Karsten Hjelt

The Role of Mycobacteria Other Than Tuberculosis (MOTT) in Patients with Cystic Fibrosis

The purpose of this study was to estimate the frequency of and evaluate the clinical impact of pulmonary mycobacterial infections among cystic fibrosis (CF) patients. 185 CF patients aged 2.2-38.5 years were screened by sputum samples and by intracutaneous skin tests against tuberculin and sensitins produced from Mycobacterium chelonae subsp. abscessus, M. avium, M. intracellulare and M. scrofulaceum (the MAIS complex). The skin tests towards the sensitins in BCG-vaccinated patients (n = 60) were significantly influenced by the vaccination. 26 of the remaining 125 non-vaccinated patients had > or = 1 positive skin test (95% confidence limits 15-29%). The majority reacted against the MAIS complex. However, the reactions were similar to those of healthy siblings and an age-matched control group. Moreover, the lung function, growth and HbA1c were similar among skin test positive and negative patients. Three patients had repeated positive sputum cultures, the point prevalence being 1.6% (M. intracellulare, n = 2 and M. chelonae subsp. abscessus, n = 1). During the subsequent 4 years, 4 additional patients with M. chelonae subsp. abscessus were identified. Based on clinical observations, 5 of the infected patients were considered asymptomatic, while 2 might have been symptomatic. In 1 patient, M. chelonae subsp. abscessus disappeared spontaneously. Despite intensive treatment with new antibiotics against Mycobacteria Other Than Tuberculosis (MOTT) in 4 patients, the mycobacteria were not eradicated. In conclusion, MOTT infection was rare and the clinical impact difficult to prove. Treatment should focus on clinical improvement in the individual patient suspected of suffering from significant symptomatic infection. Eradication of the bacteria should not be expected.

Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study.

ABSTRACT. The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent urinary tract infections (UTI) was compared by means of actuarial percentage recurrence‐free curves in a randomized, double blind study in 130 children (126 girls, 4 boys) aged 1 to 14 years (mean 7.5). The children received the antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux (n=60) as evaluated by actuarial percentage recurrence‐free analysis (p= 0.0025). However, no differences was found in patients without urinary tract abnormalities. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before (p<0.0001) and 17% after (p<0.0001) prophylaxis. The percentage of recurrences due to E. coli (70‐80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%, p<0.0001) and after (11%, p<0.001). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%, p<0.0003). Following prophylaxis there was no difference in the actuarial percentage recurrence‐free curves of the two regimens. Side effects occurred more frequently in the nitrofurantoin group (37%)than in the trimethoprim group (21%) (p=0.05). The majority of side effects in the nitrofurantoin group derived from gastrointestinal symptoms. In conclusion, nitrofurantoin is recommended as the first choice prophylactic treatment of children with recurrent UTI and urinary tract abnormalities.

Antibody response in serum and intestine in children up to six months after a naturally acquired rotavirus gastroenteritis.

Summary The aim of this study was to provide detailed information about the local and systemic antibody response and their relationship following a rotavirus gastroenteritis. Rotavirus-specific immunoglobulins were analyzed by enzyme-linked immunosorbent assay (ELISA). The study included 49 children referred to hospital with rotavirus gastroenteritis and 16 children with nonrotavirus gastroenteritis. The concentrations of rotavirus immunoglobulin A (IgA) in serum increased within the first 2 weeks and those of rotavirus IgG within the first month after the onset of diarrhea. Thereafter, they remained unchanged during the 6-month observation period. Rotavirus ScIg (i.e., antirotavirus immunoglobulin-containing secretory component) appeared in serum almost exclusively within 7–14 days after onset (i.e., 85% of the samples). After the first 2 weeks, rotavirus IgA could be detected in the majority of fecal samples, even up to 6 months after the disease. However, rotavirus ScIg was absent in the majority of fecal samples. The severity of illness correlated only with the increase of rotavirus IgG in serum. Conclusively, there is a longstanding immune response after a naturally acquired rotavirus gastroenteritis. Moreover, with the present methods, measurements of rotavirus IgA and IgG in serum can be safely used for serodiagnosis, even when samples are taken with 6-month interval. It is suggested that trials with rotavirus vaccines include measurements of rotavirus IgA and ScIg in serum and rotavirus IgA in feces.

