Viral and Bacterial Etiology of Common Respiratory Infections in Sub-Saharan Africa: A Review

1. Introduction

Respiratory viral infections are increasingly recognized as major contributors to hospitalization and mortality in all age groups of populations worldwide [1]. Most epidemiological knowledge is based on data from developed countries. In contrast, the burden of acute respiratory infections (ARI) is particularly heavy among children in developing countries, with high rates of hospital admissions and mortality [2,3]. Indeed, it is estimated that about 126 to 156 million cases of acute lower respiratory tract infections (ALRI) such as pneumonia and bronchiolitis occur in children worldwide each year, causing around 1.4 million deaths, with over 95% of which occur in Africa and Southeast Asia [4].

Upper respiratory tract infections are commonly caused by viruses or bacteria. Respiratory viruses are more often responsible for upper tract ARIs than bacteria in children under 5 years of age [3]. Common symptoms include nasal congestion, cough, sore throat, and fever. However, bacteria are less identified because of low sensitivity of bacterial culture in patients with community-acquired pneumonia [5]. Respiratory viruses such as respiratory syncytial virus, influenza viruses (A and B), parainfluenza viruses, human adenovirus, human coronaviruses OC43 and 229E, rhinovirus and metapneumovirus are currently recognized as common etiologies of ARI in young children in developed countries [2].

Recent use of molecular diagnostic techniques has identified other respiratory viruses associated with ARI, including human metapneumovirus, human Boca virus, human coronavirus NL63 and human coronavirus HKU1. In addition, human rhinovirus is implicated in the majority of cold cases and often induces lower respiratory tract infections [3].

A better understanding of the range of pathogens responsible for ARI is therefore essential for clinical cases management and the design of preventive strategies aimed at reducing childhood morbidity and mortality.

Lower respiratory tract infection (LRTI) is common in the elderly, children under five years of age and people who are immunocompromised or suffering from comorbidity [6]. People with symptoms suggestive of LRTIs can contract tuberculosis (TB) and/or other bacterial and viral infections [7]. Over the years, the most severe cases of pneumonia have been associated with Mycobacterium tuberculosis, with little information on other relevant bacterial pathogens [8]. Some common pathogens causing LRTIs other than Mycobacterium tuberculosis include: Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and Staphylococcus aureus [8].

The viral and bacterial etiologies of ARIs have been well documented in Northern Hemisphere countries. However, few studies are available in Africa [9]. Thus, the present study aimed at summarizing the literature related to the etiology of respiratory infections, in sub-Saharan African countries and to identify information gaps in order to improve essential knowledge on the subject.

We focused our research on sub-Saharan Africa, as epidemiological, socioeconomic and vaccine policy factors in North Africa would probably be very different [10].

2. Methods

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2.1. Search strategy

This review considers data from documents published online (articles, review, report, etc...) that reported information on both viral and bacterial etiology of ARIs in Africa, by searching the online bibliographic databases PubMed, HINARI and Google Scholar using the following key terms: “Acute respiratory infections”, “Upper respiratory infections”, “Lower respiratory infections”, “Viruses”, “Bacteria”, “Respiratory syndrome”, “Influenza syndrome”, “Africa”, “Prevalence”, and “etiology”. The reference list of selected articles was used as a lead for identifying further studies. The Boolean operators “AND” and “OR” were used to combine two or more terms. The search was limited to studies published in English or French, involving patients of any age in sub-Saharan Africa, in which pathogens were identified using immunofluorescence assays (IFA), Polymerase Chain Reactions (PCR), viral cultures, bacterial cultures or a combination of these methods.

2.2. Study selection

This review compiles studies focused on ARIs caused by viruses and/or bacteria. We only considered data from sub-Saharan Africa reported in papers published between 2010 and 2021, in English or French.

2.3. Inclusion criteria

Studies included were cohort, case-control, prospective, retrospective, and cross-sectional investigations reporting the prevalence of respiratory viruses in hospital and/or community settings. In the case of repeated studies, where the same population was recruited and examined over the same period, only the most recent or most complete study was included.

