Investigating outbreaks of initially unknown aetiology in complex settings: findings and recommendations from 10 case studies.

BACKGROUND: Outbreaks of unknown aetiology in complex settings pose challenges and there is little information about investigation methods. We reviewed investigations into such outbreaks to identify methods favouring or impeding identification of the cause. METHODS: We used two approaches: reviewing scientific literature and soliciting key informants. Case studies were developed through interviews with people involved and triangulated with documents available from the time of the investigation. RESULTS: Ten outbreaks in African or Asian countries within the period 2007-2017 were selected. The cause was identified in seven, of which two had an unclear mode of transmission, and in three, neither origin nor transmission mode was identified. Four events were caused by infectious agents and three by chemical poisoning. Despite differences in the outbreaks, similar obstacles were noted: incomplete or delayed description of patients, comorbidities confounding clinical pictures and case definitions wrongly attributed. Repeated rounds of data collection and laboratory investigations were common and there was limited capacity to ship samples. DISCUSSION: It was not possible to define activities that led to prompt identification of the cause in the case studies selected. Based on the observations, we conclude that basing case definitions on precise medical observations, implementing initial comprehensive data collection, including environmental, social and behavioural information; and involving local informants could save precious time and hasten implementation of control measures.

The World Health Organization COVID-19 surveillance database.

In January 2020, SARS-CoV-2 virus was identified as a cause of an outbreak in China. The disease quickly spread worldwide, and the World Health Organization (WHO) declared the pandemic in March 2020.From the first notifications of spread of the disease, the WHO's Emergency Programme implemented a global COVID-19 surveillance system in coordination with all WHO regional offices. The system aimed to monitor the spread of the epidemic over countries and across population groups, severity of the disease and risk factors, and the impact of control measures. COVID-19 surveillance data reported to WHO is a combination of case-based data and weekly aggregated data, focusing on a minimum global dataset for cases and deaths including disaggregation by age, sex, occupation as a Health Care Worker, as well as number of cases tested, and number of cases newly admitted for hospitalization. These disaggregations aim to monitor inequities in COVID-19 distribution and risk factors among population groups.SARS-CoV-2 epidemic waves continue to sweep the world; as of March 2022, over 445 million cases and 6 million deaths have been reported worldwide. Of these, over 327 million cases (74%) have been reported in the WHO surveillance database, of which 255 million cases (57%) are disaggregated by age and sex. A public dashboard has been made available to visualize trends, age distributions, sex ratios, along with testing and hospitalization rates. It includes a feature to download the underlying dataset.This paper will describe the data flows, database, and frontend public dashboard, as well as the challenges experienced in data acquisition, curation and compilation and the lessons learnt in overcoming these. Two years after the pandemic was declared, COVID-19 continues to spread and is still considered a Public Health Emergency of International Concern (PHEIC). While WHO regional and country offices have demonstrated tremendous adaptability and commitment to process COVID-19 surveillance data, lessons learnt from this major event will serve to enhance capacity and preparedness at every level, as well as institutional empowerment that may lead to greater sharing of public health evidence during a PHEIC, with a focus on equity.

Data collection for outbreak investigations: process for defining a minimal data set using a Delphi approach.