The age-related incidence of meconium ileus equivalent in a cystic fibrosis population : the impact of high-energy intake

During the decade from 1976 to 1986, the age-related incidence of meconium ileus equivalent (MIE) was calculated on the basis of 240 Danish cystic fibrosis (CF) patients. In the first 5 years, the patients were given enteric-coated granules of pancreatic enzymes (Pancreatin, Rosco, Denmark), and a low fat diet was recommended. In the last 5 years, the Center recommended supplementation with acid-resistent, enteric-coated, encapsulated microspheres (Pancrease, Cilag, Birker&phis;d, Denmark), and high-energy intake with a 40% fat content and no dietary restrictions. There was no difference in the incidence of MIE when these two 5-year periods were compared, and the overall incidence of MIE was low (5.4 MIEs/1.000 patient years). This may, at least in part, be due to the rather high intake of exocrine pancreas enzyme supplementation (EPES) (a mean intake of 0.9 capsules/kg/day). MIE occurred almost exclusively among patients >15 years old and peaked in young adults aged 20–25 years (35.5 MIEs/1.000 patient years). The daily intake of EPES/kg of body weight declined significantly with age, and the patients who developed MIE received even less than average per day. Both of these points strengthen the view that a low enzyme dosage is likely to have an effect on the incidence of MIE.

Methaemoglobinaemia among neonates in a neonatal intensive care unit

After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n= 33) of 415 neonates were found to be methb positive (denned as ≥6% methb). Mean methb was 19% (range 6.5–45.5%). Maximum methb concentrations were found on day 4–31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25–30 weeks of gestation and 60%) with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r=– 0.38,p= 0.02). Measurements of C–reactive protein and leucocytes, NADH reductase, pH, CI, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170g and that of negative controls 1380g (p < 0.006). Epidemiological data and intervention studies indicated that para–chloraniline was the direct cause of the epidemic. The substance was derived from 0.02% chlorhexidine being inadvertently added to the humidifying fluid of the new incubators. Treatment of severe methb in premature neonates with 0.3–1.0mg methylene blue/kg body weight proved efficient. In conclusion, premature neonates developed severe methb when exposed to even small amounts of para–chloraniline. Immaturity, severe illness, the time exposed to para–chloraniline and low concentrations of NADH reductase probably played a part while other well known factors such as increased nitrite and nitrate concentrations, acidosis and hyperchloraemia did not seem to be significant.

Acute gastroenteritis in children attending day-care centres with special reference to rotavirus infections. I. Aetiology and epidemiologic aspects.

Acute gastroenteritis (GE) among 214 children (aged 6 months – 7 years) attending day‐care centres (DDCs) in the Copenhagen County was studied during a 12‐month period. A total of 197 cases of GE was observed in 109 children (i.e. 51% of the participants). The aetiology was as follows: rotavirus (n=48) (24%), pathogenic bacteria (n=11) (6%), Giardia lamblia (n=3) (2%), while the aetiology of 68% remains unknown. The pathogenic bacteria included Yersinia enterocolitica, thermophilic Campylobacter, Clostridium difficile (±toxin) and enteropathogenic E. coli. In 4% of the GE the infections were multiple and Cryptosporidium was seen in one of these cases. The rate of GE declined with age from 1.35 GE per child per year (age group 1.0– <2.0 years) to 0.36 (6.0 – <8.0 years). Serum sampled at the start of the study period showed that the frequency of detectable rotavirus IgG increased with age from 48% in the 6 months – <1.0 year group to 96% in the 4.0 – <7.0 year group. The highest rates of rotavirus GE occurred from January to April (i.e. the rotavirus season). Moreover, rotavirus GE was almost absent after the age of 4. Hence, the rates of rotavirus GE per rotavirus season per child were 0.80 (age group 6 months–<1.0 year), 0.32 (1.0–<2.0), 0.14 (2.0–<3.0), 0.16 (3.0–<4.0), 0.06 (4.0–<5.0) and 0.04 (5.0–<6.0). Only 2 out of the 48 rotavirus GE were reinfections. The 32 children with asymptomatic rotavirus infections and those with rotavirus GE showed a similar distribution of age and season. A cross‐sectional study of the prevalence of rotavirus excretion during the rotavirus season revealed only a single true asymptomatic excretor.