2.4. Exclusion criteria

There were no age or gender restrictions (Figure 1). Exclusion criteria were mainly: i) respiratory infections of non-human infections; ii) comparison of PCR kits for identification of respiratory pathogens and iii) studies on respiratory infection management policy.

2.5. Data extraction

Full versions of selected articles were downloaded and reviewed by two study authors. Data were extracted using a predefined form with the following information: i) references; ii) sample collection period; iii) year of publication; iv) study country; v) target population (age); vi) study area; vii) sample size; viii) sampling type; ix) prevalence of identified pathogens and; x) study type.

2.6. Data summary

We synthesized the data by summarizing the main findings of each study. Given the variety of study types included in the review, ranging from simple descriptive to analytical studies, we have considered a synthesis more appropriate rather than a formal meta-analysis. A table was created to list all the pathogens found in each study, together with relevant study information as mentioned above on data extraction.

2.7. Ethics and distribution

This work is based on published data and therefore does not require ethical approval. This systematic review should serve as a basis for developing strategies to prevent and control respiratory infections in sub-Saharan Africa, and as a foundation for future research that can focus on identifying the gaps found. We also plan to update the study in the future to track changes and guide solutions for health services and policies.

3. Results

3.1. Literature review

The published articles included in this review were those from studies with samples collected from 2010 to 2021. In order to filter articles for this review, we initially identified a total of 115 articles from PubMed, HINARI and Google Scholar that fit with our initial search strategy. Of these, 32 articles were included and 83 were excluded, after screening each article (Figure 1).

Of the 32 articles included, 5 (three for bronchiolitis and two for influenza) focused on viral and/or bacterial strains responsible for pneumonia in children and the elderly [11,12,13,14,15] and 27 focused on the surveillance and epidemiology of viral and/or bacterial strains responsible for respiratory infections (Table 1).

Many of these studies were carried out among children under 5 years of age. Articles excluded were related to comparisons of amplification kits, respiratory infection management policy, data from countries other than Africa, and those concerning non-human respiratory infections.

3.2. Features of included items

The 32 articles involved a total of 41,164 patients. Sample size ranged from 51 to 6,381 ARI patients per study. The included studies were obviously conducted in 15 sub-Saharan African countries (Figure 2).

A total of 6 published studies were conducted in Cameroon, 3 in the Democratic Republic of Congo (DRC), Ghana, and Gabon; two studies in Burkina Faso, South Africa, Côte d'Ivoire, Kenya, Niger and Nigeria respectively, and one study in each of the following countries: Senegal, Tanzania, Mali, Central African Republic (CAR) and Madagascar.

We identified 20 (62.5%) cross-sectional studies, 9 (28.12%) prospective studies, 4 (12.5%) retrospective studies and 4 (12.5%) cohort studies. We also noted case-control, analytical, longitudinal, and descriptive studies (Table 1).

Considering settings in which these published studies were focused, there were 24 (75%) hospital-based studies and 8 (25%) community-based studies. The study setting was urban in 27 (84.37%) studies, and mixed (rural, semi-rural and pre-urban) in 5 (15.62%) studies.

Pathogens were identified in a variety of respiratory samples, including nasal swabs, oropharyngeal swabs, nasopharyngeal aspirates, induced sputum, tracheal aspirates, bronchoalveolar lavage swabs and pulmonary aspirates.

Respiratory viruses were detected using immunofluorescence tests, multiplex RT-PCR, conventional PCR and viral cultures. RT-PCR was the most frequently used diagnostic method. For the detection of individual bacteria, only bacterial cultures were performed.

3.3. Etiology of pathogens detected

All the respiratory pathogens identified in these studies were viral and bacterial (Table 1). Among 32 articles reviewed, human respiratory syncytial virus was the most frequently identified, with a prevalence ranging from 0.6% - 59%, followed by human rhinovirus (9.3% - 73%), influenza A/B virus (0.9% - 69.1%), human adenovirus (0.9% - 30.8%), human parainfluenzavirus 1-4 (3.8% - 24%), enterovirus (2.9% - 25.5%), human coronaviruses (1.4% - 13.9%), human metapneumovirus (1.7% - 13.7%), and human bocavirus (1.4% - 10.6%) (Table 2).

