Alessia Melegaro - Academia.edu (original) (raw)

Papers by Alessia Melegaro

Countries Groups contains information on which countries are considered as part of COVAX. Populat... more Countries Groups contains information on which countries are considered as part of COVAX. Population contains information on population.

a) Social contact matrix derived for Manicaland (Zimbabwe), 2013, considering all report... more a) Social contact matrix derived for Manicaland (Zimbabwe), 2013, considering all reported contacts and applying bivariate smoothing. The matrix shows the average number of contacts during working days (weekends and school holidays are excluded) of participants in the i-th age group with individuals in the j-th age group. b) As a), but for Italy (data from the POLYMOD study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0170459#pone.0170459.ref004" target="_blank">4</a>], weekends excluded).</p

Supplementary methods and results. (DOCX 6670 kb)

Social contact patterns are a critical explanatory factor of the spread of close-contact infectio... more Social contact patterns are a critical explanatory factor of the spread of close-contact infectious agents. Both indirect (via observed epidemiologic data) and direct (via diaries that record at-risk events) approaches to the measurement of contacts by age have been proposed in the literature. In this paper, the authors discuss the possibilities offered by time-use surveys to measure contact patterns and to explain observed seroprevalence profiles. The authors first develop a methodology to estimate time-of-exposure matrices, and then they apply it to time-use data for the United States (1987–2003). Finally, the authors estimate age-specific transmission param-eters for varicella, commonly known as ‘‘chickenpox,’ ’ from age-specific time-of-exposure and seroprevalence data (United States, 1988–1994). The estimated time-of-exposure matrix reveals a strong element of assortativeness by age. In addition, there are peaks of exposure between people who were born one generation apart (i.e...

arXiv: Populations and Evolution, 2020

We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 °C) and crit... more We quantified the probability of developing symptoms (respiratory or fever \geq 37.5 °C) and critical disease (requiring intensive care or resulting in death) of SARS-CoV-2 positive subjects. 5,484 contacts of SARS-CoV-2 index cases detected in Lombardy, Italy were analyzed, and positive subjects were ascertained via nasal swabs and serological assays. 73.9% of all infected individuals aged less than 60 years did not develop symptoms (95% confidence interval: 71.8-75.9%). The risk of symptoms increased with age. 6.6% of infected subjects older than 60 years had critical disease, with males at significantly higher risk.

Epidemics, 2021

In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19)... more In the night of February 20, 2020, the first epidemic of the novel coronavirus disease (COVID-19) outside Asia was uncovered by the identification of its first patient in Lombardy region, Italy. In the following weeks, Lombardy experienced a sudden increase in the number of ascertained infections and strict measures were imposed to contain the epidemic spread. We analyzed official records of cases occurred in Lombardy to characterize the epidemiology of SARS-CoV-2 during the early phase of the outbreak. A line list of laboratory-confirmed cases was set up and later retrospectively consolidated, using standardized interviews to ascertained cases and their close contacts. We provide estimates of the serial interval, of the basic reproduction number, and of the temporal variation of the net reproduction number of SARS-CoV-2. Epidemiological investigations detected over 500 cases (median age: 69, IQR: 57-78) before the first COVID-19 diagnosed patient (February 20, 2020), and suggested that SARS-CoV-2 was already circulating in at least 222 out of 1506 (14.7%) municipalities with sustained transmission across all the Lombardy provinces. We estimated the mean serial interval to be 6.6 days (95% CrI, 0.7-19). Our estimates of the basic reproduction number range from 2.6 in Pavia (95% CI, 2.1-3.2) to 3.3 in Milan (95% CI, 2.9-3.8). A decreasing trend in the net reproduction number was observed following the detection of the first case. At the time of first case notification, COVID-19 was already widespread in the entire Lombardy region. This may explain the large number of critical cases experienced by this region in a very short timeframe. The slight decrease of the reproduction number observed in the early days after February 20, 2020 might be due to increased population awareness and early interventions implemented before the regional lockdown imposed on March 8, 2020.

