[Leptospirosis in a family after whitewater rafting in Thailand]. / Leptospirose famitiate apres rafting en Thaïlande.

Leptospirosis is a zoonosis found worldwide, with an incidence that is approximately 10 times higher in the tropics than in temperate regions. The main reservoir of leptospirosis is the rat and human infection usually results from exposure to infected animal urine or tissues. Only 10% of cases are symptomatic. We present here two confirmed and two probable cases of leptospirosis in a family returning from whitewater rafting in Thailand, illustrating the wide variety of the clinical manifestations of this infection. Two of the patients were hospitalized and presented a probable Jarisch-Herxheimer reaction after initiation of beta-lactam therapy. The two others patients were treated empirically with doxycycline. We discuss here some relevant aspects of the epidemiology, clinical manifestations, therapy and the challenge of an early diagnosis of leptospirosis.

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

[An observatory of child abuse and neglect: an interactive way to look at this issue]. / Un observatoire de la maltraitance envers les enfants: une façon interactive de s'intéresser a cette problématique.

Since the second part of the 20th century, professionals from diverse backgrounds have been looking at child abuse end neglect issues without a real common approach and understanding. The objective of the Observatory is to allow these professionals, whatever their research or practice background is, to confront their views and ideas within a constructive interdisciplinary framework, aiming at better serving victims, families and perpetrators needs.

Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. The Swiss HIV Cohort Study.

BACKGROUND: Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia. In this study, we characterized the lipoprotein profile in subjects receiving ritonavir, indinavir, or nelfinavir, alone or in combination with saquinavir. METHODS AND RESULTS: Plasma lipoprotein levels were quantified in 93 HIV-infected adults receiving PIs. Comparison was done with pretreatment values and with 28 nonPI-treated HIV-infected subjects. An elevation in plasma cholesterol levels was observed in all PI-treated groups but was more pronounced for ritonavir (2.0+/-0.3 mmol/L [mean+/-SEM], n=46, versus 0.1+/-0.2 mmol/L in nonPI treated group, P<0.001) than for indinavir (0.8+/-0.2 mmol/L, n=26, P=0.03) or nelfinavir (1.2+/-0.2 mmol/L, n=21, P=0.01). Administration of ritonavir, but not indinavir or nelfinavir, was associated with a marked elevation in plasma triglyceride levels (1.83+/-0.46 mmol/L, P=0.002). Plasma HDL-cholesterol levels remained unchanged. Combination of ritonavir or nelfinavir with saquinavir did not further elevate plasma lipid levels. A 48% increase in plasma levels of lipoprotein(a) was detected in PI-treated subjects with pretreatment Lp(a) values >20 mg/dL. Similar changes in plasma lipid levels were observed in 6 children receiving ritonavir. CONCLUSIONS: Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia. The risk of pancreatitis and premature atherosclerosis due to PI-associated dyslipidemia remains to be established.

Detection of enteroviruses in the cerebrospinal fluid by polymerase chain reaction: prospective study of impact on the management of hospitalized children.

A polymerase chain reaction kit (AMPLICOR EV) for the detection of enteroviruses (EV-PCR) in the cerebrospinal fluid (CSF) was evaluated in clinical conditions in a prospective blinded-intention study. Forty-three children (mean age 2.7 years) hospitalized for suspected meningitis or fever of unclear etiology were enrolled. EV-PCR was performed on a daily basis. Results were available in less than 2 days in 72% of cases. EV-PCR was positive in nine (21%) children, including three infants without CSF pleocytosis. Knowing their EV-PCR result would have allowed a saving of 18 hospital days and 12 days of antibiotic therapy. The EV-PCR in the CSF can thus be practically useful for children hospitalized for meningitis or fever if available on-site on a daily basis.

[Chronic meningococcemia and IgA deficiency in an adolescent]. / Méningococcémie chronique et déficit en IgA chez un adolescent.

