Safety and immunogenicity of a combined DTPa-IPV vaccine administered as a booster from 4 years of age: a review.

A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed compared to 5.5% of DTPw-primed children. Large swelling involving the entire upper arm (extending to involve the elbow joint) was reported for up to 1.2% of DTPa-primed subjects, which is consistent with literature reports for other DTPa vaccines.

[Varicella and zoster vaccines]. / Vaccins contre le virus de la varicelle et du zona.

The varicella vaccine (OKA strain) first used in Japan in 70's was introduced into the routine infants immunisation schedule of United States in 1995. Two other new varicella vaccines have been just licensed: a tetravalent measles-mumps-rubella-varicella vaccine (MMRV) and a zoster vaccine for more than 60 years old adults. In Europe varicella vaccine is not introduced in routine infant schedule, except in Germany, and only used for targeted aims. This reluctance is justified by several considerations: the fear of a shift of varicella to adults by low vaccine coverage, the risk of increasing zoster in adults by a mass vaccination. Several recent varicella outbreaks in highly vaccinated children stress the possible need for a routine second dose of vaccine in infants. The cost-effectiveness studies results are not similar in different countries and the benefits are indirect (time off work).Varicella is often considered as a mild disease, in spite of a better knowledge of complications and health benefits in United-States, where vaccination has resulted in a dramatic decline of deaths, hospitalisations and varicella-related complications. The new tetravalent MMRV vaccine could stimulate Europe to implement routine vaccination, provided that an efficient surveillance for varicella and shingles be instituted.

[Treatment of uncomplicated Plasmodium falciparum malaria in children: comparison of halofantrine with mefloquine]. / Traitement de première intention de l'accès palustre non compliqué a Plasmodium falciparum chez l'enfant: comparaison de l'halofantrine avec la méfloquine.

AIMS: Halofantrine is the first regimen used for the treatment of uncomplicated Plasmodium falciparum malaria in children in France according to the recommendations of the French Consensus Conference held in 1999 and pending additional data in this population. In 1999, a high rate of clinical relapse after a single cure of halofantrine led us to switch to mefloquine for first line treatment of uncomplicated malaria. The aims of this study were to evaluate this change of attitude and to compare the efficacy of halofantrine and mefloquine in the treatment of uncomplicated P. falciparum malaria in children. PATIENTS AND METHODS: We retrospectively analysed 118 pediatric cases of malaria treated at Armand-Trousseau Children hospital in Paris between January 1st, 1999 and December 31st, 2000. RESULTS: 93 patients were treated for an uncomplicated case of P. falciparum malaria: 48 received a unique cure of halofantrine and 21 were treated with mefloquine. Nine patients relapsed, all having previously received halofantrine. No patient treated with mefloquine relapsed. CONCLUSION: These results and other recent published data suggest to recommend mefloquine instead of halofantrine as first line treatment of uncomplicated P. falciparum malaria in children with respect to specific contra-indications. A larger evaluation of mefloquine is however necessary. The association atovaquone-proguanil (Malarone) is promising but needs to be evaluated in large pediatric studies in comparison with other treatments. Its indication as a curative treatment of uncomplicated malaria is, to date, restricted to adults and children over 12 years in France.

[Imported malaria in children in 1999. Study of the Armand-Trousseau Hospital in Paris]. / Le paludisme d'importation de l'enfant en 1999. Etude parisienne à l'hôpital Armand-Trousseau.

METHODS: Eighty children were treated at the hospital Armand-Trousseau (Paris, France) for a malaria attack from 1999-01-01 to 2000-02-01. RESULTS: The parasites were: Plasmodium falciparum: 87.5%, Plasmodium malariae: 12.6%, Plasmodium ovale: 10%, Plasmodium vivax: 6.3%. Mean age was 8.1 years (range: three months to 15 y). The origin of patients was: West Africa for 60 children, Central Africa for ten children and Comores for seven. Sixty-six patients suffered from common malaria attack and seven children were admitted with a presentation of severe malaria. The severe attacks were cerebral malaria for six cases, associated with severe anemia in five cases; the 7th child had a respiratory distress (ARDS) and died. The other six cases were cured without sequelae. Relapses were observed for eight patients: one after a severe cerebral malaria, six after a common P. falciparum attack, one after a P. ovale attack. Parasitemia was higher than in preceding years (mean 2.9%) and more than 5% in 11 cases, but without clear link with severity. Treatment by halofantrine with a single cure was followed by five relapses. None of those children received an effective prophylaxis during and after travel (55/80 without any prophylaxis). CONCLUSION: These data emphasize the importance of a good appraisal of criteria of severe malaria and lead to advice hospitalization of children with malaria in temperate zone.