BACKGROUND: Timely but accurate data collection is needed during health emergencies to inform public health responses. Often, an abundance of data is collected but not used. When outbreaks and other health events occur in remote and complex settings, operatives on the ground are often required to cover multiple tasks whilst working with limited resources. Tools that facilitate the collection of essential data during the early investigations of a potential public health event can support effective public health decision-making. We proposed to define the minimum set of quantitative information to collect whilst using electronic device or not. Here we present the process used to select the minimum information required to describe an outbreak of any cause during its initial stages and occurring in remote settings. METHODS: A working group of epidemiologists took part in two rounds of a Delphi process to categorise the variables to be included in an initial outbreak investigation form. This took place between January-June 2019 using an online survey. RESULTS: At a threshold of 75 %, consensus was reached for nineteen (23.2%) variables which were all classified as 'essential'. This increased to twenty-six (31.7%) variables when the threshold was reduced to 60% with all but one variable classified as 'essential'. Twenty-five of these variables were included in the 'Time zero initial case investigation' '(T0)' form which was shared with the members of the Rapid Response Team Knowledge Network for field testing and feedback. The form has been readily available online by WHO since September 2019. CONCLUSION: This is the first known Delphi process used to determine the minimum variables needed for an outbreak investigation. The subsequent development of the T0 form should help to improve the efficiency and standardisation of data collection during emergencies and ultimately the quality of the data collected during field investigation.

A large epidemic of a necrotic skin infection in the Democratic Republic of São Tomé and Principe: an epidemiological study.

INTRODUCTION: In 2016-18, the Democratic Republic of São Tomé and Príncipe suffered a necrotic skin infection epidemic. METHODS: A surveillance system was established after increased hospitalisations for this infection. Microbiology results were available for samples analysed in December 2016 and March 2017 using whole genome sequencing and metagenomics. Negative binomial regression was used to study the association of weather conditions with monthly case counts in a time-series analysis. RESULTS: From October 2016 to October 2018, the epidemic cumulative attack rate was 1.5%. The first peak lasted 5 months, accounting for one-third of total cases. We could not conclusively identify the aetiological agent(s) due to the country's lack of microbiology capacity. Increased relative humidity was associated with increased monthly cases (incidence rate ratio (IRR) 1.05, 95% CI 1.02-1.09), and higher precipitation in the previous month with a higher number of cases in the following month (months with 0-49 mm rainfall compared with months with 50-149 mm and ≥150 mm: IRR 1.44, 95 % CI 1.13-1.78 and 1.50, 95% CI 1.12-1.99, respectively). DISCUSSION: This epidemic was favoured by increased relative humidity and precipitation, potentially contributing to community-based transmission of ubiquitous bacterial strains superinfecting skin wounds. FUNDING: World Health Organization Regional Office for Africa, Ministry of Health.

Outbreak of Neisseria meningitidis serogroup C outside the meningitis belt-Liberia, 2017: an epidemiological and laboratory investigation.

BACKGROUND: On April 25, 2017, a cluster of unexplained illnesses and deaths associated with a funeral was reported in Sinoe County, Liberia. Molecular testing identified Neisseria meningitidis serogroup C (NmC) in specimens from patients. We describe the epidemiological investigation of this cluster and metagenomic characterisation of the outbreak strain. METHODS: We collected epidemiological data from the field investigation and medical records review. Confirmed, probable, and suspected cases were defined on the basis of molecular testing and signs or symptoms of meningococcal disease. Metagenomic sequences from patient specimens were compared with 141 meningococcal isolate genomes to determine strain lineage. FINDINGS: 28 meningococcal disease cases were identified, with dates of symptom onset from April 21 to April 30, 2017: 13 confirmed, three probable, and 12 suspected. 13 patients died. Six (21%) patients reported fever and 23 (82%) reported gastrointestinal symptoms. The attack rate for confirmed and probable cases among funeral attendees was 10%. Metagenomic sequences from six patient specimens were similar to a sequence type (ST) 10217 (clonal complex [CC] 10217) isolate genome from Niger, 2015. Multilocus sequencing identified five of seven alleles from one specimen that matched ST-9367, which is represented in the PubMLST database by one carriage isolate from Burkina Faso, in 2011, and belongs to CC10217. INTERPRETATION: This outbreak featured high attack and case fatality rates. Clinical presentation was broadly consistent with previous meningococcal disease outbreaks, but predominance of gastrointestinal symptoms was unusual compared with previous African meningitis epidemics. The outbreak strain was genetically similar to NmC CC10217, which caused meningococcal disease outbreaks in Niger and Nigeria. CC10217 had previously been identified only in the African meningitis belt. FUNDING: US Global Health Security.

