This is the first multicenter study to better understand the burden of RSV-associated ARI in Cameroon. The prevalence of 33% recorded is similar to studies from Turkey, Iran, Brazil, and Egypt (17). Our result was superior to that of a previous study showing a rate of detection of RSV at 5.7% of patients with influenza-like illness visiting influenza surveillance centers in 2009 in the central region of Cameroon. One possible reason was that we included all ambulatory or hospitalized cases different from the previous study that included only outpatients made up of children and adults. Another probable cause could be that this study was conducted in the late phase of the rainy season and maybe a decreasing period of the RSV season in Cameroon [18]. Another study showed that RSV was the second most common respiratory virus (13.3%) among hospitalized children ≤ 15 years with severe acute respiratory infections (SARI) after human adenovirus in Yaoundé, Cameroon [16].
This study showed a significant RSV disease burden among children below six months which is in-line with other researchers [19] and suggest the necessity of passive protection against RSV infection at birth, either through maternal immunization or administration of a birth dose of an extended half-life mAbs at birth and the importance of developing vaccines for active infant immunization to provide durable protection against RSV disease.
Though the male-female ratio of RSV-positive patients was 1:2, gender was not a significantly associated factor. This result is similar to a prevalence study in Brazil [24[. Nevertheless, some studies in the literature have revealed being male as a risk factor to acquire RSV infection [13, 19].
More than two-thirds of the children on mixed feeding were RSV positive, a significantly higher proportion than those on exclusive breastfeeding. This finding showed that patients on mixed feeding were more likely to acquire RSV than those on exclusive breastfeeding, indicating children on exclusive breastfeeding were well protected and probably with stronger immune systems against a viral infection like RSV. Many epidemiological studies show that breastfeeding can reduce the frequency, severity, and mortality of respiratory disease in infants [20]. According to the literature, breast milk contains a series of components with immunomodulating properties, which represent a benefit for the infant. Its antimicrobial, anti-inflammatory and immunomodulatory agents are multifunctional and act synergistically.
Ninety-one percent of the RSV-positive children were inappropriately prescribed antimicrobial drugs (antibiotics). Antibiotic treatment was not appropriate for patients with RSV infection. This finding was similar to that of a study in Saudi Arabia that demonstrated a high prevalence of antibiotic misuse ranging from 42–92%, especially in children [21]. The reasons for antibiotic misuse are complex, and several contributing factors are evidently associated with the overuse of antibiotics in both the patient's (or parents of children) level and doctor's level. These factors include cultural factors, behavioral characteristics, socioeconomic status, and level of education [21]. Antimicrobial resistance is a global public health challenge, which has been accelerated by the overuse of antibiotics worldwide. Antibiotic overprescribing is a particular problem in primary care, where viruses cause most infections. General practitioners issue about 90% of all antibiotic prescriptions and respiratory tract infections are the leading reason for prescribing. Multifaceted interventions to reduce overuse of antibiotics are effective and better than single initiatives. Interventions should encompass the enforcement of the policy of prohibiting the over-the-counter sale of medicines, the use of antimicrobial stewardship programmes, the active participation of clinicians in audits, the utilization of valid rapid point-of-care tests, the promotion of delayed antibiotic prescribing strategies, the enhancement of communication skills with patients and the performance of more pragmatic studies [22]. There is a need for a global strategic effort to develop a portfolio of vaccines that target AMR [21].
Malaria infection is suspected in all patients with fever. Malaria may result in fever and raised respiratory rate; therefore, it could be a confounding infection mimicking ALRI in countries where malaria is endemic. Increasing awareness is essential for healthcare workers who should provide adequate diagnosis and treatment of both acute respiratory infections and malaria.
Infants with underlying medical conditions, prematurity, low birth weight, poor parental education, household smoking, and exposure to indoor air pollution have been revealed as risk factors to acquire RSV infections. Still, none of the elements were shown as significant associated factors in our study [23, 24].
Further large cohort and interventional studies in LMIC settings are needed to elucidate these risk factors, as these studies are best suited for this purpose. Parents and caregivers who do not have adequate knowledge concerning preventive measures put infants at higher risk. The infant's home environment is also essential. Infants from low-income families tend to be more at risk, perhaps in part due to lack of access to medical care and in part, to lack of maternal education. One of the most substantial environmental risk factors for infant respiratory infection is exposure to passive tobacco smoke [24]. A case-control study of 53 infants with bronchiolitis found that any exposure to passive smoke was the strongest predictor (p = 0.004) [24]. The study sites of our research are located in the rural and semi-rural settings in the littoral regions of Cameroon, where most of the families use solid fuel like firewood or charcoal for cooking. Exposure to household air pollution is preventable. Still, resources are limited in low-income populations with competing for health priorities: with high-quality evidence of the accurate scale of the problem and cost-effectiveness of interventions, resources to reduce the global burden of disease can be effectively allocated.
Among the RSV-positive children, the most frequent clinical symptoms/signs were fever, cough, wheezing, difficulty breathing, vomiting, and inability to drink or breastfeed. This is the typical symptomatology of acute respiratory infection; RSV is one of the etiologies indicating, therefore, that the healthcare system in settings in Cameroon and other LMICs should put in place diagnostic possibilities in their health facilities to guide management and infection control. This also shows that emphasis should be placed on prevention. An RSV vaccine will play a vital role in reducing the infant mortality that is highest in low- and middle-income countries.
A third of the RSV-positive children were clinically diagnosed to have bronchiolitis, and one-sixth had pneumonia by the clinicians or attending physicians. This indicates that RSV is an established cause for acute lower respiratory infections in children. In settings where viral etiologies are not systematically checked and resources not available, the critical solution to save lives is through preventive measures like vaccines and monoclonal antibodies.
The strength of our study lies in the uniqueness of conducting such a seroprevalence study in the rural and semi-rural communities in Cameroon faced with several human resources, infrastructural and logistical bottlenecks. The study sites were mostly first-line primary and secondary healthcare facilities with little experience in health care research. This study was integrated into their routine health care activities and has undoubtedly built a clinical research capacity that needs to be further strengthened in such settings.
A limitation of our study was that we relied on a single laboratory test for detecting RSV antigen, the ELISA test. This is likely to have led to underestimates or overestimates of the disease burden. The use of multiple methods, including polymerase chain reaction, in addition to the ELISA test, may have been the best option. However, in the field of community settings, the ELISA test was the only practical, affordable, and feasible choice. Compared to virus isolation, using the ELISA test to detect RSV has been shown to have a sensitivity of 94% and a specificity of 97%. There is also the possibility of higher false positives as compared to the standard test RT-PCR. Still, we limited this by using IgM RSV ELISA, which has a life span of just 30 days in the immune system and also included only children with acute respiratory infections with an early onset of not more than seven days. However, the evidence from this study documents a substantial disease burden associated with RSV in the littoral region of Cameroon.
In a nutshell, RSV burden is high among children less than two years with ARI in the littoral region of Cameroon. Accurate clinical and laboratory diagnosis of RSV infection among these patients with ARI is necessary to reduce the disease burden, large-scale RSV spread, and the misuse of antimicrobial drugs. Further studies are required to better understand antimicrobial drug overuse and abuse, especially in this era of antimicrobial resistance. There is a need for an effective public health RSV surveillance system with standard laboratory techniques and equipment to better understand the RSV disease age-specific incidence, seasonality, and RSV burden among patients in the communities in Cameroon.