Background and rationale:The World Health Organisation (WHO), estimates influenza globaldeaths at 290,000 to 650,000 annually. Although influenza is mostly associated with upperrespiratory tract infections (URTIs), its role in lower respiratory tract infections(LRTIs) and the associated poor clinical outcomes have been overlooked in sub-SaharanAfrica. A study conducted in eight SSA countries estimated that 8.2% of cases and 2.8% ofdeaths from LRTIs were due to primary infection with influenza. Pneumonia andinfluenza-associated illness are responsible for 8.5% of respiratory deaths in Zambia.However, in routine practice, testing to distinguish between bacterial and viral etiologyof RTIs is seldom done outside sentinel surveillance due to the high cost and lack ofavailable testing options. This consequently underestimates viral RTIs in the population.It is particularly important to diagnose flu early on in vulnerable populations so thatthey receive timely and appropriate medical care. Although Zambia is a high HIV burdencountry with a prevalence of 11%, there is presently no study that has described theburden of influenza in the HIV positive population. This research study will address gapsin current scientific knowledge, providing key insights about the prevalence, circulatingtypes, seasonality and associated clinical outcomes of influenza, RSV and SARS-CoV-2infection in Zambia in the post COVID-19 era.Objectives Primary To determine the prevalence of influenza (A and/or B) infections in ahigh HIV burden setting in Lusaka, Zambia over one or more influenza seasons.Secondary 1. To determine the prevalence of influenza co-infection with RSV and/or SARS-CoV-2 2. To determine the clinical outcomes of influenza (A and/or B) infection among Zambian adults, with and without co-infection with RSV and COVID-19, by HIV and COVID-19 vaccination status. 3. To evaluate the accuracy and yield of aerosol-based sampling for diagnosis of respiratory viruses (influenza, SARS-CoV-2, and RSV) compared to nasal/ nasopharyngeal swabs, for rapid diagnosis of infection among symptomatic individuals in Zambia. 4. To evaluate the acceptability of exhaled breath aerosol (XBA) sampling for diagnosis and screening of respiratory infections of pandemic potential.Study design and participants:Primary objective and secondary objective 1:Cross sectional surveillance study of individuals presenting with flu-like symptoms attwo first level hospitals in Lusaka, Zambia. Recruitment of 594 participants will be doneover the study period and participants will include both males and females presentingwith 2-7 days of flu-like symptoms, able to provide informed consent, aged ≥18 years,with a known HIV status or willing to be tested, with a known COVID 19 vaccination statusand available for symptom follow-up.Secondary objective 2:Prospective follow up of participants enrolled in aim 1 for 14 days will be done todocument clinical symptom progression and outcomes. Appropriate care will be provided toall participants within routine care services.Secondary objective 3 & 4:Mixed methods approach. All patients enrolled under aim 1 will be requested to provide inaddition to the routine nasopharyngeal sample, an aerosol-based sample for diagnosticaccuracy and yield evaluation. We will also conduct an investigator-administeredquestionnaire to ascertain end-user experience and preferences for either samplingmethod.Location Zambia (Kanyama and Chawama sub-districts) Duration April 2025 to November 2026(Participant enrolment duration)