BACKGROUND: Chronic meningococcemia, defined as a meningococcal septicemia without meningeal symptoms with persistence of fever for at least one week prior to any antibiotics, is uncommon. Its pathophysiology remains unclear and a defect in host immunity has been suggested. CASE REPORT: A 15 year-old adolescent was examined because he suffered from fever for 6 days, headache, arthralgias. A disseminated erythema led to consider the diagnosis of vascularitis that was confirmed by skin biopsy. At day 9, blood culture yielded Neisseria meningitis group B that was confirmed by a second blood culture; the CSF was normal and sterile. The patient was given ceftriaxone plus penicillin for 14 days and completely cured. A detailed analysis of the complement system was negative but the patient was found to be deficient in IgA. CONCLUSION: This is the first reported case in which chronic meningococcemia is associated with complete IgA deficiency.

[HIV-associated nephropathy in children]. / La néphropathie à VIH chez l'enfant.

HIV-associated nephropathy is rare in children. Proteinuria can be its first sign. In the black child, it often presents as focal and segmental glomerulosclerosis. White children are mostly affected with mesangial hyperplasia, rarely with IgA nephropathy. Its etiology is probably multifactorial: presence of the virus itself in the glomeruli, hemodynamic alterations and drug toxicity. There is no specific treatment at the moment.

[Is the use of ribavirin aerosols in respiratory syncytial virus infections justified? Clinical and economic evaluation]. / L'emploi d'aérosols de ribavirine lors d'infection à virus respiratoire syncytial est-il justifié? Evaluation clinique et économique.

UNLABELLED: The controversy about the use of ribavirin aerosol for children at risk (cardiopathy, pneumopathy, premature and immunodeficient patients), in case of respiratory syncytial virus (RSV) infection, led us to stop its prescription in 1993 and study prospectively the patients admitted during the following winters. METHODS: Criterias of inclusion for this study were those of the Committee on Infectious Diseases of the American Academy of Pediatrics concerning the use of ribavirin aerosol. Two cohorts of patients were studied: the first group included treated patients (ribavirin group: n = 22, ribavirin and support treatment: salbutamol aerosols, respiratory physiotherapy and oxygen-therapy; winters 1989-1990 to 1992-1993); the second group included patients with support treatment only (control group: n = 22; winters 1993-1994 and 1994-1995). RESULTS: The clinical gravity score at admission (4.55 vs 5.23, P = 0.46) and the risk factor scores (3.05 vs 3.27, P = 0.69) of the two groups were identical. Results showed that the children of the ribavirin group stayed much longer in hospital (14.2 vs 8.2 days, P = 0.002) and in the intensive care unit (7.2 vs 0.2 days, P < 0.001) than those of the control group. More support treatment was necessary for the ribavirin group as regard respiratory physiotherapy (3.8 vs 2.7 sessions a day, P = 0.026), the duration of oxygen-therapy (7.3 vs 3.7 days, P = 0.030) and the number of children requiring respiratory assistance (4 vs 0 children, P = 0.116). Administration of ribavirin aerosols (480 US$ a dose) and the way in which such treatment was carried out meant high daily costs for the ribavirin group (1,076 vs 604 US$, P < 0.001). As hospitalization was longer for children treated with ribavirin, the global cost was therefore much higher (15,552 vs 5,156 US$, P < 0.001). CONCLUSION: The antiviral effect of ribavirin is undeniable. However ribavirin is known to be the cause of severe bronchospasms (two cases in our study) and can also cause moderate and long term bronchospasms, aggravating therefore the clinical evolution of the disease. Our experience shows that administration of ribavirin aerosols in case of RSV infection of inferior respiratory airways seems not to be justified.

A critical pathway for the management of elderly inpatients with malnutrition: effects on serum insulin-like growth factor-I.

