Long-term prognosis of vaccine-induced contact allergy to aluminium: Third patch-test with additional test preparations.

BACKGROUND: A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re-tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity. AIM: To investigate the long-term prognosis of vaccine-induced contact allergy to aluminium by a third patch test about 20 years after Patch test I. METHODS: Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested. RESULTS: A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results. CONCLUSION: Contact allergy to aluminium caused by vaccination with aluminium-adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.

Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study.

BACKGROUND: The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. METHODS: Children (n = 677) with non-severe acute febrile illness aged 2-59 months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ("IMCI pneumonia") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia". RESULTS: Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. CONCLUSION: The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registration Clinicaltrials.gov (NCT01094431).

Ethnicity, gender and seasonal variations all play a role in vitamin D deficiency.

AIM: (1) To explore the adherence of recommendations of vitamin D supplementation to children aged 0-4 years. (2) To compare serum levels of vitamin D in children and adolescents aged 0-17 years originating from different parts of the world. (3) To compare levels between boys and girls and (4) To determine seasonal variation. METHODS: A review of vitamin D levels in children with parents from different parts of the world was conducted. 2502 children aged 0-17 years were included between 22 January 2004 and 17 May 2021. RESULTS: Fifty-nine of 363 children aged 0-4 years received the recommended vitamin D supplementation. Children from all parts of the world had lower levels of serum 25(OH)D than Swedish children. Girls from the Indian subcontinent, Middle East and Africa had the lowest levels of s-25(OH)D. Seasonal variation with higher levels during the summer was seen in children from Sweden, the rest of Europe, Russia and Latin America. Overall prevalence of vitamin D deficiency (≤25 nmol/L) was 928/2198 (42%) in children not receiving supplementation. Seven children had clinical rickets. CONCLUSION: Adherence of giving children aged 0-4 years the recommended vitamin D supplementation was very low. Vitamin D deficiency is common in immigrant children of all ages in Sweden.

Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden.

BACKGROUND: The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction. METHODS: Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher's exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test. RESULTS: With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis. CONCLUSIONS: Non-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Cost-effectiveness of childhood pneumococcal vaccination program in Ethiopia: results from a quasi-experimental evaluation.

BACKGROUND: Ethiopia was among the 15 countries that, together accounted for 64% of the world's severe episodes of pneumonia among children below the age of 5 in 2011. To reduce this burden, the 10-valent pneumococcal conjugate vaccine (PCV 10) was introduced into the general childhood national immunization program in Ethiopia in 2011. However, there is little evidence on its cost-effectiveness, and the aim of this study was to estimate the cost-effectiveness of the introduction of PCV 10 vaccination in the Ethiopian setting. METHODS: The cost-effectiveness analysis was carried out based on a quasi-experimental evaluation of implementing PCV 10 at the Butajira rural health program site in Ethiopia. The intervention and the control groups consisted 876 and 1010 children, respectively. Using data from program site's surveillance system database as a framework, health outcome and vaccination data were collected from medical records, immunization registration books and reports. Disability- Adjusted Life Year (DALY) was a main health outcome metric complimented by incidence of acute lower respiratory infection/1000-person years. Vaccination and treatment costs were collected by document review and cross-sectional household survey. RESULTS: In the intervention cohort, 626 of 876 (71.5%) children received PCV 10 vaccination. Until the first year of life, the incidence of acute lower respiratory infection was higher in the intervention group. After the first year of life, the incidence rate was 35.2 per 1000-person years in the intervention group compared to 60.4 per 1000-person years in the control group. The incremental cost-effectiveness ratio (ICER) per averted DALY for the intervention group during the total follow-up period was (2013 US$) 394.3 (undiscounted) and 413.8 (discounted). The ICER per averted DALY excluding the first year of life was (2013 US$) 225 (undiscounted) and 292.7 (discounted). CONCLUSION: Compared to the WHO's suggested cost-effectiveness threshold value, the results indicate that the general childhood PCV 10 vaccination was a cost-effective intervention in the Butajira rural health program site.

Changes in incidence and etiology of early-onset neonatal infections 1997-2017 - a retrospective cohort study in western Sweden.

