o. The number treated, newly diagnosed, as well as Fibrotic Stage, Treated Age, and SVR Rates are reported annually through 2025.
2030. For the purposes of this modelling study, elimination was defined as a 90% reduction in total viremic infections. The model was used to estimate what increases in diagnosis and treatment were necessary to achieve this overall reduction. Medical eligibility remained the same as in the Base 2017 scenario (patients ≥ F0, 15 - 79 years of age, and 95% SVR), while treatment and diagnosis were increased.
Through the literature search, 20 studies published between Jan 1, 1985, and June, 2018 were identified through PubMed (n = 7) and Embase (n = 13) searches. After removing duplicates (n = 4), 16 studies were selected for review and inclusion in the final analysis (Figure 1).
There was an estimated 392,000 (95% CI: 144,800 - 590,900) viremic infections in 2017, corresponding to a viremic prevalence of 3.3% (95% CI: 1.2% - 5.0%). Almost half of all infections were found in those aged 20 - 49 (Figure 2), with a bimodal age distribution. Due to the limited number of treatments occurring in country and aging of the infected population, the number of viremic infections is expected to decline to 347,000 by 2030, less than a 15% decrease over the next fifteen years. More so, associated liver related morbidity and mortality is expected to increase under the current standard of care. In 2017, there were an estimated 3000 decompensated cirrhosis cases and 1300 hepatocellular carcinoma
Figure 1. Flow chart of included studies.
Figure 2. Estimated viremic HCV infected population by age in 2017. The age distribution of cases shows a bimodal curve in Burundi, suggesting an older wave of infected individuals (in those aged 50 - 64) and a newer insurgence of infections, particularly in those aged 20 - 34.
cases. These numbers are forecasted to increase by 45% by 2030, to 4400 and 1900 cases, respectively. Additionally, liver related mortality is expected to increase by 40% by the year 2030. There will be an estimated 2100 deaths due to HCV if no treatment or disease management strategy is put into place.
To achieve Elimination of HCV in Burundi by 2030, drastic increases in both diagnosis and treatment are necessary. The number of treated patients will need to increase to 35,000 patients annually starting in 2025 and the number of newly diagnosed also needs to increase to 34,000 patients annually by the same year in order to achieve a 90% reduction in total viremic infections by 2030.
Under the Elimination strategy, outcomes are expected to improve significantly (Figure 3). Total viremic infections are expected to decline by 90%, to less than 39,000 infections by 2030. Liver related mortality and late stage liver disease is forecasted to decline considerably as well. Total decompensated cirrhosis cases are expected to decline by 85%, from 3000 in 2016 to 390 in 2030. HCC cases will decline by the same proportion, from 1300 to 200 in 2030. Finally, HCV-related mortality will decrease by 85% to 220 deaths in 2030. Under this scenario, 6900 incident cases of HCC and more than 5400 incident cases of decompensated cirrhosis could be averted. More than 12,470 lives could be saved by achieving elimination by 2030.
Recent global and regional estimates have shown a wide variance of viremic infections across the African continent. This is most likely due to the sensitivity and specificity of the types of serological tests used and the fluctuating modes of transmission across the continent  . A recent World Health Organization
Figure 3. Forecasted HCV-related morbidity and mortality by intervention strategy, 2016 through 2030. The Base 2017 strategy showcases the outcomes of the current standard of care. The Elimination strategy (in green) results in an 85% - 90% decrease in HCV-related infections, liver related morbidity and mortality.
(WHO) report noted that in the African region, there were an estimated 31 per 100,000 new incident HCV infections in 2015  . While the Eastern Mediterranean Region and European Regions experience almost double the number of incident cases, 62.5 and 61.8, respectively, the African region experiences a younger infected population. This may mean a new wave of infections in the continent, especially as limited prevention and treatment programs exist. Sub-Saharan Africa, specifically, was found to have more than 30 times new infections than cures in 2016  . More so, the African region was estimated to have one of the highest prevalence rates, with an estimated 1% (0.7% - 1.6%) or approximately 11 million (7,000,000 - 16,000,000) cases in 2015. Overall total infections are expected to decline minimally over the next fifteen years throughout Africa, due to the increase in mortality. According to the WHO report, the largest burden of mortality associated with hepatitis of any WHO region is in Africa, with 13.7 deaths per 100,000 in 2015. In Sub-Saharan Africa, the number of estimated deaths due to cirrhosis almost doubled from 53,000 in 1980 to 103,000 in 2010  .
