Introducing the BMC Series SDG Editorial Board Members: Gerald Mboowa

Gerald Mboowa博士是编辑委员会成员BMC Infectious Diseases。他是非洲疾病控制与预防中心(非洲CDC)的生物信息学实施科学专家,也是Makerere大学传染病研究所(IDI)的研究人员。他专门支持国家公共卫生机构在疾病爆发研究中利用DNA测序技术和计算工具,病原体表征以及抗菌素耐药性监测。

欢迎来到我们SDG编辑委员会成员博客集合。我们正在听到BMC系列期刊编辑委员会成员的消息,他们的工作与实现可持续发展目标相符。在这里,您可以在此集合中找到其他帖子,并与标签“ SDG编辑董事会成员”分组。


My work relates to the WHO Sustainable Development GoalSDG3和focuses on ensuring healthy lives and promoting well-being for all. I have experience in microbial genomics and computational approaches. My research looks at the use of genomic methods for pathogen detection, characterisation as well as understanding transmission dynamics and acquisition of antimicrobial resistance at hospitals and community settings. I am proud to collaborate in achieving SDG3 by working with National Public Health Institutes (NPHI) in Africa facilitating access to sustainable DNA sequencing technologies for rapid and timely response to common infectious disease threats, including drug resistance. Recently, my group has developed an automated & highly scalable assembly, annotation, and higher-level analyses microbial computational pipeline for genomic data calledrmap:快速微生物分析,分析管道和可视化(https://bit.ly/36g809L).

Some of the challenges I have encountered during my research include limited access to DNA sequencing technologies, competitive funding, or high-performance computing (HPC) bioinformatic environments to support large-scale data analyses. However, I have established research collaborations and networks to increase funding opportunities and access to DNA sequencing technologies and HPC. For example, in 2019, the U.S. National Institutes of Health launched the second African Center of Excellence in Bioinformatics (ACE) at the Infectious Diseases Institute in Makerere University’s College (https://ace.idi.co.ug/). This center serves as a regional bioinformatics HPC resource for training and collaborative research for institutions in Africa.

Tools that read and interpret gene variations to enable customized medical care during HIV testing, treatment & management

HIV感染是由单个或有限数量的病毒变异(病毒副本不同)的扩展而产生的。在其基因中发生稳定变化后,HIV病毒的差异出现。由于暴露于抗逆转录病毒疗法(ART)方案,因此在体内不同的HIV病毒或某些病毒基因组合之间的遗传物质交换过程中可能发生这种情况。而且,有时病毒以逻辑方式从一个阶段到另一个阶段自然不会平稳发展。艺术是用于治疗艾滋病毒/艾滋病的药物,继续挽救了数以千万人患有艾滋病毒/艾滋病(PLWHA)的人的生命。在2020年底,估计有3770万PLWHA的2750万人在全球范围内接受艺术。这种对艺术的使用增加伴随着HIV耐药性(HIVDR)的出现,近年来的水平稳步上升。HIVDR是由影响药物停止病毒繁殖能力的HIV基因的变化引起的。由于抗药性病毒菌株的出现,所有艺术药物都有部分或完全不活跃的风险。HIVDR导致HIV感染和与HIV相关的疾病和死亡的数量增加。 The World Health Organization (WHO) report revealed that in 2020, 64% of countries with a high burden of HIV infections had growing HIVDR and recommended national action plans to prevent, monitor and respond to HIVDR. HIV virological failure (VF) signals treatment effectiveness and occurs when ART fails to suppress and sustain one’s viral load to <200 viral copies per ml and is normally associated with HIVDR. It is estimated that 24% of HIV patients in Sub-Saharan Africa have experienced VF. HIVDR and VF remain barriers to reaching the Joint United Nations Programme on HIV/AIDS (UNAIDS) fast-track goal of ending AIDS by 2030.

Sanger sequencing (method of gene sequencing involving electrophoresis and is based on the random incorporation of chain-terminating dideoxynucleotides) is the gold standard for HIVDR testing but is limited by non-detection of resistance-associated variants with prevalence <20% yet these cause VF. Next-generation sequencing or NGS (multiplies millions of copies of all different genes in the virus in a massively paralleled way) detects different HIV variants and has been implemented largely in high-income countries. However, there is very limited application of NGS-based HIVDR platforms in Sub-Saharan Africa which has nearly 70% of global HIV infections.

Why HIV NGS?

对于艾滋病毒感染者,在初始测试之前或在治疗过程中对不同病毒变异的全面表征可通过确保定制治疗,同时最大程度地减少VF和HIVDR,从而改善了其生存机会。在过去的二十年中,在撒哈拉以南非洲的艾滋病毒感染控制方面取得了重大进展,这在很大程度上是由于获得艺术的机会增加。诸如第二代(Illumina,Roche 454和离子洪流)或第三代(PACBIO和纳米孔)DNA测序技术等进步,可以准确地在HIV感染的任何阶段介绍病毒变体,是有效疾病管理的关键,可以防止VF,从而防止VF,从而防止VF,从而防止VF,从而防止VF,从而预防VF,和Hivdr。紧急鉴定病毒遗传标记,可预测不同艺术方案中VF或HIVDR的风险增加,包括诸如Dolutegravir和可注射的长效Cabotegravir/rilpivirine(CAB/RPV)的新较新方案至关重要。这涉及使用生物信息学工具对临床以及病毒载荷数据和病毒基因变异的分析。DNA测序技术和分析方法的进步将有助于引导个性化的HIV管理时代,因为它们能够提供准确的快速检测和耐药性分析接近护理点测试(也称为床边测试)。

在常规HIV测试,治疗和管理中利用下一代测序(NGS)的建议方法。使用基于NGS的技术在ART启动之前,在病毒学衰竭和HIVDR中对病毒种群进行细致分析,对于精确指导治疗过程至关重要。

Virological failure and drug resistance

Non-adherence to ART as well as poor monitoring of viral load during treatment are challenges that continue to affect HIV control programs in Africa leading to the emergence of HIVDR, virological failure, increased HIVDR transmissions, morbidity, and mortality. The WHO recommends global genomic surveillance to monitor dynamics of HIV diversity and emergence of HIVDR. Countries with high infection burden must build robust national HIV genomic surveillance programs to ensure improved management of PLWHA if they are to eradicate HIV/AIDS. ART also referred to as lifetime treatment has transformed HIV infection from a gradual, normally deadly illness to a prolonged disease that endures for many years while subjecting infected individuals to different ART treatments over time. Regular monitoring of viral load is currently used for the assessment of ART response in HIV management. The drugs cause changes in the genes of the virus. These viral gene changes can offer critical insights for understanding mechanisms of drug resistance, effects of therapeutics on the virus, and guide effective vaccine development.

使用NGS和标准Sanger基因分型比较HIVDR分析。Sanger基因分型无法检测到低频HIV突变体,但这些突变体与HIVDR和病毒学衰竭有关。

结论

Considering that many African countries have implemented the universal HIV test and treat strategy (which involves providing lifelong ART to PLWHA irrespective of CD4 or WHO HIV clinical staging), national HIV control programs should utilize NGS in routine HIV testing, treatment, and surveillance. However, this also requires appropriate policy changes, substantial investment in installing NGS platforms and bioinformatics capacity building for infectious diseases control programs.

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