Long-term beneficial effects of dexamethasone on intellectual and neuropsychological outcome of children with pneumococcal meningitis.

A Substantial ratio of bacterial meningitis survivors suffers mild or serious intellectual and neuropsychological handicaps. We organized eighty subjects into three groups: 1) Pneumococcal meningitis (PM) who did not receive dexamethasone, 2) PM who received dexamethasone, 3) Other bacterial meningitis with different etiology. All subjects underwent Bender Visual Motor Gestalt test and age-appropriate Intelligence quotient (IQ) tests. The mean full-scale IQ scoring fell within normal range (90+/-17) in the post-meningitic cohort. There was no statistical difference between two pneumococcal groups regarding full scale IQ testing (88+/-16 and 91+/-18) and Bender-Gestalt scoring (4.0+/-3.3 and 3.8+/-2.6), respectively. However, the subjects with full scale IQ score <85 (below the average) were statistically less in the group with steroid therapy. PM patients who received dexamethasone therapy had statistically better academic performance. As a result, adjuvant steroid therapy has no significant impact on overall intellectual tests in PM subjects. However, dexamethasone seems to diminish development of below the average IQ scoring in PM cases. In addition, PM subjects who received steroids showed better academic achievement. These findings may support the idea of dexamethasone administration prior to first antibiotic dose in PM subjects.

Fatal necrotizing pneumonia caused by group A streptococcus.

Group A streptococcus (GAS) causes invasive, non-invasive and non-suppurative diseases. Pneumonia is one of the invasive infections caused by GAS. Although GAS is a significant and serious cause of childhood pneumonia, it is often overlooked clinically. Similarly, the recent literature is surprisingly scant on reports of GAS pneumonia and concentrates mainly on varicella-associated invasive GAS diseases. In this case report, we present a previously healthy 7-year-old child with community-acquired pneumonia that progressed rapidly and resulted in sepsis, respiratory failure and death. In both blood and pleural fluid cultures, Streptococcus pyogenes were isolated. On autopsy, macroscopic examination revealed that the lung tissue appeared to have lost its normal architecture. Necrosis was present and the lung had a spongy appearance with some solid areas. The light microscopy revealed massive oedema, haemorrhages, intense inflammatory cell infiltration and necrosis. This case report highlights the need for consideration of invasive GAS infection in the event of severe, rapidly progressing pneumonia in children.

Experience with ampicillin/sulbactam in severe infections.

The emergence of beta-lactamase-mediated resistance to established beta-lactam antibiotics prompted the development of beta-lactamase inhibitors for co-administration. Ampicillin has been combined with sulbactam for both parenteral and oral (as the mutual pro-drug sultamicillin) administration. The combination is active in vitro against a wide variety of Gram-positive and Gram-negative pathogens, including aerobic and anaerobic organisms. In clinical trials, ampicillin/sulbactam has proved clinically and bacteriologically effective against a variety of frequently encountered pediatric infections, including mild-to-moderate upper respiratory tract infections (acute otitis media, sinusitis, pharyngitis, and tonsillitis), severe post-operative and intra-abdominal infections, periorbital infections (which, left untreated, can lead to blindness, brain abscess, or death), acute epiglottitis, bacterial meningitis, and brain abscess. Ampicillin/sulbactam has also proved effective in the prevention of post-operative surgical infections in pediatric patients. The clinical efficacy profile of ampicillin/sulbactam and sultamicillin, combined with their excellent tolerability profile, make these agents attractive options for the management of many life-threatening infections in pediatric patients.

Varicella seroprevalence in a random sample of the Turkish population.

