First Reported Chikungunya Fever Outbreak in the Republic of Congo, 2011

Background

Chikungunya is an Aedes -borne disease characterised by febrile arthralgia and responsible for massive outbreaks. We present a prospective clinical cohort study and a retrospective serological study relating to a CHIK outbreak, in the Republic of Congo in 2011.

Methodology and Findings

We analysed 317 suspected cases, of which 308 (97.2%) lived in the city of Brazzaville (66.6% in the South area). Amongst them, 37 (11.7%) were CHIKV+ve patients (i.e., biologically confirmed by a real-time RT-PCR assay), of whom 36 (97.3%) had fever, 22 (66.7%) myalgia and 32 (86.5%) arthralgia. All tested negative for dengue. The distribution of incident cases within Brazzaville districts was compared with CHIKV seroprevalence before the outbreak (34.4% in 517 blood donors), providing evidence for previous circulation of CHIKV. We applied a CHIK clinical score to 126 patients recruited within the two first day of illness (including 28 CHIKV+ves (22.2%)) with sensitivity (78.6%) and specificity (72.4%) values comparing with those of the referent study in Reunion Island. The negative predictive value was high (92%), but the positive predictive value (45%) indicate poor potential contribution to medical practice to identify CHIKV+ve patients in low prevalence outbreaks. However, the score allowed a slightly more accurate follow-up of the evolution of the outbreak than the criterion "fever+arthralgia". The complete sequencing of a Congolase isolate (Brazza_MRS1) demonstrated belonging to the East/Central/South African lineage and was further used for producing a robust genome-scale CHIKV phylogenetic analysis.

Conclusions/Significance

We describe the first Chikungunya outbreak declared in the Republic of Congo. The seroprevalence study conducted amongst blood donors before outbreak provided evidence for previous CHIKV circulation. We suggest that a more systematic survey of the entomological situation and of arbovirus circulation is necessary in Central Africa for better understanding the environmental, microbiological and sociological determinants of emergence.     

Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

BackgroundChikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood.Conclusion/SignificanceImmune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.     

Chikungunya: A Potentially Emerging Epidemic?

Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005–07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts.     

Evaluation of Infectivity,Virulence and Transmission of FDMV Field Strains of Serotypes O and A Isolated In 2010 from Outbreaks in the Republic of Korea

Since the early 2000s outbreaks of foot-and-mouth disease (FMD) have been described in several previously FMD-free Asian nations, including the Republic of Korea (South Korea). One outbreak with FMD virus (FDMV) serotype A and two with serotype O occurred in South Korea in 2010/2011. The causative viruses belonged to lineages that had been spreading in South East Asia, far East and East Asia since 2009 and presented a great threat to the countries in that region. Most FMDV strains infect ruminants and pigs, as it happened during the outbreaks of FMDV serotype O in South Korea. Contrastingly, the strain of serotype A affected only ruminants. Based upon these findings, the intention of the work described in the current report was to characterize and compare the infectivity, virulence and transmission of both strains under laboratory conditions in cattle and pigs, by direct inoculation and contact exposure. As expected, FMDV serotype O was highly virulent in both cattle and swine by contact exposure and direct inoculation. Surprisingly, FMDV serotype A was highly virulent in swine, but was less infectious in cattle by contact exposure to infected swine or cattle. Interestingly, similar quantities of aerosolized FMDV RNA were detected during experiments with viruses of serotypes O and A. Specific virus-host interaction of A/SKR/2010 could affect the transmission of this strain to cattle, and this may explain in part the limited spread of the serotype A epizootic.     

A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice,with Features of Persistence,for Vaccine Safety Evaluation

Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1^-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.     

Long-Lasting Immune Protection and Other Epidemiological Findings after Chikungunya Emergence in a Cambodian Rural Community,April 2012

The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3–4 weeks after the outbreak, and determined the sensitivity and specificity of case definitions and factors associated with infection by CHIKV. Self-reported clinical presentation consisted mostly of fever, rash and arthralgia. The presence of all three clinical signs or symptoms was identified as the most sensitive (67%) and specific (84%) self-reported diagnostic clinical indicator compared to biological confirmation by MAC-ELISA or RT-PCR used as a reference. Having an indoor occupation was associated with lower odds of infection compared with people who remained at home (adjOR 0.32, 95%CI 0.12–0.82). In contrast with findings from outbreaks in other settings, persons aged above 40 years were less at risk of CHIKV infection, likely reflecting immune protection acquired when Chikungunya circulated in Cambodia before the Khmer Rouge regime in 1975. In view of the very particular history of Cambodia, our epidemiological data from Trapeang Roka are the first to support the persistence of CHIKV antibodies over a period of 40 years.     

