Dengue virus co-infections with multiple serotypes do not result in a different clinical outcome compared to mono-infections

Senaratne, U. T. N.; Murugananthan, Kalamathy; Sirisena, Pdnn; Carr, Jillian M.; Noordeen, F.

doi:10.1017/s0950268820000229

Cited by 19 publications

(19 citation statements)

References 31 publications

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“…Moreover, we found co-infection of different DENV serotypes: 23% and 30% in human and mosquito samples respectively. This finding is consistent with several studies which reported the concurrence of DENV infection in the same patient with multiple serotypes at different percentages ranging from 3% to 43% [ 38 – 41 ]. Similar observations of co-infection with multiple DENV serotypes have been reported in other countries and also in Thailand [ 31 , 42 , 43 ].…”

Section: Discussionsupporting

confidence: 93%

“…Similar observations of co-infection with multiple DENV serotypes have been reported in other countries and also in Thailand [ 31 , 42 , 43 ]. All four serotypes circulating in the region have been found in combinations within single patients [ 41 ]. Several factors might be involved in co-infection including: i) the multiple feeding behavior of Ae .…”

Section: Discussionmentioning

confidence: 99%

“…Several factors might be involved in co-infection including: i) the multiple feeding behavior of Ae. aegypti, which feeds more than once during its genotropic cycle [31,41,42], ii) the high attack rates of cases during dengue epidemics which may result in many infections with multiple serotypes in humans, and also provide opportunities for mosquitoes to become infected with multiple serotypes [42], iii) transovarial transmission of dengue viruses in mosquitoes [31], iv) asymptomatic cases as a source of infection in mosquitoes [42].…”

Section: Plos Onementioning

confidence: 99%

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Dengue virus in humans and mosquitoes and their molecular characteristics in northeastern Thailand 2016-2018

et al. 2021

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Dengue is hyperendemic in most Southeast Asian countries including Thailand, where all four dengue virus serotypes (DENV-1 to -4) have circulated over different periods and regions. Despite dengue cases being annually reported in all regions of Thailand, there is limited data on the relationship of epidemic DENV infection between humans and mosquitoes, and about the dynamics of DENV during outbreaks in the northeastern region. The present study was conducted in this region to investigate the molecular epidemiology of DENV and explore the relationships of DENV infection in humans and in mosquitoes during 2016–2018. A total of 292 dengue suspected patients from 11 hospitals and 902 individual mosquitoes (at patient’s houses and neighboring houses) were recruited and investigated for DENV serotypes infection using PCR. A total of 103 patients and 149 individual mosquitoes were DENV -positive. Among patients, the predominant DENV serotypes in 2016 and 2018 were DENV-4 (74%) and DENV-3 (53%) respectively, whereas in 2017, DENV-1, -3 and -4 had similar prevalence (38%). Additionally, only 19% of DENV infections in humans and mosquitoes at surrounding houses were serotypically matched, while 81% of infections were serotypically mismatched, suggesting that mosquitoes outside the residence may be an important factor of endemic dengue transmission. Phylogenetic analyses based on envelope gene sequences showed the genotype I of both DENV-1 and DENV-4, and co-circulation of the Cosmopolitan and Asian I genotypes of DENV-2. These strains were closely related to concurrent strains in other parts of Thailand and also similar to strains in previous epidemiological profiles in Thailand and elsewhere in Southeast Asia. These findings highlight genomic data of DENV in this region and suggest that people’s movement in urban environments may result in mosquitoes far away from the residential area being key determinants of DENV epidemic dynamics.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Plos Onementioning

confidence: 99%

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Dengue virus in humans and mosquitoes and their molecular characteristics in northeastern Thailand 2016-2018

et al. 2021

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“…However, the relevance of such events for disease severity and on the virus life cycle has not been well established. Senaratne and colleagues have demonstrated that co-infections by two or more dengue serotypes have no incidence on disease severity since the clinical presentation, the white blood cell count and viraemia were not different from mono-infected individuals [ 30 ]. Yet, neurologic impairments have been described in children co-infected by DENV-1, -2 and -3 in Brazil [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon

et al. 2021

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Acute febrile patients presenting at hospitals in Douala, Cameroon between July and December 2020, were screened for dengue infections using RT-PCR on fragments of the 5’ and 3’ UTR genomic regions. In total, 12.8% (41/320) of cases examined were positive for dengue. Dengue virus 3 (DENV-3) was the most common serotype found (68.3%), followed by DENV-2 (19.5%) and DENV-1 (4.9%). Co-infections of DENV-3 and DENV-2 were found in 3 cases. Jaundice and headache were the most frequent clinical signs associated with infection and 56% (23/41) of the cases were co-infections with malaria. Phylogenetic analysis of the envelope gene identified DENV-1 as belonging to genotype V, DENV-2 to genotype II and DENV-3 to genotype III. The simultaneous occurrence of three serotypes in Douala reveals dengue as a serious public health threat for Cameroon and highlights the need for further epidemiological studies in the major cities of this region.

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“…Although co-circulation of novel emerging arboviruses like ZIKV or CHIKV coupled with DENV has been reported [ 44 – 46 ], most countries where DENV is endemic have reported co-circulation of all four DENV serotypes, resulting in hyper-endemicity for the virus [ 47 , 48 ]. Specifically, for DENV-2 and DENV-3 infections, one study showed that from 303 human serum samples, up to 21% were infected with both viruses [ 49 ]. This phenomenon has been linked to an increased frequency of severe dengue cases and an overall increase of virulence [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

The effects of DENV serotype competition and co-infection on viral kinetics in Wolbachia-infected and uninfected Aedes aegypti mosquitoes

2021

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Background The Aedes aegypti mosquito is responsible for the transmission of several medically important arthropod-borne viruses, including multiple serotypes of dengue virus (DENV-1, -2, -3, and -4). Competition within the mosquito between DENV serotypes can affect viral infection dynamics, modulating the transmission potential of the pathogen. Vector control remains the main method for limiting dengue fever. The insect endosymbiont Wolbachia pipientis is currently being trialed in field releases globally as a means of biological control because it reduces virus replication inside the mosquito. It is not clear how co-infection between DENV serotypes in the same mosquito might alter the pathogen-blocking phenotype elicited by Wolbachia in Ae. aegypti. Methods Five- to 7-day-old female Ae. aegypti from two lines, namely, with (wMel) and without Wolbachia infection (WT), were fed virus-laden blood through an artificial membrane with either a mix of DENV-2 and DENV-3 or the same DENV serotypes singly. Mosquitoes were subsequently incubated inside environmental chambers and collected on the following days post-infection: 3, 4, 5, 7, 8, 9, 11, 12, and 13. Midgut, carcass, and salivary glands were collected from each mosquito at each timepoint and individually analyzed to determine the percentage of DENV infection and viral RNA load via RT-qPCR. Results We saw that for WT mosquitoes DENV-3 grew to higher viral RNA loads across multiple tissues when co-infected with DENV-2 than when it was in a mono-infection. Additionally, we saw a strong pathogen-blocking phenotype in wMel mosquitoes independent of co-infection status. Conclusion In this study, we demonstrated that the wMel mosquito line is capable of blocking DENV serotype co-infection in a systemic way across the mosquito body. Moreover, we showed that for WT mosquitoes, serotype co-infection can affect infection frequency in a tissue- and time-specific manner and that both viruses have the potential of being transmitted simultaneously. Our findings suggest that the long-term efficacy of Wolbachia pathogen blocking is not compromised by arthropod-borne virus co-infection. Graphic Abstract

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Dengue virus co-infections with multiple serotypes do not result in a different clinical outcome compared to mono-infections

Cited by 19 publications

References 31 publications

Dengue virus in humans and mosquitoes and their molecular characteristics in northeastern Thailand 2016-2018

Dengue virus in humans and mosquitoes and their molecular characteristics in northeastern Thailand 2016-2018

Concurrent circulation of dengue serotype 1, 2 and 3 among acute febrile patients in Cameroon

The effects of DENV serotype competition and co-infection on viral kinetics in Wolbachia-infected and uninfected Aedes aegypti mosquitoes

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