Chicken pox highly contagious and common throughout the world, is an infectious disease caused by varicella zoster virus (VZV). This study was conducted to determine the seroprevalence of VZV in a population under age 30 and to identify the relationship of VZV seroprevalence and several characteristics of the study subjects in nine provinces of Turkey. The sampling method of 30 clusters recommended for field studies was used for selecting subjects of a pre-determined number in the rural and urban areas in each province. For this, a total of 60 groups, 30 clusters in the rural and 30 in the urban areas were determined. It was planned that a total of 4800 subjects, including 600 subjects from five big provinces (Istanbul, Ankara, Izmir, Adana, Diyarbakir) and 450 subjects from the remaining smaller provinces (Samsun, Erzurum, Trabzon, Edirne), be included in the study. ELISA method was used to examine the blood samples for VZV seropositivity. Positive VZV seroprevalence was detected in 77.8% of 4387 subjects under age 30 in nine provinces of Turkey. There was no difference in seroprevalence rate between rural and urban areas. Seroprevalence was found to be 79.0% in urban areas and 76.3% in rural areas. Seroprevalence increased with age. Seroprevalence was 20% at the age of 1 year, subsequently increased to 40% at the age of 4 years, 60% at the age 6 years, 80% at the age of 8 years, 85% at the age of 10 years, and then remained at 85-90% in subjects over the age of 10 years. In order to develop vaccination protocols and take appropriate preventive health care measures against diseases in different countries, it is very important to know the seroprevalence of any disease for an individual country.

Screening for tuberculosis in a primary school in Ankara.

Tuberculosis is still an important health problem in developing countries. A screening program was conducted upon learning that one of the teachers of a primary school in Ankara was diagnosed to have active pulmonary tuberculosis. A total of 341 students in the same building with the index case were screened for tuberculosis. There were 109 students with positive tuberculin test reaction. A higher ratio of tuberculin test positivity among the students of the teacher with active tuberculosis versus students vaccinated with BCG one year previously according to the routine vaccination program was determined. Isoniazid prophylaxis was given to the students with positive tuberculin test. The study shows the importance of an urgent work-up of index cases and their environment to prevent the spread of tuberculosis.

Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age.

BACKGROUND AND METHODS: measles is a common cause of morbidity and mortality in developing countries. Although the measles-mumps-rubella vaccine (MMR) is currently in use in developed countries, monovalent measles vaccine (MV) is routinely recommended by World Health Organization (WHO) at 9 months of age in Turkey, as in many other developing countries. In this study, 442 Turkish children received MV at 9 months of age and were revaccinated with MMR vaccine at 15 months of age. In the second group 495 children received MMR at 12 months of age with no earlier measles vaccination. Antibodies were measured before the first vaccination and 6 weeks after the MMR. All children had been followed for occurrence of measles infection for 60 months. Two vaccination schedules were compared for immunogenicity and protection rates. CONCLUSIONS: seroconversion and clinical protection rates were significantly higher in children who received only MMR at 12 months of age than in children revaccinated at 15 months of age. Seroconversion rate for measles was 69.9% in children who received MMR at 12 months of age and 90.3% in children revaccinated at 15 months of age (P=0.0003). While there was no measles case in children who were revaccinated, 12 (2.7%) children in the first group acquired measles during the follow-up period. Vaccination at 12 months of age appeared to be better than the current national standard. The late elimination of maternal antibodies and the inhibitory effect of a weak antibody response after the first dose of vaccine at 9 months may explain the better immunogenicity and efficacy of the MMR vaccine given at 12 months of age.

Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.