Rapid versus Gradual Refeeding in Acute Gastroenteritis in Childhood: Energy Intake and Weight Gain

Fifty-two children aged 6–46 months (mean 19 months), hospitalized for acute gastroenteritis (GE), were randomized after oral rehydration to receive 7 days of either traditional gradual refeeding (GR) or rapid refeeding (RR), the latter consisting of a full-strength lactose-limited diet, including lactase-treated whole milk. The study focused on the effect of a high energy intake, excluding possible negative effects of lactose. Both dietary regimens were well tolerated, the only difference in the clinical symptoms between the two regimens being a higher stool frequency within the RR group(p < 0.02). The total energy intake, as well as energy derived from fat and protein, was significantly higher in the RR than in the GR group (p < 0.0001). The mean daily energy intake of the latter group never reached recommended daily allowance (RDA) levels, while that of the RR group did on day 5. Moreover, during the whole period of dietary regimen, the RR group exceeded the RDA protein requirements (mean intake ranged 175–252%), while the GR group did not reach this RDA level until day 4. Milk was a major source of energy in the RR group, providing 47–59% of the daily energy intake. The short- and long-term weight gains in the RR group were only a little higher than those of the GR group, the difference being insignificant. The chief asset of RR compared with GR was, therefore, psychological, in the sense that after rehydration the hospitalized child with mild to moderate GE can, by and large, be offered the quality and quantity of food and drink that he/she prefers without the fear of negative effects on the outcome.

Intestinal and serum immune response to a naturally acquired rotavirus gastroenteritis in children.

Seventeen children (mean age: 2.0 years, range: 36 days-8 years) hospitalized with acute gastroenteritis were investigated. Thirteen children had a rotavirus infection while four did not. Rotavirus serum IgA as well as ScIg, i.e., antirotavirus immunoglobulin containing secretory component, increased rapidly after rotavirus infection. While rotavirus IgA persisted in serum for at least 6 months, rotavirus ScIg disappeared from serum in less than 4 months. Rotavirus IgG could be detected in serum during the early stage of the infection and was still high after 6 months. The patients with nonrota-virus acute gastroenteritis did not show any of the above-mentioned serological hallmarks of those with rotavirus infection. The amounts of rotavirus ScIg found in serum about 1 week after the infection correlated to the amounts of rotavirus ScIg in duodenal fluid. Six months after the infection, rotavirus IgA was found in the feces of the majority of the patients while rotavirus ScIg could be detected only in one patient. The amounts of rotavirus IgA in sera and intestinal secretions showed identical patterns in the acute phase of the disease as well as after recovery. The same applied to rotavirus ScIg. These findings could be useful in future evaluations of vaccines and immunity against rotavirus infections.

Giardiasis: haematological status and the absorption of vitamin B12 and folic acid

The haematological status, as well as the fractional absorptions of folic acid (FAFol) and vitamin B12 (FAB12) were studied in 29 children aged 0.7–13.5 years (mean 3.3 years) with chronic diarrhoea due to giardiasis. Small intestinal biopsies revealed mucosal damage in 20 children; the biopsies of the remaining nine children were normal. At the initial investigation the FAFol and FAB12 values were below normal in approximately one‐sixth and one‐third of patients, respectively. Bacterial overgrowth of the small intestinal tract did not seem to play a role in FAB12 malabsorption. About one‐fifth of patients had mild anaemia. None of the patients showed FAB12 insufficiency and only one patient suffered from folate depletion. At follow‐up, FAFol, FAB12, haemoglobin and Erc‐folate concentrations increased significantly while P‐B12 and P‐folate remained unchanged. Iron status, as well as dietary intake of iron, appeared insufficient prior to, as well as after treatment. Serum iron, transferrin saturation and haemoglobin concentrations were lower in patients who had acquired the disease abroad or suffered from persistent diarrhoea.

Nosocomial acute gastroenteritis in a paediatric department, with special reference to rotavirus infections.

ABSTRACT. Nosocomial acute gastroenteritis caused by rotavirus as well as by non‐rotavirus gastroenteritis was registered during a 12‐month period in the paediatric department of a district hospital. The number of patients in the two groups amounted to 27 % (rotavirus) and 7 % (non‐rotavirus) of the total number of patients hospitalised with the corresponding type of acute gastroenteritis. The seasonal and age distributions for the two types of nosocomial acute gastroenteritis followed the pattern of the respective types of hospitalised community‐acquired acute gastroenteritis. Nosocomial non‐rotavirus gastroenteritis was found to occur scattered with regard to time and locality within the department. The same applied to one half of the cases with nosocomial rotavirus gastroenteritis, whereas the other half occurred during an epidemic outbreak in the general infant/toddler ward. Vomiting and diarrhoea were less significant in nosocomial rotavirus gastroenteritis as compared with community‐acquired rotavirus gastroenteritis. As to the other manifestations no difference was found between the two groups. Nosocomial rotavirus gastroenteritis prolonged the stay in hospital with on the average 3.8 days. Guidelines are suggested for isolation of patients with acute gastroenteritis in order to reduce particularly the frequency of nosocomial rotavirus infections.