Innovative platforms for data aggregation, linkage and analysis in the context of pandemic and epidemic intelligence.

During the COVID-19 pandemic, open-access platforms that aggregate, link and analyse data were transformative for global public health surveillance. This perspective explores the work of three of these platforms: Our World In Data (OWID), Johns Hopkins University (JHU) COVID-19 Dashboard (later complemented by the Coronavirus Resource Center), and Global.Health, which were presented in the second World Health Organization (WHO) Pandemic and Epidemic Intelligence Innovation Forum. These platforms, operating mostly within academic institutions, added value to public health data that are collected by government agencies by providing additional real-time public health intelligence about the spread of the virus and the evolution of the public health emergency. Information from these platforms was used by health professionals, political decision-makers and members of the public alike. Further engagement between government and non-governmental surveillance efforts can accelerate the improvements needed in public health surveillance overall. Increasing the diversity of public health surveillance initiatives beyond the government sector comes with several benefits: technology innovation in data science, engagement of additional highly skilled professionals, greater transparency and accountability for government agencies, and new opportunities to engage with members of society.

Description of the first global outbreak of mpox: an analysis of global surveillance data.

BACKGROUND: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date. METHODS: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity. FINDINGS: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001). INTERPRETATION: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission. FUNDING: WHO Contingency Fund for Emergencies. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Rigorous surveillance is necessary for high confidence in end-of-outbreak declarations for Ebola and other infectious diseases.

The World Health Organization considers an Ebola outbreak to have ended once 42 days have passed since the last possible exposure to a confirmed case. Benefits of a quick end-of-outbreak declaration, such as reductions in trade/travel restrictions, must be balanced against the chance of flare-ups from undetected residual cases. We show how epidemiological modelling can be used to estimate the surveillance level required for decision-makers to be confident that an outbreak is over. Results from a simple model characterizing an Ebola outbreak suggest that a surveillance sensitivity (i.e. case reporting percentage) of 79% is necessary for 95% confidence that an outbreak is over after 42 days without symptomatic cases. With weaker surveillance, unrecognized transmission may still occur: if the surveillance sensitivity is only 40%, then 62 days must be waited for 95% certainty. By quantifying the certainty in end-of-outbreak declarations, public health decision-makers can plan and communicate more effectively. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This issue is linked with the earlier theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.

Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013-2014(1).

During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment.

CDC's Response to the 2014-2016 Ebola Epidemic - Guinea, Liberia, and Sierra Leone.

CDC's response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa was the largest in the agency's history and occurred in a geographic area where CDC had little operational presence. Approximately 1,450 CDC responders were deployed to Guinea, Liberia, and Sierra Leone since the start of the response in July 2014 to the end of the response at the end of March 2016, including 455 persons with repeat deployments. The responses undertaken in each country shared some similarities but also required unique strategies specific to individual country needs. The size and duration of the response challenged CDC in several ways, particularly with regard to staffing. The lessons learned from this epidemic will strengthen CDC's ability to respond to future public health emergencies. These lessons include the importance of ongoing partnerships with ministries of health in resource-limited countries and regions, a cadre of trained CDC staff who are ready to be deployed, and development of ongoing working relationships with U.S. government agencies and other multilateral and nongovernment organizations that deploy for international public health emergencies. CDC's establishment of a Global Rapid Response Team in June 2015 is anticipated to meet some of these challenges. The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Notes from the field: rapidly growing nontuberculous Mycobacterium wound infections among medical tourists undergoing cosmetic surgeries in the Dominican Republic--multiple states, March 2013-February 2014.

In August 2013, the Maryland Department of Health and Mental Hygiene (MDHMH) was notified of two persons with rapidly growing nontuberculous mycobacterial (RG-NTM) surgical-site infections. Both patients had undergone surgical procedures as medical tourists at the same private surgical clinic (clinic A) in the Dominican Republic the previous month. Within 7 days of returning to the United States, both sought care for symptoms that included surgical wound abscesses, clear fluid drainage, pain, and fever. Initial antibiotic therapy was ineffective. Material collected from both patients' wounds grew Mycobacterium abscessus exhibiting a high degree of antibiotic resistance characteristic of this organism.