These outcomes, though dire, are expected, as access to HCV diagnosis and treatment remain quite limited across the African continent. According to the WHO, approximately 6% of the infected population was diagnosed in 2015, while less than 1% was on treatment  . This is echoed in Burundi, where treatment and prevention efforts have been restricted. This analysis estimates that of the infected population in 2016 (396,000), only 5% have been diagnosed and less than 1% were on treatment. If Burundi is to achieve elimination, it is clear that drastic efforts to link patients to care and initiate treatment are needed; however, some strides have recently been made in the country. In 2017, treatment restrictions were removed, thus making all patients eligible for treatment. This could potentially open access and increase the number screened and diagnosed in the country, the largest bottleneck to achieving elimination. Targeted screening strategies could be implemented throughout Burundi in order to improve this cascade of care. Recommendations from other regions throughout Southern Africa have suggested strategies focusing on key risk groups or modes of transmission  . Birth cohort screening in those aged 20 - 49 or 50 - 64 in Burundi may be justified in order to diagnose the largest portion of the infected population. More so, risk factor screening, such as screening anybody who has ever received a blood transfusion or medical procedure prior to blood screening, could be useful  . This is particularly true in Burundi, where the main modes of transmission were found to be nosocomial and related to traditional practices, as reflected in the bimodal age distribution of infections. Screening programs targeting those with tattoos, including traditional practice markings, could be included as well  .
More so, there is a need to improve the education and awareness of general practitioners and other care providers when screening and diagnosing hepatitis C patients throughout Burundi. General practitioners (GPs) can contribute significantly to improving linkage to care; however, strategic programs of health education and awareness for both professional and risk groups are warranted  . According to a surveillance report in Europe, in 2012, only 21% of hepatitis C cases were diagnosed in general practice  . Making GPs aware of risk factors may efficiently improve case identification  and diagnosed and treated  . In Burundi, where standard screening practices are lacking, educated GPs can help identify patients and improve treatment adherence. This, coupled with increased sensitization of the general population, can enhance testing uptake  , both of which are necessary steps if Burundi is to achieve elimination by 2030.
This is the first modelling analysis to forecast the current and future epidemiology of Hepatitis C virus infection in Burundi and estimate what is necessary in order to achieve elimination of the disease over the next fifteen years. However, this modelling work is dependent upon quality and availability of data, which is limited throughout Africa. Other reports have noted the scarcity of reliable prevalence data and population based studies, as well as the lack of estimates of the number diagnosed and treated annually in country   . To capture these uncertainties, all inputs were validated by experts and prevalence was estimated with a 95% uncertainty interval. However, in Burundi and across the continent, more recent nationally representative surveys are warranted. Additionally, the adoption of a national registry to track notifications and identify the treated population could be necessary if Burundi is to achieve elimination in the next fifteen years. This modelling study did not consider the costs associated with treatment and diagnosis as it was outside the scope of the original analysis. While the cost of treatment, particularly in low-income countries, has been reduced in recent years, further negotiations at the country level will be needed in order to increase access to diagnostics and treatment for all. A further evaluation examining the cost-analysis and affordability of such elimination programming would be required as the first step towards developing an elimination plan.
The goal of achieving elimination of HCV in Burundi is plausible, if efforts to substantially increase the diagnosed and treated population are implemented. Efforts to expand affordable programming and reduce the expected increase in late stage liver related morbidity and mortality could be assessed.
This study was supported through the CDA Foundation’s Polaris Observatory (www.cdafound.org). Authors wish to thank Mindi DePaola for her feedback and formatting assistance.
The authors declare no conflict of interest.
SR conducted the literature review and RN provided data. All authors contributed to the analysis, prepared the draft and final manuscript. The authors approve of the final version.