Epidemics, 2021

Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to ... more Solid estimates describing the clinical course of SARS-CoV-2 infections are still lacking due to underascertainment of asymptomatic and mild-disease cases. In this work, we quantify age-specific probabilities of transitions between stages defining the natural history of SARS-CoV-2 infection from 1,965 SARS-CoV-2 positive individuals identified in Italy between March and April 2020 among contacts of confirmed cases. Infected contacts of cases were confirmed via RT-PCR tests as part of contact tracing activities or retrospectively via IgG serological tests and followed-up for symptoms and clinical outcomes. In addition, we provide estimates of time intervals between key events defining the clinical progression of cases as obtained from a larger sample, consisting of 95,371 infections ascertained between February and July 2020. We found that being older than 60 years of age was associated with a 39.9% (95%CI: 36.2-43.6%) likelihood of developing respiratory symptoms or fever ≥37.5 °C after SARS-CoV-2 infection; the 22.3% (95%CI: 19.3-25.6%) of the infections in this age group required hospital care and the 1% (95%CI: 0.4-2.1%) were admitted to an intensive care unit (ICU). The corresponding proportions in individuals younger than 60 years were estimated at 27.9% (95%CI: 25.4-30.4%), 8.8% (95%CI: 7.3-10.5%) and 0.4% (95%CI: 0.1-0.9%), respectively. The infection fatality ratio (IFR) ranged from 0.2% (95%CI: 0.0-0.6%) in individuals younger than 60 years to 12.3% (95%CI: 6.9-19.7%) for those aged 80 years or more; the case fatality ratio (CFR) in these two age classes was 0.6% (95%CI: 0.1-2%) and 19.2% (95% CI: 10.9-30.1%), respectively. The median length of stay in hospital was 10 (IQR 3-21) days; the length of stay in ICU was 11 (IQR 6-19) days. The obtained estimates provide insights into the epidemiology of COVID-19 and could be instrumental to refine mathematical modeling work supporting public health decisions.

Scientific Reports, 2021

We investigated contact patterns in diverse social contexts in Kenya and the daily behaviours tha... more We investigated contact patterns in diverse social contexts in Kenya and the daily behaviours that may play a pivotal role in infection transmission to the most vulnerable leveraging novel data from a 2-day survey on social contacts and time use (TU) from a sample of 1407 individuals (for a total of 2705 person days) from rural, urban formal, and informal settings. We used TU data to build six profiles of daily behaviour based on the main reported activities, i.e., Homestayers (71.1% of person days), Workers (9.3%), Schoolers (7.8%), or locations at increasing distance from home, i.e., Walkers (6.6%), Commuters (4.6%), Travelers (0.6%). In the rural setting, we observed higher daily contact numbers (11.56, SD 0.23) and percentages of intergenerational mixing with older adults (7.5% of contacts reported by those younger than 60 years vs. less than 4% in the urban settings). Overall, intergenerational mixing with older adults was higher for Walkers (7.3% of their reported contacts), C...

American Journal of Epidemiology, 2021

During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedent... more During the spring of 2020, the coronavirus disease 2019 (COVID-19) epidemic caused an unprecedented demand for intensive-care resources in the Lombardy region of Italy. Using data on 43,538 hospitalized patients admitted between February 21 and July 12, 2020, we evaluated variations in intensive care unit (ICU) admissions and mortality over the course of 3 periods: the early phase of the pandemic (February 21–March 13), the period of highest pressure on the health-care system (March 14–April 25, when numbers of COVID-19 patients exceeded prepandemic ICU bed capacity), and the declining phase (April 26–July 12). Compared with the early phase, patients aged 70 years or more were less often admitted to an ICU during the period of highest pressure on the health-care system (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.41, 0.54), with longer ICU delays (incidence rate ratio = 1.82, 95% CI: 1.52, 2.18) and lower chances of dying in the ICU (OR = 0.47, 95% CI: 0.34, 0.64). Patie...

