Unsuccessful Cassava Brown Streak Disease (CBSD) evaluation attempts in western Democratic Republic of Congo and implications with cassava root necrosis disease (CRND) etiology

Open Access ArticleCassava brown streak disease (CBSD) is the second most important virus disease after Cassava mosaic disease (CMD), infecting cassava (ManihotesculetaCrantz) in Africa. The disease is caused by two distinct viruses, Cassava brown streak virus [2, 3] and Ugandan Cassava brown streak virus (family, Potyviridae: genus, Ipomovirus). Transmission of CBSV from one plant to another is reported to occur through grafting CBSV-free with infected cuttings and subsequent dissemination by infected cuttings. The basic approach to control of CBSD is selecting planting material from symptomless mother plants. Graft inoculation is the most efficient and effective of the techniques for CBSD virus transmission and consequently cuttings are the most effective way of the disease spreading. In early 2000s, cassava root necrosis similar to those of CBSD were reported in western provinces of Democratic Republic of Congo (RDC) (Kinshasa and Kongo Central) and up to date PCR diagnoses did not detect any causal agent related to the observed symptoms and the disease which was still referred as ‘CBSD-like disease’. Due to lack of molecular data and the similarity of root symptoms with CBSD, the existence of a virus has always been suspected to be the cause of CBSD-like propagation. Thus, 2 field experiments were proposed in order to verify the existence of a systematic transmission of a possible CBSD related virus, knowing that CBSD viruses are transmitted efficiently by cuttings. The first trial focused on the field evaluation of CBSD – like infected and apparently uninfected planting materials, while the second trial involved the importation of tanzanian CBSD resistant genotypes for evaluation in INERA Mvuazi research center under CBSD-like infection conditions. Results of the first trial did not show a systemic transmission of any CBSD-like pathogen while CBSD-resistant parents involved in the second trial all succumbed to CBSD-like disease

Assessing the severity and the incidence of Cassava Root Necrosis Disease (CRND) in western Democratic Republic of Congo

Open Access ArticleCassava is the staple food in the Democratic Republic of Congo (DRC) where both the roots and leaves are consumed. This crop is susceptible to several viral diseases, including Cassava Mosaic Disease(CMD) and Cassava Brown Streak Disease(CBSD) in eastern DRC. Following earlier studies that show root necrosis occurring in western DR Care not due to CBSD but to Cassava Root Necrosis Disease (CRND), an exploratory survey was conducted in western DRC from 2016 to 2017 in order to determine the distribution, the severity and the incidence of this disease (previously known as CBSD-like disease). NGS ( Next Generation Sequencing) results confirmed all the previous negative results obtained using PCR and CBSV primers. This suggests that microorganisms such as bacteria or fungi could be responsible for cassava root necrosis in western DRC and is not CBSD as predicted. Five provinces (Bas-Congo, Kinshasa, Bandundu, Equateur and Kasai-Oriental) were surveyed and data were collected according to the harmonized protocols adopted by countries within the West African Virus Epidemiology (WAVE) project. Statistical tests (ANOVA) performed on our data showed that CRND severity did not vary significantly among the provinces of Kinshasa, Bandundu and Bas-Congo which are the areas most affected by the disease. Bas-Congo and Kinshasa provinces presented the highest maximum disease severity (score 3 and 5 respectively), while Equateur province had the lowest disease severity score. Equateur province also had the highest percentage of healthy plants and few plants presented mild symptoms. The overall average of cassava root necrosis severity in western DRC ranged around 1.88 ± 0.08, an approximate score of 2. The overall mean incidence of CRND in western DRC was 22.24 ± 2.4% but reached 100% in localities considered as hotspots (Lukuakua in Bas-Congo and Nguma in Plateau des Batékés). The behaviour of cassava varieties against CRND is similar with CBSD in East Africa, most of improved varieties and landraces are susceptible to both diseases. Correlation analyses showed a positive correlation (r = 0.6940) between severity and incidence of CRND. Therefore, Bas-Congo province is the most affected province, while the province of Equateur is the least affected province in western DRC. Further investigations, including genomic surveillance, should also be conducted in the eastern DRC where CBSD is confirmed to know if CRND is found in conjunction with CBSD and to report possible instances of mixed infections. For medium-term disease control, our study suggests that the development and deployment of control measures including cultivars with resistance to CRND and CBSD should be a priority

Biofortified Bean Genotypes under Integrated Soil Fertility Soil Management in the humid mid-highlands of Democratic Republic of Congo (DRC)

Bean (Phaseolus vulgaris L) is an important crop for more than 20 millions people in Eastern, Southern and Western D.R. Congo, where its consumption can supply 60 % of dietary protein for rural and urban people with an estimated consumption of 60 kg per year and per person. It is the most grown legume that provides daily metabolic needs, on carbohydrates, proteins, and micronutrient. •Despite high bean consumption , the malnutrition in general and malnutrition due to iron and zinc deficiency remains high and almost chronic within bean production areas and the prevalence of anemia due to iron deficiency is very high (53 % among pregnant women in North and South Kivu). •Bean production level depends on many factors: yield potential, biotic and abiotic constraints and farming practices. Yield is always the first trait for famers and evidence for bio fortification breeding shows that high micronutrient concentration can be combined with yield, pests and diseases resistance. •Although identification of best genotypes (through plant breeding), Understanding of trait expression to the optimal levels requires exploring environmental conditions and elucidating genotype‐by‐environment interactions (G x E). Soil is one of most components of the environment which can be influenced by farming practices such as ISFM. • The main objective of this study was to investigate the contribution of ISFM options (in addition to breeding) on yield, micronutrient content, Pests and diseases resistance of bean genotypes in Multi‐Environment Trials ( MET), by assessing cultivar’s response and stability across environment (locations x years) in relationship with ISFM