BACKGROUND: Several guidelines recommend systematic screening for malnutrition in elderly inpatients for early dietary intakes assessment and treatment, but data demonstrating the efficacy of such interventions are scarce. The aim of this study was to evaluate a critical medical pathway for the detection and management of malnutrition in elderly inpatients. METHODS: In a 3-month prospective controlled study, 694 recently admitted inpatients were assigned to an intervention group (critical medical pathway; n=465) or a standard care control group (n=229). Nutritional status was assessed at the time of admission with a Mini Nutritional Assessment. A renutrition program tailored to the initial dietary assessment results was applied in the intervention group. The efficacy of the program was verified by measuring the evolution of serum insulin-like growth factor 1 (IGF-I) between admission and 3 weeks later. RESULTS: In the intervention group at baseline, 23% were malnourished, 51% were at risk and 26% were eunourished. Serum IGF-I increased in the intervention group (from 84±45 µg/l to 95±50 µg/l, P<0.0001; mean±s.d., n=209), but remained stable in the controls (from 79±43 µg/l to 81±35 µg/l, P=0.4; n=99), with a statistically significant between group difference (P<0.01). CONCLUSION: Early malnutrition assessment and targeted renutrition program in elderly inpatients were associated with an increase in serum IGF-I. It remains to be determined whether such variations are clinically relevant.

[Apparent life-threatening event in infants: think about star anise intoxication!]. / Malaise du nourrisson pensez à une intoxication à l'anis étoilé

UNLABELLED: In previous years, several publications have reported cases of infants presenting neurological and gastrointestinal symptoms after ingestion of star anise tea. Such teas are sometimes given in various cultures for the treatment of infant colic pains. In most cases, the cause of intoxication was contamination of Chinese star anise (Illicium verum) by Japanese star anise (Illicium anisatum). Indeed, the toxicity of Illicium anisatum, also known as Shikimi, is caused by its content in potent neurotoxins (anisatin, neoanisatin, and pseudoanisatin), due to their activity as non-competitive antagonists of GABA receptors. The main reasons explaining the frequent contaminations are the strong macroscopic resemblance of the 2 substances, as well as the fact that the fruits are often sold partially broken or in ground form. Therefore, in most cases, chemical analysis is required to determine the possible adulterations. CASE REPORT: A 2-month-old infant, in good general health, was brought to the emergency unit after 3 consecutive episodes of central cyanosis and tetany of the limbs with spontaneous recovery the same afternoon. The child was also very irritable, regurgitated a lot, and positioned himself in opisthotonos. Between these episodes, the neurological exam showed some perturbations (horizontal nystagmus and Bell's phenomenon, hypertony of the extensor muscles, and mild hypotony of the axial flexor muscles) with slow improvement over the following hours. The remaining clinical exam, the laboratory work (complete blood count, renal, hepatic, and muscular tests, capillary blood gas, plasmatic amino acids, and urinary organic acids), and the electroencephalogram findings were all normal. In the course of a detailed interview, the parents reported having given 3 bottles to their child, each one containing 200 mL of an infusion with 4 to 5 fruits of star anise, in the hours preceding the symptoms to relieve colic pains. The last seizure-like event took place approximately 8h after the last ingestion. We could prove the ingestion of anisatin, the toxic substance found in Japanese star anise, and the contamination of Chinese star anise by the Japanese species. Indeed, the anisatin analysis by liquid chromatography and mass spectroscopy (LC-MS) in a urine sample taken 22 h after the last infusion ingestion showed trace amounts of the substance. In another urine sample taken 33 h after ingestion, no anisatin could be detected. Furthermore, the analysis of the fruit sample gave an anisatin concentration of 7800 µg/kg while the maximum tolerance value in Switzerland is 1000 µg/kg. CONCLUSION: The evaluation of ALTE in infants should always include the possibility of intoxication. Star anise is generally considered a harmless medicine. Nevertheless, it can sometimes cause a severe intoxication resulting in various neurological and gastrointestinal symptoms. To prevent such events, not only the parents, but also the care personnel and pharmacists must be informed about the possible adverse effects caused either by the overdose of Chinese star anise or by the eventual contamination of herbal teas with Japanese star anise. A better control of the substances by the health authorities is also necessary.

Lymphocytic interstitial pneumonia in children with AIDS: high-resolution CT findings.