JAMA Network Open, 2021

IMPORTANCE Solid estimates of the risk of developing symptoms and of progressing to critical dise... more IMPORTANCE Solid estimates of the risk of developing symptoms and of progressing to critical disease in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are key to interpreting coronavirus disease 2019 (COVID-19) dynamics, identifying the settings and the segments of the population where transmission is more likely to remain undetected, and defining effective control strategies. OBJECTIVE To estimate the association of age with the likelihood of developing symptoms and the association of age with the likelihood of progressing to critical illness after SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS This cohort study analyzed quarantined case contacts, identified between February 20 and April 16, 2020, in the Lombardy region of Italy. Contacts were monitored daily for symptoms and tested for SARS-CoV-2 infection, by either real-time reverse transcriptase-polymerase chain reaction using nasopharyngeal swabs or retrospectively via IgG serological assays. Close contacts of individuals with laboratory-confirmed COVID-19 were selected as those belonging to clusters (ie, groups of contacts associated with an index case) where all individuals were followed up for symptoms and tested for SARS-CoV-2 infection. Data were analyzed from February to June 2020. EXPOSURE Close contact with individuals with confirmed COVID-19 cases as identified by contact tracing operations. MAIN OUTCOMES AND MEASURES Age-specific estimates of the risk of developing respiratory symptoms or fever greater than or equal to 37.5°C and of experiencing critical disease (defined as requiring intensive care or resulting in death) in SARS-CoV-2-infected case contacts. RESULTS In total, 5484 case contacts (median [interquartile range] age, 50 [30-61] years; 3086 female contacts [56.3%]) were analyzed, 2824 of whom (51.5%) tested positive for SARS-CoV-2 (median [interquartile range] age, 53 [34-64] years; 1604 female contacts [56.8%]). The proportion of infected persons who developed symptoms ranged from 18.1% (95% CI, 13.9%-22.9%) among participants younger than 20 years to 64.6% (95% CI, 56.6%-72.0%) for those aged 80 years or older. Most infected contacts (1948 of 2824 individuals [69.0%]) did not develop respiratory symptoms or fever greater than or equal to 37.5°C. Only 26.1% (95% CI, 24.1%-28.2%) of infected individuals younger than 60 years developed respiratory symptoms or fever greater than or equal to 37.5°C; among infected participants older than 60 years, 6.6% (95% CI, 5.1%-8.3%) developed critical disease. Female patients were 52.7% (95% CI, 24.4%-70.7%) less likely than male patients to develop critical disease after SARS-CoV-2 infection. (continued) Key Points Question What is the association of age Open Access. This is an open access article distributed under the terms of the CC-BY License.

BMC medicine, Jul 25, 2018

Sub-Saharan Africa (SSA) continues to suffer high communicable disease burdens as its demographic... more Sub-Saharan Africa (SSA) continues to suffer high communicable disease burdens as its demographic transition (DT) proceeds. Although the consequent changes in population structures influence age-specific contact patterns relevant for transmission, the age distribution of immunity, and the disease burden, investigation of the potential of DT to affect infectious disease epidemiology in regions of SSA has hitherto been overlooked. With a substantial disease burden and complex epidemiology, hepatitis B virus (HBV) represents a prime example of an infection whose epidemiology may be significantly influenced by the DT. An age-structured mathematical model for HBV in the Senegal and Gambia (SG) region was set within a demographic framework with varying vital rates mirroring the entire course of the DT there over 1850-2100, to investigate the effects of the DT on HBV epidemiology, with and without the combined action of vaccination. The model was run from its reconstructed ancien régime (o...