BACKGROUND: The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997-2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975. METHODS: Observational epidemiological, retrospective study on infants 0-6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997-2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975. RESULTS: The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997-2007 to 0.9/1000 LB in 2008-2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997-2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987-1996 to 0.45/1000 live births 1997-2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge. CONCLUSION: There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area. KEY NOTES: This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

Patch testing children with aluminium chloride hexahydrate in petrolatum: A review and a recommendation.

BACKGROUND: According to studies on adults, patch testing with aluminium chloride hexahydrate 2% pet. is insufficient to detect aluminium allergy, and a 10% preparation is recommended. Other studies suggest that a 2% preparation is sufficient for testing children. OBJECTIVES: To review three previously published Swedish studies on patch testing children with aluminium chloride hexahydrate 2% pet. PATIENTS/METHODS: Altogether, 601 children with persistent itching subcutaneous nodules (granulomas) induced by aluminium-adsorbed vaccines were patch tested with aluminium chloride hexahydrate 2% pet. and metallic aluminium in (a) a pertussis vaccine trial, (b) clinical practice, and (c) a prospective study. RESULTS: Overall, 459 children had positive reactions to the 2% pet. preparation. Another 10 reacted positively only to metallic aluminium. An extreme positive reaction (+++) was seen in 65% of children aged 1 to 2 years as compared with 22% of children aged 7 years. From 8 years onwards, extreme positive reactions were scarce. CONCLUSIONS: Aluminium chloride hexahydrate 2% pet. is sufficient to trace aluminium allergy in children. Small children are at risk of extreme reactions. We thus suggest that aluminium chloride hexahydrate 10% pet. should not be used routinely in children before the age of 7 to 8 years.

Comparison of reactivity to a metallic disc and 2% aluminium salt in 366 children, and reproducibility over time for 241 young adults with childhood vaccine-related aluminium contact allergy.

BACKGROUND: An aluminium hydroxide-adsorbed pertussis toxoid vaccine was studied in 76 000 children in the 1990s in Gothenburg, Sweden. Long-lasting itchy subcutaneous nodules at the vaccination site were seen in 745 participants. Of 495 children with itchy nodules who were patch tested for aluminium allergy, 377 were positive. In 2007-2008, 241 of the positive children were retested. Only in one third were earlier positive results reproduced. OBJECTIVES: To further describe patch test reactions to different aluminium compounds in children with vaccine-induced aluminium allergy. PATIENTS/METHODS: Positive patch test results for metallic aluminium (empty Finn Chamber) and aluminium chloride hexahydrate 2% petrolatum (pet.) were analysed in 366 children with vaccine-induced persistent itching nodules tested in 1998-2002. Of those, 241 were tested a second time (2007-2008), and the patch test results of the two aluminium preparations were analysed. RESULTS: Patch testing with aluminium chloride hexahydrate 2% pet. is a more sensitive way to diagnose aluminium contact allergy than patch testing with metallic aluminium. A general decrease in the strength of reactions to both aluminium preparations in 241 children tested twice was observed. CONCLUSIONS: Aluminium contact allergy can be diagnosed by patch testing without using metallic aluminium.

Rapid Clearance and Frequent Reinfection With Enteric Pathogens Among Children With Acute Diarrhea in Zanzibar.

Background: Acute infectious gastroenteritis is an important cause of illness and death among children in low-income countries. In addition to rotavirus vaccination, actions to improve nutrition status, sanitation, and water quality are important to reduce enteric infections, which are frequent also among asymptomatic children. The aim of this study was to investigate if the high prevalence of these infections reflects that they often are not cleared properly by the immune response or rather is due to frequent pathogen exposure. Methods: Rectal swabs were collected at time of acute diarrhea and 14 days later from 127 children, aged 2-59 months and living in rural Zanzibar, and were analyzed by real-time polymerase chain reaction targeting multiple pathogens. Results: At baseline, detection rates >20% were found for each of enterotoxigenic Escherichia coli, Shigella, Campylobacter, Cryptosporidium, norovirus GII, and adenovirus. At follow-up, a large proportion of the infections had become cleared (34-100%), or the pathogen load reduced, and this was observed also for agents that were presumably unrelated to diarrhea. Still, the detection frequencies at follow-up were for most agents as high as at baseline, because new infections had been acquired. Neither clearance nor reinfection was associated with moderate malnutrition, which was present in 21% of the children. Conclusions: Children residing in poor socioeconomic conditions, as in Zanzibar, are heavily exposed to enteric pathogens, but capable of rapidly clearing causative and coinfecting pathogens.