Hospitalization due to human parainfluenza virus-associated lower respiratory tract illness in rural Thailand.

BACKGROUND: Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory illness in young children but little is known about their epidemiology in the tropics. METHODS: From 2003-2007, we conducted surveillance for hospitalized respiratory illness in rural Thailand. We performed reverse-transcriptase polymerase chain reaction on nasopharyngeal specimens and enzyme immunoassay on paired sera. RESULTS: Of 10,097 patients enrolled, 573 (5%) of all ages and 370 (9%) of children <5 years of age had evidence of HPIV infection (HPIV1=189, HPIV2=54, HPIV3=305, untyped=27). Average adjusted annual incidence of HPIV-associated hospitalized respiratory illness was greatest in children aged <1 year (485 per 100,000 person years). CONCLUSIONS: In Thailand, HPIV caused substantial illnesses requiring hospitalization in young children.

Guillain-Barre syndrome during the 2009-2010 H1N1 influenza vaccination campaign: population-based surveillance among 45 million Americans.

Because of widespread distribution of the influenza A (H1N1) 2009 monovalent vaccine (pH1N1 vaccine) and the prior association between Guillain-Barré syndrome (GBS) and the 1976 H1N1 influenza vaccine, enhanced surveillance was implemented to estimate the magnitude of any increased GBS risk following administration of pH1N1 vaccine. The authors conducted active, population-based surveillance for incident cases of GBS among 45 million persons residing at 10 Emerging Infections Program sites during October 2009-May 2010; GBS was defined according to published criteria. The authors determined medical and vaccine history for GBS cases through medical record review and patient interviews. The authors used vaccine coverage data to estimate person-time exposed and unexposed to pH1N1 vaccine and calculated age- and sex-adjusted rate ratios comparing GBS incidence in these groups, as well as age- and sex-adjusted numbers of excess GBS cases. The authors received 411 reports of confirmed or probable GBS. The rate of GBS immediately following pH1N1 vaccination was 57% higher than in person-time unexposed to vaccine (adjusted rate ratio = 1.57, 95% confidence interval: 1.02, 2.21), corresponding to 0.74 excess GBS cases per million pH1N1 vaccine doses (95% confidence interval: 0.04, 1.56). This excess risk was much smaller than that observed during the 1976 vaccine campaign and was comparable to some previous seasonal influenza vaccine risk assessments.

Putting surveillance data into context: the role of health care utilization surveys in understanding population burden of pneumonia in developing countries.

BACKGROUND: Surveillance is essential to estimating the global burden of pneumonia, yet differences in surveillance methodology and health care-seeking behaviors limit inter-country comparisons. METHODS: Results were compared from community surveys measuring health care-seeking for pneumonia defined as: (1) cough and difficulty breathing for ⩾2days; or, (2) provider-diagnosed pneumonia. Surveys were conducted in six sites in Guatemala, Kenya and Thailand; these sites also conduct, active, hospital- and population-based disease surveillance for pneumonia. RESULTS: Frequency of self-reported pneumonia during the preceding year ranged from 1.1% (Thailand) to 6.3% (Guatemala) and was highest in children aged <5years and in urban sites. The proportion of persons with pneumonia who sought hospital-based medical services ranged from 12% (Guatemala, Kenya) to 80% (Thailand) and was highest in children <5years of age. Hospitals and private provider offices were the most common places where persons with pneumonia sought health care. The most commonly cited reasons for not seeking health care were: (a) mild illness; (b) already recovering; and (3) cost of treatment. CONCLUSIONS: Health care-seeking patterns varied widely across countries. Using results from standardized health care utilization surveys to adjust facility-based surveillance estimates of pneumonia allows for more accurate and comparable estimates.

Filovirus outbreak detection and surveillance: lessons from Bundibugyo.