BMC medicine, Jan 17, 2018

The present study aims to evaluate the cost-effectiveness of the newly introduced varicella and h... more The present study aims to evaluate the cost-effectiveness of the newly introduced varicella and herpes zoster (HZ) vaccination programmes in Italy. The appropriateness of the introduction of the varicella vaccine is highly debated because of concerns about the consequences on HZ epidemiology and the expected increase in the number of severe cases in case of suboptimal coverage levels. We performed a cost-utility analysis based on a stochastic individual-based model that considers realistic demographic processes and two different underlying mechanisms of exogenous boosting (temporary and progressive immunity). Routine varicella vaccination is given with a two-dose schedule (15 months, 5-6 years). The HZ vaccine is offered to the elderly (65 years), either alone or in combination with an initial catch-up campaign (66-75 years). The main outcome measures are averted cases and deaths, costs per quality-adjusted life years gained, incremental cost-effectiveness ratios, and net monetary b...

Pest Management Science, 2017

BACKGROUND: We assessed the economic impact of the invasive pest Drosophila suzukii (Matsumura) o... more BACKGROUND: We assessed the economic impact of the invasive pest Drosophila suzukii (Matsumura) on the soft fruit industry (strawberries, raspberries, blackberries, and blueberries) in Trentino, Northern Italy, using cost-benefit analysis. A conventional integrated pest management (IPM) based on insecticide, mass trapping and cultural measures is compared to an upgraded IPM strategy based on exclusion netting. Costs and benefits associated with the change between the two are estimated in order to evaluate the most profitable strategy from the societal point of view. The This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

PLOS ONE, 2017

Background Patterns of person-to-person contacts relevant for infectious diseases transmission ar... more Background Patterns of person-to-person contacts relevant for infectious diseases transmission are still poorly quantified in Sub-Saharan Africa (SSA), where socio-demographic structures and behavioral attitudes are expected to be different from those of more developed countries. Methods and Findings We conducted a diary-based survey on daily contacts and time-use of individuals of different ages in one rural and one peri-urban site of Manicaland, Zimbabwe. A total of 2,490 diaries were collected and used to derive age-structured contact matrices, to analyze time spent by individuals in different settings, and to identify the key determinants of individuals' mixing patterns. Overall 10.8 contacts per person/day were reported, with a significant difference between the peri-urban and the rural site (11.6 versus 10.2). A strong age-assortativeness characterized contacts of school-aged children, whereas the high proportion of extended families and the young population age-structure led to a significant intergenerational mixing at older ages. Individuals spent on average 67% of daytime at home, 2% at work, and 9% at school. Active participation in school and work resulted the key drivers of the number of contacts and, similarly, household size, class size, and time spent at work influenced the number of home, school, and work contacts, respectively. We found that the heterogeneous nature of home contacts is critical for an epidemic transmission chain. In particular, our results suggest that, during the initial phase of an epidemic, about 50% of infections are expected to occur among individuals younger than 12 years and less than 20% among individuals older than 35 years.

BMC Medicine, 2015

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disea... more Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and related hospitalization of young children in least developed countries. Individuals are repeatedly infected, but it is the first exposure, often in early infancy, that results in the vast majority of severe RSV disease. Unfortunately, due to immunological immaturity, infants are a problematic RSV vaccine target. Several trials are ongoing to identify a suitable candidate vaccine and target group, but no immunization program is yet in place. Methods: In this work, an individual-based model that explicitly accounts for the socio-demographic population structure is developed to investigate RSV transmission patterns in a rural setting of Kenya and to evaluate the potential effectiveness of alternative population targets in reducing RSV infant infection. Results: We find that household transmission is responsible for 39% of infant infections and that school-age children are the main source of infection within the household, causing around 55% of cases. Moreover, assuming a vaccine-induced protection equivalent to that of natural infection, our results show that annual vaccination of students is the only alternative strategy to routine immunization of infants able to trigger a relevant and persistent reduction of infant infection (on average, of 35.6% versus 41.5% in 10 years of vaccination). Interestingly, if vaccination of pregnant women boosts maternal antibody protection in infants by an additional 4 months, RSV infant infection will be reduced by 31.5%. Conclusions: These preliminary evaluations support the efforts to develop vaccines and related strategies that go beyond targeting vaccines to those at highest risk of severe disease.