The purpose of this study was to compare meropenem monotherapy with combination therapy for empirical treatment of neutropenic fever in children with lymphoma and solid tumors. Ninety episodes of neutropenic fever in children (0.7-16.0; mean age 7.7 years) with solid tumors in a single center were randomized to receive either meropenem (50 mg/kg/dose-maximum 1 g, every 8 hours) or piperacillin (200 mg/kg/dose, every 6 hours) plus amikacin (15 mg/kg daily). Failure was defined as treatment modification. Non-Hodgkin's lymphoma (NHL) accounted for 62.2 percent of all episodes, and solid tumors (37.8%) for the rest. Blood cultures were positive in 23 percent of all episodes. Sixty-seven percent of all isolated microorganisms stained Gram-positive. Overall success was 70.0 percent (63/90). The success with meropenem was comparable to that seen with piperacillin plus amikacin: 76.6 versus 64.6 percent (p = 0.25). The failure rate was 33 percent with Gram-positive culture and 78 percent with Gram-negative or mixed cultures. The solid tumor group had significantly less bacteremia (4/34 versus 17/56; p < 0.05) and treatment failure (3/34 versus 24/56; p < 0.001) than the NHL group. No serious drug-related adverse event was noticed. Meropenem monotherapy was as effective as piperacillin plus amikacin combination in the empirical treatment of neutropenic fever in children with lymphoma and solid tumors.

Two booster dose hepatitis B virus vaccination in patients with leukemia.

The aim of this study was to interpret the antibody response to hepatitis B (HB) vaccination following a two booster dose schedule in 94 acute lymphoblastic leukemia (ALL) patients. All patients were between 1-16 years of age with negative hepatitis B virus (HBV) serology and normal hepatic function. Fifty patients were vaccinated with Engerix B vaccine, and 44 patients were vaccinated with GenHevac B vaccine, with a schedule of 0, 1, 6 and 0, 1, 2, as well as booster doses, in 12 and 6 months respectively. A second booster was given as a fifth dose to 16 unresponsive patients in each vaccine group, 3 and 6 months after the first booster for Engerix B and GenHevac B vaccines respectively. Dosage was 20 microg HbsAg for all patients. Seroconversion rates with protective level antibody were 35.1% (n=33/94). The figures were 32.1% (n=16/50) and 38.6% (n=17/44) for Engerix B and GenHevac B vaccines, respectively. Seroconversion rate in patients younger than 10 years old was found to be higher (39.11%) than older patients (24%), but this was not statistically significant. This study indicates that one third of the leukemic children undergoing maintenence chemotherapy responded to HB vaccine with protective titers of anti-HBs. We recommend HB vaccination especially in developing countries.

Localized acquired hypertrichosis following cast application.

A 11-year-old boy with transient hypertrichosis following calcaneal osteotomy and cast application for 2 months is described. We postulate that hyperemia may be responsible for his hypertrichosis, which lasted 3 months and created a cosmetic problem.

Giant cell pneumonia in a leukemic child in remission: a case report.

Giant cell pneumonia is a rare and uncommon type of lung infection developing as a complication of measles, especially in immunocompromised patients, whether their immune systems are affected primarily or whether they have acquired immune defects. As well as being uncommon, it is also atypical because of absence of the characteristic rash and of absent or low antibody titers against measles in most of the cases. It is known that cellular immunity is more important than humoral immunity in the host response to measles, so hypogammaglobulinemic patients with normal cellular immunity usually recover uneventfully from measles and also have the characteristic rash. We report a case with giant cell pneumonia that was confirmed by postmortem histopathological examination. We especially want to point out that even in the absence of rash, with the clinical and radiological features of pneumonia, measles should be considered in a patient, whether in remission or not, receiving immunosuppressive treatment.

Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children.

Active immunization with hepatitis A vaccine has been shown to provide long-term protection against hepatitis A virus (HAV) infection. However, few data are available regarding use of the hepatitis A vaccine in children under two years of age. The present study was conducted to test the safety and immunogenicity of inactivated hepatitis A vaccine administered to infants, and to evaluate the correlation between mother and infant anti-HAV antibodies. A total of sixty healthy children, two months of age, were enrolled in this study and immunized with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two, four and six months of age schedule. Blood sampling was performed prior to the first vaccination and one month after the third vaccination at seven months. Venipuncture was also done on mother on admission. The reactogenicity was expressed as the percentage of reported local and systemic reactions. The most common side effects were erythema on the injection site and fever. Infants with passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT after vaccination. On admission, only one infant and his mother were seronegative and seroconversion was only detected in this infant. One month after the third dose seven infants (12.3%) were found to be seronegative. The infant without passively acquired maternal anti-HAV had the protective levels with a GMT of 3176 mIU/ml one month following the third dose. There was a significant positive correlation between the titers of mother and infant anti-HAV antibodies (n = 0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it should be used after the disappearance of maternal antibodies.

