Immune #correlates of the #Thai #RV144 #HIV #vaccine regimen in South Africa (Sci Transl Med., abstract)

[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]

Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa

Glenda E. Gray1,2,3,*, Ying Huang3, Nicole Grunenberg3, Fatima Laher1, Surita Roux4,†, Erica Andersen-Nissen3,5, Stephen C. De Rosa3, Britta Flach5, April K. Randhawa3, Ryan Jensen3, Edith M. Swann6, Linda-Gail Bekker4, Craig Innes7, Erica Lazarus1, Lynn Morris8, Nonhlanhla N. Mkhize8, Guido Ferrari9, David C. Montefiori9, Xiaoying Shen9, Sheetal Sawant9, Nicole Yates9, John Hural3, Abby Isaacs3, Sanjay Phogat10, Carlos A. DiazGranados10, Carter Lee11, Faruk Sinangil11, Nelson L. Michael12, Merlin L. Robb12, James G. Kublin3, Peter B. Gilbert3, M. Juliana McElrath3, Georgia D. Tomaras9 and Lawrence Corey3

1 Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 1864, South Africa. 2 South African Medical Research Council, Cape Town 7505, South Africa. 3 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. 4 The Desmond Tutu HIV Centre, University of Cape Town, Cape Town 8001, South Africa. 5 Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, Cape Town 8001, South Africa. 6 Vaccine Research Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. 7 The Aurum Institute, Klerksdorp 2570, South Africa. 8 National Institute for Communicable Diseases, National Health Laboratory Service, Sandringham, Johannesburg 2192, South Africa. 9 Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. 10 Sanofi Pasteur, Swiftwater, PA 18370, USA. 11 Global Solutions for Infectious Diseases, South San Francisco, CA 94080, USA. 12 US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

*Corresponding author. Email: glenda.gray@mrc.ac.za

† Present address: Synexus Clinical Research SA (Pty) Ltd., Somerset West, Cape Town, South Africa.

Science Translational Medicine  18 Sep 2019: Vol. 11, Issue 510, eaax1880 / DOI: 10.1126/scitranslmed.aax1880

 

Taking RV144 beyond Thailand

The RV144 vaccine trial in Thailand is the only HIV vaccine to show efficacy against HIV infection to date. Gray et al. designed the HVTN 097 trial to test this regimen in South Africa, where clade C HIV circulates; this clade is heterologous to the vaccine antigens. They intently examined immune protective responses previously identified in the RV144 trial and found that the vaccine seemed to be even more immunogenic in South Africans. CD4+ T cell responses were stronger and more common in HVTN 097, and the magnitude of protective antibody responses was greater compared to RV144. Their results indicate that the RV144 regimen or others like it could be protective in areas where HIV is endemic.

 

Abstract

One of the most successful HIV vaccines to date, the RV144 vaccine tested in Thailand, demonstrated correlates of protection including cross-clade V1V2 immunoglobulin G (IgG) breadth, Env-specific CD4+ T cell polyfunctionality, and antibody-dependent cellular cytotoxicity (ADCC) in vaccinees with low IgA binding. The HIV Vaccine Trials Network (HVTN) 097 trial evaluated this vaccine regimen in South Africa, where clade C HIV-1 predominates. We compared cellular and humoral responses at peak and durability immunogenicity time points in HVTN 097 and RV144 vaccinee samples, and evaluated vaccine-matched and cross-clade immune responses. At peak immunogenicity, HVTN 097 vaccinees exhibited significantly higher cellular and humoral immune responses than RV144 vaccinees. CD4+ T cell responses were more frequent in HVTN 097 irrespective of age and sex, and CD4+ T cell Env-specific functionality scores were higher in HVTN 097. Env-specific CD40L+ CD4+ T cells were more common in HVTN 097, with individuals having this pattern of expression demonstrating higher median antibody responses to HIV-1 Env. IgG and IgG3 binding antibody rates and response magnitude to gp120 vaccine– and V1V2 vaccine–matched antigens were higher or comparable in HVTN 097 than in RV144 ADCC, and ADCP functional antibody responses were elicited in HVTN 097. Env-specific IgG and CD4+ Env responses declined significantly over time in both trials. Overall, cross-clade immune responses associated with protection were better than expected in South Africa, suggesting wider applicability of this regimen.

Keywords: HIV/ADIS; Vaccines; South Africa.

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High #correlation between #Zika virus NS1 #antibodies and neutralizing antibodies in selected #serum samples from normal healthy #Thais (Sci Rep., abstract)

[Source:  Scientific Reports, full page: (LINK). Abstract, edited.]