From concept to action: a united, holistic and One Health approach to respond to the climate change crisis

It is unequivocal that human influence has warmed the planet, which is seriously affecting the planetary health including human health. Adapting climate change should not only be a slogan, but requires a united, holistic action and a paradigm shift from crisis response to an ambitious and integrated approach immediately. Recognizing the urgent needs to tackle the risk connection between climate change and One Health, the four key messages and recommendations that with the intent to guide further research and to promote international cooperation to achieve a more climate-resilient world are provided

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial

BACKGROUND: Fexinidazole has been reported as an effective oral monotherapy against non-severe gambiense human African trypanosomiasis in a recent trial in adults. We aimed to assess the safety and efficacy of fexinidazole in children across all disease stages of gambiense human African trypanosomiasis. METHODS: We did a multicentre, single-arm, open-label, phase 2-3 trial at eight district hospitals in the Democratic Republic of the Congo. We recruited children with a Karnofsky score of more than 50, those aged 6 years to younger than 15 years, weighing 20 kg or more, and with confirmed gambiense human African trypanosomiasis (any stage). Children weighing 20 kg or more and less than 35 kg received oral fexinidazole of 1200 mg (two x 600 mg tablets) once per day for 4 days (days 1-4) followed by 600 mg (one x 600 mg tablet) once per day for 6 days (days 5-10). Children weighing 35 kg or more received oral fexinidazole of 1800 mg (three x 600 mg tablets) once per day for 4 days (days 1-4), followed by 1200 mg (two x 600 mg tablets) once per day for 6 days (days 5-10). The primary endpoint was fexinidazole treatment success rate 12 months after end of treatment. A rate greater than 80% was deemed acceptable and a target value of 92% was aimed for. Safety was assessed through routine monitoring. This study is completed and registered with ClinicalTrials.gov, number NCT02184689. FINDINGS: Between May 3, 2014, and Nov 22, 2016, we screened a total of 130 paediatric patients, of whom 125 (96%) received at least one dose of fexinidazole. All 125 patients (69 [55%] patients with stage 1, 19 [15%] with early stage 2, and 37 [30%] with late stage 2 gambiense human African trypanosomiasis) completed the 10-day treatment. Treatment success rate at 12 months was 97.6% (95% CI 93.1-99.5; 122 of 125 patients). The primary endpoint was met and the targeted value of 92% was exceeded. Treatment success at 12 months was elevated across all disease stages: 98.6% (95% CI 92.2-99.9; 68 of 69 patients) in stage 1, 94.7% (74.0-99.9; 18 of 19 patients) in early stage 2, and 97.3% (85.8-99.9; 36 of 37 patients) in late stage 2 gambiense human African trypanosomiasis. No new safety issues were observed beyond those found in adult trials. Overall, 116 (93%) of 125 patients reported 586 treatment-emergent adverse events, mainly mild or moderate. The most frequently reported treatment-emergent adverse events of interest during hospital admission were vomiting (86 [69%] of 125) and headache (41 [33%]). Seven (6%) of 125 patients had severe malaria, which was often accompanied by anaemia that was unrelated to fexinidazole. One patient died following dyspnoea and injury due to traumatic aggression 172 days after end of treatment, which was considered unrelated to fexinidazole or gambiense human African trypanosomiasis. INTERPRETATION: Oral fexinidazole is a safe and effective first-line treatment option across all gambiense human African trypanosomiasis disease stages in paediatric patients. FUNDING: Through the Drugs for Neglected Diseases initiative: the Bill & Melinda Gates Foundation (USA), the Republic and Canton of Geneva (Switzerland), the Dutch Ministry of Foreign Affairs (Netherlands), the Norwegian Agency for Development Cooperation (Norway), the Federal Ministry of Education and Research through KfW (Germany), the Brian Mercer Charitable Trust (UK), and other private foundations and individuals from the human African trypanosomiasis campaign. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial

Background: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. Methods: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18–45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. Findings: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22–30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73–1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06–0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3–2·57]; hazard ratio 0·12 [0·05–0·31]; p<0·0001; risk difference –1·6% [–1·0% to –2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9–1·7); no congenital birth anomalies were reported. Interpretation: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. Funding: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support

Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults

BACKGROUND : A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS : In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS : In January 2020, prespecified criteria for non-efficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS : The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.Supported by grants (HHSN272201300033C and HHSN272201600012C) to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline [GSK] Biologicals) by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C; by the Bill and Melinda Gates Foundation Global Health Grant (OPP1017604) and NIAID for the manufacture and release of the gp120 clinical grade material; and by U.S. Public Health Service Grants — UM1 AI068614 to the HIV Vaccine Trials Network (HVTN), UM1 AI068635 to the HVTN Statistical and Data Management Center, and UM1 AI068618 to the HVTN Laboratory Center — from the NIAID. GSK Biologicals contributed financially to the provision of preexposure prophylaxis to trial participants. The South African Medical Research Council supported its affiliated research sites.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH

A ROADMAP FOR THE USE OF INTERFACIAL SYMMETRY GROUPS

La détermination et l'utilisation des groupes de symétrie des interfaces et leurs applications à l'étude des propriétés physiques des joints de grain sont présentées sous forme de diagramme synoptique. On discute la signification et les limites de validité des arguments de symétrie qui ont été utilisés jusqu'à présent dans le domaine des joints de grain. On examine en particulier la généralité relative des modèles géometriques couramment utilisés.A schematic representation of the methods of deriving interfacial symmetry groups and of their application to the study of a variety of interfacial properties is presented. We discuss both the limitations and scope of interfacial symmetry arguments and survey the reliable applications that exist to date. A critical discussion of the usefulness of various currently popular geometrical models of interfaces is included