Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care.

BACKGROUND: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. METHODS: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. RESULTS: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. CONCLUSION: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Global seroprevalence of rubella among pregnant and childbearing age women: a meta-analysis.

Background: We conducted a meta-analysis of articles published between January 2000 and July 2016 with the aim of defining the proportion of rubella seronegative women of childbearing age (WCBA), providing the best information available on the seroprevalence of rubella in this population. We selected articles published in the time period between 2000 and 2016. The pooled prevalence of rubella seronegative women was calculated by a fixed effect model and a random effect model, according to the heterogeneity among studies. Studies were sub-grouped by population type (pregnant women and WCBA with no mention of ongoing pregnancy) and by geographic area [World Health Organization (WHO) region]. Sensitivity analysis was performed to assess the stability of results. We found important differences in rubella seronegativity prevalence estimates by WHO Region. About 88% of the studies conducted on pregnant women reported a seronegativity rate >5%. The pooled rubella seronegativity prevalence was 9.3%. When considering population groups, we obtained a seronegativity pooled estimate of 9.4% for pregnant women and of 9.5% for WCBA with no mention of ongoing pregnancy. This meta-analysis shows that the proportion of WCBA who are susceptible to rubella is still high. The figures are worrisome, taking into account that the WHO set at 5% the rubella susceptibility threshold for WCBA.

Whooping cough, twenty years from acellular vaccines introduction.

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Epidemiology of pertussis in Italy: disease trends over the last century.

We reviewed the epidemiology of pertussis in Italy over the last 125 years to identify disease trends and factors that could have influenced these trends. We described mortality rates (1888-2012), case fatality rates (1925-2012), cumulative incidence rates (1925-2013) and age-specific incidence rates (1974-2013). We compared data from routine surveillance with data from a paediatric sentinel surveillance system to estimate under-notification. Pertussis mortality decreased from 42.5 per 100,000 population in 1890 to no reported pertussis-related death after 2002. Incidence decreased from 86.3 per 100,000 in 1927 to 1 per 100,000 after 2008. Vaccine coverage increased from 32.8% in 1993 to about 96% after 2006. As for under-notification, mean sentinel/routine surveillance incidence ratio increased with age (from 1.8 in <1 year-olds to 12.9 in 10-14 year-olds). Pertussis mortality decreased before the introduction of immunisation. Incidence has decreased only after the introduction of pertussis vaccine and in particular after the achievement of a high immunisation coverage with acellular vaccines. Routine surveillance does not show an increase in cumulative incidence nor in ≥ 15 year-olds as reported by other countries. Underrecognition because of atypical presentation and the infrequent use of laboratory tests may be responsible for under-notification, and therefore affect incidence reports and management of immunisation programmes.

Nasopharyngeal microbiota in hospitalized children with Bordetella pertussis and Rhinovirus infection.

Despite great advances in describing Bordetella pertussis infection, the role of the host microbiota in pertussis pathogenesis remains unexplored. Indeed, the microbiota plays important role in defending against bacterial and viral respiratory infections. We investigated the nasopharyngeal microbiota in infants infected by B. pertussis (Bp), Rhinovirus (Rv) and simultaneously by both infectious agents (Bp + Rv). We demonstrated a specific nasopharyngeal microbiome profiles for Bp group, compared to Rv and Bp + Rv groups, and a reduction of microbial richness during coinfection compared to the single infections. The comparison amongst the three groups showed the increase of Alcaligenaceae and Achromobacter in Bp and Moraxellaceae and Moraxella in Rv group. Furthermore, correlation analysis between patients' features and nasopharyngeal microbiota profile highlighted a link between delivery and feeding modality, antibiotic administration and B. pertussis infection. A model classification demonstrated a microbiota fingerprinting specific of Bp and Rv infections. In conclusion, external factors since the first moments of life contribute to the alteration of nasopharyngeal microbiota, indeed increasing the susceptibility of the host to the pathogens' infections. When the infection is triggered, the presence of infectious agents modifies the microbiota favoring the overgrowth of commensal bacteria that turn in pathobionts, hence contributing to the disease severity.

Prevention of congenital rubella and congenital varicella in Europe.

Despite the availability of safe and efficacious vaccines, cases of congenital rubella and varicella syndrome still occur in Europe. As of 2004, several countries had high proportions of women of childbearing age that were susceptible to rubella and varicella virus infection.

[Acute effects of propranolol and its association with nifedipine in aged patients with effort stable angina. Randomized double-blind crossover study, under placebo control]. / Effetti acuti del propranololo e sua associazione con nifedipina in pazienti anziani con angina stabile da sforzo. Studio a doppio cieco, randomizzato, cross-over, controllato con placebo.

Calcium-antagonist and B-blockers are effective in improving exercise tolerance in patients with effort angina. We studied the short effects of oral administration of nifedipine (10 mg) and propranolol (80 mg) alone and in combination in 15 elderly patients with chronic exertional angina pectoris in a double-blind, randomized, cross-over study. The 15 patients (13 men and 2 women, mean age 69 years) performed symptoms-limits bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration, real time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by drug alone and in combination. Propranolol and nifedipine improved exercise duration in combination; however, a different response to the three pharmacologic interventions was found in patients treated with single drug. The improvement in exercises tolerance was associated with rate-pressure product values at peak exercise tolerance was associated with rate-pressure product values at peak exercise, unchanged after placebo and significantly reduced after both propranolol alone and in combination. After placebo all patients had exercise-induced angina, in 50% and in 40% after propranolol and the combination of the two drugs, respectively. In aging patients nifedipine and propranolol are effective in the treatment of effort angina and they are superior in patients who show poor response to mono therapy, although this combination will be conditioned by different patient sensibility to the three pharmacologic interventions and then therapeutic choice would be evaluated and verified individually.