High correlation between Zika virus NS1 antibodies and neutralizing antibodies in selected serum samples from normal healthy Thais

Wannapa Sornjai, Suwipa Ramphan, Nitwara Wikan, Prasert Auewarakul & Duncan R. Smith

Scientific Reports, volume 9, Article number: 13498 (2019)

 

Abstract

Despite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutralizing antibodies (27/30 samples), and no sample (0/30) with a ZIKV plaque reduction neutralization test (PRNT)90 < 20 showed evidence of anti-ZIKV NS1 antibodies. The high correlation between the presence of ZIKV NS1 antibodies and ZIKV PRNT suggests that immunological protection against ZIKV infection in Thailand arises from prior exposure to ZIKV, and not through cross neutralization.

Keywords: Zika Virus; Serology; Thailand.

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Determinants of dihydro- #artemisinin-piperaquine #treatment #failure in #Plasmodium falciparum #malaria in #Cambodia, #Thailand, and #Vietnam: a prospective clinical, pharmacological, and genetic study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study

Rob W van der Pluijm, MD, Prof Mallika Imwong, PhD, Nguyen Hoang Chau, MD, Nhu Thi Hoa, MD, Nguyen Thanh Thuy-Nhien, PhD, Ngo Viet Thanh, MD, et al.

Open Access / Published: July 22, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30391-3

 

Summary

Background

The emergence and spread of resistance in Plasmodium falciparum malaria to artemisinin combination therapies in the Greater Mekong subregion poses a major threat to malaria control and elimination. The current study is part of a multi-country, open-label, randomised clinical trial (TRACII, 2015–18) evaluating the efficacy, safety, and tolerability of triple artemisinin combination therapies. A very high rate of treatment failure after treatment with dihydroartemisinin-piperaquine was observed in Thailand, Cambodia, and Vietnam. The immediate public health importance of our findings prompted us to report the efficacy data on dihydroartemisinin-piperaquine and its determinants ahead of the results of the overall trial, which will be published later this year.

Methods

Patients aged between 2 and 65 years presenting with uncomplicated P falciparum or mixed species malaria at seven sites in Thailand, Cambodia, and Vietnam were randomly assigned to receive dihydroartemisinin-piperaquine with or without mefloquine, as part of the TRACII trial. The primary outcome was the PCR-corrected efficacy at day 42. Next-generation sequencing was used to assess the prevalence of molecular markers associated with artemisinin resistance (kelch13 mutations, in particular Cys580Tyr) and piperaquine resistance (plasmepsin-2 and plasmepsin-3amplifications and crt mutations). This study is registered with ClinicalTrials.gov, number NCT02453308.

Findings

Between Sept 28, 2015, and Jan 18, 2018, 539 patients with acute P falciparum malaria were screened for eligibility, 292 were enrolled, and 140 received dihydroartemisinin-piperaquine. The overall Kaplan-Meier estimate of PCR-corrected efficacy of dihydroartemisinin-piperaquine at day 42 was 50·0% (95% CI 41·1–58·3). PCR-corrected efficacies for individual sites were 12·7% (2·2–33·0) in northeastern Thailand, 38·2% (15·9–60·5) in western Cambodia, 73·4% (57·0–84·3) in Ratanakiri (northeastern Cambodia), and 47·1% (33·5–59·6) in Binh Phuoc (southwestern Vietnam). Treatment failure was associated independently with plasmepsin2/3amplification status and four mutations in the crt gene (Thr93Ser, His97Tyr, Phe145Ile, and Ile218Phe). Compared with the results of our previous TRACI trial in 2011–13, the prevalence of molecular markers of artemisinin resistance (kelch13 Cys580Tyr mutations) and piperaquine resistance (plasmepsin2/3 amplifications and crtmutations) has increased substantially in the Greater Mekong subregion in the past decade.

Interpretation

Dihydroartemisinin-piperaquine is not treating malaria effectively across the eastern Greater Mekong subregion. A highly drug-resistant P falciparum co-lineage is evolving, acquiring new resistance mechanisms, and spreading. Accelerated elimination of P falciparum malaria in this region is needed urgently, to prevent further spread and avoid a potential global health emergency.

Funding

UK Department for International Development, Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, and National Institutes of Health.

Keywords: Malaria; Plasmodium falciparum; Artemisin; Drugs resistance; Thailand; Cambodia; Laos; Vietnam.

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#Evolution and #expansion of #MDR #malaria in southeast #Asia: a #genomic #epidemiology study (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study

William L Hamilton, PhD †, Roberto Amato, PhD †, Rob W van der Pluijm, MD, Christopher G Jacob, PhD, Huynh Hong Quang, PhD, Nguyen Thanh Thuy-Nhien, PhD, et al.