Molecular evolution of Zika virus as it crossed the Pacific to the Americas

Zika virus was previously considered to cause only a benign infection in humans. Studies of recent outbreaks of Zika virus in the Pacific, South America, Mexico and the Caribbean have associated the virus with severe neuropathology. Viral evolution may be one factor contributing to an apparent change in Zika disease as it spread from Southeast Asia across the Pacific to the Americas. To address this possibility, we have employed computational tools to compare the phylogeny, geography, immunology and RNA structure of Zika virus isolates from Africa, Asia, the Pacific and the Americas. In doing so, we compare and contrast methods and results for tree search and rooting of Zika virus phylogenies. In some phylogenetic analyses we find support for the hypothesis that there is a deep common ancestor between African and Asian clades (the “Asia/Africa” hypothesis). In other phylogenetic analyses, we find that Asian lineages are descendent from African lineages (the “out of Africa” hypothesis). In addition, we identify and evaluate key mutations in viral envelope protein coding and untranslated terminal RNA regions. We find stepwise mutations that have altered both immunological motif sets and regulatory sequence elements. Both of these sets of changes distinguish viruses found in Africa from those in the emergent Asia–Pacific–Americas lineage. These findings support the working hypothesis that mutations acquired by Zika virus in the Pacific and Americas contribute to changes in pathology. These results can inform experiments required to elucidate the role of viral genetic evolution in changes in neuropathology, including microcephaly and other neurological and skeletomuscular issues in infants, and Guillain‐Barré syndrome in adults.     

A Re-Examination of the History of Etiologic Confusion between Dengue and Chikungunya

Contrary to the perception of many researchers that the recent invasion of chikungunya (CHIK) in the Western Hemisphere marked the first episode in history, a recent publication reminded them that CHIK had prevailed in the West Indies and southern regions of the United States from 1827–1828 under the guise of “dengue” (DEN), and that many old outbreaks of so-called “dengue” actually represented the CHIK cases erroneously identified as “dengue.” In hindsight, this confusion was unavoidable, given that the syndromes of the two diseases—transmitted by the same mosquito vector in urban areas—are very similar, and that specific laboratory-based diagnostic techniques for these diseases did not exist prior to 1940. While past reviewers reclassified problematic “dengue” outbreaks as CHIK, primarily based on manifestation of arthralgia as a marker of CHIK, they neither identified the root cause of the alleged misdiagnosis nor did they elaborate on the negative consequences derived from it. This article presents a reconstructed history of the genesis of the clinical definition of dengue by emphasizing problems with the definition, subsequent confusion with CHIK, and the ways in which physicians dealt with the variation in dengue-like (“dengue”) syndromes. Then, the article identifies in those records several factors complicating reclassification, based on current practice and standards. These factors include terms used for characterizing joint problems, style of documenting outbreak data, frequency of manifestation of arthralgia, possible involvement of more than one agent, and occurrence of the principal vector. The analysis of those factors reveals that while some of the old “dengue” outbreaks, including the 1827–1828 outbreaks in the Americas, are compatible with CHIK, similar reclassification of other “dengue” outbreaks to CHIK is difficult because of a combination of the absence of pathognomonic syndrome in these diseases and conflicting background information.     

Genetic and Phylogenetic Characterization of a Chikungunya Virus Imported into Shenzhen,China

正Dear Editor,Chikungunya virus (CHIKV) is a mosquito-borne virus belonging to the family Togaviridae, genus Alphavirus, and was first isolated in Tanzania in the 1950s (Silva and Dermody 2017; Weaver and Lecuit 2015). Human infec-     

Genetic evidence for Rift Valley fever outbreaks in Madagascar resulting from virus introductions from the East African mainland rather than enzootic maintenance

Rift Valley fever virus (RVFV), a mosquito-borne phlebovirus, has been detected in Madagascar since 1979, with occasional outbreaks. In 2008 to 2009, a large RVFV outbreak was detected in Malagasy livestock and humans during two successive rainy seasons. To determine whether cases were due to enzootic maintenance of the virus within Madagascar or to importation from the East African mainland, nine RVFV whole genomic sequences were generated for viruses from the 1991 and 2008 Malagasy outbreaks. Bayesian coalescent analyses of available whole S, M, and L segment sequences were used to estimate the time to the most recent common ancestor for the RVFVs. The 1979 Madagascar isolate shared a common ancestor with strains on the mainland around 1972. The 1991 Madagascar isolates were in a clade distinct from that of the 1979 isolate and shared a common ancestor around 1987. Finally, the 2008 Madagascar viruses were embedded within a large clade of RVFVs from the 2006-2007 outbreak in East Africa and shared a common ancestor around 2003 to 2004. These results suggest that the most recent Madagascar outbreak was caused by a virus likely arriving in the country some time between 2003 and 2008 and that this outbreak may be an extension of the 2006-2007 East African outbreak. Clustering of the Malagasy sequences into subclades indicates that the viruses have continued to evolve during their short-term circulation within the country. These data are consistent with the notion that RVFV outbreaks in Madagascar result not from emergence from enzootic cycles within the country but from recurrent virus introductions from the East African mainland.     