PloS one, 2011

The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccinatio... more The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen in the US. A previous model of pneumococcal vaccination was re-parameterised using data on vaccine coverage and IPD from England and Wales between 2006 and 2009. Disease incidence was adjusted for the increasing trend in reported IPD cases prior to vaccination. Using this data we estimated that individuals carrying PCV7 serotypes have much higher protection (96%;95% CI 72%-100%) against acquisition of NVT carriage than the 15% previously estimated from US data, which leads to greater replacement. However, even with this level of replacement, the annual number of IPD cases may be 560 (95% CI, -100 to ...

PLoS ONE, 2013

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in man... more The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries because of, among other factors, the possibility of a large increase in Herpes Zoster (HZ) incidence in the first decades after the initiation of vaccination, due to the expected decline of the boosting of Cell Mediated Immunity caused by the reduced varicella circulation. A multi-country model of VZV transmission and reactivation, is used to evaluate the possible impact of varicella vaccination on HZ epidemiology in Italy, Finland and the UK. Despite the large uncertainty surrounding HZ and vaccine-related parameters, surprisingly robust medium-term predictions are provided, indicating that an increase in HZ incidence is likely to occur in countries where the incidence rate is lower in absence of immunization, possibly due to a higher force of boosting (e.g. Finland), whereas increases in HZ incidence might be minor where the force of boosting is milder (e.g. the UK). Moreover, a convergence of HZ post vaccination incidence levels in the examined countries is predicted despite different initial degrees of success of immunization policies. Unlike previous model-based evaluations, our investigation shows that after varicella immunization an increase of HZ incidence is not a certain fact, rather depends on the presence or absence of factors promoting a strong boosting intensity and which might or not be heavily affected by changes in varicella circulation due to mass immunization. These findings might explain the opposed empirical evidences observed about the increases of HZ in sites where mass varicella vaccination is ongoing.

Vaccine, 2011

This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) f... more This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes.

Vaccine, 2002

This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NH... more This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The use of the acellular pertussis vaccine in children and adults. Type of intervention Primary prevention (vaccination). Economic study type Cost-effectiveness analysis. Study population The study referred to the general population. The analysis focused on a hypothetical cohort of children aged 4 or 15 years, because these represented the ages at which diphtheria and tetanus boosters doses were routinely given in the UK.

Proceedings of the Royal Society B: Biological Sciences, 2011

Despite the fact that the 2009 H1N1 pandemic influenza strain was less severe than had been feare... more Despite the fact that the 2009 H1N1 pandemic influenza strain was less severe than had been feared, both seasonal epidemics of influenza-like-illness and future influenza pandemics have the potential to place a serious burden on health services. The closure of schools has been postulated as a means of reducing transmission between children and hence reducing the number of cases at the peak of an epidemic; this is supported by the marked reduction in cases during school holidays observed across the world during the 2009 pandemic. However, a national policy of long-duration school closures could have severe economic costs. Reactive short-duration closure of schools in regions where health services are close to capacity offers a potential compromise, but it is unclear over what spatial scale and time frame closures would need to be made to be effective. Here, using detailed geographical information for England, we assess how localized school closures could alleviate the burden on hospi...

Supplementary methods and results. (DOCX 6670 kb)

arXiv: Populations and Evolution, 2020

Epidemics, 2021

Scientific Reports, 2021

American Journal of Epidemiology, 2021

JAMA Network Open, 2021

BMC medicine, Jul 25, 2018

BMC medicine, Jan 17, 2018

Pest Management Science, 2017

PLOS ONE, 2017

BMC Medicine, 2015

PloS one, 2011

PLoS ONE, 2013

Vaccine, 2011

Vaccine, 2002

Proceedings of the Royal Society B: Biological Sciences, 2011