Among the bacteria detected (Table 1), the most prevalent were Streptococcus pneumoniae (14.2% - 96%), followed by Haemophilus influenzae type b (2.5% - 54%), and Klebsiella pneumoniae (1.4% - 49.9%). Other bacterial species, notably Staphylococcus aureus (7.1% - 12.2%), Pnseudomonas aeruginosa (1.4% - 15.2%), and Mycobacterium tuberculosis (6.5%) were the least identified (Table 2).

4. Discussion

This review updates known information on respiratory infections of viral and/or bacterial etiology, in sub-Saharan Africa over the last twelve years. The overall aim of this systematic review was to inform public health actors and researchers on the etiology of respiratory infections (viral and bacterial) in Africa, and to provide information that can support actions to optimize decision-making by health authorities for the control of these infections.

A wide variety of detection techniques have been found in this review, including molecular viral detection, bacterial culture which are universal and reference methods for the characterization of respiratory infection pathogens. The results highlight a predominance of human respiratory syncytial virus and a strong association between human rhinovirus and influenza A/B virus in children aged under 5 years old presenting with influenza-like illness. The other most frequently detected viruses were adenovirus and all four types of human Parainfluenzae virus. This study also showed respiratory infections of bacterial origin, with the most frequently identified species being Streptococcus pneumoniae and Haemophilus influenzae in bacterial culture mainly as well as on sputum and Branco-alveolar lavage (BAL) samples in adults.

Little or no data were found on the etiology of respiratory infections in many sub-Saharan African countries. Of the 48 countries in sub-Saharan Africa (wikipedia.org/wiki/Afique_sub-saharienne), the 32 articles included in this review were carried out in only 15 countries, the majority of which were in Central and West Africa (Figure 2). No published studies were carried out in the Republic of Congo, although it borders with two (Cameroon and DRC) of the five countries where the number of deaths from childhood pneumonia is or was highest [39]. This lack of data could probably be due to the poor implementation of respiratory infection surveillance activities.

The pattern of predominance of human respiratory syncytial virus in this study is consistent with that reported by several previous narrative reviews [3,40]. Regardless of various factors, including screening test, type of sample tested, age of children, type of education and severity of infection, most studies indicated that human respiratory syncytial virus is the predominant causative agent of cases of respiratory diseases such as bronchiolitis, asthma, and wheezing with an incidence of between 50 and 80% [41]. Rhinovirus and influenzae A/B, the second most common viruses observed, have long been considered a cause of benign respiratory tract infections such as the common cold [9].

We found five studies that presented cases of viral and bacterial co-infections at rates of around 14% in our review [9,12,13,14,15]. Although Streptococcus pneumoniae is known to be more prevalent in superinfection in some respiratory syndromes, such as influenza [42,43], Haemophilus influenzae, and Klebsiella spp were also identified mostly in co-infection. This observation correlates with the review by Lansbury et al. who also showed that Klebsiella pneumoniae and Haemophilus influenzae were among the most frequent co-infecting bacterial pathogens [44]. Staphylococcus aureus was one of the least present, as expected [11]. Irrespective of testing issues, co-infection with other respiratory pathogens has important implications for diagnosis and prognosis.

Seasonality and study duration could clearly also lead to variability in the prevalence of viruses/bacteria responsible of respiratory infections.

5. Conclusion

This review shows that a number of viruses are associated with ARIs in children and adults in sub-Saharan Africa. The WHO’s global strategy for the control of ARI in children under 5 years of age must rigorously consider the importance of both viral and bacterial cases. Moreover, the results highlight the lack of data for several sub-Saharan African countries. Further high-quality studies are needed to determine the role of viruses and bacteria in ARI.

6. Study limits

This study has several limitations. Firstly, only publications in English or French were taken into account, excluding data published in Portuguese, which is the official language of five African countries (Angola, Cape Verde, Guinea-Bissau, Mozambique and Sao Tome and Principe), and in Spanish, the official language of Equatorial Guinea. Secondly, unpublished literature also constitutes an information bias in this systematic review. Finally, we did not assess the statistical quality of the studies by meta-analysis, but included all articles that met the inclusion criteria.