Salmonella septic arthritis in a patient with acute idiopathic thrombocytopenic purpura treated with steroid.

Salmonella has three clinical presentations: self-limiting gastroenteritis, a systemic syndrome (enteric or typhoid fever), and bacteremia with focal infection. Hematogenous infections can cause focal lesions, but unusual manifestations occur more often when predisposing factors such as T cell defect, hemolytic disorders (sickle cell disease, malaria) or trauma are present. Salmonella tend to invade bones and joints. There is no mention of acute idiopathic (immune) thrombocytopenic purpura as a predisposing factor for salmonella septic arthritis; however there are reports about the importance of platelets for the immune response. Here we present a case of Salmonella enteritidis septic arthritis following acute idiopathic (immune) thrombocytopenic purpura in a 15-year-old female patient who has been on steroid therapy for the last two weeks.

Reactogenicity and immunogenicity of a new measles-mumps-rubella vaccine containing RIT 4385 mumps virus strain in healthy Turkish children.

A total of 44 children aged between 15-18 months were randomly vaccinated either with a new measles-mumps-rubella (MMR) vaccine (Priorix, SmithKline Beecham) or a commercially available MMR vaccine (MMR-II, Merck) to compare the reactogenicity and immunogenicity. No local symptoms or fever was reported. Seroconversion rates of the study vaccine were 100, 95 and 100 percent for measles, mumps and rubella, respectively. The seroconversion rates for the control vaccine were 100, 94.7 and 95.5 percent, respectively. The geometric mean titers (GMT's) for the study and control groups were 1695, 95, 58; and 2198, 1183 and 47; respectively. In conclusion, the new MMR vaccine containing RIT 4385 mumps strain derived from the Jeryl Lynn strain was shown to be immunogenic and safe in healthy Turkish children. Further post-marketing surveillance should be conducted.

Safety and immunogenicity of live attenuated varicella vaccine in 9-month-old children.

BACKGROUND: The present study was conducted to evaluate the safety and immunogenicity of live attenuated varicella vaccine (Oka-strain) in 9-month-old infants. METHODS: One hundred and fourteen infants were vaccinated once with live attenuated varicella vaccine (Valrix; SmithKline Beecham Biologicals, Rixensart, Belgium) containing a mean virus titer of 10(4.0) plaque-forming units (p.f.u.) per dose. Signs and/or symptoms after vaccination were followed for 42 days. Home visits were made to detect solicited local reactions (0-3 days) and solicited general reactions (0-21 days), as well as unsolicited reactions. Specific varicella antibodies were determined by an indirect immunofluorescence method. The geometric mean titer and seroconversion rate were calculated. RESULTS: Signs and/or symptoms were reported in 47.4% (54/114) of cases following vaccination. The only local symptom reported was pain on digital pressure at the injection site and this was reported in 28.1% (32/114) of infants. General symptoms were reported in 38.6% (44/114) of cases. The most frequently reported findings were fever (27.2%), which was mostly mild, restlessness (20.2%) and cough (11.4%). Only four unsolicited symptoms were reported and they were all unrelated to vaccination. No serious adverse event was reported. Of the 109 infants included in the immunogenicity analysis, 105 were seronegative and four were seropositive for antibodies against varicella before vaccination. The vaccine elicited seroconversion in 97.1% of initially seronegative cases. The post-vaccination geometric mean titer for these infants was 30.9 geometric mean titer (GMT). CONCLUSIONS: The vaccine was found to be safe and immunogenic when given to infants as young as 9 months of age. This may be of clinical significance during outbreaks of varicella and especially for developing countries.