Avian influenza (H5N1) virus of clade 2.3.2 in domestic poultry in India

South Asia has experienced regular outbreaks of H5N1 avian influenza virus since its first detection in India and Pakistan in February, 2006. Till 2009, the outbreaks in this region were due to clade 2.2 H5N1 virus. In 2010, Nepal reported the first outbreak of clade 2.3.2 virus in South Asia. In February 2011, two outbreaks of H5N1 virus were reported in the State of Tripura in India. The antigenic and genetic analyses of seven H5N1 viruses isolated during these outbreaks were carried out. Antigenic analysis confirmed 64 to 256-fold reduction in cross reactivity compared with clade 2.2 viruses. The intravenous pathogenicity index of the isolates ranged from 2.80-2.95 indicating high pathogenicity to chickens. Sequencing of all the eight gene-segments of seven H5N1 viruses isolated in these outbreaks was carried out. The predicted amino acid sequence analysis revealed high pathogenicity to chickens and susceptibility to the antivirals, amantadine and oseltamivir. Phylogenetic analyses indicated that these viruses belong to clade 2.3.2.1 and were distinct to the clade 2.3.2.1 viruses isolated in Nepal. Identification of new clade 2.3.2 H5N1 viruses in South Asia is reminiscent of the introduction of clade 2.2 viruses in this region in 2006/7. It is now important to monitor whether the clade 2.3.2.1 is replacing clade 2.2 in this region or co-circulating with it. Continued co-circulation of various subclades of the H5N1 virus which are more adapted to land based poultry in a highly populated region such as South Asia increases the risk of evolution of pandemic H5N1 strains.     

Genotypic and Phenotypic Characterization of Chikungunya Virus of Different Genotypes from Malaysia

Background

Mosquito-borne Chikungunya virus (CHIKV) has recently re-emerged globally. The epidemic East/Central/South African (ECSA) strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia.

Methods and Findings

CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36). Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates.

Conclusions

The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species.     

Genetic characterization of Chikungunya virus from New Delhi reveal emergence of a new molecular signature in Indian isolates

ABSTRACT: BACKGROUND: Chikungunya (CHIK) is currently endemic in South and Central India and exist as co-infections with dengue in Northern India. In 2010, New Delhi witnessed an outbreak of CHIK in the months October-December. This was the first incidence of a dominant CHIK outbreak in Delhi and prompted us to characterize the Delhi virus strains. We have also investigated the evolution of CHIK spread in India. FINDINGS: Clinical samples were subjected to RT-PCR to detect CHIK viral RNA. The PCR amplified products were sequenced and the resulting sequences were genetically analyzed. Phylogenetic analysis based on partial sequences of the structural proteins E1 and E2 revealed that the viruses in the latest outbreak exhibited ECSA lineage. Two novel mutations, E1 K211E and E2 V264A were observed in all Delhi isolates. In addition, CHIKV sequences from eight states in India were analyzed along with Delhi sequences to map the genetic diversity of CHIKV within the country. Estimates of average evolutionary divergence within states showed varying divergence among the sequences both within the states and between the states. We identified distinct molecular signatures of the different genotypes of CHIKV revealing emergence of a new signature in the New Delhi clade. Statistical analyses and construction of evolutionary path of the virus within the country revealed gradual spread of one specific strain all over the country. CONCLUSION: This study has identified unique mutations in the E1 and E2 genes and has revealed the presence of ancestral CHIKV population with maximum diversity circulating in Maharashtra. The study has further revealed the trend of CHIK spread in India since its first report in 1963 and its subsequent reappearance in 2005.     

Rabies outbreak in African Wild Dogs (Lycaon pictus) in the Tuli region,Botswana: Interventions and management mitigation recommendations

We describe an outbreak of rabies in a pack of African wild dogs (Lycaon pictus) in the Limpopo-Lipadi Private Game and Wilderness Reserve in the Tuli region of south-eastern Botswana. We define the pack’s behavioural response to the disease, clinical signs, and management interventions undertaken and make recommendations to mitigate against future disease outbreaks of this nature. The outbreak, which occurred in late 2014 and early 2015, resulted in the death or disappearance of 29 individuals out of a pack of 35 wild dogs. The disruption to the social structure within the pack, the behaviour of the animals and clinical signs were similar to that documented during previous rabies outbreaks amongst African wild dogs in Southern and East Africa in recent years. Management interventions taken during the outbreak were aimed at preventing extirpation of the pack and reducing the risk of further disease spread to other mammals in the reserve.     

