It lacked expressed adherence factors and did not belong to the uropathogenic O:K:H serotypes. Strain 83972 was transformed with the pap and pil DNA sequences encoding Gal alpha 1-4Gal beta- and mannose-specific (type 1) adhesins. Patients were colonized with a mixture of the wild-type and the transformed strains. E. coli 83972 caused stable bacteriuria for greater than 30 days in 7 of 12 individuals. In contrast, the Gal alpha 1-4 Gal beta-recognizing or mannose-binding transformants were eliminated within 48 h. The consistent superiority of the wild-type strain in establishing stable bacteriuria when compared with the adhesive transformants did not appear to be due to differences in growth rates or to plasmid segregation. Rather, the transformants expressing the adhesin determinants were selectively eliminated by the host. This suggested that the acquisition of adherence factors is not sufficient to increase the fitness of E. coli for survival in the urinary tract of humans.

Interleukin-6 response to deliberate colonization of the human urinary tract with gram-negative bacteria.

Intravesical inoculation of patients with Escherichia coli provided an opportunity to examine the interleukin-6 (IL-6) response to a gram-negative bacterial urinary tract infection in humans. All patients secreted IL-6 as a result of infection. Urinary IL-6 was not continuously secreted but appeared as a series of similar peaks during the first 48 h after infection. There was no significant difference in the ability to trigger IL-6 secretion between isogenic adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria per ml of urine was necessary to fully stimulate IL-6 secretion. There was no detectable increase in IL-6 levels in the serum of the colonized individuals, suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a part of the human mucosal response to gram-negative urinary tract infections.

Pregnancies in women with and without renal scarring after urinary infections in childhood.

OBJECTIVE: To compare the outcome of pregnancy in women with and without renal scarring after childhood urinary infections with that in unmatched controls. DESIGN: Retrospective study of pregnancies in women prospectively followed up from their first recognised urinary infection. SETTING: Tertiary referral centre in Gothenburg. SUBJECTS: 111 Women attending an outpatient clinic for women with urinary infection during 1975-83, of whom 41 (65 pregnancies) were studied (19 women with renal scarring (32), 22 without scarring (33)), and 65 controls (65) randomly selected and matched for parity, age, smoking habits, and date of delivery. MAIN OUTCOME MEASURES: Urinary infections and complications in pregnancy. RESULTS: The incidence of bacteriuria during first pregnancies was significantly greater in women with (9, 47%) and without (6, 27%) renal scarring after childhood urinary infection than in controls (1, 2%) (p less than 0.001, 0.01 respectively). Symptomatic infections were seen only among women with a history of urinary infection: four women with renal scarring (three of whom had vesicoureteric reflux) developed pyelonephritis and three cystitis, and one woman without scarring developed pyelonephritis. Mean blood pressure was higher among women with severe renal scarring than controls (4/11 v 3/44; p less than 0.05) before and during pregnancy. There was no significant difference in the incidence of pre-eclampsia, operative delivery, prematurity, or birth weight. CONCLUSIONS: Women with a history of previous urinary infections had a high incidence of bacteriuria during pregnancy, and those with renal scarring and persistent reflux were prone to develop acute pyelonephritis. The risk of serious complications in pregnancy, however, was not increased in women with severe renal scarring, possibly owing to their continuous clinical supervision.

Selective use of excretory urography in women with acute pyelonephritis.

The outcome of excretory urography was analyzed in 103 nonpregnant women followed prospectively after community acquired acute pyelonephritis. Radiological abnormality was found in 40 per cent of the patients (17 per cent had major abnormalities, including renal scarring, calculi and obstruction). All 5 women with surgically correctable lesions had rapid bacteriological relapse or recurrent acute pyelonephritis. Neither a history of urinary tract infection, the acute inflammatory response nor infection due to Escherichia coli with or without adhesins specific for Gal alpha 1----4Gal beta-containing receptors was efficient in predicting major radiographic lesions or the outcome of treatment. Bacteremia was detected in 27 per cent of the patients but in the absence of obstruction. These results suggest that excretory urography is dispensable in most women with acute pyelonephritis, and that those needing such investigation may be identified by failure to respond to antibiotic treatment or by the recurrence pattern.

Bacteriuria in pregnancy. Frequency and risk of acquisition.

A total of 3,254 pregnant women attending two antenatal clinics in Göteborg, Sweden, were screened for bacteriuria. The coverage of the pregnant population in the areas served by the two clinics was estimated to be 88%. Of the women who were registered at the two clinics, 99% took part in at least one screening; 71% were screened during each of the three intervals. The high frequency of screening of the women made it possible to estimate the risk of acquiring bacteriuria during pregnancy. This risk increased with the duration of pregnancy from 0.8% of bacteriuric women in the 12th gestational week to 1.93% at the end of pregnancy. The risk of onset of bacteriuria was highest between the ninth and 17th gestational weeks. The 16th gestational week was the optimal time for a single screening for bacteriuria calculated as the number of bacteriuria-free gestational weeks gained by treatment.

Host response in women with symptomatic urinary tract infection.

The agreement between clinical signs and host response was analysed in 174 women with symptomatic urinary tract infection. C-reactive protein (CRP) confirmed the clinical diagnosis in that 94% of non-pregnant and 91% of pregnant women with acute pyelonephritis had serum levels greater than or equal to 30 mg/l, compared with only 5% of cystitis patients. There was a significant increase in the erythrocyte sedimentation rate (ESR) and reduction of the renal concentrating capacity in patients with acute pyelonephritis, although the overlap with the cystitis group was greater than for CRP. The transient decrease in urine osmolality was unrelated to age, as were CRP, ESR and the total white blood cell count. Pregnant women had higher ESR but lower CRP levels than non-pregnant women with acute pyelonephritis. The renal concentrating capacity was more reduced in those infected with Escherichia coli expressing adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors on uroepithelial cells.

Bacterial adhesion as an indicator of renal involvement in bacteriuria of pregnancy.

The association of bacterial virulence with the host response to bacteriuria was evaluated in 70 pregnant women with acute pyelonephritis or bacteriuria detected at screening. Patients infected with Escherichia coli attaching to Gal alpha 1----4Gal beta-containing receptors, had significantly higher levels of C-reactive protein and lower renal concentrating capacity than patients infected with strains lacking this specificity. The renal concentrating capacity ranged from 419-1151 mOsm/kg in the women with bacteriuria on screening. 5/11 women with a renal concentrating capacity less than or equal to 784 mOsm/kg were infected with Gal alpha 1----4Gal beta-specific bacteria, compared to 0/16 of patients who concentrated the urine greater than 784 mOsm/kg. According to earlier studies the risk for progression to pyelonephritis and recurrences during pregnancy was increased in bacteriuric women with a reduced renal concentrating capacity. The present study demonstrates that this risk group can be identified in part by the properties of the infecting E. coli strains.

Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection.

The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.