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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.

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 seventy-five percent, 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 will improve the efficiency and standardisation of data collection during emergencies.

Introduction In 2016–18, the Democratic Republic of Sao Tome and Principe 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

Summary 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.

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.

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.

On April 3 and 7, 2000, four cases of Neisseria meningitidis serogroup W135 infection were diagnosed in France in Raj pilgrims and their close relatives. Two cases were fatal. Due to the rarity of this strain in France, a strain belonging to a clonal complex implicated in several epidemics in Europe and North America, and it high mortality observed, The French General Direction of Heal issued recommendations on April 8th for rifampicin chemotherapy for all pilgrims and relatives living in their home. The national disease watch (Institut de Veille Sanitaire, InVS) conducted an investigation to describe the epidemic and follow the diffusion of the strain in the population and assess the impact of preventive measures taken as well as need for other specific measures.A case was considered to be confirmed when the strain isolated from usually sterile media after March 22 was found to be identical to the epidemic strain (W135, 2a: P1-2.5--clonal complex ET37). A case was considered probable when a pilgrim or in a person in contact with a pilgrim had clinical meningitis (purulent cerebrospinal fluid or purpura fulminans) or when the identified strain was in the W135 serogroup but could not be further identified. A standardized questionnaire developed in collaboration with the European countries concerned by the epidemic was filled out.By November 20, 2000, 25 confirmed and 2 probable cases were identified; 85% of the cases occurred during the first 7 weeks of the epidemic. Mortality was 18%. Patients aged over 50 years accounted for 66% of the cases (6/9) occurring before April 9, 2000 and 17% of the cases (3/18) observed after this data. Four patients had single-joint arthritis. No cluster cases could be identified. Four cases occurred among 19,100 pilgrims (attack rate 21/100,000), 9 among persons living with pilgrims, 7 among subjects in direct contact with pilgrims but not living with them, and 7 among persons who had no identifiable contact with pilgrims. These last 7 cases occurred after the 3rd week of the epidemic. No cases occurred among persons who had taken rifampicin chemoprophylaxis. Eighteen cases occurred after diffusion of the prophylaxis recommendations including 5 in a population directly concerned by the recommendations.These data suggest that the epidemic strain is not different from other strains in terms of virulence and transmissibility. Eight months after the Raj, the number of cases related to the epidemic remained limited in France. The characteristics of the most recent cases do however suggest an epidemic clone persists in the general population. The Direction of Health recommends vaccination using the quadrivalent A,C,W135,Y vaccine for the 2001 Raj.

Efficient surveillance of communicable diseases involves dose collaboration between physicians, epidemiologist and bacteriologists. The characterization of meningococcal infections is a medical emergency due to their lethality and their epidemic behavior. The recent expansion of Neisseria meningitidis of serogroup W135 among pilgrims and their contacts underlines the need of a multidisciplinary procedure of alert.Meningococcal strains are usually received by the National Reference Center for Meningococci (CNRM). They are identified and then typed to determine their antigenic formula (serogroup:serotype:serosubtype). For cluster analysis, the CNRM as well as the WHO collaborating center, perform molecular typing of isolated strains. Should an epidemic is suspected, the institut de Veille Sanitaire and the Direction Générale de la Santé are immediately informed.Between the 22th of March and the 20th of November 2000, 27 cases of systemic meningococcal infections due to N. meningitidis of the antigenic formula W135:2a:P1-2.5 were identified. Molecular typing of these strains showed that they were clonal and belonged to the complex ET-37. The dissemination of this clone among pilgrims who were vaccinated against serogroups A and C may suggest the selection of a new variant by an escape alteration in the capsule. However, such strains were detected in France as early as 1994.The global spread of N. meningitidis of serogroup W135 belonging to the ET-37 clonal complex should be kept under a close surveillance since epidemics may occur particularly in Africa. New vaccination procedures (quadrivalent vaccines and multivalent conjugate meningococcal vaccines) are therefore needed.