Global human security in the post–COVID-19 era: The rising role of East Asia

Kenji Shibuya and coauthors discuss the potential contribution of East Asian countries to global health in the light of COVID-19.

Summary points

• East Asia, comprising the 10 ASEAN countries, China, Japan, and the countries of the Korean peninsula, has achieved comparatively good outcomes during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic.
• This can be explained by sociological imprinting of and learning from past outbreaks, as well as competent governance.
• Concomitantly, East Asian nations have also been expanding capacity in global health development and diplomatic outreach, although there is as yet no coherent regional bloc vision, shared strategy, or a common set of operating principles, thus limiting synergistic impact.
• We believe that concrete next steps to bolster cooperation and extend influence could include the establishment of an East Asian Center for Disease Control, joint work in health and human security by the Asian Development Bank (ADB) and Asian Infrastructure and Investment Bank, and a region-wide research funding programme.
• Much, however, depends on evolving geopolitics writ large, notably the instability and reorientation of global alliances, which have the potential to adversely affect relations between neighbouring East Asian member states.
• Health diplomacy for global human security has the potential to become a stabilising influence and can be a topic around which all actors can more comfortably rally.

While the constituent countries of East Asia share common elements of history and culture, there is great diversity and rapid transition in social systems, economic development, demography, and epidemiological profiles (S1 Table). These factors fundamentally lead to the full range of major global health challenges, including those concerning epidemics and pandemics of novel and reemerging pathogens.Here, in the light of Coronavirus Disease 2019 (COVID-19), we discuss East Asia’s experience in this and past major outbreaks, its capacity and willingness to share best practice and support global health development, and the regional bloc’s potential in reshaping the global architecture for human security.Geographically and ethnoculturally, East Asia has conventionally referred to the region comprising China, Japan, Republic of Korea (South Korea), Democratic People’s Republic of Korea (North Korea), and Mongolia. More recently, the term has been broadened to encompass Southeast Asia (viz the 10 member states of ASEAN, the Association of South East Asian Nations), largely due to expanded regional economic cooperation and latterly for geopolitical reasons.     

Origin and diversification of African ferns with special emphasis on Polypodiaceae

Although Africa harbors low species diversity compared to the neotropics or South East Asia, the African fern flora is of interest because of its specific composition and geographic location between the neotropics and Asia. We address the question of how the evolution of the African fern flora may have been enriched by repeated input from the neotropics and Asia. For the purpose of this paper we consider ihree major biogeographic regions: the neotropics, Africa and Madagascar, and Asia including Malesia and Australasia. We interpret distribution data for six clades of Polypodiaceae in a molecular phylogenetic framework. We conclude that African fern taxa shared with or closely related to ones in the neotropics or Asia have been brought about by ancient and recent dispersal events with or without subsequent speciation. The African fern flora is interpreted as being composed of endemic, neotropical, and Asian elements and as being situated in a zone of overlap of typical neotropical and Asian fern floras.     

Application of a Simplified Molecular Protocol to Reveal Mixed Infections with Begomoviruses in Cassava

Samples of cassava leaves exhibiting severe symptoms of cassava mosaic disease (CMD) were collected with the PhytoPASS kit in fields surrounding the city of Bujumbura (Burundi). These materials were then sent to Belgium for polymerase chain reaction determination of the CMD begomoviruses inducing the observed symptoms. Different pairs of specific primers were used to amplify DNA sequences specific to African cassava mosaic virus (ACMV), East African cassava mosaic virus (EACMV), East African cassava mosaic Cameroon virus (EACMCV), East African cassava mosaic Malawi virus (EACMMV), East African cassava mosaic Zanzibar virus (EACMZV), the Uganda variant of East African cassava mosaic virus (EACMV-UG) and South African cassava mosaic virus (SACMV). It was revealed that mixed infections were prevailing in the analyzed materials. Most of the samples submitted to this analysis were found to be co-infected by three different begomoviruses (ACMV + EACMV + EACMV-UG). The so revealed mixed infections could explain the high severity of CMD symptoms noticed on cassava in the region of Bujumbura while the diversity within the CMD causal agents illustrates the importance to take this parameter into consideration for a successful use of plant genetic resistance to control the disease.     

The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas

Since first isolation in 1947 from the Zika forest in Uganda, Zika virus(ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016,an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins,dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.