The first outbreak of Ebola hemorrhagic fever (EHF) due to Bundibugyo ebolavirus occurred in Uganda from August to December 2007. During outbreak response and assessment, we identified 131 EHF cases (44 suspect, 31 probable, and 56 confirmed). Consistent with previous large filovirus outbreaks, a long temporal lag (approximately 3 months) occurred between initial EHF cases and the subsequent identification of Ebola virus and outbreak response, which allowed for prolonged person-to-person transmission of the virus. Although effective control measures for filovirus outbreaks, such as patient isolation and contact tracing, are well established, our observations from the Bundibugyo EHF outbreak demonstrate the need for improved filovirus surveillance, reporting, and diagnostics, in endemic locations in Africa.

Economic feasibility of a new method to estimate mortality in crisis-affected and resource-poor settings.

INTRODUCTION: Mortality data provide essential evidence on the health status of populations in crisis-affected and resource-poor settings and to guide and assess relief operations. Retrospective surveys are commonly used to collect mortality data in such populations, but require substantial resources and have important methodological limitations. We evaluated the feasibility of an alternative method for rapidly quantifying mortality (the informant method). The study objective was to assess the economic feasibility of the informant method. METHODS: The informant method captures deaths through an exhaustive search for all deaths occurring in a population over a defined and recent recall period, using key community informants and next-of-kin of decedents. Between July and October 2008, we implemented and evaluated the informant method in: Kabul, Afghanistan; Mae La camp for Karen refugees, Thai-Burma border; Chiradzulu District, Malawi; and Lugufu and Mtabila refugee camps, Tanzania. We documented the time and cost inputs for the informant method in each site, and compared these with projections for hypothetical retrospective mortality surveys implemented in the same site with a 6 month recall period and with a 30 day recall period. FINDINGS: The informant method was estimated to require an average of 29% less time inputs and 33% less monetary inputs across all four study sites when compared with retrospective surveys with a 6 month recall period, and 88% less time inputs and 86% less monetary inputs when compared with retrospective surveys with a 1 month recall period. Verbal autopsy questionnaires were feasible and efficient, constituting only 4% of total person-time for the informant method's implementation in Chiradzulu District. CONCLUSIONS: The informant method requires fewer resources and incurs less respondent burden. The method's generally impressive feasibility and the near real-time mortality data it provides warrant further work to develop the method given the importance of mortality measurement in such settings.

Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis.

Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966-2009), Embase (1988-2009), Cinahl (1981-2009) and CABI (1973-2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[-12.0771 + 0.01813(age in years)] × 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.

Virus detection and duration of illness among patients with 2009 pandemic influenza A (H1N1) virus infection in Texas.

Knowledge from early outbreaks is limited regarding the virus detection and illness duration of the 2009 pandemic influenza A (H1N1) infections. During the period from April to May 2009 in Texas, we collected serial nasopharyngeal (NP) and stool specimens from 35 participants, testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) and culture. The participants were aged 2 months to 71 years; 25 (71%) were under 18. The median duration of measured fever was 3.0 days and of virus detection in NP specimens was 4.2 days; however, few specimens were collected between days 5-9. The duration of virus detection (4.2 days) was similar to the duration of fever (3.5 days) (RR, 1.14; 95% CI, .66-1.95; P = .8), but was shorter than the duration of cough (11.0 days) (RR, .41; 95% CI, .24-.68; P < .001). We detected viral RNA in two participants' stools. All cultures were negative. This investigation suggests that the duration of virus detection was likely similar to the seasonal influenza virus.

Diagnosis of 2009 pandemic influenza A (pH1N1) and seasonal influenza using rapid influenza antigen tests, San Antonio, Texas, April-June 2009.