Toward a new vaccine for pertussis.

To overcome the limitations of the current pertussis vaccines, those of limited duration of action and failure to induce direct killing of Bordetella pertussis, a synthetic scheme was devised for preparing a conjugate vaccine composed of the Bordetella bronchiseptica core oligosaccharide with one terminal trisaccharide to aminooxylated BSA via their terminal ketodeoxyoctanate residues. Conjugate-induced antibodies, by a fraction of an estimated human dose injected into young outbred mice as a saline solution, were bactericidal against B. pertussis, and their titers correlated with their ELISA values. The carrier protein is planned to be genetically altered pertussis toxoid. Such conjugates are easy to prepare, stable, and should add both to the level and duration of immunity induced by current vaccine-induced pertussis antibodies and reduce the circulation of B. pertussis.

Relation between BCG vaccine scar and an interferon-gamma release assay in immigrant children with "positive" tuberculin skin test (≥10 mm).

BACKGROUND: Immigrants from countries with high incidence of tuberculosis (TB) are usually offered screening when they arrive to low incidence countries. The tuberculin skin test (TST) is often used. The interferon gamma release assays (IGRAs) are more specific and not affected by BCG vaccination. The aims of this study were 1. To see if there if there is a correlation between a positive IGRA (QFT) and presence of a BCG scar in children with TST ≥10 mm, 2. To compare the TST diameter with QFT result, 3. To see if chest X-ray can be omitted in QFT negative children despite TST ≥10 mm. METHODS: 762 healthy children/adolescents (median age 14 years) arriving to Gothenburg and surroundings with TST ≥10 mm were tested with QFT. RESULTS: A total of 163/492 (33 %) children with BCG scar had positive QFT, whereas 205/270 (76 %) without BCG scar had positive QFT (p < 0.0001). The median TST was 12 mm in QFT negative and 18 mm in QFT positive children (p < 0.0001) but with considerable overlap. Median TST was the same (12 mm) in QFT negative children with and without BCG scar. Among the QFT positive children 25/368 had chest X-ray changes compared to 2/393 among the QFT negative children (p < 0.0007). CONCLUSIONS: Previous BCG vaccination had an effect on the TST diameter so an IGRA is recommended to diagnose latent TB. Using only TST for screening of latent TB would lead to overdiagnosis. The TST diameter was larger in QFT positive than in QFT negative children but could not predict QFT in the individual patient. Chest X ray contributes little to the diagnosis of TB in QFT negative children but can not be omitted because of late seroconversion of QFT in some patients. TRIAL REGISTRATION: Not applicable.

Epidemiology of invasive pneumococcal infections: manifestations, incidence and case fatality rate correlated to age, gender and risk factors.

BACKGROUND: Incidence, manifestations and case-fatality rate (CFR) of invasive pneumococcal disease (IPD) vary with age and comorbidities. New vaccines, changing age distribution, prolonged survival among immunocompromised patients and improved sepsis management have created a need for an update of basic facts to inform vaccine recommendations. METHODS: Age, gender and comorbidities were related to manifestations and death for 2977 consecutive patients with IPD in a Swedish region with 1.5 million inhabitants during 13 years before introduction of pneumococcal conjugate vaccines (PCV) in the infant vaccination program. These data were related to population statistics and prevalence of several comorbidities, and compared with two previous studies giving a total follow-up of 45 years in the same area. RESULTS: The annual incidence was 15/100,000 for any IPD and 1.1/100,000 for meningitis; highest among elderly followed by children < 2 years. It was 2238/100,000 among myeloma patients, followed by chronic lymphatic leukemia, hemodialysis and lung cancer, but not elevated among asthma patients. CFR was 10 % among all patients, varying from 3 % below 18 years to 22 % ≥ 80 years. During 45 years, the IPD incidence increased threefold and CFR dropped from 20 to 10 %. Meningitis incidence remained stable (1.1/100,000/year) but CFR dropped from 33 to 13 %. IPD-specific mortality decreased among children <2 years from 3.1 to 0.46/100,000/year but tripled among those ≥65 years. CONCLUSIONS: IPD incidence and CFR vary widely between age and risk groups and over time even without general infant vaccination. Knowledge about specific epidemiological characteristics is important for informing and evaluating vaccination policies.