[Impact of vaccinations on the epidemiology of infective diseases]. / Influence des vaccinations sur l'épidémiologie des maladies infectieuses.

Immunizations may progressively modify the epidemiology and the clinical features of some infectious diseases, partially explained by a shift of ages towards adults. For measles, the coverage in France is low (80%) and mean age of measles cases has raised from 7 to 9 years (40% of cases are more than 10 years old). Measles may be more severe diseases in adolescents and adults, and for this reason a second dose of MMR vaccine has been recommended using a predictive mathematical model of measles epidemiology. Nevertheless, an important focus of measles remains in France (17,954 cases in 1999) and the risk of outbreaks in adolescents and adults is always present if immunization coverage for 24 months infants and catch-up are not improved quickly. Rubella has the same profile, with two outbreaks in young adults (1993 and 1997) followed by a peak of congenital rubella. Pertussis immunization has always been well applied in France. Resurgence started in the 90's, with pertussis in young adults (some being immunized in infancy) who transmitted pertussis to very young infants, not yet properly immunized. The situation requires a better immunity for old children and adults. For this reason, a booster is recommended in France at 11-13 years, and perhaps in adult later, these late boosters are practicable with the new acellular pertussis vaccines. Varicella vaccine is not in the french immunization schedule, for the same argument of risk of varicella in adults in cases of insufficiency of the coverage. Now USA recommend the vaccine in children, but a strong surveillance has been established. Those four examples observed in the french recent immunization policy emphasize the necessity for a stronger and new surveillance of immunizations and infectious preventable diseases.

[Severe infections in children with sickle cell disease: clinical aspects and prevention]. / Infections graves chez l'enfant drépanocytaire: aspects cliniques et prévention.

Sickle-cell disease (SCD) is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumonococcal bacteremia and meningitis due to S. pneumoniae are often lethal and justify the penicillin prophylaxis, which has provided a dramatic decrease in early mortality bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia, because they are often intricated. Osteomyelitis is generally due to Salmonella, most often S. enteritidis. Multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Osteomyelitis is less frequent in developed countries and must been differentiated with bone infarction by use of bone scintigraphy. Parvovirus B19 infection causes acute erythroblastopenias. Malaria does not result in cerebral malaria, but can lead to severe anaemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (osteomyelitis, meningitis), and M. pneumoniae (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at three months of age and no closely-spaced immunizations, most notably against peumococci, hepatitis B virus, S. typhi and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. New conjugated pneumococcal vaccines are effective in protecting very young infants and should therefore be used in sickle cell patients.

[Cholelithiasis in children with sickle cell disease: experience of a French pediatric hospital]. / Lithiase biliaire chez l'enfant drépanocytaire: expérience d'un hôpital pédiatrique parisien.

BACKGROUND: Gallstones are frequently encountered in sickle cell disease. Their complications are difficult to distinguish from vaso-occlusive abdominal pain and they can sometimes threaten the patient's life. The aim of this study was to describe our local experience with cholelithiasis in children with sickle cell disease. PATIENTS AND METHODS: We analyzed the follow-up records and abdominal sonography results of 185 children with sickle cell anemia, aged zero to 18 years, followed up in Trousseau Children's Hospital (Paris) from 1982 to 1998. RESULTS: Cholelithiasis was detected in 26 patients. The youngest patient was five years old. Cholelithiasis was discovered because of clinical manifestations in 12 patients. Asymptomatic cholelithiasis patients developed clinical manifestations in 28% cases in a maximum delay of two and a half years after its diagnosis. Laparoscopic cholecystectomy was performed in nine cases and open cholecystectomy in 17 cases. The mean postoperative length of stay was significantly shorter in the group of patients with laparoscopy in comparison with the group with open cholecystectomy. Histologic analysis of the gallbladders noted 85% of acute or chronic cholecystis. CONCLUSION: We suggest that cholelithiasis should be carefully sought in the presence of abdominal manifestations in sickle cell patients. We recommend that annual abdominal sonography be performed in sickle cell patients as early as seven years of age and elective cholecystectomy be performed on patients with cholelithiasis.

