Lay summary of the research article published under the DOI: 10.1371/journal.pntd.0006629
Why was this study done? (problem statement and background)
The United Nations Sustainable Development Goals (SDG 3) call for viral hepatitis to be eliminated as a public health problem by 2030. This means improving how viral hepatitis is prevented, diagnosed and treated. However, certain mutations of the hepatitis B virus (HBV) weaken efforts to prevent and treat it.
These issues are present in Africa where there is a high prevalence of HBV and HIV co-infection. There is also little data about the prevalence and impact of mutations that allow HBV to become resistant to certain drugs or to escape the immune response produced by vaccines.
What was the purpose of this study? (Aims and objectives)
In this study, researchers reviewed the little data that is available for sub-Saharan Africa and made it available in a single online database. The database describes the frequency, prevalence, and co-occurrence of mutations associated with HBV drug resistance mutations (RAMs) and vaccine escape mutations (VEMs) in Africa.
What did the researchers do (summary or overview of methods, the big picture)
The researchers searched the published literature in the scientific journal libraries of MEDLINE, SCOPUS, and EMBASE, between October 2017 and January 2018. They recorded the publication year, study design, sample size, study population, antiviral treatment and other relevant information found in each publication.
What were the results of the study?
They found the most common resistance-associated mutation in Africa is called rtM204I/V, identified both in adults who have not received treatment and those who have. The study found the mutations rtM204V/I, rtL180M, and rtV173L associated with vaccine escape, that were reported to be presente in a third of cohorts, which are the groups of people investigated in the many studies.
The researchers observed, with concern, that the drug tenofovir has some early indications that it also might be causing drug resistance, even though it has been considered unlikely for this drug until now.
The findings suggest a high prevalence of these mutations in some populations in sub-Saharan Africa. Scarce resources have contributed to the lack of HBV diagnostic screening, inconsistent supply of drugs, and poor access to clinical monitoring, all of which contribute to drug and vaccine resistance.
How do these findings add to what was already known? (impact on the current science)
This is the first systematic review that assesses RAMs and VEMs for HBV in Africa. The high rates of HBV infection among HIV infected individuals in some locations including Cameroon and South Africa could be an indication that HBV infection has been previously under-reported, possibly due to lack of routine screening, poor awareness, stigma, high costs and limited clinical and laboratory infrastructure.
What are the potential weaknesses/uncertainties/controversies of the study? (If the paper talks about them at all, but most important for where they mention where future research is needed, or where the data was lacking)
Screening for HBV infection is not routinely performed in many African settings and therefore the true prevalence and characteristics of HBV infection are not known. The researchers were only able to identify very few published studies of patients who had HBV genetic sequencing. This highlights the substantial problem of HBV neglect in Africa, and a specific blind-spot relating to genetic sequence data.
“How will these findings help solve a challenge in Africa?” (question speaking to the impact of the research on society as a whole, outside of the scientific community).
With the results of this study, the researchers recommend sustainable long-term investment to expand consistent drug and vaccine supply, and to provide screening to diagnose infections and to detect drug resistance.
Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in the highly vulnerable setting of sub-Saharan Africa.
Number of words: 594
Glossary terms for translation and coining:
Viral mutations: A mutation of a virus is a change in the genetic code of a virus, so that many mutations of a virus can exist at the same time, which makes creating vaccines for them difficult.
Hepatitis B: A serious liver infection caused by the hepatitis B virus that's easily preventable by a vaccine. This disease is most commonly spread by exposure to infected bodily fluids. Symptoms are variable and include yellowing of the eyes, abdominal pain and dark urine. Some people, particularly children, don't experience any symptoms. In chronic cases, liver failure, cancer or scarring can occur. The condition often clears up on its own. Chronic cases require medication and possibly a liver transplant.
Human immunodeficiency virus (HIV): HIV is a virus that attacks the body's immune system. If HIV is not treated, it can lead to AIDS (acquired immunodeficiency syndrome).
Other keywords for ease of understanding
Vaccine escape (escape variants): These future versions of the viruses are “escape variants” that have evolved in the environment of weak immune responses — the body in this case has produced a strong enough immune response to tamp down the infection but not strong enough to keep mutated viruses from spreading. “How do we overcome escape variants? We do so by using the full strength of the tools we have available to us. We provide immunity that is capable of eliminating the virus quickly and we don’t expose the virus to lots of people with low levels of immunity,” Corey writes. Corey adds that the coronavirus variants currently spreading require a stronger immune response to beat, and current versions of the two-dose vaccines were designed to battle the original versions of the virus.
Coendemic: This refers to two endemic diseases in one person or community, as in the case of the study where researchers considered individuals who had infections of both HIV and HBV.
tenofovir disoproxil fumarate (TDF): Tenofovir disoproxil, sold under the trade name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals.
International sustainable development goals for the elimination of viral hepatitis as a public health problem by 2030 highlight the pressing need to optimize strategies for prevention, diagnosis and treatment. Selected or transmitted resistance associated mutations (RAMs) and vaccine escape mutations (VEMs) in hepatitis B virus (HBV) may reduce the success of existing treatment and prevention strategies. These issues are particularly pertinent for many settings in Africa where there is high HBV prevalence and co-endemic HIV infection, but lack of robust epidemiological data and limited education, diagnostics and clinical care. The prevalence, distribution and impact of RAMs and VEMs in these populations are neglected in the current literature. We therefore set out to assimilate data for sub-Saharan Africa through a systematic literature review and analysis of published sequence data, and present these in an on-line database (https://livedataoxford.shinyapps.io/1510659619-3Xkoe2NKkKJ7Drg/). The majority of the data were from HIV/HBV coinfected cohorts. The commonest RAM was rtM204I/V, either alone or in combination with associated mutations, and identified in both reportedly treatment-naïve and treatment-experienced adults. We also identified the suite of mutations rtM204V/I + rtL180M + rtV173L, that has been associated with vaccine escape, in over 1/3 of cohorts. Although tenofovir has a high genetic barrier to resistance, it is of concern that emerging data suggest polymorphisms that may be associated with resistance, although the precise clinical impact of these is unknown. Overall, there is an urgent need for improved diagnostic screening, enhanced laboratory assessment of HBV before and during therapy, and sustained roll out of tenofovir in preference to lamivudine alone. Further data are needed in order to inform population and individual approaches to HBV diagnosis, monitoring and therapy in these highly vulnerable settings.
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