Immunogenicity study of a combined diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis vaccine used to reconstitute a freeze-dried Haemophilus influenzae type b vaccine (DTaP-IPV//PRP-T) administered simultaneously with a hepatitis B vaccine at two, three and four months of life.

This study was designed to assess the immunogenicity of a vaccine combining diphtheria and tetanus toxoids, acellular pertussis vaccine, and inactivated poliovirus vaccine reconstituting Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (DTaP-IPV//PRP-T; Pasteur Mérieux Connaught, Lyon, France) administered simultaneously in association with hepatitis B vaccine (RECOMBIVAX (¿trade mark omitted¿) Merck, Sharp & Dohme, West Point, PA, USA) for the primary immunization of infants. The vaccines were administered at two, three and four months of age. One hundred and sixty-two healthy infants, aged 8-10 weeks, were enrolled in the study. Blood samples were taken before the first dose and 4 weeks after the third dose. The infants were observed for 15 minutes after vaccination for any immediate reaction. Adverse events requiring a medical consultation were recorded by the parents in a diary over the 7 days following vaccination. Four weeks after the third immunization, the percentages of infants fulfilling seroconversion criteria were 98.9% for pertussis toxin, 95.9% for filamentous haemagglutinin, 100.0% for tetanus, 100.0% for diphtheria, 99.3% for poliovirus type 1, 100.0% for both poliovirus types 2 and 3, 98.0% for Haemophilus influenzae type b, and 100% for hepatitis B surface antigen. No vaccine-related serious adverse event was reported. The simultaneous administration of DTaP-IPV//PRP-T and hepatitis B vaccines at two, three and four months of age yielded clinically satisfactory immune responses to all antigens compared with historical controls and gave a good safety profile.

Aluminum content of vaccines used in Turkey.

Aluminum salts have been used in the preparation of a number of vaccines, toxoids, and allergen injectants as an adjuvant for many years. Although aluminum allergy is rare, there are many reported cases caused by aluminum-precipitated vaccines or hyposensitization therapy. Therefore, determination of the aluminum content of these vaccines is necessary information regarding adverse reactions related to these vaccines. In the present study, the aluminum contents of several vaccines (n = 19) routinely used in Turkey were, determined by electrothermal atomic absorption spectrophotometry. We found that aluminum levels in the vaccines ranged from 0.0 to 1438 mg/L.

Priming effect, immunogenicity and safety of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular pertussis (DTaP) combination vaccine administered to infants in Belgium and Turkey.

To evaluate the priming effect, immunogenicity and safety of an Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-acellular (two component) pertussis (DTaP) combination vaccine, a randomized, comparative study was conducted in two centers, one in Belgium and one in Turkey. A total of 410 healthy infants, 160 in Belgium and 250 in Turkey, randomly received DTaP and PRP-T vaccines in one of three fashions. One group (N = 138) received DTaP and PRP-T vaccines reconstituted immediately prior to injection at 3, 4 and 5 months of age, and are referred to as the combined, short schedule group (Co-S). A second group (N = 135) received DTaP + PRP-T simultaneously but injected at different sites according to the same schedule, and are referred to as the associated, short schedule group (As-S). The third group (N = 137) also received DTaP + PRP-T at separate sites, but at 2, 4 and 6 months, and are referred to as the associated, long schedule group (As-L). The As-L group allowed for serological bridging with a Senegalese two-component pertussis vaccine efficacy trial, using the same batch of DTaP vaccine. Children of both short-schedule groups (Co-S and As-S) received, at the age of 12-14 months, a booster dose of DTaP vaccine associated with unconjugated PRP vaccine. Mixing of the vaccines did not affect the immune response to the antigens included in the DTaP vaccine. The immune response to Hib capsular polysaccharide, however, was significantly lower after combined administration (Co-S group) than after associated (As-S group) administration (P < 0.0001), with a similar trend among both countries (GMTs, 1.78 microg/ml and 6.19 microg/ml in Belgium, and 5.02 microg/ml and 11.67 microg/ml in Turkey). Booster vaccination with the unconjugated PRP induced a vigorous and similar anamnestic response in both groups. Belgian infants showed a significantly lower immune response to all antigens than Turkish infants (P < or = 0.001 for all antigens), with a similar trend among each study group. In all groups, the incidence of adverse events was lower than that usually reported after DTwP(whole-cell) vaccine. Higher rates of systemic reactions were observed in the Belgian population, possibly due to differences in reporting practice. Our results indicate (1) that the combination vaccine, DTaP//PRP-T, represents an important improvement over the existing uncombined vaccines; (2) that immunogenicity studies should include at least one booster injection to evaluate priming effects by combined vaccines; and (3) that it is feasible and valuable to co-randomize combination vaccine studies in sufficiently different geographical areas and child populations.