Clinicians frequently use influenza rapid antigen tests for diagnostic testing. We tested nasal wash samples from 1 April to 7 June 2009 from 1538 patients using the QuickVue Influenza A+B (Quidel) rapid influenza antigen test and compared the results with real-time reverse transcription polymerase chain reaction (rRT-PCR) assay (gold standard). The prevalence of 2009 pandemic influenza A (pH1N1) was 1.98%, seasonal influenza type A .87%, and seasonal influenza type B 2.07%. The sensitivity and specificity of the rapid test for pH1N1 was 20% (95% CI, 8-39) and 99% (95% CI, 98-99), for seasonal influenza type A 15% (95% CI, 2-45) and 99% (95% CI, 98-99), and for influenza type B was 31% (95% CI, 9-61) and 99% (95% CI, 98-99.7). Rapid influenza antigen tests were of limited use at a time when the prevalence of pH1N1 and seasonal influenza in the United States was low. Clinicians should instead rely on clinical impression and laboratory diagnosis by rRT-PCR.

Household transmission of 2009 pandemic influenza A (H1N1) and nonpharmaceutical interventions among households of high school students in San Antonio, Texas.

San Antonio, Texas, was one of the first metropolitan areas where 2009 pandemic influenza A (H1N1) virus (pH1N1) was detected. Identification of laboratory-confirmed pH1N1 in 2 students led to a preemptive 8-day closure of their high school. We assessed transmission of pH1N1 and changes in adoption of nonpharmaceutical interventions (NPIs) within households of students attending the affected school. Household secondary attack rates were 3.7% overall and 9.1% among those 0-4 years of age. Widespread adoption of NPIs was reported among household members. Respondents who viewed pH1N1 as very serious were more likely to adopt certain NPIs than were respondents who viewed pH1N1 as not very serious. NPIs may complement influenza vaccine prevention programs or be the only line of defense when pandemic vaccine is unavailable. The 2009 pandemic provided a unique opportunity to study NPIs, and these real-world experiences provide much-needed data to inform pandemic response policy.

Serial intervals and the temporal distribution of secondary infections within households of 2009 pandemic influenza A (H1N1): implications for influenza control recommendations.

A critical issue during the 2009 influenza A (H1N1) pandemic was determining the appropriate duration of time individuals with influenza-like illness (ILI) should remain isolated to reduce onward transmission while limiting societal disruption. Ideally this is based on knowledge of the relative infectiousness of ill individuals at each point during the course of the infection. Data on 261 clinically apparent pH1N1 infector-infectee pairs in households, from 7 epidemiological studies conducted in the United States early in 2009, were analyzed to estimate the distribution of times from symptom onset in an infector to symptom onset in the household contacts they infect (mean, 2.9 days, not correcting for tertiary transmission). Only 5% of transmission events were estimated to take place >3 days after the onset of clinical symptoms among those ill with pH1N1 virus. These results will inform future recommendations on duration of isolation of individuals with ILI.

A new method to estimate mortality in crisis-affected and resource-poor settings: validation study.

BACKGROUND: Data on mortality rates are crucial to guide health interventions in crisis-affected and resource-poor settings. The methods currently available to collect mortality data in such settings feature important methodological limitations. We developed and validated a new method to provide near real-time mortality estimates in such settings. METHODS: We selected four study sites: Kabul, Afghanistan; Mae La refugee camp, Thailand; Chiradzulu District, Malawi; and Lugufu and Mtabila refugee camps, Tanzania. We recorded information about all deaths in a 60-day period by asking key community informants and decedents' next of kin to refer interviewers to bereaved households. We used the total number of deaths and population estimates to calculate mortality rates for 60- and 30-day periods. For validation we compared these rates with a best estimate of mortality using capture-recapture analysis with two further independent lists of deaths. RESULTS: The population covered by the new method was 76 ,476 persons in Kabul, 43,794 in Mae La camp, 54,418 in Chiradzulu District and 80,136 in the Tanzania camps. The informant method showed moderate sensitivity (55.0% in Kabul, 64.0% in Mae La, 72.5% in Chiradzulu and 67.7% in Tanzania), but performed better than the active surveillance system in the Tanzania refugee camps. CONCLUSIONS: The informant method currently features moderate sensitivity for accurately assessing mortality, but warrants further development, particularly considering its advantages over current options (ease of implementation and analysis and near-real estimates of mortality rates). Strategies should be tested to improve the performance of the informant method.