[Eradication of infectious diseases and vaccination]. / Eradication des maladies infectieuses et vaccination.

Immunizations in man may act upon the infectious diseases development in three evolutive patterns: eradication, elimination, or disease control. Since the eradication of smallpox, very few diseases are at present candidates for a next eradication; poliomyelitis will be the first, perhaps followed by measles in many years. In spite of efficacious vaccines and a solely human reservoir, the eradication requires very strict conditions. However some diseases have been recently successfully eliminated: poliomyelitis (Americas, Europe, West Pacific regions), measles (i.e. Finland, United States), rubella (i.e. Finland). In spite of some limits, diphtheria, pertussis, hepatitis B are well controlled providing to get a sufficient vaccine coverage and to improve a sustained surveillance of those diseases. Regarding Haemophilus influenzae b, infections it is premature to predict a near elimination and the control is not yet well defined. National and regional programs have often to improve immunisation coverage and a better surveillance.

[Sickle cell disease: from childhood to adolescence. Management in 2001]. / La drépanocytose: de l'enfant à l'adolescent. Prise en charge en 2001.

Sickle cell anaemia is a chronic disease which evolves on the background of a basal state punctuated by critical periods, often with complications requiring overall treatment. The management of both periods must be well integrated into the treatment programme. In order to treat occlusive crisis, medical staff must be well trained and equipped for the complicated clinical diagnoses involved in drepanocytosis: bone infarction or osteomyelitis, pneumonia or acute chest syndrome, multifocal crisis or severe infectious disease. Neonatal diagnosis is the best way for early treatment by preventing severe pneumococcal diseases, ensuring sufficient hydration and appropriate surveillance, as well as providing family education. Much progress has been made over the last decade in the early treatment of retinitis, biliary lithiasis, and aseptic hip necrosis. It is also important to ensure accurate prescriptions for hydroxyurea. Specialised centres for drepanocytosis treatment are now a growing necessity and should be encouraged in order to provide treatment for dispersed patients against a relatively little known disease.

[Acute diarrhea and rotavirus infection in the child: assessment of data from emergency care and and the microbiology laboratory of the Armand-Trousseau (Paris) Hospital between 1988 and 2001]. / La diarrhée aiguë et l'infection à rotavirus chez l'enfant: confrontation des données d'activité des urgences médicales et du laboratoire de microbiologie de l'hôpital Armand-Trousseau (Paris) entre 1988 et 2001.

MATERIAL AND METHODS: Between October 1, 1988 and March 31, 2001, a longitudinal survey was conducted at the French pediatric hospital Armand-Trousseau in Paris. Following data were simultaneously collected: consultations and hospitalizations for acute diarrhea at the emergency room, and identifications of rotavirus from diarrheic stools at the laboratory. RESULTS: Acute diarrhea represented 9.3% to 11.1% of all consultations. The activity was continuous through the year with several epidemic peaks, the largest occurring during the winter months. The hospitalization rate was high and stable since 1989 (16.5% to 21%), reaching 22-26% at the winter peak. Overall, rotaviruses were identified in 22.4% of stool samples but the detection rate increased from 10% in 1989 to 31% in 1997. Rotaviruses were isolated mainly in winter, reaching the rate of 50-70% at the peak. DISCUSSION: Despite numerous biases of methodology and the fact that data were extracted from two different sources, acute diarrhea appeared as a major epidemic phenomenon in Paris, and rotaviruses were the main pathogens identified in diarrheic infants in winter. The extent of the winter epidemic increased each year since ten years, in parallel with the increase of the global activity of the emergency room. Despite attempts to develop ambulatory care, admission rates remained high in patients with acute diarrhea and searching for care at the emergency room of our hospital, especially in winter. CONCLUSION: These preliminary data were restricted to a single pediatric hospital in Paris. They need to be extended to a national level before considering a strategy for prevention using vaccination.

Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease.

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.