Open Access / Published: July 22, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30392-5

 

Summary

Background

A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008–13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.

Methods

For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project. Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population.

Findings

We analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615. Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016–17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos. In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites. KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin. Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions. The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam. These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions. Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016–17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%).

Interpretation

After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts.

Funding

Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

Keywords: Malaria; Plasmodium falciparum; Drugs resistance; Artemisin; Cambodia; Laos; Thailand; Vietnam.

—–

#Vertical #transmission of #Zika virus in #Culex quinquefasciatus Say and #Aedes aegypti (L.) #mosquitoes (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Mar 27;9(1):5257. doi: 10.1038/s41598-019-41727-8.
Vertical transmission of Zika virus in Culex quinquefasciatus Say and Aedes aegypti (L.) mosquitoes.

Phumee A1,2, Chompoosri J3, Intayot P4, Boonserm R2, Boonyasuppayakorn S5, Buathong R6, Thavara U3, Tawatsin A3, Joyjinda Y1, Wacharapluesadee S1, Siriyasatien P7.

Author information: 1 Thai Red Cross Emerging Infectious Health Science Centre, Neuroscience Center for Research and Development & WHO-CC for Research and Training on Viral Zoonoses King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 2 Vector Biology and Vector Borne Disease Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 3 National Institute of Health, Department of Medical Sciences, Nonthaburi, 11000, Thailand. 4 Medical Science Program, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 5 Applied Medical Virology Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 6 Department of Disease Control, Bureau of Epidemiology, Ministry of Public Health, Nonthaburi, 11000, Thailand. 7 Vector Biology and Vector Borne Disease Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. padet.s@chula.ac.th.

 

Abstract

Several mosquito species have been described as vectors for the Zika virus (ZIKV), such as those in the Aedes, Anopheles, Mansonia and Culex genera. Our previous survey studies were found the ZIKV RNA positive in both male, female and larvae of Culex quinquefasciatus Say and Aedes aegypti (L.) mosquitoes collected from active ZIKV infected patients’ homes in Thailand. Therefore, the aims of this study were to investigate whether ZIKV could be vertically transmitted in Cx. quinquefasciatus, Ae. aegypti and Ae. albopictus. Laboratory and field colonies of these mosquito species were maintained and artificially fed with ZIKV in human blood. Fully engorged mosquitoes (F0) were selected and reared for the vertical transmission study. The subsequent mosquito generations were fed with human blood without the virus. ZIKV in the mosquitoes was detected by hemi-nested RT-PCR and sequencing. C6/36 cells were used to isolate ZIKV from samples that tested positive by hemi-nested RT-PCR. Moreover, ZIKV was identified by immunocytochemical staining 7 days after infection in several organs of infected F0 females, including the salivary glands, midguts, yoke granules and facet cells of the eye. The localization of the ZIKV antigen was identified by the presence of the specific antibody in the salivary glands, midguts, yoke granules and facet cells. ZIKV was detected in female and male Cx. quinquefasciatus until the F6 and F2 generations, respectively. The isolated virus showed cytopathic effects in C6/36 cells by 5 days postinfection. The results suggested that the vertical transmission of ZIKV occurs in Cx. quinquefasciatus in the laboratory. However, we were able to detect the presence of ZIKV in Ae. aegypti in only the F1 generation in both male and female mosquitoes, and Ae. albopictus mosquitoes were not able to vertically transmit the virus at all. Data obtained from this study could be valuable for developing a better understanding of the role of Cx. quinquefasciatus as a potential vector for ZIKV transmission in Thailand and may be useful in creating more effective mosquito vector control strategies in the future.

PMID: 30918310 DOI: 10.1038/s41598-019-41727-8

Keywords: Zika Virus; Aedes aegypti; Culex quinquefasciatus; Mosquitoes.

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#Travellers as #sentinels of #chikungunya #epidemics: a #family #cluster among Finnish travellers to Koh Lanta, #Thailand, January 2019 (Euro Surveill., abstract)

[Source: Eurosurveillance, full page: (LINK). Abstract, edited.]

