In our study, about 1/3 of patients experienced severe dengue episode. The most common severity signs observed were renal failure followed by severe bleeding, and plasma leakage. Severe bleeding was statistically more common in primary dengue fever.
According to the WHO, nearly 500,000 cases of severe dengue (DHF and DSS) occur each year with nearly 20,000 deaths in the world. In the Americas, the incidence of severe dengue has been estimated at more than 200 cases per 100 000 persons in 2010 (24). Prothapregada et al. reported 37.4% of severe dengue in hospitalized children in India which is quite similar to the 33,5% of prevalence reported in our study (25).
Severe dengue fever is underestimated, particularly in Africa, where many cases probably remain undiagnosed due to the high frequency of other febrile non-malarial diseases and limited diagnostic capabilities (8,26).
The high prevalence of severe dengue in this study may be related both to the WHO classification used for organ failure and to the definition of severity signs that vary from one study to another (27). Indeed, these severity signs are not precisely defined by WHO, and most studies published so far have used the 1997 definition. The new WHO definition has improved sensitivity for earlier identification of severe cases and better screening of patients (28).
Renal failure appears in this study as the most common severity sign (13.1%). In the literature, the frequency of renal failure during severe dengue fever varies widely (0.2 to 36%) (29–31). In addition, the thresholds defining renal failure during dengue fever are also variable according to these studies. The high frequency of renal failure in our study could be explained by the choice of creatinine threshold at 120 μmol/l. There are few published studies on renal failure during dengue fever in Africa. However, renal failure is common in this region, particularly because of malaria or other tropical infections. During dengue infection, several mechanisms may cause renal failure: renal hypoperfusion in the setting of sepsis, immunological damage and other unsolved mechanisms. Renal failure may also be a result of severe bleeding and plasma leakage. Sepsis, advanced age, use of nephrotoxic drugs, a history of high blood pressure or diabetes are also risk factors for renal failure during dengue fever (17,32).
The frequency of severe bleeding varies from one study to another. This can be explained by a lack of homogeneity in the definitions of severe bleeding between studies. In our study, we considered severe bleeding patients with extensive bleeding and significant deglobulization that required blood transfusion. This strict definition may explain the lower frequency of severe bleeding in our study compared to those reported in several studies (33). However, in West Africa, although the majority of the published work is case studies or small series, bleeding is the most common clinical severity sign that usually leads to the biological diagnosis of dengue fever and patients hospitalization (8,33). This could be explained by the fact that, in the context of limited resources, hemorrhage is a sign of severity that is easier to identify than other signs for which laboratory diagnosis remains essential. It is also one of the symptoms that is increasingly leading to the use of rapid diagnostic tests.
Plasma leakage was observed in 6.9% of study’s patients and only 1.4% of the patients experienced hypovolemic shock.
In India, the frequency of DSS was 39% in children and was higher than the frequency of DHF (34). A frequency of 11.1% of DSS was reported by Abdallah et al. in East Sudan (35). Plasma leakage is suspected being underestimated complication in West-Africa due to lack of knowledge about the disease, the lack of systematic measurement of vital parameters and the unavailability of hematocrit test (4,36).
Regular monitoring of these clinical and biological parameters during the disease evolution is rarely done in the West- African context and more especially in Burkina Faso. As previously described, plasma leakage occurs during the critical phase of the disease, which varies according to the individual from 3 to 7 days, thus after the onset of symptoms and corresponds to the moment of thermal decline. A standardized surveillance study would better assess the frequency and importance of plasma leakage, its risk factors in the West- African context and therefore take appropriate measures to prevent patient deaths.
In our study, the rate of hemorrhage was significantly higher in primary dengue. This is in contrast with the majority of studies reporting that severe bleeding complications occur during secondary dengue infection which is consistent with ADE theory. Similar to our findings other authors have reported, a higher prevalence of DHF in primary dengue infection (12,37). Furthermore, Soo et al. in a meta-analysis showed that the severity of dengue fever during primary infection was related to the virulence of the viral serotype (38). Tee et al. showed that severe bleeding occurred more frequently in elderly patients with primary dengue fever (39). An important pathogenic role of pro-inflammatory cytokines, including a significant elevation of IFN-γ, IL-12, TNF-α and IL-6 during primary dengue with serotype 2 could explain the severity of the disease during primary infection (40). Data from the national reference laboratory during the same outbreak in 2016 showed a predominant circulation of DENV-2 in Burkina Faso (41).
The difference between primary dengue and secondary dengue fever is often difficult and requires more advanced diagnostic techniques, including the measurement of antibody titration and for this, WHO also recommended haemagglutination inhibition technique which is limited in Burkina Faso (42). Therefore, the results of our study need to be interpreted with caution, since only 4% of our patients were confirmed and tested by PCR primary dengue infection. Thanachartwet et al. reported similar results with 3.5% of patients with primary dengue fever (43). Previous data from studies of patients who developed fever in community showed a seroprevalence of 66% IgG and confirm the endemic circulation of the dengue virus in the country (21). The proportion of severe dengue in these two groups may influence a difference in favor of the lower strength group.
The limits of our study are mainly related to the nature of the diagnostic test being performed. In addition, the type of cross-sectional study did not enable to standardize the biological checkup performed and standardize the periods of achievement of dengue rapid diagnostic test to facilitate results interpretation. Meanwhile the absence of IgG is a good negative predictive value of a primary dengue, however, its presence, does not exclude primary dengue since IgG can appear from the 7th day of the disease occurrence. The isolated presence of IgG excluded patients from the study since the antibody titration test was not feasible.