Safety, tolerability and immunogenicity of a Haemophilus influenzae type b vaccine containing aluminum phosphate adjuvant administered at 2, 3 and 4 months of age.

The primary aim of this study was to assess the tolerability and immunogenicity of a new Haemophilus influenzae type b (Hib)/AlPO4 (CHIRON, SpA) vaccine, in two-month-old healthy infants. Twenty-three subjects were enrolled and administered the new Hib vaccine containing AlPO4 adjuvant at two, three and four months of age concomitantly with diphtheria-pertussis-tetanus (DPT) and hepatitis B vaccines according to the local program. Children were observed for 30 minutes after each immunization for any immediate local and systemic reactions. An active surveillance for side effects was performed on the 2nd and 7th days following each immunization by telephone. Families also filled out diaries for the first seven days. From the 2nd day to the next immunization only data about adverse events necessitating a physician's visit or about serious adverse events were collected. Blood samples were obtained before the first immunization and one month after the third dose for evaluation of anti-polyribosylribitol phosphate (PRP) antibody response. Local reactions at the Hib site were mild and less frequent compared to those observed at the DPT site. Systemic reactions noted after the three immunizations were fever in 70 percent, irritability in 48 percent, persistent crying in 26 percent, change in eating habits in 22 percent, diarrhea in 17 percent, sleepiness in 17 percent, vomiting in 9 percent, and unusual crying in 4 percent of the cases. There was no serious adverse event. One hundred percent and 95 percent of children achieved an anti-PRP antibody response over 0.15 microg/ml and 1.0 microg/ml, respectively. The geometric mean titer was 15 microg/ml and the geometric mean ratio 84. It was concluded that the new (Hib)/AlPO4 vaccine is safe and well tolerated, and induced a good PRP antibody response in healthy two-month-old infants.

Leukocytoclastic vasculitis in a child with epidermolysis bullosa simplex.

A 10-year-old boy with epidermolysis bullosa simplex (Weber-Cockayne variant) together with leukocytoclastic vasculitis is presented. He was admitted to the hospital with the provisional diagnoses of infected epidermolysis bullosa simplex or drug eruption. On the sixth day of hospitalization he developed palpable purpura, abdominal pain and bloody diarrhea, together with hematuria and proteinuria. A generalized tonic-clonic convulsion, changes in mental status, fluctuations in arterial blood pressure and intractable pain in his extremities occurred during the course of hospitalization. Systemic pulse steroid therapy, antibiotics, and antihypertensive and anticonvulsive drugs were given. On the 30th day of hospitalization, a skin graft was performed to replace a large tissue defect on his left hand. Despite high dose steroid therapy, his hematuria, proteinuria and hypertension continued after his discharge, suggesting a steroid-resistant renal pathology, such as focal glomerulosclerosis, that occurred secondary to leukocytoclastic vasculitis.