Immunization coverage and timeliness of vaccination in Italian children with chronic diseases.

Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months-18 years were included in the study. Coverage for diphtheria-tetanus-pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles-mumps-rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.

[Myocardial damage following neonatal severe asphyxia]. / Daño miocárdico secundario a asfixia neonatal grave.

Sixteen newborn infants with severe asphyxia were prospectively studied for evidence of secondary myocardial damage and, in that case, their clinical findings. Myocardial damage was diagnosed in three term newborn infants of adequate weight for gestational age (18.7%) by means of serial electrocardiograms taken in the first 72 hours of life. Two of them showed evidence of diffuse subendocardial ischemia and a third one showed electrocardiographic signs suggesting necrosis of the left ventricular posteroinferior wall. Neither creatine-phosphokinase serum activity nor its muscle brain MB isoenzyme were useful in the identification of myocardial damage. All three affected neonates developed respiratory distress syndrome without signs of cardiac failure and one of them died. The histopathological study of this late one showed localized hemorrhage of the papillary muscles and interventricular septum. These finding underscore the need for serial electrocardiographic recordings in newborns with severe asphyxia, since cardiac dysfunction may inadvertently occur under the appearance of respiratory distress syndrome.

[Correlation of clinical, radiologic and pathologic aspects of the thymus in newborn infants]. / Correlación clínica, radiológica y patológica del timo en recién nacidos.

The thymus of 30 autopsied neonates who died from different causes (hyaline membrane disease: 13 cases; severe infections: 11 cases; congenital malformations: 4 cases; severe asphyxia: 2 cases) were prospectively examined in order to look for the most frequent macroscopic and microscopic morphological changes in this organ. Findings were correlated with clinical and radiological data. In hyaline membrane disease patients moderate decrease of thymic weight and slight depletion of cortical lymphocytes as to reference values were observed; such changes were likewise seen in cases with malformations and severe asphyxia. Newborns who died from severe infections exhibited early and pronounced decrease of thymic weight as well as severe depletion of cortical lymphocytes, more noticeable at all times than in the remaining groups. It is concluded that the predominant finding in examined patients is thymic involution secondary to stress, whose intensity would depend upon the type and duration of the main disease, being most severe the longer the evolutionary time. The variability observed in thymic size of individuals with similar physical features and the lack of an accurate correlation between radiology and post mortem findings with respect to thymic size are remarkable.

Trigeminal neuralgia and cerebellopontine-angle lipoma in a child.

Trigeminal neuralgia and cerebellopontine-angle lipomas are very rare in children. We describe the history and findings of an 8-year-old boy with right trigeminal neuralgia and a lipoma detected by magnetic resonance imaging at the level of the root-entry zone of the right seventh cranial nerve. We propose a possible mechanism of infiltration of the trigeminal rootlets by the lipoma.

Marchantin M trimethyl ether.

The title macrocycle, C(31)H(30)O(5), is comprised of two bibenzyl ether moieties linked cyclically by spacers which each consist of two-carbon alkyl chains. The observed conformation of the macrocycle may be partly stabilized by intramolecular C-H.O close contacts. The packing appears to be directed by van der Waals forces. This work explains the occurrence of a signal found in the (1)H NMR spectra of both marchantinquinone and marchantin M trimethyl ether at delta = 5. 49 and 5.56 p.p.m., respectively. The shift in the position of the expected peak can be explained by the proximity of an H atom belonging to one of the aromatic rings to another ring in the same molecule.

Nematocidal activity of natural polyphenols from bryophytes and their derivatives.

The nematocidal in vitro activity of three natural perotetins (phenolic bisbibenzyiethers) and eleven diphenyl ethers used as synthetic precursors has been assayed using two different experimental models, Caenorhabditis elegans and Nippostrongylus brasiliensis. Nine compounds showed some activity against C. elegans and nine against N. brasiliensis. For the former model, three compounds displayed an activity similar to that of the standards, whereas for N. brasiliensis none of the tested compounds was as active as the standards. From the in vitro results, five compounds (3, 4, 8, 9, 13) could be selected as lead compounds to continue the search for improved activity.

[Comparison of nisoldipine and diltiazem in the treatment of effort angina pectoris]. / Confronto tra nisoldipina e diltiazem nel trattamento dell'angina da sforzo.

BACKGROUND: In order to evaluate the benefits of a calcium-antagonist medium-term treatment, 20 patients with effort stable angina pectoris were treated with nisoldipine in comparison to diltiazem. METHODS: Twenty patients with stable effort angina completed a double-blind, placebo controlled trial, comparing 10 twice daily nisoldipine per os and diltiazem 120 three times daily per os for 28 days. After wash-out, placebo and drug period, ergometer stress tests were performed. Exercise tolerance, angina frequency, nitrate consumption and side effects were evaluated. RESULTS: Our results showed that both drugs significantly increased exercise tolerance. Exercise duration was 330 +/- 107 sec after placebo, 397 +/- 106 sec after nisoldipine (p < 0.05) and 378 +/- 99 sec after diltiazem (p < 0.05). Effort angina episodes decreased from 20 after placebo to 8 after nisoldipine and diltiazem. Both drugs reduced rate-pressure product at submaximal exercise in comparison to placebo. There were no differences at peak exercise between placebo or drug periods. Both drugs similarly reduced nitrate consumption and weekly effort angina attacks. No patients referred serious side-effects. CONCLUSIONS: nisoldipine, like diltiazem, is an effective drug in the treatment of stable effort angina. Moreover, the therapeutic effects of nisoldipine during medium-term treatment are probably related to decrease in oxygen consumption.