Enzyme linked immunosorbent assay (ELISA) is a sensitive and quantifiable diagnostic method that has been used in the detection of different aetiologies . Sera antibodies are often used to correlate influenza detection in the assay . This study detected a total percentage seroprevalence of 20.9% to influenza virus among paediatric patients attending different healthcare centers in Lagos, Nigeria. Healthcare attendees were studied in order to increase the likelihood of detecting exposure of humans to the pathogens since parents of children with febrile illness or influenza-like illness are more likely to seek healthcare attention. The finding is similar to the prevalence of 22.1% influenza infection reported in Russian children between 2013 and 2017 . A study conducted in Germany (2008- 2010) showed a higher IgG seroprevalence of 87.6% to influenza virus using ELISA technique . The observable difference could be due to the measurement of IgG, an indication of past exposure to infection compared to the IgM ELISA used to measure recent infection in this study.
On the contrary, Dilantika, Sedyaningsih , Norowitz, Kohlhoff , and Alsuwaidi, Al-Mekaini  using ELISA method reported lower seroprevalence of 11.6% and 14.9%, and 15.8% respectively to influenza virus in children. In Africa, studies have reported influenza in pregnancy, HIV patients, sickle cell anaemia patients, and tuberculosis patients with prevalences of 48%, 3.9%, 2.0%, and 10% respectively [29-32] while others have shown co-infection of influenza with asthma, pneumonia and malaria but there is dearth of information on co-infection of influenza with typhoid fever, and malaria and typhoid, hence the importance of this study.
Our findings showed that a good number of children having monotypic seropositivity to influenza virus had co-infection with malaria parasitaemia and/or with typhoid fever with 61.8% co-infection of influenza and malaria higher than that of 55.3% for influenza and typhoid, and 27.6% co-infection of the trio of influenza, malaria and typhoid. Studies have shown that influenza is one of the viruses that may lead to complication of malaria infection [33, 34], while findings from this study is suggestive of malaria parasitaemia complicating influenza infection in children. However, Thompson, Breiman  reported uncommon co-infection of malaria and influenza in Kenya in 2009-2011. A good reason for this might be that both malaria parasitaemia and influenza can be sub-clinical or incidental to the presenting illness [36, 37].
Our findings of 55.3% monotypic infection of influenza, 31.9% co-infection of influenza and malaria, 50% coinfection of influenza and typhoid, and 42.9 % coinfection of influenza, malaria and typhoid respectively showed that children in the age group 1-4 years were the most affected by all the infections when compared to other age groups and the difference was statistically significant (Table 1). This is a pointer that children of age 1- 4 years had the highest recent exposure to influenza virus, mosquito bite and contamination with S. typhi, that call for urgent and serious public health attention. The influenza monotypic infection unlike influenza, malaria and typhoid co-infection is consistent with the study of Tempia, Walaza  that reported a similar prevalence of influenza virus in children less than 5 years of age. Studies from India and Bangladesh also reported highest prevalence of influenza in children less than 5 years [39, 40]. Gessner, Shindo  showed that in Sub-Saharan Africa, children less than 5 years are more exposed to influenza than other age group. According to CDC , the highest hospitalization for influenza epidemiology was reported in children age 0-4 years with the lowest prevalence in children of 5-14 years. Our finding is also consistent with that of Riquelme, Torres  that estimated high rate of influenza infection in children less than 5 years, unlike Mancinelli, Onori ; and Shang, Blanton  that concluded that influenza seropositivity was highest among children less than 1 year. This could be argued with the fact that their immune system is immunologically immature, making them to be more susceptible to influenza .
The male children had higher 61.8% (47/76) IgM seroprevalence to influenza virus unlike their female counterpart with 38.2% (29/76). This is similar to the finding reported by Tivane, Daniels  that influenza virus is higher among male children. This position was also supported by Mancinelli, Onori .
The commonest 27.6% (n= 21) clinical symptom of influenza virus presented in the study was fever. This agrees with the finding of Taşar, Bilge  that fever is the commonest symptom of influenza-like-illness.
Exposure to recent influenza activity was confirmed through-out the months in which samples were collected with a higher occurrence recorded in the month of March. This is in line with the findings of Tivane, Daniels  which showed that influenza occurred through-out the year but the activity was peak in February and August. In contrast to this study, Sanou, Wandaogo  showed that influenza was most prevalent in September to October. The basic difference in the prevalence at each point in time is due to the favourable weather condition.
Children having underlying health condition of asthma in this study tested negative to IgM seroprevalence to influenza virus. This finding agrees with the earlier investigation by Tivane, Daniels  which opined that no relationship exist between children having asthma and influenza. However, previous studies have shown correlation between influenza, sickle cell and asthma  in support of the 2.6 % seroprevalence of influenza in sickle cell patients detected in this study. This is further supported by Bundy, Strouse  that reported prevalence of influenza in children with sickle cell. According to Adewoyin , Nigeria has 20%– 30% carrier rate for sickle cell gene with sickle cell disease affecting 2%– 3% of the entire population. However, influenza with malaria parasitaemia and typhoid fever coinfection must be urgently prevented in such individuals in order to prevent likely fatal consequences.
Part of the limitations of this study is that we were unable to further analyse the ELISA positive samples by molecular assay due to limited resources. Therefore, there is need for a future study that can generate nucleotide sequences for global data sharing and possible consideration as vaccine candidates from sub-Saharan Africa.