Pulmonary involvement in children with acquired immunodeficiency syndrome (AIDS) represents a wide spectrum of diseases. Among the non-infectious, non-neoplastic affections associated with AIDS, lymphocytic interstitial pneumonia (LIP) is now a well-recognized entity, but its radiological pattern studied with high-resolution computed tomography (HRCT) has rarely been described in children. The aim of this study was to illustrate the HRCT spectrum of pulmonary involvement in children with LIP and to evaluate its usefulness in the early diagnosis of this entity. Twelve children with AIDS, aged 3-9 years (mean age 5 years 7 months), underwent chest radiographs and HRCT. A control group of 7 healthy aged-matched children was also studied in the same conditions. Diagnosis of LIP was based on clinical data and HRCT findings. Eight children of 12 had a reticulonodular pattern on chest radiographs. Two children had normal chest films and two children showed peribronchiolar thickening. High-resolution CT displayed micronodules, 1-3 mm in diameter, with a perilymphatic distribution in all patients. High-resolution CT demonstrated also subpleural nodules in children without reticulonodular opacities on chest radiographs. High-resolution CT is able to define a more specific pattern of abnormalities than conventional chest radiographs in children with LIP, allows an earlier and more confident diagnosis and may be useful for the detection of other pathologies associated with AIDS, such as opportunistic infections or superimposed malignancies.

Parvovirus B19 associated monoarthritis in a 5-year-old boy.

We describe the case of a 5-year-old boy who presented with parvovirus B19 associated arthritis of the left knee lasting for 6 weeks. Other features included flu-like symptoms, a mild "slapped cheek" sign, and a macular, erythematous, lace-like rash over the chest and limbs. The analysis of the synovial fluid showed a high white cell count with a predominance of polymorphonuclear cells. The characteristic features related to parvovirus B19 associated arthropathy in children are reviewed.

Long-term responses to treatment including ritonavir or nelfinavir in HIV-1-infected children. Pediatric AIDS Group of Switzerland.

BACKGROUND: Knowledge concerning the long-term antiretroviral and immunological efficacy of protease inhibitors in children is limited. PATIENTS AND METHODS: An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3-16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the current treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed. RESULTS: Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log10 copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/microl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log10 copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was -2.17 and -1.30 log10 copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patients -2.70 vs -1.39 log10 copies/ml (p < or = 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels < 400 copies/ml. Increases in CD4 cells were higher in ART-naive compared to non-naive patients (p < 0.04). CONCLUSION: The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.

[Pneumocystis carinii pneumonia in infants with vertically acquired HIV infection in Switzerland]. / Pneumocystis-carinii-Pneumonie bei Säuglingen mit vertikaler HIV-Infektion in der Schweiz.

OBJECTIVE: Review of incidence, clinical picture, therapy, and outcome of Pneumocystis carinii pneumonia (PCP) in infants with vertically-acquired HIV infection in Switzerland. METHODS: Inquiry among members of the Swiss Pediatrics AIDS Group, review of the data base of the Swiss Neonatal HIV Study and retrospective analysis of the charts from infants with PCP. RESULTS: Since 1986 PCP has been diagnosed in 10 out of 107 infants with vertically-acquired HIV infection. PCP occurred in 7 infants at the age of 3-6 months and in 3 at the age of 9-11 months. 4 infants showed symptoms related to HIV infection before developing PCP. Before the development of PCP, infection with HIV had been ascertained in 6 infants. In 2 the diagnosis was still unclear and in the 2 remaining the risk of HIV infection was not known. None of the infants was on primary prophylaxis against PCP. Signs and symptoms of PCP included cough and tachypnea (100%) as well as high fever up to 40 degrees C (90%). Transcutaneous oxygen saturation was 70-95%. Chest X-rays revealed interstitial infiltrates in 6 infants, localized infiltrates in 2 and interstitial as well as localized infiltrates in 2. The CD4+ cell count was, with one exception, < 1500/microliters, i.e. below the normal value for age. Side effects of high dose cotrimoxazole were noted in 6 patients. 5 infants required intubation and mechanical ventilation. 4 infants died due to PCP, including 3 of those who required intubation and mechanical ventilation. CONCLUSIONS: PCP in infants with vertically-acquired HIV infection preferentially occurs at the age of 3 to 6 months and is often lethal, especially in patients requiring intubation. Evaluation for HIV infection should be done as early as possible in order to introduce primary PCP prophylaxis in infants at risk for this opportunistic infection.