Travellers as sentinels of chikungunya epidemics: a family cluster among Finnish travellers to Koh Lanta, Thailand, January 2019

Anu Kantele 1

Affiliations: 1 Inflammation Center, Department of Infectious Diseases, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Correspondence:  Anu Kantele

Citation style for this article: Kantele Anu. Travellers as sentinels of chikungunya epidemics: a family cluster among Finnish travellers to Koh Lanta, Thailand, January 2019. Euro Surveill. 2019;24(11):pii=1900162. https://doi.org/10.2807/1560-7917.ES.2019.24.11.1900162

Received: 04 Mar 2019;   Accepted: 14 Mar 2019

 

Abstract

In January 2019, five of 11 travellers to Koh Lanta, Thailand, contracted chikungunya, symptoms starting 4 days after presumed transmission. Four cases were hospitalised, one child treated in intensive care; 6 weeks after disease onset, all three adults have persistent arthralgias/arthritis, incapacitating for two. Together with a recent report of eight chikungunya cases among travellers to various destinations in Thailand, the high attack rate in our cluster points to an ongoing outbreak in the country.

© This work is licensed under a Creative Commons Attribution 4.0 International License.

Keywords: Chikungunya fever; Finland; Thailand.

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#Molecular #Epidemiology and Genetic #Diversity of #Zika Virus from Field-Caught #Mosquitoes in Various Regions of #Thailand (Pathogens, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Pathogens. 2019 Mar 6;8(1). pii: E30. doi: 10.3390/pathogens8010030.

Molecular Epidemiology and Genetic Diversity of Zika Virus from Field-Caught Mosquitoes in Various Regions of Thailand.

Phumee A1,2, Buathong R3, Boonserm R4, Intayot P5, Aungsananta N6, Jittmittraphap A7, Joyjinda Y8, Wacharapluesadee S9, Siriyasatien P10.

Author information: 1 Thai Red Cross Emerging Infectious Diseases-Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, Chulalongkorn Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. amphumee@gmail.com. 2 Vector Biology and Vector Borne Disease Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. amphumee@gmail.com. 3 Bureau of Epidemiology, Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand. romebua@hotmail.com. 4 Vector Biology and Vector Borne Disease Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. sky_rung123@hotmail.com. 5 Medical Science Program, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. khunproaw@gmail.com. 6 Public Health Center 22 Wat Pak Bor, Health Department, Bangkok Metropolitan Administration, Bangkok 10250, Thailand. thephonee@gmail.com. 7 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand. akanitt@hotmail.com. 8 Thai Red Cross Emerging Infectious Diseases-Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, Chulalongkorn Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. yutthana.jjd@gmail.com. 9 Thai Red Cross Emerging Infectious Diseases-Health Science Centre, World Health Organization Collaborating Centre for Research and Training on Viral Zoonoses, Chulalongkorn Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. spwa@hotmail.com. 10 Vector Biology and Vector Borne Disease Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand. padet.s@chula.ac.th.

 

Abstract

Zika virus (ZIKV) infection is an emerging and re-emerging arbovirus disease that is transmitted to humans through the bite of infected mosquitoes. ZIKV infections were first described in Thailand in 1954 from the sera of indigenous residents and several travelers returning from Thailand in 2014. However, reported cases in Thailand have been increasing since 2015 and 2016, and epidemiological information about the vectors of ZIKV is unclear. We investigated the molecular epidemiology and genetic diversity of ZIKV from mosquitoes collected from different geographic regions experiencing ZIKV outbreaks in Thailand. Polymerase chain reaction was used to amplify the non-structural protein (NS5) gene of ZIKV, which was then sequenced. A total of 1026 mosquito samples (626 females, 367 males, and 33 larvae) were collected from active ZIKV patients’ houses. ZIKV was detected in 79 samples (7.7%), including Aedes aegypti (2.24% female, 1.27% male, and 0.19% larvae), Culex quinquefasciatus (1.85% female, 1.66% male, and 0.29% larvae), and Armigeres subalbatus (0.1% female and 0.1% male), whereas no ZIKV was detected in Aedes albopictus. Phylogenetic analysis of the 79 positive samples were classified into two clades: Those closely related to a previous report in Thailand, and those related to ZIKV found in the Americas. This is the first report of the detection of ZIKV in Ae. aegypti, Cx. quinquefasciatus, and Ar. subalbatus mosquitoes, and genetic variations of ZIKV in the mosquitoes collected from several geographic regions of Thailand were examined. Detection of ZIKV in male and larval mosquitoes suggests that vertical transmission of ZIKV occurred in these mosquito species. This study provides a more in-depth understanding of the patterns and epidemiologic data of ZIKV in Thailand; the data could be used for future development of more effective prevention and control strategies of ZIKV in Thailand.

KEYWORDS: Thailand; Zika virus; genetic diversity; molecular epidemiology; mosquitoes

PMID: 30845707 DOI: 10.3390/pathogens8010030

Keywords: Zika Virus; Moquitoes; Aedes aegypti; Culex quinquefasciatus; Thailand.

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