Surveillance of invasive pneumococcal disease in 30 EU countries: Towards a European system?

In this era of new pneumococcal conjugate vaccines (PCV), we described and compared surveillance of invasive pneumococcal disease (IPD) and PCV policies in 30 European countries to provide guidance for Europe-wide surveillance. We confirmed the heterogeneity of surveillance systems and case definitions across countries but identified elements common to all countries, such as the availability of serotyping and the surveillance of pneumococcal meningitis. PCV impact was monitored in 11/15 countries using it. We propose steps for the monitoring of incidence rates and serotype distribution at EU level, to assess the need to introduce PCV and monitor its impact once introduced.

[Epidemiology of bacterial meningitis in France in 2002]. / Epidémiologie des méningites bactériennes en France en 2002.

In France, two sources of data, the mandatory notification and the hospital laboratory network EPIBAC, allow the health authorities to monitor the incidence of bacterial meningitis. In 2002 around 1,500 cases were estimated in France. The more common microorganisms were: Streptococcus pneumoniae 49% (incidence 1.19/100,000), Neisseria meningitidis 33% (incidence 0.83) and Streptococcus agalactiae (Streptococcus B) 11% (incidence 0.27). Listeria monocytogenes accounted for 4% of the cases (incidence 0.11) and Haemophilus influenzae accounted for 3% (incidence 0.08). Trends in incidence showed an increase of meningococci meningitis since 1996, a steady decrease of H. influenzae and Listeria meningitis since 1992, and a quasi stable number of pneumococci meningitis, streptococci B meningitis and tuberculosis meningitis in the last 10 years. The impact of preventive measures on the incidence of Listeria meningitis and H. influenzae b meningitis has been clearly demonstrated through the dramatic decrease of meningitis due to these microorganisms.

[Epidemiology of bacterial meningitis in France in 1999]. / Epidémiologie des méningites bactériennes en France en 1999.

In France, two sources of data, the mandatory notification and the laboratory network EPIBAC, allow the health authorities to follow the incidence of bacterial meningitis (BM) and to assess the relative frequency of the micro-organisms responsible for such infection. In 1999, more than 1,000 cases of BM were notified in France. The more common micro-organisms were: Streptococcus pneumoniae 46%, Neisseria meningitidis 32% and Streptococcus agalactiae(or Streptococcus B) 11%. Listeria monocytogenes and Haemophilus influenzae accounted for 6% and 5% of the cases respectively. In 1999, the incidence per 100,000 inhabitants of meningitis due to pneumococci (0.81), to streptococci B (0.19) and tuberculosis meningitis (0.17) were stable since 1995. The incidence rate of meningitis due to Listeria (0.10) and to H. influenzae (0.08) shows a regular decrease since 1992. The impact of preventive measures of meningitis due to Listeria and H. influenzae B has been clearly demonstrated through the dramatic decrease of meningitis due to these micro-organisms.

Outbreak of serogroup W135 meningococcal disease after the Hajj pilgrimage, Europe, 2000.

The 2000 Hajj (March 15-18) was followed by an outbreak of Neisseria meningitidis W135 2a: P1.2,5 in Europe. From March 18 to July 31, 2000, some 90 cases of meningococcal infection were reported from nine countries, mostly the United Kingdom (UK) and France; 14 cases were fatal. Although most early cases were in pilgrims, the outbreak spread to their contacts and then to those with no known pilgrim contact. In France and the UK, the outbreak case-fatality rate was compared with the rate reported from national surveillance. The risk of dying during this outbreak was higher in France and the UK, although the difference was not statistically significant. Prophylaxis for all pilgrims and their household contacts was offered in France; in the UK and other European countries, prophylaxis was recommended only for close contacts. No difference in transmission rates following intervention was detected between France and the UK.