A comparison of ceftriaxone and cefuroxime for the treatment of bacterial meningitis in children.

To compare ceftriaxone with cefuroxime for the treatment of meningitis, we conducted a study in which 106 children with acute bacterial meningitis were randomly assigned to receive either ceftriaxone (100 mg per kilogram of body weight per day, administered intravenously once daily; n = 53) or cefuroxime (240 mg per kilogram per day, administered intravenously in four equal doses; n = 53). The mean age of the children was 3 years (range, 42 days to 16 years), and the characteristics of the two treatment groups were comparable at admission. Excluded from the study were eight other children who died within 48 hours of admission. After 18 to 36 hours of therapy, cultures of cerebrospinal fluid remained positive for 1 of the 52 children (2 percent) receiving ceftriaxone for whom cultures were available and 6 of 52 (12 percent) receiving cefuroxime (P = 0.11). In both groups the mean duration of antibiotic therapy was 10 days. The clinical responses to therapy were similar in the two treatment groups, and all 106 children were cured. Reversible biliary pseudolithiasis was detected by serial abdominal ultrasonography only in the children treated with ceftriaxone (16 of 35 vs. 0 of 35; P less than 0.001). The treatment of three children was switched from ceftriaxone to alternative antibiotics because these children had upper abdominal pain. Other side effects were infrequent in both groups. At follow-up examination two months later, moderate-to-profound hearing loss was present in two children (4 percent) treated with ceftriaxone and in nine (17 percent) treated with cefuroxime (P = 0.05); other neurologic abnormalities were similar in the two treatment groups. We conclude that ceftriaxone is superior to cefuroxime for the treatment of acute bacterial meningitis in children and that the benefits of milder hearing impairment and more rapid sterilization of the cerebrospinal fluid with ceftriaxone outweigh the problem of reversible biliary pseudolithiasis with this drug.

Growth in human immunodeficiency virus type 1-infected children treated with protease inhibitors.

UNLABELLED: To determine the long-term impact of antiretroviral treatment (ART) including a protease inhibitor (PI) on growth in children infected with the human immunodeficiency virus type I (HIV-1), a prospective multi-centre study was conducted in Switzerland on HIV-1-infected children treated with ritonavir (350 mg/m2 twice a day) or nelfinavir (20-30 mg/kg three times a day) in addition to two nucleoside reverse transcriptase inhibitors. Length or height of HlV-1-infected children from before (weeks -72, -48, -24, and 0) and after (weeks +24, +48, and +72) introducing a PI to the ART were compared. To allow for age- and gender-independent assessment, values were expressed in standard deviations from the mean. Complete data sets on body length were available for 44 children after 72 weeks of treatment with a PI. Preceding initiation of a PI, there was an overall decline in growth to -0.3 SD. Following start of a PI, an increase in growth was noted from weeks 0 to +24 (+0.33 SD, P=0.02) and from weeks +48 to +72 (+0.21 SD, P=0.03). The increase in growth was restricted to children with stunting before a PI was introduced (P=0.03), and was more marked in children younger than 3 years of age. CONCLUSION: children infected with human immunodeficiency virus type 1 showed catch-up growth after addition of a protease inhibitor to their antiretroviral treatment, but this phenomenon was observed almost exclusively in children under 3 years of age.

Nosocomial outbreak of multiple bloodborne viral infections.

In resource-limited countries, nosocomial transmission of bloodborne pathogens is a major public health concern. After a major outbreak of human immunodeficiency virus (HIV) infection in approximately 400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of parents' serology. The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed. HIV and HCV genotypic analyses identified a HIV monophyletic group, whereas 4 clusters of HCV sequences were identified. To our knowledge, this is the largest documented outbreak of nosocomial HIV transmission.