Identification of co-circulating pathogens that are clinically indistinguishable from Lassa fever during the 2018 Lassa outbreak in Nigeria

Abstract

Background: The burden of undiagnosed febrile illness in low and middle-income countries is high and infectious diseases remain the leading cause of morbidity and mortality. The aetiology of systemic febrile illness and sepsis are particularly badly described partly because many pathogens cause a similar initial clinical presentation. In early 2018, Nigeria experienced its largest recorded outbreak of Lassa fever (LF). During this period of heightened transmission, there were 1,968 persons who met the clinical case definition for LF. However, only 431 could be laboratory confirmed, while for 1,537 no causative pathogen could be identified. The unprecedented scale of this outbreak prompted the Nigeria Centre for Disease Control (NCDC) and the WHO to reconsider their diagnostic strategy and re-prioritise LF diagnostics. A joint research collaboration between the NCDC and the United Kingdom Public Health Rapid Support Team (UK-PHRST) has worked to address this question. Methods and materials: Archived clinical diagnostic samples collected under the auspices of the Nigerian National Lassa Virus Testing Algorithm taken from patients who met NCDCs case definition for LF during the 2018 LF outbreak in Nigeria were sought and a non-probability sampling technique on consecutive cases who meet the selection criteria (lassa-negative by PCR and malaria-negative by RDT) was employed. RNA extracts were screened TaqMan array card system for 50 pathogens known to occur in West Africa and a subset of TAC+/- samples underwent unbiased metagenomic sequencing to determine which pathogen(s) are co-circulating and potentially mimicking the presentation of LF. Associations between pathogens and selected epidemiological and clinical variables were tested by Chi-square with significance level set at p < 0.05. Results: Results from this study indicate that there was no one specific pathogen responsible for patients developing clinical presentations indistinguishable from LF. Rather, a variety of pathogens (both viral and bacterial) were found to be co-circulating at the time of heightened LF transmission resulting in both single and co-infections (particularly in the immunocompromised). Conclusion: We anticipate that this study will help ensure proper and expedited diagnosis of diseases in the differential diagnosis for LF, helping to target treatment of patients with both LF and non-LF acute febrile illnesses in Nigeria.