Serotypes of group B streptococci in western Sweden and comparison with serotypes in two previous studies starting from 1988.

BACKGROUND: Group B Streptococci (GBS) are the most common neonatal pathogens and infect immunocompromised and elderly individuals. The species has 10 different serotypes. Serotypes have been studied in the south-west area of Sweden in 1988-1997 and 1998-2001. The aim of this study was to study serotypes in the same area from 2004 to 2009. METHODS: Invasive GBS isolates were collected prospectively from 2004 to 2009 in two counties in western Sweden with a population of 1.8 million, and were serotyped by latex agglutination. Clinical data were obtained from hospital records. During the study period 410 invasive GBS isolates from 398 patients were collected (multiple episodes ≥ 1 month apart). Clinical data were not available for two patients who are excluded. Four isolates were from stillborn neonates, 88 were from live born neonates and infants, and 318 from adults. RESULTS: Serotype III was the most common serotype (48%) in neonates and infants followed by serotypes Ia (18%) and V (16%). In adults serotype V (39%) dominated followed by serotypes III (20%) and Ib (14%). There was a significant increase of serotype V in comparison with the first study (1988-1997) but there were no significant changes in the serotype distribution between the present study and the second study (1998-2001). There were a few cases of serotype VI-IX, both in children and adults, not seen in the previous studies. Serotype V was more common among patients with arthritis than with any other manifestation. CONCLUSIONS: Changes in GBS serotypes occur over time in the same region, which must be considered when GBS vaccines are formulated.

Incidence, risk factors and hospital burden in children under five years of age hospitalised with respiratory syncytial virus infections.

AIM: Respiratory syncytial virus (RSV) infections are among the most common lower respiratory tract infections in infants, but few studies have determined the age-specific incidence of hospitalisation in defined populations. This study gathered Swedish data on RSV in Gothenburg and its 10 surrounding municipalities from 2004 to 2011. METHODS: Information was obtained from hospital databases of all patients up to five years of age who had a discharge diagnosis of an RSV infection and had a positive antigen detection or polymerase chain reaction test. RESULTS: A total of 1764 children fulfilled the inclusion criteria and 238 of these were preterm. The incidence under one year of age was 17.4/1000/year, and in children aged one to four years it was 0.6/1000/year. RSV patients occupied a mean of 1141 hospital beds per year: 65 were treated in the intensive care unit, 27 needed ventilator support, 19 needed continuous positive airway pressure, 408 (23%) received antibiotics, 399 (23%) received steroids, and all but four patients received a bronchodilator. All children survived. CONCLUSION: The incidence of RSV infections was high, medication use was high, and complications were low. Preterm infants had a higher risk, but most infants needing hospitalisation for RSV are full term and have no known risk factors.

Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.

Real-time PCR threshold cycle cutoffs help to identify agents causing acute childhood diarrhea in Zanzibar.

Molecular assays might improve the identification of causes of acute diarrheal disease but might lead to more frequent detection of asymptomatic infections. In the present study, real-time PCR targeting 14 pathogens was applied to rectal swabs from 330 children aged 2 to 59 months in Zanzibar, including 165 patients with acute diarrhea and 165 asymptomatic control subjects. At least one pathogen was detected for 94% of the patients and 84% of the controls, with higher rates among patients for norovirus genogroup II (20% versus 2.4%; P<0.0001), rotavirus (10% versus 1.8%; P=0.003), and Cryptosporidium (30% versus 11%; P<0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)-estA (33% versus 24%), ETEC-eltB (44% versus 46%), Shigella (35% versus 33%), and Campylobacter (35% versus 33%), but for these agents threshold cycle (CT) values were lower (pathogen loads were higher) in sick children than in controls. In a multivariate analysis, CT values for norovirus genogroup II, rotavirus, Cryptosporidium, ETEC-estA, and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents and provides CT values that may be critical for the interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that the assessment of pathogen loads may improve the identification of agents causing gastroenteritis in children.

Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden.

BACKGROUND: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y. METHODS: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. RESULTS: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February-April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. CONCLUSIONS: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study.

UNLABELLED: The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. CONCLUSION: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.